tag:theconversation.com,2011:/us/topics/sepsis-4833/articlesSepsis – The Conversation2023-09-07T13:52:57Ztag:theconversation.com,2011:article/2129412023-09-07T13:52:57Z2023-09-07T13:52:57ZMartha’s rule: second-opinion law can work – but only if organisational shortcomings are addressed<figure><img src="https://images.theconversation.com/files/546925/original/file-20230907-24-fx7gmg.jpg?ixlib=rb-1.1.0&rect=11%2C11%2C7337%2C4891&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Martha's Rule would empower patients and their families to call for treatment reviews and formal second opinions.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/everything-will-be-ok-promise-329003795">gpointstudio/ Shutterstock</a></span></figcaption></figure><p>As things stand, hospital patients in England have <a href="https://elht.nhs.uk/patients/how-seek-second-opinion#:%7E:text=The%20General%20Medical%20Council%2C%20which,opinion%2C%20they%20should%20do%20so.">no legal right</a> to a second medical opinion. But that could soon change, as a campaign to give patients formal entitlement to an urgent second opinion is gathering momentum and gaining support from <a href="https://www.theguardian.com/society/2023/sep/05/labour-backs-call-for-marthas-rule-on-right-to-second-medical-opinion">key figures</a>, including those in <a href="https://www.bbc.co.uk/news/health-66705490">government</a> as well as the <a href="https://www.bbc.co.uk/news/health-66715670">NHS England Ombudsman</a>. The proposal, called <a href="https://demos.co.uk/research/marthas-rule-a-new-policy-to-amplify-patient-voice-and-improve-safety-in-hospitals/">Martha’s rule</a>, is named after a young girl whose life might have been saved by it. </p>
<p>In 2021, 13-year-old <a href="https://www.theguardian.com/lifeandstyle/2022/sep/03/13-year-old-daughter-dead-in-five-weeks-hospital-mistakes">Martha Mills died</a> following an injury she sustained while on holiday with her family. Martha was treated at King’s College Hospital in London, where she developed life-threatening sepsis. The inquest following Martha’s death found <a href="https://www.standard.co.uk/news/health/martha-mills-sepsis-death-kings-hospital-london-b1104626.html">it was avoidable</a>, and that she would have survived were it not for tragic failures in the medical care she received. These failures included doctors withholding important information about Martha’s condition from her parents and ignoring their concerns.</p>
<p>The proposal, championed by Martha’s mother, Merope Mills, seeks to improve patient safety in hospitals and prevent avoidable deaths like Martha’s by empowering patients and their families to call for treatment reviews and <a href="https://demos.co.uk/research/marthas-rule-a-new-policy-to-amplify-patient-voice-and-improve-safety-in-hospitals/">formal second opinions</a>. </p>
<p>Guidance from the <a href="https://www.gmc-uk.org/-/media/documents/GMC-guidance-for-doctors---Consent---English-2008---2020_pdf-48903482">General Medical Council</a> (the regulatory body for doctors in England) mentions that in some circumstances – typically when a patient doesn’t agree with a doctor’s decision or opinion – it may be appropriate for doctors to discuss the option of a second opinion. But though patients have a right to <a href="https://elht.nhs.uk/patients/how-seek-second-opinion#:%7E:text=The%20General%20Medical%20Council%2C%20which,opinion%2C%20they%20should%20do%20so.">ask for a second opinion</a>, there’s no legal requirement for doctors to provide one.</p>
<p>Martha’s rule would give patients and families the right to seek a rapid review by a separate clinical team – or a second opinion from another specialist doctor based in the same hospital but independent of the team around the patient.</p>
<h2>Second opinion</h2>
<p>There are several similar systems in place around the world. Many of these were introduced following cases like Martha’s.</p>
<p>For example, in Queensland, Australia, <a href="https://clinicalexcellence.qld.gov.au/priority-areas/safety-and-quality/ryans-rule">Ryan’s rule</a> (named after Ryan Saunders, who died in 2007) gives patients and families the right to escalate concerns beyond the hospital and request a clinical review of the patient’s case. As of 2022, Ryan’s rule had been <a href="https://www.abc.net.au/news/2022-06-27/queensland-hospital-treatment-called-ryan-rule/101157236">deployed 7,300 times</a> since it was introduced in 2013. The process has led to <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/ans.17584">clearer communication</a> about care between patients, their families and doctors.</p>
<figure class="align-center ">
<img alt="Two intensive care nurses attend to a sick female patient." src="https://images.theconversation.com/files/546928/original/file-20230907-29-moccqm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/546928/original/file-20230907-29-moccqm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=391&fit=crop&dpr=1 600w, https://images.theconversation.com/files/546928/original/file-20230907-29-moccqm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=391&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/546928/original/file-20230907-29-moccqm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=391&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/546928/original/file-20230907-29-moccqm.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=491&fit=crop&dpr=1 754w, https://images.theconversation.com/files/546928/original/file-20230907-29-moccqm.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=491&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/546928/original/file-20230907-29-moccqm.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=491&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Similar policies in other parts of the world have benefited patients.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/staff-nurses-attending-patient-adult-intensive-2261068623">Peakstock/ Shutterstock</a></span>
</figcaption>
</figure>
<p>Family-initiated <a href="https://cdn.mdedge.com/files/s3fs-public/jhm012030157.pdf">rapid response teams</a> also operate in many US hospitals. When used by a family member, this process provides patients with immediate bedside care from a specialist team. There’s some indication rapid response teams can lead to improved outcomes for patients, including fewer deaths. In one medical centre where this system was introduced, it resulted in markedly <a href="https://pubmed.ncbi.nlm.nih.gov/20655645">fewer cardiac arrests</a> and fewer fatalities from these. </p>
<p>Numerous NHS trusts in England have also introduced “<a href="https://pubmed.ncbi.nlm.nih.gov/21139519/">Call 4 Concern</a>” (C4C) – a system which enables patients and families who feel their concerns are not being addressed to escalate the issue to a “critical care outreach team”. </p>
<p><a href="https://demos.co.uk/wp-content/uploads/2023/08/Marthas-Rule_finalversion.pdf">A 2019 review</a> of how the system was operating in the Royal Berkshire Trust (where the model was pioneered) found the service had been used 534 times in seven years – and that 95% of the calls placed were using the service appropriately. In a fifth of cases, significant interventions were required. As the service became established, some staff used it too. There have since been calls to <a href="https://www.rcn.org.uk/news-and-events/Blogs/implementing-call-4-concern-patient-and-relative-activated-critical-care-outreach-210623">implement the system</a> in all NHS trusts. </p>
<p>It’s clear that such systems can work to improve care for patients. But they are <a href="https://www.rcpjournals.org/content/futurehosp/8/3/e609.full.pdf">not always straightforward</a> to implement. Some people may lack the confidence to <a href="https://cdn.mdedge.com/files/s3fs-public/jhm012030157.pdf">challenge healthcare staff</a> or may not feel they should second-guess a doctor’s opinion, which may inhibit their ability to ask for help. There may be organisational barriers to putting effective systems in place – such as staffing levels and budgetary constraints. There have also been concerns about the potential for inappropriate use or overuse of the facility to request a rapid response (though, as the Royal Berkshire review found, this was minimal). </p>
<p>Over the past decade, there have been considerable changes within the NHS to give greater power and voice to patients and their families. For instance, in 2013 the <a href="https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/170656/NHS_Constitution.pdf">NHS Constitution</a> was published, which brought patient rights to the fore. In 2015, the landmark case of <a href="https://www.supremecourt.uk/cases/uksc-2013-0136.html">Montgomery v Lanarkshire Health Board</a> raised the standard that doctors must meet when informing patients about the risks of proposed medical procedures, and about reasonable alternatives.</p>
<p>In 2014, a statutory <a href="https://www.gmc-uk.org/ethical-guidance/ethical-guidance-for-doctors/candour---openness-and-honesty-when-things-go-wrong/the-professional-duty-of-candour#:%7E:text=This%20means%20that%20health%20and,put%20matters%20right%20(if%20possible)">duty of candour</a> was introduced in England. This includes a legal obligation on health professionals to inform patients and families when something goes wrong, and to apologise.</p>
<p><a href="https://demos.co.uk/research/marthas-rule-a-new-policy-to-amplify-patient-voice-and-improve-safety-in-hospitals/">Advocates for Martha’s rule</a> say it would further “re-balance the power between patients and medics”, and this would undoubtedly be welcome. While the proposal is a necessary step, however, other problems within the NHS – including <a href="https://www.bma.org.uk/advice-and-support/nhs-delivery-and-workforce/pressures/an-nhs-under-pressure">staff shortages and underfunding</a> – could undermine its impact.</p><img src="https://counter.theconversation.com/content/212941/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mary Neal does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Although patients in England have a right to ask for a second opinion, there’s no legal requirement for doctors to provide one.Mary Neal, Reader in Law, University of Strathclyde Licensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2038022023-04-23T08:52:48Z2023-04-23T08:52:48ZWhat is sepsis? How to spot, manage and prevent it<figure><img src="https://images.theconversation.com/files/521601/original/file-20230418-16-vske13.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In healthcare facilities prevention of the sepsis include practising appropriate infection prevention and control measures.</span> <span class="attribution"><span class="source">GettyImages </span></span></figcaption></figure><p><em>South African television personality, <a href="https://www.news24.com/life/arts-and-entertainment/celebrities/exclusive-derek-watts-is-back-in-hospital-but-not-for-long-i-am-feeling-better-feeling-stronger-20230412">Derek Watts</a>, recently shared that he was suffering from sepsis and “would basically have to learn to walk again”. Sepsis, a life threatening condition, happens when the body has an excessive immune response to an infection in the blood stream. This overreaction can lead to organ damage. Sepsis must be <a href="https://pubmed.ncbi.nlm.nih.gov/34605781/">diagnosed early and treated immediately</a> to prevent <a href="https://www.who.int/health-topics/sepsis#tab=tab_1">septic shock</a>. <a href="https://www.thelancet.com/article/S0140-6736(19)32989-7/fulltext">In 2017</a>, around 48.9 million people were affected, and 11 million died from sepsis worldwide. The Conversation Africa’s Ina Skosana spoke to pathologists from the National Institute of Communicable Diseases about the illness and its impact.</em></p>
<hr>
<h2>What causes sepsis?</h2>
<p>Bacterial, fungal and viral infections can lead to sepsis and septic shock. The condition can occur from infections acquired while an individual is hospitalised, however, it can also occur from infections acquired in the community.</p>
<p>There are common causes of sepsis. These include infections of the respiratory system (pneumonia for example), genitourinary system (such as urinary tract and or kidney infections), gastrointestinal infections, and in the healthcare setting, indwelling catheter sites. Infections of the central nervous system (meningitis) as well as skin and soft tissue (surgical site, wounds or burns) are also common causes of sepsis. </p>
<p>The most common infection in septic patients worldwide is <a href="https://err.ersjournals.com/content/29/157/200038#:%7E:text=Pneumonia%20was%20found%20to%20be,of%20these%20patients%20%5B30%5D.">pneumonia</a> caused mainly by bacterial pathogens. </p>
<h2>Who is at risk of sepsis?</h2>
<p>Any patient with an infection can develop sepsis. But babies up to one month old and people older than 65 years have a higher risk of developing the condition. </p>
<p>The risk of sepsis is also high among people with weakened immune systems such as those with HIV or patients undergoing chemotherapy. Prolonged hospital stays or admission to an intensive care unit (ICU) can also increase the risk of sepsis. </p>
<p>Other risk factors include chronic diseases such as diabetes, kidney disease or chronic obstructive pulmonary disease, patients with medical devices inserted into the body and having history of prolonged use of antibiotics.</p>
<h2>What are the symptoms of sepsis and septic shock?</h2>
<p>Symptoms of sepsis are not specific. These may include one or more of these:</p>
<ul>
<li><p>Fever</p></li>
<li><p>Tachycardia (elevated heart rate) </p></li>
<li><p>Tachypnea (rapid breathing) </p></li>
<li><p>Altered mental state (confusion) </p></li>
<li><p>Lethargy especially in children</p></li>
</ul>
<p>Septic shock is a progression of sepsis. It’s characterised by hypotension (low blood pressure), hypovolaemia (loss of bodily fluids such as water and blood) and organ dysfunction. </p>
<p>Patients typically present with extreme confusion or loss of consciousness.</p>
<h2>How is sepsis and septic shock diagnosed?</h2>
<p>There are various tests available to diagnose sepsis and septic shock. Sepsis and septic shock are clinical syndromes defined by a combination of signs, symptoms, laboratory and physiological abnormalities. </p>
<p>A variety of clinical variables and tools such as vital signs (heart rate, respiratory rate, temperature and blood pressure), laboratory blood tests (confirmation of infection) and clinical examinations have to be reviewed for sepsis screening. </p>
<p>Commonly, blood samples are taken to test for causative bacterial and fungal pathogens. Other laboratory tests can be performed to try find the source of the infection.</p>
<p>Imaging studies can be used to identify or detect the site of infection. Chest x-ray for example, is used to diagnose pneumonia. An ultrasound can show infections in the gallbladder and kidneys. Computerised tomography (CT) scans are used for infections in the liver, pancreas or abdomen. And magnetic resonance imaging (MRI) can detect soft tissue or bone infections.</p>
<h2>How is sepsis managed?</h2>
<p>Once diagnosed, sepsis needs early, thorough, aggressive and appropriate management to increase the likelihood of patient recovery. Patients with sepsis need close monitoring and treatment in a hospital ICU. This is because septic patients may need lifesaving measures to be stabilised.</p>
<p>Intravenous fluids should be started as soon as possible, preferably within the first three hours of sepsis being identified.</p>
<p>It is also recommended that patients are admitted to an ICU and that mechanical ventilation is used for respiratory support in patients with acute respiratory distress syndrome. The source of sepsis should also be controlled. This could take place by draining an abscess or changing of an intravenous line.</p>
<h2>How is sepsis prevented?</h2>
<p>To prevent sepsis, both the community and healthcare workers have a responsibility to ensure that infections don’t develop. </p>
<p>In the community, infections can be prevented by controlling chronic medical conditions. Vaccinations, for example, prevent between <a href="https://www.who.int/news-room/facts-in-pictures/detail/immunization">four and five million deaths</a> annually by preventing infections or reducing their severity. Practising proper hand hygiene reduces the <a href="https://tropmedhealth.biomedcentral.com/articles/10.1186/s41182-021-00315-1#:%7E:text=Despite%20the%20fact%20that%20proper,%2Doral%20route%20%5B7%5D.">risk of diarrhoea</a> by 40%. And safe water and sanitation reduces the global burden of disease by <a href="https://www.cdc.gov/healthywater/global/wash_statistics.html#:%7E:text=Universal%20access%20to%20safe%20drinking,global%20disease%20burden%20by%2010%25.&text=Increasing%20access%20to%20safe%20drinking,can%20prevent%20many%20diarrheal%20deaths">10%</a>. </p>
<p>In healthcare facilities prevention of the sepsis include practising appropriate infection prevention and control measures which can reduce infections by <a href="https://www.who.int/teams/integrated-health-services/infection-prevention-control">50%</a>. Recognising sepsis early and introducing antibiotics treatment early can reduce the likelihood of sepsis progressing to mortality. Anyone who has signs and symptoms of sepsis, even when the underlying infection is not apparent, should seek medical care immediately. </p>
<p>Sepsis is a major public health burden. Controlling it can create healthier societies.</p><img src="https://counter.theconversation.com/content/203802/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Many infections, including bacterial, fungal and viral infections can lead to sepsis and septic shock.Caroline Maluleka, Senior Pathologist, National Institute for Communicable DiseasesLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2008152023-02-28T05:53:22Z2023-02-28T05:53:22ZGenomics has helped identify a new strep A strain in Australia – and what has made it dangerous<figure><img src="https://images.theconversation.com/files/512584/original/file-20230228-1747-a7sbvw.jpg?ixlib=rb-1.1.0&rect=10%2C26%2C3486%2C2157&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/abnormal-neutrophil-pleural-fluid-smear-septicaemia-412363624">Shutterstock</a></span></figcaption></figure><p>Group A streptococci, also known as “strep A”, has been on the rise around the world with a new strain <a href="https://www.theguardian.com/society/2022/dec/15/strep-a-kills-three-more-children-as-uk-activates-new-medicines-plan">reported</a> in the United Kingdom and Europe. This variant has been linked with surges of scarlet fever and a marked increase in life-threatening invasive strep A infections. </p>
<p>Now genomic <a href="https://www.nature.com/articles/s41467-023-36717-4">research</a> by our team of scientists has identified this new strain in the Australian community for the first time. In parallel, we have seen an increase in invasive strep A cases across New South Wales, Queensland, Western Australia and <a href="https://www.health.vic.gov.au/health-advisories/health-warning-on-invasive-group-a-streptococcal-disease">Victoria</a>. </p>
<p>Strep A is a common bacteria carried by people primarily in their throat. It can cause <a href="https://www.cdc.gov/groupastrep/diseases-public/index.html">mild illness</a> including sore throat, scarlet fever (named for the red rash it causes) and impetigo (“school sores”). But it can also cause “invasive” disease, such as sepsis. Repeated strep A infections can lead to other serious conditions including acute rheumatic fever and rheumatic heart disease. </p>
<p>We investigated the genetic composition of the new strep A strain called “M1UK” and zeroed in on what makes it different to the previous strain.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/strep-a-three-doctors-explain-what-you-need-to-look-out-for-195972">Strep A: three doctors explain what you need to look out for</a>
</strong>
</em>
</p>
<hr>
<h2>What we know about strep A</h2>
<p>Strep A only infects humans, with around <a href="https://doi.org/10.1542/peds.2009-2648">10% of school-aged children</a> carrying it. It causes more than <a href="https://pubmed.ncbi.nlm.nih.gov/16253886/">half a million deaths</a> worldwide per year. </p>
<p>We’ve known about the bacteria for over 100 years and it was a <a href="https://pubmed.ncbi.nlm.nih.gov/1571445/">major cause of childhood death</a> in the 19th and early 20th centuries. But it’s been less of a public health threat since antibiotic medications were developed to treat it. In the 1980s, one type of strep A strain called “M1” emerged as the major cause of invasive strep A infections in high-income settings.</p>
<p>Over the last decade, resurgence of scarlet fever strep A infections has been reported in the <a href="https://www.eurosurveillance.org/content/10.2807/1560-7917.ES2014.19.12.20749">United Kingdom</a> and <a href="https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(18)30014-8/fulltext">China</a>. </p>
<p>Invasive infection is <a href="https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON429">rare</a>. But when it occurs, the death rate can be <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6474463/">as high as 20%</a> of those infected.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/512564/original/file-20230228-24-obo37h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="woman getting throat checked by health worker using tongue depressor" src="https://images.theconversation.com/files/512564/original/file-20230228-24-obo37h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/512564/original/file-20230228-24-obo37h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=383&fit=crop&dpr=1 600w, https://images.theconversation.com/files/512564/original/file-20230228-24-obo37h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=383&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/512564/original/file-20230228-24-obo37h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=383&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/512564/original/file-20230228-24-obo37h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=481&fit=crop&dpr=1 754w, https://images.theconversation.com/files/512564/original/file-20230228-24-obo37h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=481&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/512564/original/file-20230228-24-obo37h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=481&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Strep A can cause a sore throat or be much more serious.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/doctor-checking-woman-throat-medical-stick-339999557">Shutterstock</a></span>
</figcaption>
</figure>
<h2>What’s different about this strain?</h2>
<p>The M1UK variant of strep A was first reported in the UK in <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30446-3/fulltext">2019</a> and identified using <a href="https://www.who.int/news-room/questions-and-answers/item/genomics">genomics</a> – the study of the DNA sequence to identify changes in the genetic makeup of an organism.</p>
<p>UK scientists identified that the M1UK variant expressed up to five times more of a specific strep A toxin than the previous M1 <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(19)30446-3/fulltext">strain</a>, but they weren’t sure how. This toxin, originally termed the “scarlet fever toxin”, is associated with the development of invasive strep A by short-circuiting the host’s immune system.</p>
<p>Our laboratory team went about trying to understand which changes in the bacteria led to this increased expression. </p>
<p>We <a href="https://www.nature.com/articles/s41467-023-36717-4">looked at the genetic code</a> of the strep A M1UK variant and compared it to previous ones. We found a number of mutations, one of which was located near the toxin gene.</p>
<p>Then we worked backwards to repair that change and see how it affected the amount of toxin expressed. In this way, we identified the mechanism of how M1UK strep A became toxin supercharged. </p>
<h2>Will we see more dangerous strep A strains?</h2>
<p>Genomics helps us identify and track bacterial variants. Then scientists need to use that knowledge within a biological context to figure out how a strain is gaining competitive advantage to become dominant over a previous strain – as M1UK <a href="https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30279-6/fulltext">has in the UK</a>. </p>
<p>It’s possible this new strain of strep A is better at transmitting from person to person, but we’ll need more research to know if this is the case. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1603414373355044864"}"></div></p>
<h2>Invasive strep A is now a notifiable disease</h2>
<p>Invasive strep A infection was added to Australia’s National Notifiable Diseases List in <a href="https://www.legislation.gov.au/Details/F2021L00778">July 2021</a>, paving the way for it to be formally recorded across states and territories. This means that detected invasive strep A cases get reported to a central registry so authorities can keep track of outbreaks and case numbers.</p>
<p>Our researchers will have access to a repository of national strep A strains. We will be piloting a national strep A genomic surveillance program within the <a href="https://www.auspathogen.org.au/">AusPathoGen</a> program, which will speed up our ability to identify and track emerging strep A variants. </p>
<p>We’ve seen how this type of genomic research has helped <a href="https://theconversation.com/as-new-zealands-omicron-infections-rise-rapidly-genome-surveillance-is-shifting-gears-177441">track COVID changes</a> and guide public health response. By undertaking this pilot program with public health partners, we aim to build a national invasive strep A surveillance framework. </p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/strep-a-cases-are-rising-we-must-remember-our-earliest-hygiene-lessons-as-vaccine-trials-continue-197617">Strep A cases are rising. We must remember our earliest hygiene lessons as vaccine trials continue</a>
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</em>
</p>
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<h2>How can people protect themselves?</h2>
<p>Invasive strep A is still extremely rare, so there’s no need to panic – but we shouldn’t be complacent either.</p>
<p>Basic hygiene practices and staying away from other people when sick remain <a href="https://www.healthdirect.gov.au/group-a-streptococcal">important</a> for preventing spread. </p>
<p>Kids or the elderly are <a href="https://www.ncbi.nlm.nih.gov/books/NBK333415/">more likely</a> to get invasive disease, so if you note <a href="https://www.health.vic.gov.au/health-advisories/health-warning-on-invasive-group-a-streptococcal-disease">symptoms</a> such as high fever (especially with a skin rash), severe pain from an infected skin sore, and any difficulties with breathing then you should go to your local hospital’s emergency department or consult a GP immediately. </p>
<p>Antibiotics are highly effective at treating infection, provided they are <a href="https://www.cdc.gov/groupastrep/igas-infections-investigation.html">available</a>. </p>
<p>We also need to think about alternative ways of controlling infection. Australian scientists are at the <a href="https://imb.uq.edu.au/article/2023/02/funding-injection-strep-vaccine-research">forefront</a> of efforts to develop a global strep A vaccine. </p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/antibiotics-shortages-whats-causing-them-and-how-countries-can-minimise-the-impact-196540">Antibiotics shortages: what's causing them and how countries can minimise the impact</a>
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<img src="https://counter.theconversation.com/content/200815/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark Davies receives funding from the National Health and Medical Research Council of Australia. </span></em></p>The new M1UK strain of strep A has a dangerous ability to make the disease trigger more toxin release in the body.Mark Davies, Laboratory Head, Doherty Institute, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1965682022-12-23T18:59:52Z2022-12-23T18:59:52ZSepsis is one of the most expensive medical conditions in the world – new research clarifies how it can lead to cell death<figure><img src="https://images.theconversation.com/files/502237/original/file-20221220-20-d0pk4l.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1639%2C1001&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Bacteria (clusters of light pink, surrounded by larger magenta blood cells) can cause deadly infections, but overreactive immune responses can deliver the lethal blow.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/gram-negative-bacterial-bloodstream-infection-seen-royalty-free-image/1063050118">Scharvik/iStock via Getty Images Plus</a></span></figcaption></figure><p><a href="https://www.cdc.gov/sepsis/what-is-sepsis.html">Sepsis</a> is a life-threatening condition arising from the body’s overreactive response against an infection, leading it to injure its own tissues and organs. The first known reference to “sepsis” dates back <a href="https://doi.org/10.1007/s00134-006-0392-2">more than 2,700 years</a>, when the Greek poet Homer used it as a derivative of the word “sepo,” meaning “I rot.”</p>
<p>Despite dramatic improvements in understanding the immunological mechanisms behind sepsis, it still remains a major medical concern, affecting <a href="https://doi.org/10.3949/ccjm.87a.18143">750,000 people in the U.S.</a> and <a href="https://doi.org/10.1016/S0140-6736(19)32989-7">nearly 50 million people globally</a> each year. Sepsis accounted for <a href="https://doi.org/10.1016/S0140-6736(19)32989-7">11 million deaths worldwide</a> in 2017, and is the <a href="https://doi.org/10.1177/2050312119835043">most expensive medical condition</a> in the U.S., costing <a href="https://doi.org/10.1097/CCM.0000000000003342">over tens of billions of dollars</a> annually.</p>
<p><a href="https://medicine.tufts.edu/people/faculty/alexander-poltorak">We</a> <a href="https://scholar.google.com/citations?user=VMa6rFgAAAAJ&hl=en">are</a> <a href="https://medicine.tufts.edu/people/faculty/hayley-muendlein">researchers</a> who study how certain types of bacteria <a href="https://doi.org/10.1126/science.282.5396.2085">interact with cells</a> during infections. We wanted to understand exactly how an overreactive immune response can result in detrimental and even lethal effects like sepsis. In our <a href="https://www.science.org/doi/10.1126/sciimmunol.add0665">newly published research</a>, we discovered the cells and molecules that potentially trigger death from sepsis.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/NsPDjOX8QHA?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Sepsis results from a potentially lethal overreactive immune response to infection.</span></figcaption>
</figure>
<h2>TNF in autoimmunity and sepsis</h2>
<p>The body’s response to infection starts when immune cells recognize components of the invading pathogen. These cells then release molecules like cytokines that help eliminate the infection. Cytokines are a broad group of small proteins that recruit other immune cells to the site of infection or injury.</p>
<p>While cytokines play an essential role in the immune response, excessive and uncontrolled cytokine production can lead to a dangerous <a href="https://doi.org/10.1007/s00281-017-0639-8">cytokine storm</a> associated with sepsis. Cytokine storms were first seen in the context of <a href="https://pubmed.ncbi.nlm.nih.gov/8442093/">graft versus host disease</a>, arising from transplant complications. They can also occur during <a href="https://doi.org/10.1089/vim.2019.0032">viral infections</a>, including <a href="https://doi.org/10.1016/S0140-6736(20)30628-0">COVID-19</a>. This uncontrolled immune response can lead to <a href="https://doi.org/10.3389/fimmu.2020.01446">multi-organ failure and death</a>. </p>
<p>Among the hundreds of cytokines that exist, <a href="https://doi.org/10.1073/pnas.72.9.366">tumor necrosis factor, or TNF</a>, stands tall as the most potent and the most studied for nearly the past 50 years. </p>
<p>Tumor necrosis factor owes its name to its ability to induce tumor cells to die when the immune system is stimulated by a bacterial extract called <a href="https://pubmed.ncbi.nlm.nih.gov/1984929/">Coley’s toxin</a>, named after the researcher who identified it over a century ago. This toxin was later recognized to be <a href="https://doi.org/10.1073/pnas.72.9.3666">lipopolysaccharide, or LPS</a>, a component of the outer membrane of certain types of bacteria. LPS is the strongest known trigger of TNF, which, once on alert, aids in the recruitment of immune cells to the infection site to eliminate invading bacteria.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/xnlCjudODyI?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Severe COVID-19 infections can trigger cytokine storms.</span></figcaption>
</figure>
<p>In normal conditions, TNF promotes beneficial processes such as <a href="https://doi.org/10.1038/nrrheum.2015.169">cell survival and tissue regeneration</a>. However, TNF production must be tightly regulated to avoid sustained inflammation and continuous proliferation of immune cells. Uncontrolled TNF production can lead to the <a href="https://doi.org/10.3389/fimmu.2020.591365">development of rheumatoid arthritis</a> and similar inflammatory conditions. </p>
<p>In infection conditions, TNF must also be tightly regulated to prevent excessive tissue and organ damage from inflammation and an overactive immune response. When TNF is left uncontrolled during infections, it can <a href="https://doi.org/10.1016/0090-1229(92)90036-N">lead to sepsis</a>. For several decades, studies of septic shock were modeled by investigating responses to bacterial LPS. In this model, LPS activates certain immune cells that trigger the production of inflammatory cytokines, in particular TNF. This then leads to excessive immune cell proliferation, recruitment and death, ultimately resulting in tissue and organ damage. Too strong of an immune response is not a good thing.</p>
<p>Researchers have shown that <a href="https://doi.org/10.3390/ijms22052719">blocking TNF activity</a> can effectively treat numerous autoimmune diseases, including rheumatoid arthritis, psoriatic arthritis and inflammatory bowel disease. Use of TNF blockers has dramatically increased in the past decades, reaching a market size of <a href="https://www.reportlinker.com/p06151677/TNF-Alpha-Inhibitors-Global-Market-Report-COVID-19-Growth-And-Change-To.html">roughly $40 billion</a>.</p>
<p>However, <a href="https://doi.org/10.1001/jama.1995.03520360048038">TNF blockers have been unsuccessful</a> in preventing the cytokine storm that can arise from COVID-19 infections and sepsis. This is in part because exactly how TNF triggers its toxic effects on the body is still poorly understood despite years of research.</p>
<h2>How TNF can be lethal</h2>
<p>Studying sepsis might provide some clues as to how TNF mediates how the immune system responds to infection. In acute inflammatory conditions such as sepsis, TNF blockers are less able to address TNF overproduction. However, studies in mice show that <a href="https://doi.org/10.1126/science.3895437">neutralizing TNF</a> can prevent the death of the animal from bacterial LPS. Although researchers do not yet understand the reason for this discrepancy, it highlights the need for further understanding how TNF contributes to sepsis.</p>
<p>Blood cells made in the bone marrow, or myeloid cells, are known to be the <a href="https://pubmed.ncbi.nlm.nih.gov/1083433/">major producers of TNF</a>. So we wondered if myeloid cells also mediate TNF-induced death. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration of TNF bound to a cell membrane" src="https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/502234/original/file-20221220-26-lesr2a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">TNF (blue) is implicated in a number of inflammatory diseases.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/the-tumor-necrosis-factor-receptor-with-tnf-bound-royalty-free-image/1247890721">selvanegra/iStock via Getty Images Plus</a></span>
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<p>First, we identified which particular molecules might offer protection from TNF-induced death. When we injected mice with a lethal dose of TNF, we found that mice lacking either <a href="https://www.science.org/doi/10.1126/sciimmunol.add0665">TRIF or CD14</a>, two proteins typically associated with immune responses to bacterial LPS but not TNF, had improved survival. This finding parallels our <a href="https://doi.org/10.1038/s41467-020-20357-z">earlier work</a> identifying these factors as regulators of a protein complex that controls cell death and inflammation in response to LPS.</p>
<p>Next, we wanted to figure out which cells are involved in TNF-induced death. When we injected a lethal dose of TNF in mice lacking the two proteins in two specific types of myeloid cells, neutrophils and macrophages, mice had reduced symptoms of sepsis and improved survival. This finding positions macrophages and neutrophils as major triggers for TNF-mediated death in mice.</p>
<p>Our results also suggest TRIF and CD14 as potential treatment targets for sepsis, with the ability to both reduce cell death and inflammation.</p><img src="https://counter.theconversation.com/content/196568/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>An overactive immune response to infection can be deadly. Studying how one key player called tumor necrosis factor, or TNF, induces lethal immune responses could provide new treatment targets.Alexander (Sasha) Poltorak, Professor of Immunology, Tufts UniversityHayley Muendlein, Research Assistant Professor of Immunology, Tufts UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1883612022-08-11T03:00:19Z2022-08-11T03:00:19ZSepsis is serious during pregnancy, but thankfully it is still rare<figure><img src="https://images.theconversation.com/files/478470/original/file-20220810-14-z1zgd6.jpg?ixlib=rb-1.1.0&rect=23%2C46%2C5152%2C3399&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://image.shutterstock.com/image-photo/asian-pregnant-woman-patient-on-600w-454486129.jpg">Shutterstock</a></span></figcaption></figure><p>The tragic case of <a href="https://www.theage.com.au/national/victoria/a-cascade-of-failures-how-annie-moylan-lost-her-child-and-her-life-in-melbourne-s-private-hospitals-20220802-p5b6je.html">Annie Moylan</a>, who died in Melbourne in 2017 from sepsis, when 18 weeks pregnant, has put a spotlight on this life-threatening condition. </p>
<p>Delay in receiving blood results, admission to a private hospital that did not provide obstetric care, and communication breakdown when Annie transferred to another private hospital all seem to have played a role in what has been described as a “cascade of failures”. A <a href="https://www.theage.com.au/national/victoria/a-cascade-of-failures-how-annie-moylan-lost-her-child-and-her-life-in-melbourne-s-private-hospitals-20220802-p5b6je.html">coronial inquest</a> into her death begins on Monday. </p>
<p>Sepsis can also happen after birth, as was seen in the devastating loss of <a href="https://www.abc.net.au/news/2018-02-27/michaela-perrin-coroner-findings-say-inadequate-care-given/9489790">Michaela Perrin</a> who died in 2014, six days having a healthy baby girl via caesarean section.</p>
<p>Women who are currently pregnant may worry about how cases such as these can happen in a country like Australia with an excellent health system. </p>
<p>Sepsis is a serious health condition for anyone, and pregnant women are no exception to this. Thankfully it is still rare for young women to die from the condition. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/sepsis-still-kills-1-in-5-people-worldwide-two-icu-physicians-offer-a-new-approach-to-stopping-it-175650">Sepsis still kills 1 in 5 people worldwide – two ICU physicians offer a new approach to stopping it</a>
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<hr>
<h2>When the body fights itself</h2>
<p><a href="https://www.cdc.gov/sepsis/what-is-sepsis.html">Sepsis</a> is syndrome (or group of symptoms) mostly caused by a bacterial infection. It results when the body is trying to fight an infection and begins to damage its own tissues. This can lead to a serious drop in blood pressure, and organ damage. </p>
<p>In Australia, <a href="https://www.safetyandquality.gov.au/sites/default/files/2020-05/epidemiology_of_sepsis_-_february_2020_002.pdf">around 12%</a> of people hospitalised with sepsis will die from it. Very young (less than 12 months) and older people (over 85 years) are most vulnerable. The death rate for pregnant women with sepsis worldwide is estimated to be <a href="https://www.ajog.org/article/S0002-9378(19)30246-7/fulltext">between 1% and 4.6%</a>. </p>
<p>Treatment relies on early identification, antibiotics, intravenous fluids (fluid through a drip) and skilful medical care. For those who survive, there can be lifelong damage, both <a href="https://www.sepsis.org/sepsisand/amputations/">physically</a> and <a href="https://www.sepsis.org/sepsisand/post-traumatic-stress-disorder-ptsd/">psychologically</a>.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1556227148683296768"}"></div></p>
<h2>What causes sepsis during pregnancy, or after birth?</h2>
<p>When sepsis happens during pregnancy, it is sometimes called maternal sepsis. After birth it is called postpartum or puerperal sepsis. </p>
<p>The syndrome can result from an infection anywhere in the body (such as pneumonia or a urinary tract infection) or it can be introduced during medical procedures like a caesarean section. </p>
<p>For this reason, all women who have a caesarean section are given intravenous antibiotics in the operating theatre to prevent sepsis. </p>
<p>For around <a href="https://www.ajog.org/article/S0002-9378(19)30246-7/fulltext">30% of cases</a>, no source of infection is found. </p>
<p>When identified, the <a href="https://www.somanz.org/content/uploads/2020/07/2017SepsisGuidelines.pdf">most common causes</a> of sepsis during and after pregnancy are <em>Escherichia coli</em> (<em>E. coli</em>) and group B <em>Streptococcus</em>. As mixed infections are also possible with sepsis, broad-spectrum antibiotics are given as soon as possible.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/vaginal-birth-after-caesarean-increases-the-risk-of-serious-perineal-tear-by-20-our-large-scale-review-shows-173249">Vaginal birth after caesarean increases the risk of serious perineal tear by 20%, our large-scale review shows</a>
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<h2>Sepsis was a major cause of women dying after birth</h2>
<p>Puerperal sepsis was once one of the main causes of women dying following childbirth. As knowledge about hygiene practices advanced and then antibiotics were introduced, this declined rapidly. However, sepsis has never been eliminated.</p>
<p>The work of Viennese physician <a href="https://ajph.aphapublications.org/doi/full/10.2105/AJPH.2009.185363">Ignaz Philipp Semmelweis</a> in the mid-1800s led to the discovery that health provider hand-washing could reduce infection rates in women. </p>
<p>Semmelweis observed there was a much lower rate of women dying when cared for by midwives than doctors in two clinics and realised the midwives were not involved in autopsies and hence not carrying bacteria from the autopsy rooms into the maternity ward. </p>
<p>Semmelweis told anyone attending autopsies to scrub their hands with chloride and lime before entering the maternity ward. Soon after this, the rate of maternal deaths in the doctors’ clinics fell. </p>
<p>It took nearly another 30 years for Semmelweis’s ideas to be fully embraced. He <a href="https://www.npr.org/sections/health-shots/2015/01/12/375663920/the-doctor-who-championed-hand-washing-and-saved-women-s-lives">suffered a tragic death</a> in an asylum and ironically succumbed to sepsis from a gangrenous wound to his hand.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/478471/original/file-20220810-4975-i1fx4v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="doctors washing hands" src="https://images.theconversation.com/files/478471/original/file-20220810-4975-i1fx4v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/478471/original/file-20220810-4975-i1fx4v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/478471/original/file-20220810-4975-i1fx4v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/478471/original/file-20220810-4975-i1fx4v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/478471/original/file-20220810-4975-i1fx4v.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/478471/original/file-20220810-4975-i1fx4v.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/478471/original/file-20220810-4975-i1fx4v.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">Rates of maternal sepsis improved with the advent of better clinical hygiene.</span>
<span class="attribution"><a class="source" href="https://image.shutterstock.com/image-photo/couple-surgeons-washing-hands-before-600w-633363035.jpg">Shutterstock</a></span>
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<p>It has been estimated nearly a half of all maternal deaths in the pre-antibiotic era (before the 1930s) were due to <a href="https://ajph.aphapublications.org/doi/full/10.2105/AJPH.2009.185363">infection</a>. </p>
<p>“<a href="https://fivethirtyeight.com/features/what-the-history-of-back-alley-abortions-can-teach-us-about-a-future-without-roe/">Back-alley abortions</a>” were once another major cause of sepsis and death in women before better access to proper medical care for abortions was legislated in many countries. </p>
<p>Today, around <a href="https://msf.org.au/article/project-news/unsafe-abortion-forgotten-emergency">one in 12 maternal deaths</a> are from lack of access to safe abortion care and infection remains a big part of this. This is one reason why there is such grave concern over the recent overturning of <a href="https://www.ajog.org/article/S0002-9378(19)30246-7/fulltext">Roe vs Wade</a> in the United States.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/monkeypox-can-be-transmitted-to-babies-during-and-after-pregnancy-we-should-be-watchful-but-not-alarmed-188283">Monkeypox can be transmitted to babies during and after pregnancy. We should be watchful but not alarmed</a>
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<h2>Rates of maternal sepsis today</h2>
<p>While sepsis is considered to be a <a href="https://www.ajog.org/article/S0002-9378(19)30246-7/fulltext">preventable cause</a> of maternal death, it continues to be a major cause of women dying during or after childbirth, even in high resource countries such as Australia. </p>
<p>Sepsis was the <a href="https://www.aihw.gov.au/reports/mothers-babies/maternal-deaths-australia#maternal-deaths">second most common cause</a> of maternal death between 2010 and 2019 in Australia (22 deaths). </p>
<p>According to the <a href="https://www.cdc.gov/reproductivehealth/maternal-mortality/pregnancy-mortality-surveillance-system.htm?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Freproductivehealth%2Fmaternalinfanthealth%2Fpregnancy-mortality-surveillance-system.htm">Centres for Disease Control and Prevention</a> sepsis is the second leading cause of pregnancy related deaths in the US, leading to around 14% of pregnancy-related deaths. </p>
<p>Investigations into sepsis cases during pregnancy and following birth in the United Kingdom <a href="https://www.ogmagazine.org.au/21/4-21/managing-the-septic-patient-in-labour/">found</a> 63% of deaths were associated with substandard care, such as delays in recognising or managing sepsis.</p>
<p>Delays in diagnosing sepsis or misdiagnosis of sepsis in childbearing women is made more complicated due to the physical changes in women’s bodies during pregnancy, labour and the postnatal period. Sepsis can also <a href="https://www.ogmagazine.org.au/21/4-21/managing-the-septic-patient-in-labour/">progress more rapidly</a> in pregnant women. </p>
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<h2>We should all be alert</h2>
<p>If you are unwell during pregnancy or following birth let your health care provider know and persist in seeking care if you are not satisfied. </p>
<p>Most of the time everything will be fine but there are signs of sepsis that can be detected by health providers, such as low blood pressure, temperature or via blood tests.</p>
<p>Health providers have processes for <a href="https://www.cec.health.nsw.gov.au/__data/assets/pdf_file/0008/292193/Maternal-Sepsis-Pathway-December-2016.pdf">suspected maternal sepsis</a>, <a href="https://www.somanz.org/content/uploads/2020/07/2017SepsisGuidelines.pdf">guidelines</a> to follow and regular training on this important health emergency. </p>
<p>Health providers need to listen to women and take them seriously when they are unwell, and have the possibility of sepsis in mind. </p>
<p>The brave and persistent actions of <a href="https://www.theage.com.au/national/victoria/a-cascade-of-failures-how-annie-moylan-lost-her-child-and-her-life-in-melbourne-s-private-hospitals-20220802-p5b6je.html">Annie Moylan</a>’s parents in seeking answers about their daughter’s death from sepsis will make care safer for other women.</p><img src="https://counter.theconversation.com/content/188361/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Hannah Dahlen does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>While sepsis is considered to be a preventable cause of maternal death, it continues to be a major cause of women dying during or after childbirth, even in Australia.Hannah Dahlen, Professor of Midwifery, Associate Dean Research and HDR, Midwifery Discipline Leader, Western Sydney UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1756502022-06-10T12:29:55Z2022-06-10T12:29:55ZSepsis still kills 1 in 5 people worldwide – two ICU physicians offer a new approach to stopping it<figure><img src="https://images.theconversation.com/files/467853/original/file-20220608-22-nfife2.jpg?ixlib=rb-1.1.0&rect=59%2C0%2C6540%2C2642&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Sepsis begins with infection by bacteria or a virus. This panoramic ilustration inside a blood vessel shows rod-shaped bacteria, red blood cells and immune cells called leukocytes.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/bacteria-in-blood-illustration-royalty-free-illustration/685024929?adppopup=true">Kateryna Kon/Science Photo Library via Getty Images</a></span></figcaption></figure><p>Can an otherwise healthy young woman die from what starts out as something akin to a common cold? The answer is, <a href="https://www.bbc.com/news/uk-wales-45498914">shockingly, yes</a>, when certain telltale signs of a more serious problem go undetected. </p>
<p>Though many people haven’t even heard of it, sepsis – the body’s extreme response to infection – is <a href="https://www.natlawreview.com/article/sepsis-accounts-1-5-deaths-leading-cause-death-hospitals#">the leading killer of hospitalized patients</a> in the United States. Worldwide, sepsis is responsible <a href="https://doi.org/10.1016/S0140-6736(19)32989-7">for 1 in 5 deaths every year</a>. <a href="https://www.sccm.org/MyICUCare/THRIVE/Post-intensive-Care-Syndrome">Even among those who survive</a>, many will never be able to return to work, and some won’t be able to return home from the hospital, requiring life support or ongoing critical care.</p>
<p>We <a href="https://pre.ccm.pitt.edu/?q=content/rudd-kristina">are two researchers</a> and <a href="https://www.ccm.pitt.edu/node/1211">critical care doctors</a> at the University of Pittsburgh School of Medicine who are working to change the way scientists and doctors think about sepsis. We are interested in understanding and spreading awareness about how sepsis starts and how it can elude even the most astute physicians. </p>
<p>We are also learning more about how community factors are at play and how a better understanding of the communities we all live in could help everyday people and health care workers alike recognize and stop this deadly disease.</p>
<h2>What is sepsis?</h2>
<p>Sepsis is a medical emergency that begins with an infection – perhaps even a mild infection. Upon detecting bacteria or a virus, your body releases a choreographed cascade of chemicals into the bloodstream. This chemical alert beckons <a href="https://theconversation.com/how-long-does-protective-immunity-against-covid-19-last-after-infection-or-vaccination-two-immunologists-explain-177309">an artillery of immune cells</a> that work in concert to fight the bug. </p>
<p>When this system works well, your body clears the infection and you get better. But when the system doesn’t work well, sepsis can ensue.</p>
<p>The onset of sepsis occurs when your immune cells pivot from fighting the infection to fighting your own tissues and organs. This reaction can be similar to an autoimmune response, a condition in which <a href="https://medlineplus.gov/autoimmunediseases.html">the body’s immune system turns on itself</a>. Many people are familiar with chronic autoimmune diseases such as <a href="https://www.cdc.gov/arthritis/basics/rheumatoid-arthritis.html#">rheumatoid arthritis</a> or <a href="https://www.mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes/syc-20353304#">Crohn’s disease</a>, but sometimes this type of autoimmune response can occur even in healthy people. </p>
<p>When sepsis occurs, the immune system can commonly injure the heart, lungs, kidneys or blood cells, among other important body systems. Inflammation in the blood vessels can make them leaky, causing blood flow to the brain and other organs to become severely diminished. When this occurs, a person’s blood pressure may become dangerously low, which is a severe form of sepsis known as septic shock. </p>
<p>Without prompt and proper treatment – and sometimes even despite treatment – sepsis can cause organ damage and even death. Once shock develops, mortality from sepsis is estimated <a href="https://doi.org/10.1001/jama.2016.0287">to jump from 10% to as high as 40%</a>.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/6NdLnHbLZMU?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">An illustrated explanation of how sepsis attacks the body.</span></figcaption>
</figure>
<p>Sepsis can result from nearly any infection. Most commonly it develops from pneumonia or a urinary tract infection. Severe <a href="https://www.ama-assn.org/delivering-care/public-health/sepsis-survival-has-lessons-severe-covid-19-care-recovery">COVID-19 can also cause sepsis</a>. Often, sepsis patients are seen by a medical professional for infection symptoms <a href="https://doi.org/10.4037/ajcc2021456">in the week preceding sepsis hospitalization</a>. However, predicting which infected patients will go on to develop sepsis is very difficult.</p>
<h2>Treatment options</h2>
<p>The cornerstones of sepsis treatment are prompt recognition of sepsis symptoms, followed by antibiotics and fluids. But even the most careful and attentive physicians can miss the early signs of sepsis. </p>
<p>This is largely because there is no single test to positively diagnose sepsis. Sepsis symptoms may mimic other life-threatening conditions such as heart attacks, blood clots, bleeding or even an allergic reaction. Patients often display vague and variable symptoms such as weakness, lightheadedness and rapid breathing, making the diagnosis even more challenging. </p>
<p>For example, a young, otherwise healthy person with sepsis due to pneumonia may look much different from an older diabetic who develops sepsis from a smoldering skin infection.</p>
<p>Sepsis patients nearly always require admission to the hospital or even the ICU, and those with severe forms of sepsis often require life support. This may include dialysis or mechanical ventilation to support failing organs. The source of infection needs to be identified and, in some cases, surgically removed. Delaying sepsis treatment by even a few hours <a href="https://doi.org/10.1007/s00134-021-06506-y">can have deadly consequences</a>. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/I9UwETuh9IA?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Sepsis can affect those of any age, not just the elderly.</span></figcaption>
</figure>
<h2>Recognizing sepsis before it’s too late</h2>
<p>Differences in sepsis go beyond symptoms. COVID-19 has laid bare that severe illness isn’t a game of chance. Like COVID-19 infection, sepsis susceptibility – and who is most likely to get sick and die – is part of a complex interplay of social influences that <a href="https://doi.org/10.1001/jama.2021.22583">include racism, poverty, geography and community dynamics</a>.</p>
<p>Research strongly suggests that certain people are at <a href="https://doi.org/10.1093/ofid/ofy305">far higher risk of developing sepsis</a> than others. Much like COVID-19, older people with underlying chronic diseases like obesity and diabetes face a heightened risk for sepsis. Such factors as race, poverty and even driving distance to the hospital <a href="https://doi.org/10.1016/j.chest.2016.07.004">may have a significant impact</a> on who survives sepsis. </p>
<p>Most of the work done to improve sepsis detection and treatment has focused on the hospital setting. Doctors, researchers and even government agencies have concentrated their efforts on improving sepsis recognition and treatment once a patient reaches the hospital. Research aimed at understanding an individual’s sepsis risk has focused on personal health history and social and economic factors such as income and race, or community features such as primary care access. </p>
<p>While these approaches have advanced the field’s understanding of sepsis, they have led to little progress in reducing the incidence of sepsis in the U.S.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/69s6ezhwTWQ?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Sepsis is sometimes mistaken for the flu.</span></figcaption>
</figure>
<h2>New approaches to catching a killer</h2>
<p>Given what is known about the importance of early sepsis treatment, researchers like us are taking a closer look at the role of communities in improving sepsis detection and understanding sepsis risk.</p>
<p>The early stages of sepsis can evolve rapidly when a patient is at home. Scientists estimate that <a href="https://www.cdc.gov/sepsis/what-is-sepsis.html">87% of sepsis cases start outside the hospital</a>. When a patient does present for care, it’s often in a clinic or emergency medical services setting in the days and even hours <a href="https://doi.org/10.1164/rccm.201204-0713OC">preceding sepsis hospitalization</a>. These critical treatment windows may mean the difference between life and death for a sepsis patient. </p>
<p>Alongside researchers based at Kaiser Permanente Northern California, we are now working to advance sepsis care by studying sepsis patient symptoms, community factors, diagnosis and treatment patterns outside the hospital. We are also expanding work to <a href="https://doi.org/10.1038/s41746-022-00580-2">improve sepsis diagnosis among hospitalized patients</a>. This coast-to-coast collaboration will study patients cared for at over 40 hospitals, 30 EMS agencies and a critical mass of ambulatory clinics. We hope that our work will shed light on the early stages of sepsis, including signs that may signal that an infected patient is progressing to sepsis, and explore diagnostic and treatment approaches that could help stop sepsis before it advances too far. </p>
<p>We are also learning a great deal more about the complicated role of community factors like poverty on health outcomes, including sepsis. Using “syndemic theory” – a framework to describe synergistic epidemics that <a href="https://doi.org/10.1016/S0140-6736(17)30003-X">arise from harmful social conditions</a> – we are studying how two co-occurring epidemics, like poverty and asthma, can work together to increase negative health outcomes. Though this framework is only beginning to be used to study acute illness, it has the potential to transform the way we think about sepsis.</p><img src="https://counter.theconversation.com/content/175650/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Emily Brant works for the University of Pittsburgh School of Medicine and UPMC Health System. She has received grant funding from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) and the Gordon and Betty Moore Foundation. She has no relevant conflicts of interest to report. </span></em></p><p class="fine-print"><em><span>Kristina E. Rudd works for the University of Pittsburgh and UPMC Health System. She consults for Janssen Pharmaceuticals. She receives grant funding from the National Institute of General Medical Sciences and the National Heart, Lung, and Blood Institute (National Institutes of Health).</span></em></p>Sepsis onset can be difficult to recognize, in part because its symptoms can mimic those of many other conditions. A treatment delay of even a few hours can make the difference between life and death.Emily Brant, Assistant Professor of Critical Care and Emergency Medicine, University of PittsburghKristina E. Rudd, Assistant Professor of Critical Care Medicine, University of PittsburghLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1784632022-03-11T13:19:52Z2022-03-11T13:19:52ZGuns, not roses – here’s the true story of penicillin’s first patient<figure><img src="https://images.theconversation.com/files/451134/original/file-20220309-25-206ycs.jpg?ixlib=rb-1.1.0&rect=62%2C209%2C3357%2C2439&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Penicillin ushered in the antibiotics revolution, with amazing results during war and peace.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/in-1928-alexander-fleming-a-scottish-researcher-discovered-news-photo/90736822">Science & Society Picture Library/SSPL via Getty Images</a></span></figcaption></figure><p>Albert Alexander was dying. World War II was raging, and this police officer of the county of Oxford, England, had developed a severe case of sepsis after a cut on his face became badly infected. His blood was now teeming with deadly bacteria. </p>
<p><a href="https://doi.org/10.1136/bmj.289.6460.1721">According to his physician</a>, Charles Fletcher, Alexander was in tremendous pain, “desperately and pathetically ill.” The bacterial infection was eating him alive: He’d already lost one eye and had oozing abscesses all over his face and in his lungs.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="man in 1940s police uniform" src="https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=829&fit=crop&dpr=1 600w, https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=829&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=829&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1041&fit=crop&dpr=1 754w, https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1041&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/451124/original/file-20220309-28-1p5rh2n.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1041&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Albert Alexander in uniform.</span>
<span class="attribution"><span class="source">Courtesy of Linda Willason</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Since all known treatment options were exhausted and death appeared imminent, Fletcher decided that Alexander was the perfect candidate to try a new, experimental therapy. On Feb. 12, 1941, Alexander became the first known person to be treated with penicillin. Within days he began to make a stunning recovery.</p>
<p>I am a <a href="https://medicine.iu.edu/faculty/13502/sullivan-william">professor of pharmacology</a>, and Alexander’s story is the prelude to my yearly lecture on antibiotics. Like many other microbiology instructors, I’d always told students that Alexander’s septicemia arose after he scratched his cheek on a thorn while pruning rosebushes. This popular account dominates the scientific literature as well as recent articles and books.</p>
<p>The problem is, while descriptions of the miraculous effect of penicillin in this case are accurate, the details of Alexander’s injury were muddled, likely by wartime propaganda.</p>
<h2>Breaking the mold</h2>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="man looking into microscope" src="https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=672&fit=crop&dpr=1 600w, https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=672&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=672&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=845&fit=crop&dpr=1 754w, https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=845&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/451136/original/file-20220309-13-5iedmw.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=845&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Bacteriologist Alexander Fleming discovered antibiotic penicillin in 1928.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/alexander-fleming-scottish-bacteriologist-18-december-1943-news-photo/102730610">Daily Herald Archive/SSPL via Getty Images</a></span>
</figcaption>
</figure>
<p>The promise of penicillin as an antibiotic was first noted in 1928, when microbiologist Alexander Fleming noticed something funny in his petri dishes at St. Mary’s Hospital in London. Fleming’s cultures of <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2048009/">staphylococcal bacteria did not grow well</a> on plates contaminated with a penicillium mold. Fleming discovered that the mold’s “juice” was lethal to some types of bacteria. </p>
<p>A decade later, a team of scientists led by Howard Florey at Oxford University began the arduous task of purifying the active substance from the “mold juice” and formally testing its antimicrobial properties. In August 1940, Florey and his colleagues published their striking findings that <a href="https://doi.org/10.1016/S0140-6736(01)08728-1">purified penicillin safely wiped out numerous bacterial infections</a> in mice.</p>
<p>Florey then sought Fletcher’s help to try penicillin in a human patient. That patient would be Alexander, whose death seemed inevitable otherwise. As Fletcher stated, “There was all to gain for him in a trial of penicillin and <a href="https://doi.org/10.1136/bmj.289.6460.1721">nothing to lose</a>.”</p>
<p>At the time, purified penicillin was extremely scarce, since the mold was slow to grow and yielded precious little of the drug. Despite recycling unprocessed penicillin from Alexander’s urine, there just wasn’t enough available to finish off the infection once and for all. After 10 days of improvement, Alexander gradually relapsed. <a href="https://doi.org/10.1136/bmj.289.6460.1721">He died on March 15, 1941</a>, at the age of 43.</p>
<p>Despite the tragic outcome, Alexander’s case turbocharged interest in penicillin research. As Fletcher observed, “There was <a href="https://doi.org/10.1136/bmj.289.6460.1721">no doubt about the temporary clinical improvement</a>, and, most importantly, there had been no sort of toxic effect during the five days of continuous administration of penicillin.”</p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="magazine ad with drawing of wounded soldier" src="https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=789&fit=crop&dpr=1 600w, https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=789&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=789&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=992&fit=crop&dpr=1 754w, https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=992&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/451131/original/file-20220309-20-mcpueg.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=992&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">An ad promoting penicillin and its role in the war effort.</span>
<span class="attribution"><a class="source" href="https://www.nlm.nih.gov/exhibition/fromdnatobeer/exhibition-making-yellow-magic.html">Schenley Laboratories, Inc. advertisement, 1944</a></span>
</figcaption>
</figure>
<p>Almost exactly a year later, on March 14, 1942, doctors in Connecticut administered the antibiotic to a woman named <a href="https://www.nytimes.com/1999/06/09/us/anne-miller-90-first-patient-who-was-saved-by-penicillin.html">Anne Miller</a> who was deathly ill with streptococcal septicemia. She made a full recovery and became the first patient cured with penicillin. <a href="https://www.washingtonpost.com/history/2020/07/11/penicillin-coronavirus-florey-wwii-infection/">Mass production of penicillin</a> became a top priority of the U.S. War Department, second only to the Manhattan Project. It is widely believed that <a href="https://us.macmillan.com/books/9780805077780/the-mold-in-dr-floreys-coat">penicillin helped the Allies during World War II</a>, preventing wound infections and helping soldiers diagnosed with gonorrhea to return to the battlefield.</p>
<h2>The rosebush tale has been a thorn in their sides</h2>
<p>Albert Alexander has earned a place in history as the first known person to be treated with penicillin for a clinical condition. Almost as famous as his name is the purported cause of death: sepsis due to a scratch from rosebushes.</p>
<p>However, an alternative explanation was revealed in a <a href="https://www.ox.ac.uk/news/science-blog/penicillin-oxford-story">2010 interview with Eric Sidebottom</a>, a historian and author of “<a href="http://www.offoxpress.com/oxford-medicine-a-walk-through-nine-centuries.html">Oxford Medicine: A Walk Through Nine Centuries</a>.” He claimed that Alexander was injured when his police station was hit during a German bombing raid on Nov. 30, 1940. Shrapnel from this attack caused the facial lacerations that led to Alexander’s fatal blood poisoning, he said.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="elderly woman holds up a black and white photo" src="https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=538&fit=crop&dpr=1 600w, https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=538&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=538&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=676&fit=crop&dpr=1 754w, https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=676&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/451127/original/file-20220309-1729-ehbqqf.jpeg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=676&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Sheila LeBlanc holding photo of her father, Albert Alexander, in 2012.</span>
<span class="attribution"><span class="source">Courtesy of Linda Willason</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>Alexander’s daughter, Sheila LeBlanc, who moved to California and became an artist, confirmed Sidebottom’s account in a <a href="https://www.pe.com/2012/11/02/redlands-local-artists-share-childhood-bond/">2012 interview</a> with a local newspaper. She also revealed the grim consequences Alexander’s death had on his family. Since they’d lived in a house provided by the village, for the village constable, his death forced them to move out. LeBlanc, who was seven at the time, and her older brother were sent to an orphanage, since their mother had to find work.</p>
<p>Michael Barrett, a professor of biochemical parasitology at the University of Glasgow, also spoke to LeBlanc about the cause of Alexander’s injury. <a href="https://mosaicscience.com/story/penicillin-first-patient-history-albert-alexander-AMR-DRI/">Writing in 2018, Barrett stated</a> that while LeBlanc recalled that the constable’s house did have a beautiful rose garden, <a href="http://www.fnrcnewbury.org.uk/biography.asp?BiogID=225&PersonID=2467">her father’s fatal cut</a> was sustained during the German blitz.</p>
<p>In February 2022, I contacted Alexander’s granddaughter, Linda Willason, who is also an artist in California, to help set the record straight. Willason validated the shrapnel account and suggested that the rosebush story was “a bit of wartime propaganda.” By downplaying bombing injuries, the government likely hoped to maintain the public’s stiff upper lip.</p>
<p>While the nature of Alexander’s injury may seem a trivial detail, correcting the historical record is important. Alexander died in the line of duty, and the apocryphal rosebush story obscures his honorable actions. His descendants are hopeful the true account of his injury will now eclipse the false one.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="blue plaque with white text on brick wall" src="https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=413&fit=crop&dpr=1 600w, https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=413&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=413&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=519&fit=crop&dpr=1 754w, https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=519&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/450839/original/file-20220309-27-pxnrfz.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=519&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
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<span class="caption">A plaque dedicated in 2021 shares the real story of Alexander’s injury.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Albert_Alexander_plaque.jpg">Newbury Town Council/Wikimedia Commons</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span>
</figcaption>
</figure>
<p>In 2021, <a href="https://www.bbc.com/news/uk-england-berkshire-57208267">a plaque commemorating Alexander</a> was installed in Newbury that reads: “On war support duty in Southampton on 30th November 1940, Albert was injured in an air raid. Contracting staphylococcal and streptococcal septicaemia, he was transferred to the Radcliffe Infirmary in Oxford, where he was selected for the first clinical application of penicillin. … His place in the history of antibiotics is secure.”</p>
<p>[<em>You’re smart and curious about the world. So are The Conversation’s authors and editors.</em> <a href="https://memberservices.theconversation.com/newsletters/?source=inline-youresmart">You can read us daily by subscribing to our newsletter</a>.]</p><img src="https://counter.theconversation.com/content/178463/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bill Sullivan does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Albert Alexander was the first known person treated with penicillin. While his ultimately fatal case is well known in medical histories, the cause of his illness has been misattributed for decades.Bill Sullivan, Professor of Pharmacology & Toxicology, Indiana University School of MedicineLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1243572019-09-30T13:40:33Z2019-09-30T13:40:33ZAntibiotic resistance: why tests are key to arresting the trend<figure><img src="https://images.theconversation.com/files/294549/original/file-20190927-185359-17bgmal.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The lack diagnostic laboratory systems exacerbates antibiotic resistance in Africa.</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Infections are a <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31012-1/fulltext">leading cause of death</a> worldwide. But widespread resistance to almost all available antibacterials is a reality in low and middle-income countries. It is thought to be most acute in <a href="https://apps.who.int/iris/bitstream/handle/10665/112642/9789241564748_eng.pdf;jsessionid=E9E801D1437BE321AC9256B80F9B7A8E?sequence=1">sub-Saharan Africa</a>. </p>
<p>Antibiotic resistance makes it impossible to treat some infections, such as urinary infections or pneumonia, that would otherwise be easily cured. It <a href="https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf">threatens every aspect of medical care</a>. This includes routine surgery for things like appendicitis, or hospital care following motor vehicle accidents. </p>
<p>In sub-Saharan Africa the problem is compounded by the lack of diagnostic laboratory systems. This means that healthcare workers often have to guess <a href="https://www.sciencedirect.com/science/article/pii/S1198743X1830483X?via%3Dihub">which antibiotic</a> to use for presumed infections. In many cases they may not be required at all. This fuels overuse and the crisis of resistance in regions that can least afford it. It also affects <a href="https://www.ncbi.nlm.nih.gov/pubmed/30243300">clinical care</a> and the ability to control <a href="https://www.ncbi.nlm.nih.gov/pubmed/29649602">infectious disease outbreaks</a>. </p>
<p>In these settings, access to <a href="https://www.sciencedirect.com/science/article/pii/S1473309918300938?via%3Dihub">clinical bacteriology testing</a> is a key bottleneck. Not having access to testing can prevent individual patients from receiving the right treatment for severe infections. It makes it impossible to implement effective interventions to prevent overuse. </p>
<p>Last year the World Health Organisation <a href="https://www.who.int/medical_devices/diagnostics/selection_in-vitro/edl-model-lists/en/">finally declared</a> the availability of on-site bacteriology infrastructure to be a necessity for secondary-level hospitals. </p>
<p>The importance of being able to test people before they get treatment can’t be overstated. Working with colleagues from McGill University, the University of British Columbia and Harvard Medical School, we looked at how antibiotics affected people’s blood results. </p>
<p>In <a href="https://annals.org/aim/fullarticle/2751453/blood-culture-results-before-after-antimicrobial-administration-patients-severe-manifestations">our study</a> we show that the initiation of antibacterial therapy significantly reduces the sensitivity of blood cultures drawn shortly after treatment starts. This reduces the ability to detect the specific bacteria causing the infection.</p>
<p>Our research is significant because it is the first data in humans to show that the timing of antimicrobial administration makes a difference to blood culture results. The study was performed in North America. But its main findings are likely to be broadly relevant across the world.</p>
<h2>The research</h2>
<p>The study was performed in seven health centres across Canada and the US, mostly in Montreal and Vancouver. We recruited 325 patients who were very sick. Choosing the right treatment was a question of life and death.</p>
<p>We modified the standard treatment protocols by adding a post-treatment blood culture, which was obtained within two hours of starting antibiotics. We then compared the results of blood cultures obtained before and after the start of therapy.</p>
<p>We found that among patients who had positive blood cultures before treatment, about 50% had falsely negative cultures shortly after treatment. This showed that treatment interfered with the results of blood tests. </p>
<p>Our results underscore how important testing is. Testing bacterial cultures (particularly before any treatment starts) allows health workers to identify the bacteria causing the infection. And then to target treatment. They can then prescribe the right antibiotic and discontinue those that are not needed. This is beneficial to the patient and the community because reducing unnecessary antibiotic use is key to controlling resistance. </p>
<h2>Why it matters</h2>
<p>Our work highlights the importance of having access to bacteriology testing before starting antibiotic treatment. This is also relevant for health officials across Africa because it provides hard data of how much critical information is lost when antibiotics are used without the support of laboratory diagnostics. </p>
<p>This information adds weight to the international momentum to identify ways to fill the void between high-level recommendations and feasible implementation of bacteriology services in low-resource settings.</p>
<p>The impending catastrophe of antibacterial resistance is frequently cast as an unstoppable phenomenon. But <a href="https://www.researchgate.net/publication/335996760_Diagnostic_Bacteriology_in_District_Hospitals_in_Sub-Saharan_Africa_At_the_Forefront_of_the_Containment_of_Antimicrobial_Resistance">diagnostic clinical bacteriology laboratories</a> can serve as keystones for interventions that are proven to work. These include infection control and prevention in hospitals, as well as programmes that provide guidelines for antibiotic use that are multidisciplinary. Crucially, all of these depend on the availability of laboratory identification and testing of the bacteria that are causing infection.</p>
<p>The longstanding neglect of diagnostic infrastructure in sub-Saharan Africa stems from the fact that the laboratory sector has been under-prioritised. This has been exacerbated by the emphasis of the global health community on tackling single diseases instead of health systems as a whole. </p>
<p>The world can no longer be complacent in the face of a crisis that has its origins in the weakness of health systems, and the resolution of which includes strengthening them. </p>
<p>Several policy-level decisions are needed. These include the secure funding of the diagnostic laboratory sectors in African countries. Additionally, medical microbiology must be recognised as a medical speciality in sub-Saharan Africa. This will ensure that there’s a viable career path for much needed experts in laboratory medicine.</p><img src="https://counter.theconversation.com/content/124357/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Cédric Yansouni has received in-kind support from bioMerieux, for an investigator-initiated research project, in the form of donated equipment.</span></em></p><p class="fine-print"><em><span>Matthew P Cheng does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Healthcare workers in sub-Saharan Africa lack access to laboratory diagnostics and often have to guess which antibiotics to use for presumed infections.Cédric Yansouni, Associate Director, J.D. MacLean Centre for Tropical Diseases, Division of Infectious Diseases, McGill UniversityMatthew P Cheng, Research Fellow, Harvard UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1215082019-08-09T06:00:47Z2019-08-09T06:00:47ZWhat is sepsis and how can it be treated?<figure><img src="https://images.theconversation.com/files/287462/original/file-20190809-144855-pktxcv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">At least 5,000 Australians die each year as a result of sepsis, more commonly known as blood poisoning.</span> <span class="attribution"><span class="source">From shutterstock.com</span></span></figcaption></figure><p>Sepsis, colloquially known as blood poisoning, occurs as a result of an infection, usually from bacteria. Bacteria can enter the blood stream via an open wound, from another part of the body after a surgical procedure, or even from a urinary tract infection.</p>
<p>In Australia, more than <a href="https://www.australiansepsisnetwork.net.au/healthcare-providers/sepsis-epidemiology">15,700 new cases</a> of sepsis are reported each year. Of these, more than 5,000 people will die. Some who survive will need to have limbs amputated, and be left with lifelong disability.</p>
<p>Each intensive care unit admission to treat sepsis costs <a href="https://www.australiansepsisnetwork.net.au/healthcare-providers/sepsis-epidemiology">close to A$40,000</a>.</p>
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Read more:
<a href="https://theconversation.com/1-in-10-patients-are-infected-in-hospital-and-its-not-always-with-what-you-think-120095">1 in 10 patients are infected in hospital, and it's not always with what you think</a>
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<p>But according to <a href="https://www.georgeinstitute.org.au/sites/default/files/world-sepsis-day-2016-report.pdf">a recent Australian survey</a>, only 40% of people have heard of sepsis. Even fewer know what the condition is.</p>
<p>More and more people <a href="https://ccforum.biomedcentral.com/articles/10.1186/s13054-017-1914-8">are aware of sepsis globally</a>, but there’s still a long way to go. If more people know about it (health professionals included), we’re more likely to recognise the condition early and intervene early, which will lead to improved survival rates.</p>
<p>Meanwhile, with the emergence of antibiotic resistant bacteria and the ageing population, the need to find a cure is becoming even more pressing. While a variety of treatments exist, rates of illness and death from sepsis haven’t dropped as they have for infectious diseases over recent decades.</p>
<h2>Sepsis has two phases</h2>
<p>The first phase occurs when an infection enters the bloodstream. This is called septicaemia. Our body’s immune system over-reacts – a process known as hyper inflammation, or septic shock – which leads to the failure of multiple organs. This phase normally lasts for seven to ten days, or longer, depending on the severity of infection.</p>
<p>If the condition is not caught and successfully treated during this first stage, an immune paralysis phase follows. During this phase, the body is left with no functional immune system to fight off the infection. This second phase accounts for the vast majority of sepsis-related deaths.</p>
<p>Sepsis can affect anyone, but is <a href="https://www.georgeinstitute.org.au/sites/default/files/world-sepsis-day-2016-report.pdf">most dangerous</a> in older adults, pregnant women, children younger than one year, and in those with a weakened immune system such as premature babies and people with chronic diseases like diabetes. </p>
<p>Patients in intensive care units are especially vulnerable to developing infections, which can then lead to sepsis.</p>
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Read more:
<a href="https://theconversation.com/why-are-only-some-viruses-transmissible-by-blood-and-how-are-they-actually-spread-75460">Why are only some viruses transmissible by blood and how are they actually spread?</a>
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<h2>Symptoms and treatments</h2>
<p>The pathogens causing sepsis can vary, with bacteria accounting for <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488423/">almost 80%</a> of the cases. Pathogenic fungi and viruses contribute to the rest. For this reason, the symptoms aren’t always identical; and they often overlap with other common infections. </p>
<p>A person will be diagnosed with sepsis if they have a confirmed infection together with low systolic blood pressure (less than 100 mmHg), high fever (in some instances hypothermia), delirium and an increased breathing rate.</p>
<p>Treatment often includes antibiotics as well as dialysis. This is because the kidneys are one of the organs often affected when someone gets sepsis. </p>
<p>Other treatment methods such as <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303907/">blood purification</a> by removing endotoxins (bacterial cell wall products that trigger the immune response) have been trialled with little or no success. This is most likely because these methods fail to remove infectious agents hidden in the body’s tissue.</p>
<p>Alternative treatments such as vitamin D have been reported but <a href="http://rcm.mums.ac.ir/article_3256.html">have not been proven</a> to offer any clinical benefits. </p>
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<img alt="" src="https://images.theconversation.com/files/287460/original/file-20190809-144888-tyfe0h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/287460/original/file-20190809-144888-tyfe0h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/287460/original/file-20190809-144888-tyfe0h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/287460/original/file-20190809-144888-tyfe0h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/287460/original/file-20190809-144888-tyfe0h.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/287460/original/file-20190809-144888-tyfe0h.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/287460/original/file-20190809-144888-tyfe0h.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Sepsis can be particularly dangerous in babies.</span>
<span class="attribution"><span class="source">From shutterstock.com</span></span>
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<p>Many doctors choose to treat with <a href="https://www.nhsinform.scot/tests-and-treatments/medicines-and-medical-aids/types-of-medicine/corticosteroids">corticosteroids</a>, a type of steroid. Although treatment with steroids reduces the time patients spend in intensive care units, it’s shown <a href="https://www.georgeinstitute.org/media-releases/study-ends-debate-over-role-of-steroids-in-treating-septic-shock">no reduction</a> in mortality rates. Importantly, while corticosteroids reduce inflammation, they cause a steep reduction in the number of immune cells, which are needed to fight infection.</p>
<p>In spite of intensive care treatments involving antibiotics, <a href="https://ccforum.biomedcentral.com/track/pdf/10.1186/cc5346">neither the prevalence of sepsis nor death rates from the condition have changed</a> in Australia over the last three decades. They both have actually risen slightly due to the emergence of drug-resistant bacteria and the ageing population.</p>
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Read more:
<a href="https://theconversation.com/what-are-septic-shock-and-sepsis-the-facts-behind-these-deadly-conditions-60599">What are septic shock and sepsis? The facts behind these deadly conditions</a>
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<h2>Where to from here?</h2>
<p>Australian experts have recently called for <a href="https://onlinelibrary.wiley.com/doi/abs/10.5694/mja2.50279">a national action plan</a> to reduce preventable death and disability from sepsis. This would be a positive step to bring more attention to the condition. But reducing the harm sepsis causes also relies on advances in treatment.</p>
<p>Experimental drug therapies for sepsis are at a crossroads, with more than 100 drug trials around the world <a href="https://www.ncbi.nlm.nih.gov/pubmed/24581450">failing to show any benefit</a> over the last 30 years.</p>
<p>The common thread among all these trials was these treatments targeted the initial inflammatory phase of sepsis. But this phase accounts for <a href="https://www.thoracic.org/patients/patient-resources/breathing-in-america/resources/chapter-22-sepsis.pdf">less than 15%</a> of all sepsis-related deaths. </p>
<p>And it’s the inflammation that alerts our immune system to an infection. If you completely block this response (for example, by using steroids), the body will not recognise there is an infection.</p>
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Read more:
<a href="https://theconversation.com/explainer-how-is-septicaemia-treated-2464">Explainer: how is septicaemia treated?</a>
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<p>Researchers have now switched their efforts to identifying the molecular mechanisms that lead to the immune-paralysis phase of sepsis. Understanding this better will hopefully lead to the development of new immunotherapies to target the second phase of the condition.</p>
<p>The time is ripe for measuring the success of sepsis treatment by the number of lives saved rather than the cost saved by reducing the time patients spend in intensive care units.</p><img src="https://counter.theconversation.com/content/121508/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Hamsa Puthalakath receives funding from La Trobe University's SIF and RFA (UD) for developing novel antibody-based therapeutics for treating poly-microbial sepsis.</span></em></p>With an ageing population, and the growing threat of antibiotic resistance, now is the time to be worried about sepsis.Hamsa Puthalakath, Associate Professor, Biochemistry, La Trobe UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1200952019-07-15T00:12:23Z2019-07-15T00:12:23Z1 in 10 patients are infected in hospital, and it’s not always with what you think<figure><img src="https://images.theconversation.com/files/283457/original/file-20190710-44472-1mqt2eb.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Drips and other medical devices were potential sources of infection. But no-one expected to find hospital-acquired pneumonia and urinary tract infections.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/anesthesiologist-nurse-open-intravenous-fluid-225255157?src=oS27Q0yT7trUvePFlYlWwg-1-43&studio=1">from www.shutterstock.com</a></span></figcaption></figure><p>Most people expect hospital treatment to make them better. But for some, a stay in hospital can actually make them sicker. Their wound might get infected after an operation or they might get a blood infection as a result of a medical procedure.</p>
<p>Our study, published today in the international journal <a href="https://aricjournal.biomedcentral.com/articles/10.1186/s13756-019-0570-y">Antimicrobial Resistance and Infection Control</a>, found one in ten adult patients in hospital with an acute (short-term) condition had a health care associated infection.</p>
<p>In the first study of its kind in Australia for over 30 years, we also uncovered unexpected infections, like pneumonia and urinary tract infections, as well as high numbers of patients with multi-drug resistant organisms (superbugs).</p>
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Read more:
<a href="https://theconversation.com/infections-complications-and-safety-breaches-why-patients-need-better-data-on-how-hospitals-compare-86748">Infections, complications and safety breaches: why patients need better data on how hospitals compare</a>
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<h2>Why do we need to keep track of infections?</h2>
<p>Most of these infections can be prevented. So it is important to know what type of infections they are, how common they are and which patients get them. Once we have this information, we can work out a way to prevent them. </p>
<p>Left unchecked, these infections can make already sick patients sicker, can divert hospital resources unnecessarily, and can kill.</p>
<p>Most hospitals in Australia have ongoing surveillance for specific infections, such as wound and bloodstream infections. </p>
<p>Some states have well coordinated programs like the Victorian program <a href="https://www.vicniss.org.au">VICNISS</a>, leading to <a href="https://www.ncbi.nlm.nih.gov/pubmed/25782895">detailed data</a> on health care associated infections. This data is then used to inform hospital strategies on how to prevent infections. However, this type of surveillance method requires extensive resources and does not capture all infections that occur in a hospital.</p>
<p>Instead, we conducted a “point prevalence” survey, which takes a snapshot of the current situation on any given day. This is less resource intensive than ongoing surveillance and it provides valuable information on the distribution and occurrence of <em>all</em> infections in a hospital.</p>
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Read more:
<a href="https://theconversation.com/some-private-hospitals-are-safer-than-others-but-we-dont-know-which-77096">Some private hospitals are safer than others, but we don't know which</a>
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<p>In Europe, the <a href="https://ecdc.europa.eu/en/healthcare-associated-infections-acute-care-hospitals/facts/about">European Centre for Disease Prevention and Control</a> co-ordinates national point prevalence studies every four years. These have provided valuable insight into the burden of health care associated infections. They have also been used to track the emergence of multi-drug resistant organisms in Europe. The US, Singapore and many other countries also run them. </p>
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<img alt="" src="https://images.theconversation.com/files/284013/original/file-20190715-173366-dg76d4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/284013/original/file-20190715-173366-dg76d4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=401&fit=crop&dpr=1 600w, https://images.theconversation.com/files/284013/original/file-20190715-173366-dg76d4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=401&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/284013/original/file-20190715-173366-dg76d4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=401&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/284013/original/file-20190715-173366-dg76d4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/284013/original/file-20190715-173366-dg76d4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/284013/original/file-20190715-173366-dg76d4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Most hospital infections can be prevented.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/633363035?src=jhlWisgjKa449M1gf5-h5A-1-101&studio=1&size=huge_jpg">Santypan/Shutterstock</a></span>
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<p>Unlike <a href="https://www.cdc.gov/nhsn/index.html">most OECD countries</a>, Australia does not have a national health care associated infection surveillance program and does not undertake national point prevalence studies. </p>
<p>The only national data routinely collected relates to <a href="https://www.myhospitals.gov.au/our-reports/healthcare-staphylococcus-aureus-bloodstream/february-2019/overview">bloodstream infections</a> caused by the microorganism <em>Staphylococcus aureus</em>. These infections are serious but rare and only represent a tiny fraction of all infections in hospitals.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/golden-staph-the-deadly-bug-that-wreaks-havoc-in-hospitals-39790">Golden staph: the deadly bug that wreaks havoc in hospitals</a>
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<p>To improve our understanding of health care associated infections across Australia, we used the same study method as the Europeans. Over a four month period in 2018, we visited 19 large hospitals across Australia and collected information on all infections in adult acute inpatients. Four of the hospitals were regional, the others major city hospitals.</p>
<h2>What infections did we find?</h2>
<p>Of the 2,767 patients we surveyed, we found 363 infections in 273 patients, meaning some patients had more than one infection. The most common infections were wound infections after surgery (surgical site infections), pneumonia and urinary tract infections. These accounted for 64% of all the infections we found. </p>
<p>This is important as most hospitals do not normally look for pneumonia or urinary tract infections and there is no routine statewide or national surveillance for these. </p>
<p>Our findings mean these infections are commonly occurring but undetected. A potential source of information on these types of infections is hospital <a href="https://www.ihpa.gov.au/what-we-do/ar-drg-classification-system">administrative coding data</a>. However, these codes were mainly designed for billing purposes and have been shown to be <a href="https://www.ncbi.nlm.nih.gov/pubmed/24218103">unreliable</a> when it comes to identifying <a href="https://www.ncbi.nlm.nih.gov/pubmed/26316651">infections</a>.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/we-know-why-bacteria-become-resistant-to-antibiotics-but-how-does-this-actually-happen-59891">We know _why_ bacteria become resistant to antibiotics, but _how_ does this actually happen?</a>
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<p>We also found patients with a medical device, such as a <a href="https://www.cdc.gov/hai/bsi/catheter_faqs.html">large intravenous drip</a>, or <a href="https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/urinary-catheterisation">urinary catheter</a> (a flexible tube inserted into the bladder to empty it of urine), were more likely to have an infection than those who did not. </p>
<p>Intensive care units treat patients who are gravely unwell and at greater risk of infection. So it was unsurprising to find that 25% of patients in intensive care units had a health care associated infection.</p>
<p>The emergence of multi-drug resistant organisms (<a href="https://theconversation.com/explainer-what-are-superbugs-and-how-can-we-control-them-44364">superbugs</a>) is a concern worldwide. Previously unknown, our study revealed that 10% of the adult acute inpatients in our study had a multi-drug resistant organism.</p>
<h2>What have other studies found?</h2>
<p>For the first time in 34 years we have a glimpse of how common health care associated infections are in Australian hospitals. Although the only other <a href="https://www.ncbi.nlm.nih.gov/pubmed/3143900">previous study</a> was larger, a major strength of our study is that we used the same two trained data collectors to collect the data from all hospitals. </p>
<p>This reduced the potential inconsistency in finding infections that might occur if hospital staff collected their own data. It also minimised the use of hospital resources to undertake the survey.</p>
<p>Importantly though, we did not survey all types of hospitals. It is possible that if the same survey was extended to include children, babies and cancer hospitals, higher rates of infection may be found given the vulnerability of these patients.</p>
<h2>What can we do better?</h2>
<p>As one of the authors has <a href="https://theconversation.com/heres-how-many-people-get-infections-in-australian-hospitals-every-year-82309">previously noted</a>, a major gap in Australia’s effort to combat health care associated infections, and the emergence of multi-drug resistance organisms, is the lack of robust national data.</p>
<p>This means we cannot measure the effect of national policy or <a href="https://www.nhmrc.gov.au/health-advice/public-health/preventing-infection">guidelines</a> despite significant investment.</p>
<p>In the absence of a national surveillance program, we recommend that large-scale point prevalence surveys, including smaller hospitals, specialist hospitals and the private sector be undertaken regularly. Data generated from these studies could then be used to inform and drive national infection prevention initiatives.</p><img src="https://counter.theconversation.com/content/120095/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Philip Russo receives funding from a National Health and Medical Research Council Early Career Fellowship, and is also President Elect of the Australasian College for Infection Prevention and Control. He was a member of the NHMRC Infection Control Guideline Advisory Committee, and a former member of the Healthcare Infection Advisory Committee of the Australian Commission for Safety and Quality in Health Care.
This project was wholly funded by a grant from the Rosemary Norman Foundation, a philanthropic nursing charity. None of the researchers receive any income from the funding or have any role with the charity. The Foundation was not involved in the design nor the conduct of the study, and will not benefit in any form from the results of the study. In-kind support was provided by the Centre for Quality and Patient Safety Research, Deakin University, Monash University and Avondale College of Higher Education.</span></em></p><p class="fine-print"><em><span>Brett Mitchell has received funding from the HCF Foundation and the NHMRC. Brett is the Editor-in-Chief of Infection, Disease and Health. This project was wholly funded by a grant from the Rosemary Norman Foundation, a philanthropic nursing charity. None of the researchers receive any income from the funding or have any role with the charity. The Foundation was not involved in the design nor the conduct of the study, and will not benefit in any form from the results of the study. In-kind support was provided by the Centre for Quality and Patient Safety Research, Deakin University, Monash University and Avondale College of Higher Education.</span></em></p>A surprising number of people are catching pneumonia or urinary tract infections in hospital, a new Australian study shows for the first time.Philip Russo, Associate Professor, Director Cabrini Monash University Department of Nursing Research, Monash UniversityBrett Mitchell, Professor of Nursing, University of NewcastleLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/990512018-07-04T11:57:55Z2018-07-04T11:57:55ZI nearly died from sepsis – and ignorance of this condition is killing millions<figure><img src="https://images.theconversation.com/files/226012/original/file-20180703-116123-1btt1vm.jpg?ixlib=rb-1.1.0&rect=31%2C101%2C967%2C473&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/532149166?src=A23XOMyvhe9QvY2XhnCk2g-1-3&size=medium_jpg">napocska/Shutterstock.com</a></span></figcaption></figure><p>A visit to family in Glasgow for Christmas in 2015 nearly had a tragic ending for me. Two days earlier I had been repairing the lock on my garden gate, when I scratched my hand on a nail. By the time I arrived in Glasgow I was feeling unwell. Twenty-four hours later I was in University Hospital Hairmyres in a coma. I had developed sepsis. My family were told that I had almost no chance of surviving the night.</p>
<p>I woke from my coma three months later and spent another year getting back to full health. I’m one of the lucky ones. Sepsis affects more than <a href="http://www.who.int/news-room/fact-sheets/detail/sepsis">30m people</a> a year worldwide and kills an estimated 6m people, of whom nearly 2m are children. Of those who do survive, 40% will have <a href="https://academic.oup.com/intqhc/advance-article/doi/10.1093/intqhc/mzy137/5040109">post-sepsis syndrome</a>, which leaves them with lasting physical and mental symptoms.</p>
<p>Sepsis starts with a viral or bacterial infection, usually of the <a href="https://books.google.co.uk/books?id=73pYBAAAQBAJ&pg=PA914&redir_esc=y#v=onepage&q&f=false">lungs, abdomen or urinary tract</a>, but it can also begin in a whole host of other ways, including a scratch (as happened in my case) or a bite. It’s not the bug that causes the potentially life-threatening condition, however, it’s the body’s response to the infection. A complex cascade of events is triggered to <a href="http://needtoknow.nas.edu/id/infection/how-pathogens-make-us-sick/">fight an infection</a> – in <a href="https://www.sepsis.org/sepsis/definition/">sepsis</a>, this process becomes uncontrolled, rapidly accelerating and resulting in the failure of vital organs in the body, including the kidneys, heart and lungs.</p>
<p>Like a match being lit, a tiny spark at one end of the match head spreads out rapidly, the flame grows quickly and the match is destroyed by the flame, unless it’s blown out in time. The “flame” of sepsis in a body moves very quickly, and if my brother had not spotted those critical signs in time, or my treatment in the hospital had been delayed by even an hour, I would have died.</p>
<p>Sepsis <a href="https://www.healthline.com/health/sepsis">symptoms</a> can include pale and mottled skin, severe breathlessness, severe shivering or severe muscle pain, not urinating all day, nausea or vomiting. If you or someone you know has one or more of these symptoms, you should call the emergency services immediately and ask: “Could it be sepsis?”</p>
<p>Anyone can get sepsis, although research suggests that people with a <a href="https://www.webmd.com/diet/guide/vitamin-d-deficiency#1">vitamin D deficiency</a> have a higher risk of contracting sepsis than most. Vitamin D deficiency has also been <a href="https://www.sciencedirect.com/science/article/pii/S1201971217302059?via%3Dihub">linked</a> to an increased risk of <a href="https://www.webmd.com/cold-and-flu/news/20170216/vitamin-d-linked-to-lower-risk-of-respiratory-infections">getting an infection</a>, which may then go on to cause sepsis.</p>
<h2>Promising avenues</h2>
<p>Unfortunately, while it may be possible to treat the original infection with antibiotics, there is no specific cure for sepsis – only the symptoms can be treated. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6000220/">New research</a>, however, shows that metformin, a drug used to treat type 2 diabetes, can reduce the impact of sepsis by limiting the body’s immune reaction and protecting it from damage by <a href="https://www.livescience.com/54901-free-radicals.html">free radicals</a> (oxygen-rich molecules that can damage cells).</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/226013/original/file-20180703-116132-z62k2a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/226013/original/file-20180703-116132-z62k2a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/226013/original/file-20180703-116132-z62k2a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/226013/original/file-20180703-116132-z62k2a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/226013/original/file-20180703-116132-z62k2a.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/226013/original/file-20180703-116132-z62k2a.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/226013/original/file-20180703-116132-z62k2a.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">New research suggests that the diabetes drug, metformin, might help to reduce the impact of sepsis.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/524812273?src=QYLitJJ5B31olxoor9Yt6w-1-1&size=medium_jpg">Sherry Yates Young/Shutterstock.com</a></span>
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<p>Other promising <a href="https://www.sciencedirect.com/science/article/pii/S0014299918303637?via%3Dihub">research</a> suggests that gene therapy may prove important in tackling sepsis, by <a href="https://www.khanacademy.org/science/biology/gene-expression-central-dogma/translation-polypeptides/a/protein-targeting-and-traffic">targeting a protein</a> produced in the body called <a href="https://en.wikipedia.org/wiki/NF-%CE%BAB">NF-kB</a>, which malfunctions during sepsis. If successful, these and other treatments in development have the potential to save lives and reduce the long-term impact of the disease on survivors. </p>
<p>The latest research seems promising, but the greatest defence we have against sepsis is awareness of the condition in medical professionals and the public. But at the moment <a href="https://www.huffingtonpost.co.uk/entry/sepsis-in-america-us_us_57083401e4b014223249196d?guccounter=1">awareness</a> is alarmingly low across the world. </p>
<p><a href="https://www.nejm.org/doi/full/10.1056/NEJMp1707170">Surveys suggest</a> that only 40% of people in Australia have heard of sepsis and only one-third of this group are able to identify a single symptom. Figures are even lower in Brazil where only <a href="https://www.nejm.org/doi/full/10.1056/NEJMp1707170">14% of the public</a> know what it is. And, although <a href="https://www.bbc.co.uk/news/uk-scotland-42943092">campaigning in the UK</a> and Germany has created an awareness in over 60% of people, knowledge of the warning signs is still limited.</p>
<p>As you’d expect, awareness is higher among <a href="https://ccforum.biomedcentral.com/articles/10.1186/cc2959">healthcare professionals</a> – but there is a need for greater education within this group. A definite diagnosis is <a href="https://www.medicinenet.com/sepsis/article.htm">often difficult</a>, and efforts are being made to establish clear guidance for healthcare workers across the world, including the roll-out of an internationally recognised protocol called <a href="https://bestpractice.bmj.com/topics/en-gb/245/management-approach">Sepsis6</a>.</p>
<p>With time, scientific research may provide new treatments – but in the short term, greater awareness of the condition among the public and medical professionals is likely to have the biggest effect on saving lives and minimising harm. So always ask: “Could it be sepsis?”</p><img src="https://counter.theconversation.com/content/99051/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Michael Porter does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Sepsis can maim or kill within hours. Here’s how to identify the condition.Michael Porter, Lecturer in Molecular Genetics, University of Central LancashireLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/970492018-05-23T14:49:02Z2018-05-23T14:49:02ZJaundice in newborns could be an evolutionary safeguard against death from sepsis<figure><img src="https://images.theconversation.com/files/220120/original/file-20180523-51121-18kjdfv.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Yellow peril. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/newborn-child-baby-having-treatment-jaundice-624535592?src=fCLtwpRr2ja8PIb7-cm8MA-1-0">Petr Bonek</a></span></figcaption></figure><p>In newborn babies, jaundice is so common as to be termed physiological. It affects around 60% of term babies and around 80% of preterm babies in the first week of their lives. Clinicians need to monitor it carefully and sometimes treat it, since it can lead to conditions like <a href="https://medlineplus.gov/ency/article/007309.htm">acute bilirubin encephalopathy</a> and <a href="https://www.nhs.uk/conditions/jaundice-newborn/complications/">kernicterus</a> that can damage the infant’s brain and cause developmental problems. </p>
<p>But it now looks as though this jaundice is not merely one of the pitfalls of entering the world. <a href="https://www.nature.com/articles/s41598-018-24811-3">New research</a> just published in Scientific Reports, in which we have been involved, suggests that it is one of the gifts of evolution. Humans may develop jaundice as newborns to protect from something even more serious: sepsis. </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/220122/original/file-20180523-51121-s8364d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/220122/original/file-20180523-51121-s8364d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/220122/original/file-20180523-51121-s8364d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=654&fit=crop&dpr=1 600w, https://images.theconversation.com/files/220122/original/file-20180523-51121-s8364d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=654&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/220122/original/file-20180523-51121-s8364d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=654&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/220122/original/file-20180523-51121-s8364d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=822&fit=crop&dpr=1 754w, https://images.theconversation.com/files/220122/original/file-20180523-51121-s8364d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=822&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/220122/original/file-20180523-51121-s8364d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=822&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Bilirubin molecule.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/bilirubin-heme-breakdown-product-molecular-model-138171362?src=FcgjidycRAh37V_cRQMYlA-2-3">Molekuul_b</a></span>
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<p>When most people think of jaundice, they probably think of yellow skin. This is caused by too much of an orange-yellow pigment known as bilirubin in the blood. Bilirubin is released when old red blood cells are being broken down. </p>
<p>Normally it travels to the liver to be converted into a water-soluble form before being excreted in both faeces and urine, but this process can go awry when there has been some upset to the liver that prevents it doing its job properly. In adults, this can be a sign of <a href="https://www.nhs.uk/conditions/jaundice/">underlying conditions</a> ranging from hepatitis to alcoholic cirrhosis. </p>
<p>With newborns, the situation is slightly different: the body needs to make the transition from fetal to adult blood, but the liver does not yet have the capacity to cope with the bilirubin released in the turnover of red blood cells. The resulting jaundice usually passes uneventfully. </p>
<p>The risk of complications like encephalopathy and kernicterus comes when the bilirubin circulates in high levels for prolonged periods, enabling it to cross the blood-brain barrier and deposit deep within the brain. As a result, neonatologists treat high bilirubin levels with blue and white light phototherapy lamps, which convert the bilirubin into a more water-soluble form – temporarily doing the liver’s job. Complications are <a href="https://www.nice.org.uk/guidance/cg98/update/CG98/documents/appendix-b-health-economics2">now thankfully</a> extremely rare as a result – at least in wealthy countries.</p>
<h2>The unexplained why</h2>
<p>In this lies a mystery: why have humans not evolved to overcome this temporary bilirubin problem? Richard started wondering about this when he was doing his PhD in gut microbiology at the University of Aberdeen, while regularly working on call at the neonatal unit as a registrar at the city’s maternity hospital. </p>
<p>One night he was looking after a baby boy who had <a href="https://www.nhs.uk/conditions/sepsis/">sepsis</a>, which is where the immune system goes into overdrive to protect against infection, potentially leading to severe inflammation, organ failure and death. This baby was profoundly unwell in intensive care, suffering from inflammation and a strikingly high bilirubin count that was only just being controlled with three phototherapy lamps. Usually this kind of difficult jaundice is caused by an immune reaction between mum’s and baby’s blood groups, but not in this case. </p>
<p>Richard began wondering if the bilirubin was directly linked to the infection, and if it was part of the baby’s body’s attempt to clear the sepsis (in this case the baby survived). He started thinking about the problem in evolutionary terms – if jaundice can harm the baby, what benefit does it offer to balance this?</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/220121/original/file-20180523-51105-1nimn9s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/220121/original/file-20180523-51105-1nimn9s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/220121/original/file-20180523-51105-1nimn9s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/220121/original/file-20180523-51105-1nimn9s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/220121/original/file-20180523-51105-1nimn9s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/220121/original/file-20180523-51105-1nimn9s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=425&fit=crop&dpr=1 754w, https://images.theconversation.com/files/220121/original/file-20180523-51105-1nimn9s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=425&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/220121/original/file-20180523-51105-1nimn9s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=425&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Jaundiced baby being treated with blue light.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/neonatal-hyperbilirubinemia-newborn-high-bilirubin-under-573576205?src=FcgjidycRAh37V_cRQMYlA-1-31">Happypix</a></span>
</figcaption>
</figure>
<p>Looking at the literature, most people were talking about the fact that bilirubin has <a href="http://pediatrics.aappublications.org/content/113/6/1776.full">antioxidant effects</a> that might counteract <a href="https://www.hindawi.com/journals/omcl/2016/2768365/">oxidative stress</a> caused by birth. But the timing looked unconvincing: when jaundice develops in most babies, the highly oxidant process of being born is usually at least 24 hours in the past. </p>
<p>Thinking about babies in caves in days gone by, with no healthcare and certainly no antibiotics, Richard realised that the biggest threat to their life after surviving delivery would probably be overwhelming sepsis in the first few days – exactly when the bilirubin level rises naturally. Could jaundice be an evolutionary mechanism to protect against this?</p>
<h2>The search begins</h2>
<p>Richard got to work with an 11-strong team at the University of Aberdeen and NHS Grampian, recruiting a willing medical student to spend his summer holiday working with blood plates, bilirubin and bacteria grown originally from neonatal blood cultures taken from septic babies. </p>
<p>Some early signals supporting the hypothesis first emerged in 2009 when the team found that bilirubin seemed to impact the growth of the bacteria that most commonly causes early sepsis in babies, <a href="http://www.ppdictionary.com/bacteria/gpbac/agalactiae.htm">Gram-positive <em>Streptococcus agalactiae</em></a>. With other bacteria implicated in sepsis, the results were mixed: bilirubin also affected some types of <em>Staphylococci</em>, but not Gram-negative <em>Escherichia coli</em>. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/220125/original/file-20180523-117628-1rnyme0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/220125/original/file-20180523-117628-1rnyme0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/220125/original/file-20180523-117628-1rnyme0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/220125/original/file-20180523-117628-1rnyme0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/220125/original/file-20180523-117628-1rnyme0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/220125/original/file-20180523-117628-1rnyme0.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/220125/original/file-20180523-117628-1rnyme0.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/220125/original/file-20180523-117628-1rnyme0.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Colonies of Streptococcus agalactiae.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/holding-plate-bacterial-colonies-streptococcus-agalactiae-645102790?src=g5dBkb4WEHqkAMK0alT7Lw-1-0">angellodeco</a></span>
</figcaption>
</figure>
<p>It was enough to secure a PhD grant from the Medical Research Council and develop ideas further. This went to Sophie Gibson, who developed a new liquid culture system to test the hypothesis further and look at the direct impact on the bacteria. </p>
<p>The results of this project have <a href="https://www.nature.com/articles/s41598-018-24811-3">just been</a> published. Our team have shown that even modest concentrations of bilirubin reduced by one third the growth of Gram-positive <em>Streptococcus agalactiae</em>. We also showed that bilirubin may alter substrate metabolism in the bacteria. </p>
<p>In short, it looks like the hypothesis is bearing out. We now need to do more work, probably in animal experiments of sepsis. This will enable us to think about whether clinicians should raise the accepted bilirubin threshold for <a href="https://www.sepsis.org/sepsis-and/children/">babies at risk</a> of sepsis – those born prematurely, for example. </p>
<p>It feels like we’re discovering something new about the physiology of newborn babies. It’s the excitement of being a clinician scientist: taking an idea from a real patient into the laboratory and testing then developing it to hopefully help future patients. When newborn babies develop jaundice in future, we’ll still need to treat it carefully. But quite possibly we will also be thankful that it’s protecting them from something potentially life-threatening. </p>
<hr>
<p><em>More on articles about pregnancy and babies, written by researchers:</em></p>
<ul>
<li><em><a href="https://theconversation.com/folic-acid-in-pregnancy-mthfr-gene-explains-why-the-benefits-may-differ-95302?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement">Folic acid in pregnancy – MTHFR gene explains why the benefits may differ</a></em></li>
<li><em><a href="https://theconversation.com/women-need-more-freedom-during-labour-not-a-medicalised-birth-script-to-follow-92079?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement">Women need more freedom during labour, not a medicalised birth script to follow</a></em></li>
<li><em><a href="https://theconversation.com/babies-prefer-the-sounds-of-other-babies-to-the-cooing-of-their-parents-95825?utm_source=TCUK&utm_medium=linkback&utm_campaign=TCUKengagement">Babies prefer the sounds of other babies to the cooing of their parents</a></em></li>
</ul><img src="https://counter.theconversation.com/content/97049/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Richard Hansen receives funding from the Chief Scientist Office, Scotland; NHS Research Scotland; National Institute for Health Research; Glasgow Children's Hospital Charity; Crohn's in Childhood Research Association; Crohn's and Colitis UK; CORE; British Society of Paediatric Gastroenterology, Hepatology and Nutrition; and the Catherine McEwan Foundation.</span></em></p><p class="fine-print"><em><span>Elaina Collie-Duguid received funding from BBSRC for capital equipment used in this study. </span></em></p><p class="fine-print"><em><span>Georgina Hold received Medical Research Council Funding including the funding for a PhD studentship to Sophie Gibson, who was the first author on this study.</span></em></p>No mother wants their baby to develop jaundice, but it turns out that they should probably be grateful.Richard Hansen, Honorary Clinical Associate Professor, University of GlasgowElaina Collie-Duguid, Manager, Centre for Genome-Enabled Biology & Medicine, University of AberdeenGeorgina Hold, Professor of Gut Microbiology, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/956932018-04-27T10:45:08Z2018-04-27T10:45:08ZGeorge H. W. Bush has sepsis - why is it so dangerous?<figure><img src="https://images.theconversation.com/files/216578/original/file-20180426-175035-1fidwsu.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Former Presidents George W. Bush and George H.W. Bush attend Barbara Bush's funeral service.</span> <span class="attribution"><span class="source">AP Photo/David J. Phillip</span></span></figcaption></figure><p>Former president George H.W. Bush <a href="https://www.usatoday.com/story/news/nation-now/2018/04/25/president-george-h-w-bush-icu-houston-sepsis-responding/549154002/">was hospitalized April 21 with sepsis</a>, a life-threatening condition caused by complications of the body fighting back against an infection. The former fighter pilot was <a href="https://www.usatoday.com/story/news/nation-now/2018/04/25/president-george-h-w-bush-icu-houston-sepsis-responding/549154002/">released from an intensive care unit</a> at a Houston hospital on April 25. </p>
<p>Between <a href="http://www.ncbi.nlm.nih.gov/pubmed/23442987">1 in 8 and 1 in 4 patients</a> with sepsis will die during hospitalization. Sepsis contributes to <a href="http://jama.jamanetwork.com/article.aspx?articleid=1873131">one-third to one-half</a> of all in-hospital deaths. </p>
<p>Sepsis, sometimes inaccurately referred to as <a href="http://www.sepsisalliance.org/sepsis_and/blood_poisoning/">blood poisoning</a>, is sparked by your body’s reaction to infection. </p>
<p>When you get an infection, your body fights back. When this process works the way it is supposed to, your body quickly takes care of the infection, and you get better. </p>
<p>However, the body’s response to infection sometimes results in collateral damage. This is known as sepsis. The collateral damage can impair kidney, brain, heart or other organ functions. </p>
<p>Sepsis can result from any type of infection. Most commonly, it starts as pneumonia, a urinary tract or intra-abdominal infection such as appendicitis. Most often it starts at home.</p>
<p>Once a person is diagnosed with sepsis, he or she will be treated with antibiotics, IV fluids and support for failing organs, such as dialysis or mechanical ventilation. This usually means a person needs to be hospitalized, often in an intensive care unit, as was the 41st president. Sometimes the source of the infection must be removed, as with appendicitis or an infected medical device. </p>
<p>Many conditions can mimic sepsis, including severe allergic reactions, bleeding, heart attacks, blood clots and medication overdoses. Sepsis requires particular prompt treatments, so getting the diagnosis right matters. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/86768/original/image-20150629-9056-37jco7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/86768/original/image-20150629-9056-37jco7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/86768/original/image-20150629-9056-37jco7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/86768/original/image-20150629-9056-37jco7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/86768/original/image-20150629-9056-37jco7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/86768/original/image-20150629-9056-37jco7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/86768/original/image-20150629-9056-37jco7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Back so soon?</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-213923368/stock-photo-hospital-corridor-hospital-hallway-hospital-interior.html?src=cpb613T6PpuXulgtMwvv4A-1-47">Hospital corridor via www.shutterstock.com.</a></span>
</figcaption>
</figure>
<h2>The revolving door of sepsis care</h2>
<p>As recently as a decade ago, doctors believed that sepsis patients were <a href="http://www.frontline.in/static/html/fl2120/stories/20041008001708600.htm">out of the woods</a> if they could just survive to hospital discharge. Unfortunately, that isn’t the case for many patients. Rather, patients commonly experience <a href="https://jamanetwork.com/journals/jama/fullarticle/2667724">weakness, fatigue confusion, cloudy thinking, anxiety or depression</a>. Collectively, these common symptoms after sepsis are known as <a href="http://www.myicucare.org/Adult-Support/Pages/Post-intensive-Care-Syndrome.aspx">post-intensive care syndrome (PICS)</a>.</p>
<p>In addition to new disabling symptoms, patients are also vulnerable to further health setbacks after sepsis. As many as <a href="http://jama.jamanetwork.com/article.aspx?articleid=2190975">40 percent of sepsis patients go back</a> into the hospital within just three months of heading home, creating a “revolving door” that gets costlier and riskier each time, as patients get weaker with each hospital stay. </p>
<p>Post-intensive care syndrome and rehospitalization mean that we have dramatically underestimated how much sepsis care costs. On top of the US$5.5 billion we now spend on initial hospitalization for sepsis, we must add the costs of rehospitalizations, nursing home and professional in-home care, and unpaid care provided by devoted spouses and families at home.</p>
<p>Raising public awareness increases the likelihood that patients will get to the hospital quickly when they are developing sepsis. This in turn allows prompt treatment, which lowers the risk of long-term problems. Doctors and policymakers are also working to improve the care of sepsis once patients get to the hospital. </p>
<p>The high number of repeat hospitalizations after sepsis, however, suggests another <a href="http://www.uofmhealth.org/news/archive/201503/stopping-revolving-door-study-finds-sepsis-survivors-return">opportunity for improving care</a>. Common reasons for rehospitalization are recurrent infection or sepsis; flares of heart, lung or kidney disease; and aspiration (swallowing food into the lungs).</p><img src="https://counter.theconversation.com/content/95693/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Hallie Prescott receives funding from NIH and Department of Veterans Affairs. </span></em></p><p class="fine-print"><em><span>Theodore Iwashyna receives funding from NIH, VA, and CDC.</span></em></p>Former President George H.W. Bush was hospitalized for sepsis, which can be serious. Just what is this disease that accounts for one-third of all hospital deaths? A speed read explains the dangers.Hallie Prescott, Assistant Professor in Internal Medicine, University of MichiganTheodore Iwashyna, Associate Professor, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/892662017-12-18T14:58:14Z2017-12-18T14:58:14ZYes we must prescribe fewer antibiotics, but we’re ignoring the consequences<figure><img src="https://images.theconversation.com/files/199700/original/file-20171218-27538-12t0hgx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Pills and ills. </span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/drug-prescription-treatment-medication-pharmaceutical-medicament-541252936?src=95CVAFs3xpmQn3gb0gGjlg-1-62">Adul10</a></span></figcaption></figure><p>Antibiotic resistance is one of the greatest challenges facing mankind. We <a href="http://www.who.int/antimicrobial-resistance/en/">risk a future</a> of common infections and minor injuries once again proving fatal – plus longer hospital stays and higher medical costs. Some infections are already no longer treatable with current drugs. <a href="https://amr-review.org">Around</a> 700,000 people die each year around the world as a result, and some studies predict 10m by 2050 – more than die from cancer. </p>
<p>To avoid this “<a href="https://www.theguardian.com/society/2017/oct/13/antibiotic-resistance-could-spell-end-of-modern-medicine-says-chief-medic">antibiotic apocalypse</a>”, everyone acknowledges we need to limit the quantities of antibiotics people are taking. One key strategy to achieve this is <a href="https://theconversation.com/we-need-more-than-just-new-antibiotics-to-fight-superbugs-44054">antimicrobial stewardship</a> – putting systems in place in hospitals and doctors’ surgeries that restrict antibiotic prescriptions by paying more attention to the type, timing, dosage and duration of courses of treatment. </p>
<p>With the UK currently close to completing a <a href="https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/244058/20130902_UK_5_year_AMR_strategy.pdf">five-year implementation plan</a> across the health service, and various <a href="http://www.who.int/hrh/news/2017/AMR2017-2.pdf">other countries also</a> at different stages of development, stewardship is undoubtedly proving <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003543.pub4/epdf">effective</a>. There is growing evidence that interventions by managers improve best practice and reduce the length of time that patients spend on antibiotics, <a href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003543.pub4/abstract">without increasing</a> mortality rates. </p>
<p>When <a href="https://academic.oup.com/jac/article-abstract/72/12/3223/4100561?redirectedFrom=fulltext">we analysed</a> the data, however, it became clear that there are also important lessons that need to be learned. The wider effects of stewardship are not well enough understood. The majority of studies into the effectiveness of tighter antibiotic restrictions have only focused on their intended outcome – cutting the quantities of drugs being prescribed. </p>
<p>Few studies have looked at other consequences, and sometimes these are not easy to predict. Even interventions that reduce the use of antibiotics can lead to unwelcome effects elsewhere in the system. </p>
<h2>Knowns and unknowns</h2>
<p>Since many consequences from tighter antibiotic restrictions are predictable, it’s important we start monitoring them from the outset. Measures commonly involve, for example, requiring frontline medics to get prior permission from a more senior colleague to make sure they’re prescribing the right antibiotic. </p>
<p>Another example is introducing stop orders, which end a course of treatment on a particular date if the clinician hasn’t specified one from the outset. Steps like these can interrupt or delay treatments, but we know little about to what extent. </p>
<p>Some restrictions will inevitably be too unwise to justify. When patients are showing symptoms of infectious pneumonia, for instance, it is common practice to start them on antibiotics before the diagnosis has been confirmed. People who turn out not to be infected will sometimes end up taking unnecessary antibiotics. But since the risks outweigh the benefits with this kind of potentially life-threatening condition, this is difficult to avoid. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/199701/original/file-20171218-27585-pkr8g6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/199701/original/file-20171218-27585-pkr8g6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/199701/original/file-20171218-27585-pkr8g6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/199701/original/file-20171218-27585-pkr8g6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/199701/original/file-20171218-27585-pkr8g6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/199701/original/file-20171218-27585-pkr8g6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/199701/original/file-20171218-27585-pkr8g6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/199701/original/file-20171218-27585-pkr8g6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Here’s the plan …</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/drug-prescription-treatment-medication-pharmaceutical-medicament-541252936?src=95CVAFs3xpmQn3gb0gGjlg-1-62">Rawpixel.com</a></span>
</figcaption>
</figure>
<p>But if this kind of problem is foreseeable and needs to be exempted from any stewardship system, <a href="https://academic.oup.com/jac/article-abstract/72/12/3223/4100561?redirectedFrom=fulltext">our research</a> has also thrown up consequences that couldn’t have been anticipated. In 2009, for example, the Scottish government aimed to reduce by 30% over two years rates of the <em>Clostridium difficile</em> bug, which causes stomach pains, sickness and diarrhoea. This effort involved changing the type of antibiotic normally given to patients prior to various types of surgery to protect them from post-surgical infections. </p>
<p>One result was that more orthopaedic patients <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214537/">ended up</a> developing acute kidney infections – ten more cases per month in one hospital. The managers setting up the stewardship system did not realise that stopping the antibiotic could lead to kidney infections in these patients. They ended up having to stay longer in hospital and needing more clinical interventions as a result. </p>
<p>Unexpected consequences can also be positive sometimes. One example is <a href="https://smw.ch/article/doi/smw.2014.13981">a study</a> of over 10,000 babies thought to be at risk of sepsis, a potentially deadly infection in the blood. The study looked at whether dispensing with the routine diagnostic blood test on these babies and relying only on other clinical examinations delayed the point at which you could start those testing positive for sepsis on a course of antibiotics. </p>
<p>If so, it would mean they would need more antibiotics for a longer duration and that the blood test was therefore a necessary means of controlling levels of prescriptions. Instead, however, the study confirmed that it made no difference, and in fact meant the infants could be given antibiotics earlier – so reducing the need for prescriptions. </p>
<h2>Pause for reflection</h2>
<p>This hopefully gives a glimpse into the complexity in this area, and the limitations in simply looking at cause and effect. <a href="https://siscc.dundee.ac.uk/work/improvement-science-methods/">As part</a> of our research, we have worked with practitioners around Scotland to understand how to monitor and predict consequences more effectively. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/199702/original/file-20171218-27538-1a2ybov.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/199702/original/file-20171218-27538-1a2ybov.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/199702/original/file-20171218-27538-1a2ybov.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=392&fit=crop&dpr=1 600w, https://images.theconversation.com/files/199702/original/file-20171218-27538-1a2ybov.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=392&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/199702/original/file-20171218-27538-1a2ybov.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=392&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/199702/original/file-20171218-27538-1a2ybov.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=493&fit=crop&dpr=1 754w, https://images.theconversation.com/files/199702/original/file-20171218-27538-1a2ybov.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=493&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/199702/original/file-20171218-27538-1a2ybov.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=493&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Until next time.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/patient-meeting-doctor-735167506?src=o5PGEE9iW88_z_4OqIXZXA-1-4">Rawpixel.com</a></span>
</figcaption>
</figure>
<p>We’ve now produced a <a href="https://siscc.dundee.ac.uk/work/improvement-science-methods/">framework</a> to help managers to identify risks from the outset. It promotes the idea of an “improvement pause” to review the new system after a few months and make any necessary adjustments – hopefully making all the professionals involved more confident that the changes are benefiting patients and families. Unpleasant surprises in particular need to be carefully evaluated to see if any harm being caused is enough to stop or adapt the intervention.</p>
<p>The point is that to protect patients, all outcomes associated with changes to antibiotic prescriptions need to be monitored carefully. We’re not seeing nearly enough of this happening after systems are put in place. While interventions are vital to protect us all from antibiotic apocalypse, they still need to be balanced against the needs of patients today.</p><img src="https://counter.theconversation.com/content/89266/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Madalina Toma has received funding from the Economic and Social Research Council. </span></em></p><p class="fine-print"><em><span>Julie Anderson does not receive relevant direct funding but the SISCC receives funding from Scotland's Chief Scientist Office, Health Foundation, NHS Education for Scotland and Scottish Funding Council.</span></em></p>Antimicrobial stewardship is proving effective, but we’re not fully across what is happening.Madalina Toma, Research fellow, University of DundeeJulie Anderson, Associate Director, Scottish Improvement Science Collaborating Centre, University of DundeeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/808642017-07-18T23:09:15Z2017-07-18T23:09:15ZCanada could lead the fight for life in a post-antibiotic world<figure><img src="https://images.theconversation.com/files/178530/original/file-20170717-6084-14ldnjt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Drug-resistant strains of gonorrhoea, once easily dispatched with penicillin, are spreading across the globe resulting in chronic pain and sterility</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>Infectious diseases that once were tamed are roaring back, past the last line of our antibiotic defences. They threaten the lives of millions, but where is the public outcry? </p>
<p>Drug-resistant strains of gonorrhoea, once easily dispatched with penicillin, are spreading across the globe. The result: chronic pain, sterility and a <a href="http://www.who.int/mediacentre/news/releases/2017/Antibiotic-resistant-gonorrhoea/en/">call for new drugs by the World Health Organization</a>. In North America, <a href="https://www.cdc.gov/mmwr/volumes/66/wr/mm6601a7.htm?s_cid=mm6601a7_w&utm_source=Global+Health+NOW+Main+List&utm_campaign=813e656ea4-EMAIL_CAMPAIGN_2017_01_12&utm_medium=email&utm_term=0_8d0d062dbd-813e656ea4-890763">people are dying</a> from infections caused by bacteria that are resistant to all available drugs. And sepsis, a deadly syndrome triggered by untreatable bacterial infections, is causing <a href="http://www.contagionlive.com/news/sepsis-remains-significant-challenge-for-hospitals-public-health-watch-weekly-report">millions of deaths</a> and <a href="https://www.bloomberg.com/news/articles/2017-07-14/america-has-a-27-billion-sepsis-crisis">massive health-care costs</a> among the elderly and very young.</p>
<p>Where is the Canadian co-ordination, leadership and resolve to develop new antimicrobial substances? To move innovations into the marketplace?</p>
<p>This spring, we represented Canada at the Drug-Resistant Infections Conference in Brisbane, Australia — an event that featured academic, public health and pharmaceutical industry researchers from around the world. The goal of the conference was to showcase the best research and development available to battle the antibiotics crisis. We are proud to report that Canadian research is among the most innovative in the world. </p>
<p>The time is right to launch a Canadian Anti-Infectives Innovation Network. It is time to coalesce and co-ordinate Canadian academic, private sector, not-for-profit and government research to solve the antibiotics crisis. Such a network would galvanize Canadian antibiotic research and development. It could ensure that we play a role on the international stage commensurate with our ability and promise.</p>
<h2>The microbes are winning</h2>
<p>The incredible scientific advances of the last century have allowed us to live longer and better lives by preventing or treating many diseases that were once fatal. Pneumonia, blood infections and tuberculosis were once common killers. Now they are generally cured with antibiotics. Cheap and abundant antibiotics have allowed us to <a href="http://dx.doi.org/10.1016/S1473-3099(13)70318-9">cure illnesses, keep fragile pre-term babies alive, carry out safe surgeries and treat cancer</a>.</p>
<p>Those very benefits have lulled us into ignoring a frightening problem that has been looming for decades, undermining that progress and threatening to undo those advances. </p>
<p>While we were enjoying the benefits of antibiotics, the microbes were fighting back. They were finding ways around the obstacles science and medicine had placed in their way. Now the microbes are starting to <a href="http://www.who.int/mediacentre/news/releases/2017/bacteria-antibiotics-needed/en/">win</a>. And although we have good reason to believe <a href="http://www.pewtrusts.org/en/research-and-analysis/analysis/2017/01/18/why-the-antibiotic-pipeline-is-broken-and-how-to-fix-it">new weapons</a> could beat them back again, for some reason the world is not making enough effort to preserve our fragile safety.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/178534/original/file-20170717-6075-x8zy1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/178534/original/file-20170717-6075-x8zy1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/178534/original/file-20170717-6075-x8zy1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/178534/original/file-20170717-6075-x8zy1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/178534/original/file-20170717-6075-x8zy1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/178534/original/file-20170717-6075-x8zy1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/178534/original/file-20170717-6075-x8zy1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Sepsis dates back to ancient Greece and is now a global public health challenge, resulting in millions of death every year.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>We are in this situation because of the ever-increasing number of <a href="https://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf">bacteria</a> that are no longer sensitive to the antibiotics we discovered decades ago. And because most pharmaceutical companies no longer see profitability in new antibiotic drugs. The <a href="http://petrieflom.law.harvard.edu/assets/publications/Outterson_Health_Law_Workshop_paper.pdf">business case </a>is not strong for inventing drugs that patients will only need for a short time, compared to lifelong prescriptions to treat heart and blood-pressure conditions, for example. </p>
<p>But this is not a business case. This is a public health crisis.</p>
<h2>Ordinary illnesses could kill millions</h2>
<p>We are perilously close to plunging back into a time when illnesses we consider ordinary could kill tens of millions. For some deadly strains of bacteria, we are already in a post-antibiotic world. Clinicians are out of options. Once curable diseases are incurable. <a href="http://www.contagionlive.com/news/sepsis-remains-significant-challenge-for-hospitals-public-health-watch-weekly-report">Six million people already die of sepsis</a> every year for want of effective antibiotics, and the cost to the U.S. alone is <a href="https://www.bloomberg.com/news/articles/2017-07-14/america-has-a-27-billion-sepsis-crisis">$27 billion annually</a>. Highly resistant <a href="http://www.cbsnews.com/news/superbug-gene-spotted-on-us-pig-farm/">superbugs are being found on our farms</a>.</p>
<p>In September 2016, 193 members of the United Nations came together to announce that <a href="http://www.un.org/pga/71/2016/09/21/press-release-hl-meeting-on-antimicrobial-resistance/">anti-microbial resistance (AMR) is the largest threat to medicine</a>. This was reaffirmed this month in the final statement from the <a href="https://www.g20.org/gipfeldokumente/G20-leaders-declaration.pdf">G20 meeting in Hamburg</a>. Without urgent action to overcome AMR, the <a href="https://amr-review.org/">UK’s Review On Antimicrobial Resistance</a> estimates the world could witness 10 million extra deaths every year by 2050. That is an increase of total deaths by one sixth.</p>
<p>Even those who survive drug-resistant infections will need twice as much time in hospital. And that is just one expense flowing from a problem that is expected to cost the global economy <a href="https://amr-review.org/">$100 trillion by 2050</a>.</p>
<h2>Canada could lead</h2>
<p>In a context of neglect and inaction, and the misconception that antibiotic discovery is the job of the private sector, no country is ideally positioned to solve this problem alone. Canada, however, is in a position to lead if it wants to.</p>
<p>Canadian researchers have pioneered creative solutions: alternatives to antibiotics that block and inhibit resistance, innovative drug combinations that boost antibiotic activity and enhance host immunity to prevent infection.</p>
<p>Canada’s natural resources, including the Arctic and three oceans, have the potential to deliver new antimicrobial and anti-infective substances. Vaccine development for animals and humans can reduce our need for new drugs. Our innovative thinking can deliver alternatives to reduce dependency on antibiotics. </p>
<h2>Canadian Anti-Infectives Innovation Network</h2>
<p>Innovations alone won’t help. We must do more to get Canadian know-how into action immediately. Canada is a global leader in many areas of basic and applied research that can contribute to solving the problem. But we lack co-ordination, common objectives and resolve.</p>
<p>We need to develop our innovations so we can lead the world in alternatives and adjuncts to antibiotics. We need to become an essential partner in international initiatives such as CARB-X, a public-private accelerator funded by the U.K. and U.S., to move creative antibiotic discoveries into the marketplace. Ironically, two discoveries made at McMaster University are being considered by CARB-X for funding, following licensing to U.S.-based companies. Two others developed at the University of British Columbia, and originally the basis of Canadian spinoffs, are in advanced clinical trials with U.S. companies.</p>
<p>The opportunity to grow these discoveries here in Canada has been lost. So has the associated commercial, employment and skills benefits.</p>
<p>Canada is competing and leading in anti-infective innovation, but we are rapidly falling behind in our ability to capitalize on these discoveries, foster and support new research and commercialization in Canada. </p>
<p>We must act now to ensure that we not only do our share on the international stage to solve the antibiotic crisis, but also provide a made-in-Canada innovative approach. We can do so, with support and leadership, in the form of a Canadian Anti-Infectives Innovation Network that assembles leading researchers in universities, hospitals, government and the private sector.</p><img src="https://counter.theconversation.com/content/80864/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gerry Wright is a Professor and Director of the Michael G. DeGroote Institute for Infectious Disease Research at McMaster University. He is a co-founder and owns shares in the company Symbal Therapeutics that seeks to identify new anti-infective agents and strategies to address the antibiotic crisis. He consults widely for private sector and not-for profit agencies in the antibiotics field. His laboratory receives funding from federal and provincial funding agencies and not-for-profit groups such as the Bill and Melinda Gates Foundation. His lab has received funding over the years from both large and small pharmaceutical companies working in the area of antibiotic research and discovery.</span></em></p><p class="fine-print"><em><span>Bob Hancock has been awarded 56 patents for his UBC discoveries, largely in the area of alternatives to antibiotics, and these have been assigned to his university and licensed to several companies. If these products are successful in the long run there is the possibility that he and his co-inventors could receive milestone payments or royalties.
His laboratory has been highly funded in the past by Canadian funding agencies, and his current research is funded by CIHR, NSERC, CFI, Cystic Fibrosis Canada, and Genome Canada, as well as funding from NIH and the Australian granting agency NHMRC. He believes that he has a responsibility to ensure that his inventions are developed for the good of the Canadian public, and as such he recently founded, and is a majority shareholder in, two virtual companies - ABT Innovations and Sepset Inc - that are developing new anti-infective therapeutics and sepsis diagnostics, respectively. He consults extensively with both large Pharma and small to medium-sized biotech companies.</span></em></p>Without leading edge innovations and coordination, Canadians will die from the epidemic of antibiotic resistant infections.Gerry Wright, Professor of Biochemistry and Biomedical Sciences, McMaster UniversityBob Hancock, Professor of Microbiology and Immunology, University of British ColumbiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/605992016-06-06T20:43:30Z2016-06-06T20:43:30ZWhat are septic shock and sepsis? The facts behind these deadly conditions<figure><img src="https://images.theconversation.com/files/125404/original/image-20160606-13080-sco7ag.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-342951869/stock-photo-blurred-icu-room-in-a-hospital-with-medical-equipments-and-patient.html?src=6UQOHJ_TE-dGjOB7rNrZZQ-1-1">ICU image via www.shutterstock.com.</a></span></figcaption></figure><p>Most Americans have never heard of it, but according to recent federal data, <a href="http://www.sepsis.org">sepsis</a> is the <a href="http://www.hcup-us.ahrq.gov/reports/statbriefs/sb204-Most-Expensive-Hospital-Conditions.pdf">most expensive</a> cause of hospitalization in the U.S., and is now the <a href="http://www.ncbi.nlm.nih.gov/pubmed/26968023">most common cause of ICU admission</a> among older Americans.</p>
<p><a href="http://www.ncbi.nlm.nih.gov/pubmed/26903338">Sepsis</a> is a complication of infection that leads to organ failure. <a href="https://www.hcup-us.ahrq.gov/reports/statbriefs/sb204-most-expensive-hospital-conditions.pdf">More than one million patients</a> are hospitalized for sepsis each year. This is more than the number of <a href="http://www.hcup-us.ahrq.gov/reports/statbriefs/sb160.jsp">hospitalizations for heart attack and stroke combined</a>. People with chronic medical conditions, such as neurological disease, cancer, chronic lung disease and kidney disease, are at particular risk for developing sepsis.</p>
<p>And it is deadly. Between <a href="http://dx.doi.org/10.1097/CCM.0b013e31827c09f8">one in eight and one in four patients</a> with sepsis will die during hospitalization – as most notably <a href="http://www.nbcnews.com/news/sports/cause-muhammad-ali-s-death-septic-shock-targets-sick-elderly-n585926">Muhammad Ali did</a> in June 2016. In fact sepsis contributes to <a href="http://dx.doi.org/10.1001/jama.2014.5804">one-third to one-half</a> of all in-hospital deaths. Despite these grave consequences, <a href="https://www.sepsis.org/news/new-survey-shows-americans-never-heard-sepsis-despite-sepsis-costly-hospital-condition-u-s/">fewer than half</a> of Americans know what the word sepsis means.</p>
<h2>What is sepsis and why is it so dangerous?</h2>
<p>Sepsis a severe health problem sparked by your body’s reaction to infection. When you get an infection, your body fights back, releasing chemicals into the bloodstream to kill the harmful bacteria or viruses. When this process works the way it is supposed to, your body takes care of the infection and you get better. With sepsis, the chemicals from your body’s own defenses trigger inflammatory responses, which can impair blood flow to organs, like the brain, heart or kidneys. This in turn can lead to organ failure and tissue damage.</p>
<p>At its most severe, the body’s response to infection can cause dangerously low blood pressure. This is called septic shock.</p>
<p>Sepsis can result from any type of infection. Most commonly, it starts as a pneumonia, urinary tract infection or intra-abdominal infection such as appendicitis. It is sometimes referred to as “<a href="https://www.sepsis.org/sepsisand/blood-poisoning/">blood poisoning</a>,” but this is an outdated term. Blood poisoning is an infection present in the blood, while sepsis refers to the body’s response to any infection, wherever it is.</p>
<p>Once a person is diagnosed with sepsis, she will be treated with antibiotics, IV fluids and support for failing organs, such as dialysis or mechanical ventilation. This usually means a person needs to be hospitalized, often in an ICU. Sometimes the source of the infection must be removed, as with appendicitis or an infected medical device.</p>
<p>It can be difficult to distinguish sepsis from other diseases that can make one very sick, and there is no lab test that can confirm sepsis. Many conditions can mimic sepsis, including severe allergic reactions, bleeding, heart attacks, blood clots and medication overdoses. Sepsis requires particular prompt treatments, so getting the diagnosis right matters.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/125406/original/image-20160606-13045-1ks5v62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/125406/original/image-20160606-13045-1ks5v62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/125406/original/image-20160606-13045-1ks5v62.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/125406/original/image-20160606-13045-1ks5v62.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/125406/original/image-20160606-13045-1ks5v62.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/125406/original/image-20160606-13045-1ks5v62.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/125406/original/image-20160606-13045-1ks5v62.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Back so soon?</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-160642211/stock-photo-blurred-motion-of-nurses-walking-in-hospital-corridor.html?src=zyD5Pyq9yKfg3Hm9BxKbUA-1-47">Hospital hallway image via www.shutterstock.com.</a></span>
</figcaption>
</figure>
<h2>The revolving door of sepsis care</h2>
<p>As recently as a decade ago, doctors believed that sepsis patients were <a href="http://www.frontline.in/static/html/fl2120/stories/20041008001708600.htm">out of the woods</a> if they could just survive to hospital discharge. But that isn’t the case – <a href="http://dx.doi.org/10.1001/jama.2015.1410">40 percent of sepsis patients go back</a> into the hospital within just three months of heading home, creating a “revolving door” that gets costlier and riskier each time, as patients get weaker and weaker with each hospital stay. Sepsis survivors also have an <a href="http://dx.doi.org/10.1136/bmj.i2375">increased risk of dying</a> for months to years after the acute infection is cured.</p>
<p>If sepsis wasn’t bad enough, it can lead to another health problem: <a href="https://www.youtube.com/watch?v=Rwch2_9mSQA%22%22">Post-Intensive Care Syndrome (PICS)</a>, <a href="https://my.vanderbilt.edu/getthenac/2013/11/wall-street-journal-covers-vumcs-post-icu-delirium-research/">a chronic health condition that arises from critical illness</a>. Common symptoms include <a href="http://dx.doi.org/10.1001/jama.2010.1553">weakness, forgetfulness</a>, <a href="http://dx.doi.org/10.1097/CCM.0000000000000882">anxiety</a> and <a href="http://dx.doi.org/10.1016/S2213-2600(14)70051-7">depression</a>. </p>
<p>Post-Intensive Care Syndrome and frequent hospital readmissions mean that we have dramatically underestimated how much sepsis care costs. On top of the <a href="https://www.cms.gov/Newsroom/MediaReleaseDatabase/Fact-sheets/2015-Fact-sheets-items/2015-06-01.html">US$5.5 billion</a> we now spend on initial hospitalization for sepsis, we must add untold billions in rehospitalizations, nursing home and professional in-home care, and unpaid care provided by devoted spouses and families at home.</p>
<p>Unfortunately, progress in improving sepsis care has lagged behind improvements in cancer and heart care, as attention has shifted to the treatment of <a href="http://www.who.int/chp/about/en/">chronic diseases</a>. However, sepsis remains a common cause of death in patients with chronic diseases. One way to help reduce the death toll of these chronic diseases may be to improve our treatment of sepsis.</p>
<h2>Rethinking sepsis identification</h2>
<p>Raising public awareness increases the likelihood that patients will get to the hospital quickly when they are developing sepsis. This in turn allows prompt treatment, which lowers the risk of long-term problems.</p>
<p>Beyond increasing public awareness, doctors and policymakers are also working to improve the care of sepsis patients in the hospital.</p>
<p>For instance, a new <a href="http://dx.doi.org/10.1001/jama.2016.0287">sepsis definition</a> was released by several physician groups in February 2016. The goal of this new definition is to better distinguish people with a healthy response to infection from those who are being harmed by their body’s response to infection. </p>
<p>As part of the sepsis redefinition process, the physician groups also developed a new prediction tool called <a href="http://www.qsofa.org/">qSOFA</a>. This instrument identifies patients with infection who are at high risk of death or prolonged intensive care. The tools uses just three factors: thinking much less clearly than usual, quick breathing and low blood pressure. Patients with infection and two or more of these factors are at high risk of sepsis. In contrast to prior methods of screening patients at high risk of sepsis, the new qSOFA tool was developed through examining millions of patient records.</p>
<h2>Life after sepsis</h2>
<p>Even with great inpatient care, some survivors will still have problems after sepsis, such as memory loss and weakness.</p>
<p>Doctors are wrestling with how to best care for the growing number of sepsis survivors in the short and long term. This is <a href="http://dx.doi.org/10.7326/0003-4819-153-3-201008030-00013">no easy task</a>, but there are several exciting developments in this area.</p>
<p>The Society of Critical Care Medicine’s <a href="https://www.youtube.com/watch?v=Rwch2_9mSQA">THRIVE</a> initiative is now building a network of support groups for patients and families after critical illness. THRIVE will forge new ways for survivors to work with each other, like how cancer patients provide each other advice and support.</p>
<p>As medical care is increasingly complex, many doctors contribute to a patient’s care for just a week or two. Electronic health records let doctors see how the sepsis hospitalization fits into the broader picture – which in turn helps doctors counsel patients and family members on what to expect going forward.</p>
<p>The high number of repeat hospitalizations after sepsis suggests another <a href="http://www.uofmhealth.org/news/archive/201503/stopping-revolving-door-study-finds-sepsis-survivors-return">opportunity for improving care</a>. We could analyze data about patients with sepsis to target the right interventions to each individual patient.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/125411/original/image-20160606-13051-1rbljch.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/125411/original/image-20160606-13051-1rbljch.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/125411/original/image-20160606-13051-1rbljch.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/125411/original/image-20160606-13051-1rbljch.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/125411/original/image-20160606-13051-1rbljch.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/125411/original/image-20160606-13051-1rbljch.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/125411/original/image-20160606-13051-1rbljch.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Better care.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-336642854.html?src=download_history">Intensive care image via www.shutterstock.com.</a></span>
</figcaption>
</figure>
<h2>Better care through better policy</h2>
<p>In 2012, New York state passed <a href="http://www.governor.ny.gov/news/governor-cuomo-announces-new-york-state-lead-nation-fighting-sepsis-1-killer-hospitals-and-make">regulations</a> to require every hospital to have a formal plan for identifying sepsis and providing prompt treatment. It is too early to tell if this is a strong enough intervention to make things better. However, it serves as a clarion call for hospitals to <a href="http://dx.doi.org/10.1001/jama.2014.11350">end the neglect of sepsis</a>.</p>
<p>The Centers for Medicare & Medicaid Services (CMS) are also working to improve sepsis care. Starting in 2017, CMS will <a href="https://www.cms.gov/newsroom/mediareleasedatabase/fact-sheets/2014-fact-sheets-items/2014-08-04-2.html">adjust hospital payments</a> by quality of sepsis treatment. Hospitals with good report cards will be paid more, while hospitals with poor marks will be paid less.</p>
<p>To judge the quality of sepsis care, CMS will require hospitals to <a href="http://www.medicare.gov/hospitalcompare/search.html?aspxautodetectcookiesupport=1">publicly report</a> compliance with National Quality Forum’s “<a href="https://www.cms.gov/newsroom/mediareleasedatabase/fact-sheets/2014-fact-sheets-items/2014-08-042.html">Sepsis Management Bundle</a>.” This includes a handful of proven practices such as heavy-duty antibiotics and intravenous fluids.</p>
<p>While policy fixes are notorious for producing <a href="http://dx.doi.org/10.1377/hlthaff.2014.0778">unintended consequences</a>, the reporting mandate is certainly a step in the right direction. It would be even better if the mandate focused on helping hospitals work collaboratively to improve their detection and treatment of sepsis.</p>
<p>Right now, sepsis care varies greatly from hospital to hospital, and patient to patient. But as data, dollars and awareness converge, we may be at a tipping point that will help patients get the best care, while making the best use of our health care dollars.</p>
<p><em>This is an updated version of an article originally published on July 1, 2015. You can read the original version <a href="https://theconversation.com/sepsis-the-largely-unknown-condition-that-puts-one-million-people-in-the-hospital-each-year-43327">here</a>.</em></p><img src="https://counter.theconversation.com/content/60599/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Hallie Prescott receives funding from National Institutes of Health and the American Thoracic Society Foundation.</span></em></p><p class="fine-print"><em><span>Theodore Iwashyna receives funding from the US NIH and Veterans Affairs Health Services Research & Development. The views expressed here are not necessarily those of the US Government or the Department of Veterans Affairs. </span></em></p>Boxer Muhammad Ali died of septic shock, after being admitted to the hospital for a respiratory problem. Despite the fact more than a million people are hospitalized with sepsis each year, fewer than half of Americans know what the word sepsis means.Hallie Prescott, Assistant Professor in Internal Medicine, University of MichiganTheodore Iwashyna, Associate Professor, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/433272015-07-01T10:06:56Z2015-07-01T10:06:56ZSepsis: the largely unknown condition that puts one million people in the hospital each year<figure><img src="https://images.theconversation.com/files/86766/original/image-20150629-9099-ppt96b.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Diagnosing sepsis isn't easy.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-205406395/stock-photo-intensive-care-unit.html?src=qNxYnrOH20bsbFjrArwlaQ-1-1">Intensive care unit image via www.shutterstock.com.</a></span></figcaption></figure><p><em>An updated version of this piece is at: <a href="https://theconversation.com/what-are-septic-shock-and-sepsis-the-facts-behind-these-deadly-conditions-60599">What are septic shock and sepsis? The facts behind these deadly conditions</a>.</em></p>
<hr>
<p>Most Americans have never heard of it, but according to new federal data, <a href="http://www.sepsisalliance.org/sepsis/definition/">sepsis</a> is the <a href="http://www.hcup-us.ahrq.gov/reports/statbriefs/sb160.jsp">most expensive</a> cause of hospitalization in the US. </p>
<p>Sepsis is a complication of infection that leads to organ failure. One million patients are hospitalized for sepsis each year (across all types of health insurance). This is more than the number of <a href="http://www.hcup-us.ahrq.gov/reports/statbriefs/sb160.jsp">hospitalizations for heart attack and stroke combined</a>. Sepsis can be a particular risk for older people. In 2013 alone, <a href="http://www.cms.gov/Newsroom/MediaReleaseDatabase/Fact-sheets/2015-Fact-sheets-items/2015-06-01.html">400,000</a> Medicare beneficiaries were hospitalized because of sepsis at a cost of US$5.5 billion. </p>
<p>And it is deadly. Between <a href="http://www.ncbi.nlm.nih.gov/pubmed/23442987">one in eight and one in four patients</a> with sepsis will die during hospitalization. In fact sepsis contributes to <a href="http://jama.jamanetwork.com/article.aspx?articleid=1873131">one-third to one-half</a> of all in-hospital deaths. </p>
<p>Despite these grave consequences, <a href="https://www.sepsis.org/news/new-survey-shows-americans-never-heard-sepsis-despite-sepsis-costly-hospital-condition-u-s/">fewer than half</a> of Americans know what the word sepsis means. </p>
<h2>What is sepsis and why is it so dangerous?</h2>
<p>Sepsis a severe health problem sparked by your body’s reaction to infection. When you get an infection, your body fights back, releasing chemicals into the bloodstream to kill the harmful bacteria or viruses. When this process works the way it is supposed to, your body takes care of the infection and you get better. With sepsis, the chemicals from your body’s own defenses trigger inflammatory responses, which can impair blood flow to organs, like the brain, heart or kidneys. This in turn can lead to organ failure and tissue damage.</p>
<p>Sepsis can result from any type of infection. Most commonly, it starts as a pneumonia, urinary tract or intra-abdominal infection such as appendicitis. It is sometimes referred to as “<a href="https://www.sepsis.org/sepsisand/blood-poisoning/">blood poisoning</a>,” but this is not an accurate term. Blood poisoning is an infection present in the blood, while sepsis refers to the body’s response to any infection, wherever it is. </p>
<p>Once a person is diagnosed with sepsis, she will be treated with antibiotics, IV fluids and support for failing organs, such as dialysis or mechanical ventilation. This usually means a person needs to be hospitalized, often in an ICU. Sometimes the source of the infection must be removed, as with appendicitis or an infected medical device. </p>
<p>Part of the problem we face with sepsis is agreeing on just what it is, from a medical standpoint. Experts last defined sepsis in <a href="http://www.ncbi.nlm.nih.gov/pubmed/12682500">2001</a>. </p>
<p>However, <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1415236">recent studies</a> suggest the current definition does a poor job distinguishing sepsis from other diseases that can make one very sick. Many conditions can mimic sepsis, including severe allergic reactions, bleeding, heart attacks, blood clots and medication overdoses. Sepsis requires particular prompt treatments, so getting the diagnosis right matters. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/86768/original/image-20150629-9056-37jco7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/86768/original/image-20150629-9056-37jco7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/86768/original/image-20150629-9056-37jco7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/86768/original/image-20150629-9056-37jco7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/86768/original/image-20150629-9056-37jco7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/86768/original/image-20150629-9056-37jco7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/86768/original/image-20150629-9056-37jco7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Back so soon?</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-213923368/stock-photo-hospital-corridor-hospital-hallway-hospital-interior.html?src=cpb613T6PpuXulgtMwvv4A-1-47">Hospital corridor via www.shutterstock.com.</a></span>
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<h2>The revolving door of sepsis care</h2>
<p>As recently as a decade ago, doctors believed that sepsis patients were <a href="http://www.frontline.in/static/html/fl2120/stories/20041008001708600.htm">out of the woods</a> if they could just survive to hospital discharge. But that isn’t the case – <a href="http://jama.jamanetwork.com/article.aspx?articleid=2190975">40% of sepsis patients go back</a> into the hospital within just three months of heading home, creating a “revolving door” that gets costlier and riskier each time, as patients get weaker and weaker with each hospital stay. </p>
<p>If sepsis wasnt’t bad enough, it can lead to another health problem: <a href="http://www.myicucare.org/Adult-Support/Pages/Post-intensive-Care-Syndrome.aspx">Post-Intensive Care Syndrome (PICS)</a>, <a href="https://my.vanderbilt.edu/getthenac/2013/11/wall-street-journal-covers-vumcs-post-icu-delirium-research/">a chronic health condition that arises from critical illness</a>. Common symptoms include <a href="http://jama.jamanetwork.com/article.aspx?articleid=186769">weakness, forgetfulness</a>, <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=Posttraumatic+Stress+Disorder+in+Critical+Illness+Survivors%3A+A+Metaanalysis">anxiety</a> and <a href="http://www.eurekalert.org/pub_releases/2014-04/tl-1i3040314.php">depression</a>.</p>
<p>Post-Intensive Care Syndrome and frequent hospital re-admissions mean that we have dramatically underestimated how much sepsis care costs. On top of the $5.5 billion we now spend on initial hospitalization for sepsis, we must add untold billions in re-hospitalizations, nursing home and professional in-home care, and unpaid care provided by devoted spouses and families at home.</p>
<p>Unfortunately, progress in improving sepsis care has lagged behind improvements in cancer and heart care, as attention has shifted to the treatment of <a href="http://www.who.int/chp/about/en/">chronic diseases</a>.</p>
<h2>Rethinking treatment and care</h2>
<p>Raising public awareness increases the likelihood that patients will get to the hospital quickly when they are developing sepsis. This in turn allows prompt treatment, which lowers the risk of long-term problems. </p>
<p>Beyond increasing public awareness, doctors and policymakers are also working to improve the care of sepsis once patients get to the hospital. </p>
<p>Several physician groups are collaborating to develop a new prediction tool called <a href="https://oxicmblog.wordpress.com/2015/03/17/isicem-2015-blog-day-1/">qSOFA</a>. This instrument identifies patients with infection who are at high risk of death or prolonged intensive care. In contrast to existing methods for identifying sepsis, the new tool is data-driven. It was developed through examining millions of electronic patient records. </p>
<p>Researchers are also refining a mainstay of sepsis treatment – antibiotic therapy. These medications must be given within hours of diagnosis, but how long they are needed is unclear.</p>
<p>Newer studies indicate that <a href="http://www.nejm.org/doi/full/10.1056/NEJMoa1411162">shorter treatment</a> courses may be as effective as longer courses, while potentially limiting <a href="http://www.wired.com/2011/08/killing-beneficial-bacteria/">disruption to healthy bacteria</a> living on and within us. </p>
<p>Preliminary research by us and our colleagues suggests that the <a href="http://www.atsjournals.org/doi/abs/10.1164/rccm.201503-0483OC#.VYDDHGDho2w">risk for sepsis is temporarily increased</a> when healthy bacteria are disturbed. This raises the intriguing possibility that diet or supplements aimed at restoring healthy bacteria may reduce the risk of future sepsis.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/86769/original/image-20150629-9056-f32rq9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/86769/original/image-20150629-9056-f32rq9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/86769/original/image-20150629-9056-f32rq9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/86769/original/image-20150629-9056-f32rq9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/86769/original/image-20150629-9056-f32rq9.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/86769/original/image-20150629-9056-f32rq9.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/86769/original/image-20150629-9056-f32rq9.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Care after sepsis matters.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-33663229/stock-photo-doctor-or-nurse-taking-a-patient-s-blood-pressure.html?src=mn5gj8XwClwHTGO2wDTTTg-1-60">Blood pressure image via www.shutterstock.com.</a></span>
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</figure>
<h2>Life after sepsis</h2>
<p>Even with great inpatient care, some survivors will still have problems after sepsis, such as memory loss and weakness. </p>
<p>Doctors are wrestling with how to best care for the growing number of sepsis survivors in the short and long term. This is <a href="http://annals.org/article.aspx?articleid=745945">no easy task</a>, but there are several exciting developments in this area. </p>
<p>The Society of Critical Care Medicine’s <a href="http://www.sccm.org/Research/Quality/thrive/Pages/default.aspx">THRIVE</a> initiative is now building a network of support groups for patients and families after critical illness. THRIVE will forge new ways for survivors to work with each other, like how cancer patients provide each other advice and support. </p>
<p>As medical care is increasingly complex, many doctors contribute to a patient’s care for just a week or two. Electronic health records let doctors see how the sepsis hospitalization fits into the broader picture – which in turn helps doctors counsel patients and family members on what to expect going forward. </p>
<p>The high number of repeat hospitalizations after sepsis suggests another <a href="http://www.uofmhealth.org/news/archive/201503/stopping-revolving-door-study-finds-sepsis-survivors-return">opportunity for improving care</a>. We could analyze data about patients with sepsis to target the right interventions to each individual patient.</p>
<h2>Better care through better policy</h2>
<p>In 2012, New York State passed <a href="http://www.governor.ny.gov/news/governor-cuomo-announces-new-york-state-lead-nation-fighting-sepsis-1-killer-hospitals-and-make">regulations</a> to require every hospital to have a formal plan for identifying sepsis and providing prompt treatment. It is too early to tell if this is a strong enough intervention to make things better. However, it serves as a clarion call for hospitals to <a href="http://jama.jamanetwork.com/article.aspx?articleid=1911335">end the neglect of sepsis</a>.</p>
<p>The Centers for Medicare & Medicaid Services (CMS) are also working to improve sepsis care. Starting in 2017, CMS will <a href="https://www.cms.gov/Newsroom/MediaReleaseDatabase/Fact-sheets/2014-Fact-sheets-items/2014-08-04-2.html">adjust hospital payments</a> by quality of sepsis treatment. Hospitals with good report cards will be paid more, while hospitals with poor marks will be paid less. </p>
<p>To judge the quality of sepsis care, CMS will require hospitals to <a href="http://www.medicare.gov/hospitalcompare/search.html?AspxAutoDetectCookieSupport=1">publicly report</a> compliance with National Quality Forum’s “<a href="https://www.cms.gov/Newsroom/MediaReleaseDatabase/Fact-sheets/2014-Fact-sheets-items/2014-08-042.html">Sepsis Management Bundle</a>.” This includes a handful of proven practices such as heavy-duty antibiotics and intravenous fluids. </p>
<p>While policy fixes are notorious for producing <a href="http://content.healthaffairs.org/content/34/6/907">unintended consequences</a>, the reporting mandate is certainly a step in the right direction.</p>
<p>Right now, sepsis care varies greatly from hospital to hospital, and patient to patient. But as data, dollars and awareness converge, we may be at a tipping point that will help patients get the best care, while making the best use of our health care dollars.</p><img src="https://counter.theconversation.com/content/43327/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Hallie Prescott receives funding from US National Institutes of Health.</span></em></p><p class="fine-print"><em><span>Theodore Iwashyna receives funding to study outcomes of sepsis and other critical illnesses from the US National Institutes of Health, the US Department of Veterans Affairs, the American Thoracic Society, and the Society of Critical Care Medicine.</span></em></p>Even though sepsis is growing more common, doctors still have trouble diagnosing it.Hallie Prescott, Assistant Professor in Internal Medicine, University of MichiganTheodore Iwashyna, Associate Professor, University of MichiganLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/317152014-09-18T05:28:15Z2014-09-18T05:28:15ZNew device uses nano-magnets to cleanse bad blood when sepsis strikes<figure><img src="https://images.theconversation.com/files/59301/original/44b32sw6-1410954682.jpg?ixlib=rb-1.1.0&rect=34%2C188%2C971%2C740&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Clean up act.</span> <span class="attribution"><a class="source" href="https://www.flickr.com/photos/denn/4311117490/sizes/o/in/photolist-7yXB2U-ab6DAy-dX2TzK-4AUY2j-dTnLJx-oyvv9M-4sUZTC-eE9WzD-6Nvp2-7KZrSc-9BAAXQ-bE9kx4-bE9jtV-aRMCGH-aRMCfc-aRMCKe-aRMCDr-oeCD64-oeQ5gx-bE9kVB-breorY-bE9i7T-bE9jPP-brermu-bE9iRr-owhYxX-ovGocu-oetWVa-owmcGB-oeCCep-ovU9aC-ou1P65-oeYDvy-dwZFit-otQyRo-oeShPK-oemA7S-oetzCc-ovEuXh-oeZjyL-oeye3W-oenRfW-owsJ1N-ovWwbf-oyewRD-oeUmYT-ovS4zF-aRMChM-aRMCkH-aRMCjn-aRMCgz/">Denn</a>, <a class="license" href="http://creativecommons.org/licenses/by-sa/4.0/">CC BY-SA</a></span></figcaption></figure><p>Sepsis claims the lives of 8m people worldwide each year. It is <a href="http://kdvr.com/2014/09/15/sepsis-little-known-illness-that-is-leading-cause-of-hospital-deaths-in-u-s/">the leading cause</a> of hospital deaths in the US, a major threat to soldiers wounded in battle and a killer of children, particularly in under-resourced areas around the world.</p>
<p><a href="http://www.mayoclinic.org/diseases-conditions/sepsis/basics/definition/con-20031900">Sepsis</a> occurs when bacteria, fungi or viruses multiply in a patient’s blood and trigger a chain reaction that causes inflammation, blood clotting, and organ damage. Traditional treatment requires doctors to race against the clock to pinpoint the specific type of pathogen causing the infection so that the right antibiotic therapy can be administered. But in many cases blood cultures never make a positive identification, so we often treat them blindly. </p>
<p>Patients generally receive broad-spectrum antibiotics along the way, but things <a href="http://www.nhs.uk/Conditions/Blood-poisoning/Pages/Treatment.aspx">often go downhill fast</a> and can end in septic shock, where blood pressure drops to dangerous levels. This is a challenge made greater still by the growing population of antibiotic-resistant superbugs and viruses where we currently have no treatment at all.</p>
<p>But there is some hope. Here at <a href="http://wyss.harvard.edu/viewpage/about-us/about-us">Harvard’s Wyss Institute</a>, we are hot on the trail of the sepsis problem. In collaboration with other Harvard colleagues and two hospitals, we’ve developed a dialysis-like therapeutic device that could radically transform the way doctors treat sepsis, which we <a href="http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.3640.html">announced in Nature Medicine</a>.</p>
<h2>Meet ‘the biospleen’</h2>
<p>The “biospleen” is a device inspired by the human spleen, <a href="http://www.webmd.com/digestive-disorders/picture-of-the-spleen">which filters pathogens and toxins</a> from flowing blood without requiring doctors to identify the pathogen causing the problem – and it captures antibiotic-resistant bacteria as well. We found that it was able to remove more than 90% of bacteria from the blood of rats in a few hours. It also increased survival when these animals were injected with a lethal bacterial toxin. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=207&fit=crop&dpr=1 600w, https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=207&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=207&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=260&fit=crop&dpr=1 754w, https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=260&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/59288/original/g8qmqvzt-1410953222.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=260&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Pathogen’s find it magnetic.</span>
<span class="attribution"><span class="source">Harvard's Wyss Institute</span></span>
</figcaption>
</figure>
<p>The biospleen works outside the body like a dialysis machine. It consists of two hollow channels that are connected to each other by a series of slits: one channel contains flowing blood and the other has a saline solution. Key to its success are tiny nanometer-sized magnetic beads that are coated with a genetically engineered version of a natural immune system protein called mannose binding lectin (MBL). </p>
<p>The magnetic beads are added to the blood after it flows from a patient’s vein and before it enters the device. After the beads bind to pathogens, they are pulled from the flowing blood, through the slits, and into the neighbouring saline channel by a magnet in the device, which cleans the blood before being returned to the patient. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=251&fit=crop&dpr=1 600w, https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=251&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=251&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=315&fit=crop&dpr=1 754w, https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=315&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/59290/original/s4wvhvqh-1410953407.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=315&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Stuck on you.</span>
<span class="attribution"><span class="source">Harvard Wyss Institute</span></span>
</figcaption>
</figure>
<p>Best of all? The device simply and effectively cleans the blood without the need to first pinpoint the pathogen responsible for the infection because the MBL protein binds to more than 90 different causes of infection and sepsis, including bacteria, fungi, viruses, parasites and toxins.</p>
<h2>Getting ideas out of the lab</h2>
<p>Very innovative and potentially groundbreaking ideas often get stuck in the mire of traditional academic laboratories because they cannot be validated to the degree required by financial investors, for example, by working through manufacturing and regulatory challenges. </p>
<p>At the Wyss Institute, we’ve teamed up in-house inventors, engineers and entrepreneurs to speed up the commercialisation of our technologies. They’ll work with the blood cleansing device to get it out of the laboratory as soon as possible to begin saving lives. </p>
<p>The major reason no-one ever explored this idea in the past is that most clinicians and researchers assume that because blood cultures are negative, there are no circulating pathogens. But the reality is that there is circulating dead pathogen debris and many toxins, which are primary triggers of the inflammatory cascade that leads to sepsis. The power of this device is that it binds to dead pathogens and toxins as well as live bugs.</p>
<p>The next step will be to test and validate the technology in large animal studies and from there into human clinical trials.</p><img src="https://counter.theconversation.com/content/31715/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Donald Ingber is founding director of the Wyss Institute for BIologically Inspired Engineering, and a professor at Harvard's schools of medicine and engineering. The biospleen was developed in collaboration with the Harvard School of Engineering and Applied Sciences, Boston Children’s Hospital, Harvard Medical School, and Massachusetts General Hospital</span></em></p>Sepsis claims the lives of 8m people worldwide each year. It is the leading cause of hospital deaths in the US, a major threat to soldiers wounded in battle and a killer of children, particularly in under-resourced…Donald Ingber, Founding Director of the Wyss Institute, Harvard UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/122372013-02-21T03:41:21Z2013-02-21T03:41:21ZOf mice and men: role of mice in biomedical research questioned<figure><img src="https://images.theconversation.com/files/20472/original/gjsgpvf2-1361404417.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The authors say their findings raise important questions about the central role of animal models in biomedical research.</span> <span class="attribution"><span class="source">Understanding Animal Research</span></span></figcaption></figure><p><a href="http://www.pnas.org/content/early/2013/02/07/1222878110.short">A study recently published</a> in the peer-reviewed journal <a href="http://www.pnas.org/">PNAS</a> (Proceedings of the National of Academy Sciences) shows that mice are poor models for human inflammatory diseases. The paper, which focused on <a href="https://theconversation.com/explainer-how-is-septicaemia-treated-2464">sepsis</a>, burns and trauma, raises questions about the fundamental role of mice in biomedical research.</p>
<p>Bodily responses to burn injuries and acute infections look similar in mice and humans, but the study authors found they’re driven by fundamentally different genetic and molecular mechanisms. They spent ten years examining which genes in human white blood cells are activated during infection. Data from 167 patients suggested there are particular patterns of genomic change associated with acute inflammation. </p>
<p>After having their paper rejected by several journals, the researchers decided to redesign their study. Apparently, one objection from <a href="http://www.nytimes.com/2013/02/12/science/testing-of-some-deadly-diseases-on-mice-mislead-report-says.html?nl=todaysheadlines&emc=edit_th_20130212&_r=0">reviewers</a> was that the results had not been validated by mouse studies. But when the researchers looked at the genomic response to different forms of inflammation in mice, they made a number of startling discoveries:</p>
<ol>
<li><p>The relatively uniform gene changes found in human patients were not found in mice.</p></li>
<li><p>Genomic changes in mice were completely different to humans, and there was no discernible pattern of gene modification.</p></li>
<li><p>None of the mouse models for sepsis, bacterial blood poisoning, trauma or burns predicted the magnitude or direction of inflammation in humans. </p></li>
</ol>
<p>These findings have significant ramifications. </p>
<p>There have been almost 150 clinical trials of drugs designed to block immune responses to acute sepsis in humans. These trials were all based on research in mice and have all failed to produce a positive result. </p>
<p>Clinical trials are expensive. The costs of a failed trial include financial losses and opportunity costs (other things that could have been done with the resources used). These opportunity costs are both scientific, and in terms of the health and well-being of human participants.</p>
<p>As specified by the <a href="http://www.wma.net/en/30publications/10policies/b3/">Declaration of Helsinki</a>, which governs the ethics of research involving people, before a candidate drug can be given to humans, it must first be tested on at least two different animal models. So the drugs used in human trials were run through standardised mouse models, and each model was designed specifically to replicate human inflammatory responses. </p>
<p>The authors of the PNAS study make clear their findings don’t invalidate mouse models of other human diseases. But they do think their experience raises important questions about how biomedicine is researched, particularly, the central role of animal models. </p>
<p>In an interview in the <a href="http://www.nytimes.com/2013/02/12/science/testing-of-some-deadly-diseases-on-mice-mislead-report-says.html?nl=todaysheadlines&emc=edit_th_20130212&_r=0">New York Times</a>, one of the authors said, </p>
<blockquote>
<p>They were so used to doing mouse studies that they thought that was how you validate things. They are so ingrained in trying to cure mice that they forget we are trying to cure humans. </p>
</blockquote>
<p>The study also highlights a problem for researchers who study animal models to better understand and treat human diseases. The practice depends on the assumption that some properties of humans and non-human animals are both functionally and causally similar. But to assume that the first leads to the second is to commit what some <a href="http://www.jstor.org/stable/10.2307/2220412">philosophers of science</a> describe as the “modeller’s functional fallacy”. </p>
<p>Digital watches and sundials can both tell the time, for instance, but they do this in completely different ways. A cloudy day obscures the time on the sundial but it doesn’t have the same effect on the digital watch. Similar functions can clearly have different causes.</p>
<p>Other biomedical researchers are beginning to take a <a href="http://digitalcommons.calpoly.edu/bts/vol15/iss1/4/">different approach</a> to devising therapies. They advocate a comparative strategy that prioritises the study of naturally occurring human and animal disease. They believe this form of <a href="http://www.clinsci.org/cs/112/cs1120217.htm">“translational research”</a> could solve many of the quandaries raised by this and <a href="http://www.bmj.com/content/334/7586/197">other examples</a> of research where animal models have been poor predictors of human disease. </p>
<p>Public support for animal experimentation rests on its purported value to human health. But <a href="https://theconversation.com/animal-research-provides-a-flawed-model-so-why-not-stop-7890">arguments against the practice</a> are increasingly based on examples of how it has misled medicine. Unfortunately, however, so much is invested in current research models that it’s unlikely to see significant change anytime soon.</p><img src="https://counter.theconversation.com/content/12237/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Chris Degeling is affiliated with the NHMRC Centre for Research Excellence in Critical and Emerging Infectious Disease</span></em></p><p class="fine-print"><em><span>Jane Johnson is a Chief Investigator on an ARC Linkage Grant. </span></em></p>A study recently published in the peer-reviewed journal PNAS (Proceedings of the National of Academy Sciences) shows that mice are poor models for human inflammatory diseases. The paper, which focused…Christopher Degeling, Researcher, University of SydneyJane Johnson, Macquarie University Research Fellow, Macquarie UniversityLicensed as Creative Commons – attribution, no derivatives.