Category Archives: Physiology

Physiology

Suicide rate increases during the week of a full moon – Earth.com

A new study from the Indiana University School of Medicine has found that deaths by suicide significantly increase during the week of a full moon. The research, which was published in the journal Discover Mental Health, analyzed data from the Marion County coroners office in Indiana about suicides that took place from 2012-2016.

Study lead author Dr. Alexander Niculescu explained the rationale behind the research: We wanted to analyze the hypothesis that suicides are increased during the period around full moons and determine if high-risk patients should be followed more closely during those times.

The researchers found that people over the age of 55 showed an even higher increase in suicides during the week of a full moon. In addition, the experts looked at the time of day and month when suicides occurred and found that 3 to 4 p.m. and the month of September were peak times.

From a clinical perspective and a public health perspective, we found some important take-home messages in this study, said Dr. Niculescu. High-risk patients should possibly be followed more closely the week of the full moon, during late afternoons and perhaps the month of September.

The team of researchers also previously developed blood biomarker tests for other mental health conditions such as anxiety, depression, and post-traumatic stress disorder, as well as for pain. In this study, they were able to use blood samples previously taken by the coroner from some of the people who died by suicide to determine which biomarkers were present.

We tested a list of top blood biomarkers for suicidality that we identified in previous studies, said Dr. Niculescu. The biomarkers for suicidality that are predictive of death by suicide during full moon, peak hour of day and peak month of the year compared to outside of those periods appear to be genes that regulate the bodys own internal clock, so called circadian clock. Using the biomarkers, we also found people with alcohol-use disorder or depression may be at higher risk during these time periods.

According to Dr. Niculescu, the surge in suicides during the full moon phase could be attributed to the heightened luminosity. The bodys circadian rhythm, which regulates our sleep-wake cycle over 24 hours, is significantly influenced by the surrounding light. Moonlight could be disrupting peoples natural rhythms during the period when it should be dimmer.

The effect of ambient light and body clocks in suicide needs to be studied more closely, along with how people sleep and their exposure to light, Niculescu said. Changes in light can affect vulnerable people, in conjunction with other risk factors.

Dr. Niculescu mentioned that there are two additional peak periods for suicides. The first peak occurs from 3 to 4 p.m. and may be connected to the accumulation of stressors throughout the day, as well as a reduction in daylight which leads to lower expression of circadian clock genes and cortisol. The second peak happens in September, which coincides with the end of summer vacations and the onset of seasonal affective disorder symptoms as the amount of daylight decreases during this time of year.

Our work shows the full moon, fall season and late afternoon are temporal windows of increased risk for suicide, particularly in individuals who suffer from depression or alcohol use disorders.

In the future, Dr. Niculescu hopes to study if exposure to screens at night contributes to increased suicidality in people, especially younger people. Some people have a full moon in their hand every night. Its an area we absolutely need to study further.

While the idea that a full moon can cause strange behavior has been around for centuries, there is little scientific evidence to support the claim. However, this study provides some evidence that there may be a correlation between the full moon and an increased risk of suicide, particularly among older adults.

Its important to note that correlation does not necessarily equal causation, and the study has limitations, such as being limited to data from one county in Indiana. Further research will be needed to determine if these findings can be replicated in other locations and populations.

Nonetheless, the findings provide important insights into the patterns of suicide, and could help inform suicide prevention efforts. As Niculescu noted, These findings underscore the importance of more research into the factors contributing to suicide risk, and suggest that paying closer attention to the timing of suicides could help save lives.

Full moons and human behavior

There is ongoing debate and controversy regarding the extent to which the full moon can impact human behavior. While some studies have suggested that the full moon may have a subtle influence on human physiology and behavior, other studies have failed to find any significant effects.

One of the most commonly discussed effects of the full moon is its potential to influence sleep patterns. Some researchers have found that people tend to sleep less deeply and experience more interrupted sleep around the time of the full moon.

This may be due to the moons gravitational pull, which can affect the tides and may also affect the fluids in our bodies. However, other studies have failed to replicate these findings, so the evidence for this effect is mixed at best.

Another potential impact of the full moon on human behavior is its association with changes in mood and mental health. Some people report feeling more anxious or agitated around the time of the full moon, while others may experience a boost in energy and creativity.

However, again, the evidence for these effects is inconclusive and may be influenced by a range of other factors, such as cultural beliefs and expectations.

It is also worth noting that many of the studies on the effects of the full moon have been criticized for being poorly designed or for relying on anecdotal evidence rather than rigorous scientific methods. To fully understand the potential impact of the full moon on human behavior, more research is needed using rigorous experimental designs and objective measures of behavior and physiology.

In summary, while there is some evidence to suggest that the full moon may have a subtle influence on human behavior, the scientific evidence for this effect is far from conclusive. As with many other areas of scientific inquiry, more research is needed to fully understand the potential impact of the full moon on human physiology and behavior.

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Suicide rate increases during the week of a full moon - Earth.com

Physiology

Innovative method predicts the effects of climate change on cold … – Science Daily

In the face of a warming climate that is having a profound effect on global biodiversity and will change the distribution and abundance of many animals, a Penn State-led research team has developed a statistical model that improves estimates of habitat suitability and extinction probability for cold-blooded animals as temperatures climb.

Cold-blooded animals -- a diverse group including fish, reptiles, amphibians and insects -- comprise most species on Earth. The body temperature of cold-blooded animals is strongly influenced by the temperature of their environment. Because their growth, reproductive success and survival is tightly coupled to environmental temperatures, climate change represents a significant threat to them.

Understanding the future effects of climate change on biodiversity is a global priority, according to research team leader Tyler Wagner, a scientist with the U.S. Geological Survey and a Penn State adjunct professor of fisheries ecology. But predicting where a species will exist and in what abundance under future temperatures is extremely challenging, he noted, because for many species this means estimating responses to temperatures that the animals have not yet experienced, and scientists have not yet observed.

To more precisely estimate the effects of climate change on cold-blooded animals, in a new study, the researchers developed a statistical method to fuse data collected in the field describing the distribution and abundance of many cold-blooded animals with laboratory-derived information about species-specific temperature performance and tolerance.

In findings published today (April 3) in the Proceedings of the National Academy of Sciences, Wagner and colleagues report the development of an innovative statistical modeling approach. Their newly developed model, which they call the "Physiologically Guided Abundance Model," or PGA Model, can be applied across almost all cold-blooded animals, and is believed to have great potential to help inform the formation of climate adaptation and management strategies.

"The challenge was how to combine these two sources of information and use laboratory-derived information to help inform landscape-scale predictions under future climates not experienced by animals in their current ranges," said Wagner, who is assistant unit leader of the Pennsylvania Cooperative Fish and Wildlife Research Unit in the College of Agricultural Sciences. "The model we created accomplishes that."

The PGA model combines observations of species abundance and environmental conditions with laboratory-derived data on the physiological response of cold-blooded animals to temperature to predict species geographical distributions and abundance in response to a warming world. Without including species' physiological preferences in a model, Wagner suggests, it is difficult to realistically forecast cold-blooded animals' fate.

"When trying to predict, or extrapolate, the effects of climate change on animal distribution and abundance, scientists now often only use information that describes the relationships between abundance and distributions and temperature under current conditions," he said. "These relationships are then used to extrapolate under future temperature conditions."

However, this approach assumes that species-environment relationships are biologically meaningful under future temperatures and, importantly, fails to account for the tight link between environmental temperatures and cold-blooded animal physiology, Wagner explained.

"Although cold-blooded animals are understudied when it comes to understanding how their distributions and abundance will respond to climate change, these animals are relatively well-studied when it comes to laboratory-derived information about how changes in environmental temperatures affect physiology and performance," he said. "In fact, most cold-blooded animals share a similar functional response in relative performance with increasing temperatures, which can be generalized across a diversity of taxa."

The researchers developed their PGA model using data from three fish species that differ in their thermal preference and tolerance across more than 1,300 lakes located in the U.S. Midwest. They compared the PGA model's results to those from a traditional model that does not incorporate species' physiological responses. Fishes considered in the research were cisco (coldwater), yellow perch (coolwater) and bluegill (warmwater).

The researchers predicted species distributions and abundance at each lake under current conditions and for 1.8-, 3.6-, 5.4- and 7.2-degree (Fahrenheit) increases in mean July water temperatures. A 7.2-degree F increase corresponds to the predicted average regional increase in air temperature across the Midwest region for the 2071-2100 time period.

While the results of the traditional model did not predict that any of the fish species would be extirpated, or locally driven out, by climate change, the PGA model revealed that cold-adapted fish would be extirpated in 61% of their current habitat with rising temperature.

Gretchen Hansen, assistant professor at the University of Minnesota and a coauthor on the study, suggested that models that do not include physiological preferences may lead to underestimations of the risk climate change may pose to cold-adapted species.

"We showed that temperature-driven changes in distribution, local extinction, and abundance of cold-, cool- and warm-adapted species varied substantially when physiological information was incorporated into the model," she said. "The PGA model provided more realistic predictions under future climate scenarios compared with traditional approaches and has great potential for more realistically estimating the effects of climate change on cold blooded species."

Also contributing to the research at Penn State was Christopher Custer, doctoral degree student in the Department of Ecosystem Science and Management; as well as Erin Schliep, Department of Statistics, North Carolina State University; Joshua North, Climate and Ecosystem Sciences Division, Lawrence Berkeley National Laboratory; and Holly Kundel and Jenna Ruzich, Department of Fisheries, Wildlife, and Conservation Biology, University of Minnesota.

This research was funded by the U.S. Geological Survey Midwest Climate Adaptation Science Center and the National Science Foundation.

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Innovative method predicts the effects of climate change on cold ... - Science Daily

Physiology

Research Staff Awards honor contributions to discovery | VUMC … – VUMC Reporter

Recipients of the 2023 Research Staff Awards are, front row from left, Laura Stevens, MS, Kate Von Wahlde, MJ, CCRP, and JoAnn Gottlieb, RDMS, RDCS. Presenting the awards were, back row from left, Jennifer Pietenpol, PhD, Gordon Bernard, MD, and John Kuriyan, PhD. (photo by Susan Urmy)

by Bill Snyder

Laboratory and administrative personnel at Vanderbilt University Medical Center were honored on March 31 for research excellence during the 19th annual Research Staff Awards Ceremony at the Aertson Hotel in Nashville.

Presenting the awards were Jennifer Pietenpol, PhD, VUMC Chief Scientific & Strategy Officer, John Kuriyan, PhD, dean of Basic Sciences, Vanderbilt University School of Medicine, which sponsors the awards, and Gordon Bernard, MD, VUMC Executive Vice President for Research.

The awards and 2022 recipients are:

Each honoree received an award check and crystal trophy.

Von Wahlde, a certified clinical research professional who has a Master of Jurisprudence degree, has played a pivotal role since 2010 in elevating the research enterprise in the Department of Otolaryngology, including steering several high-profile clinical trials of human device implants through regulatory review and approval.

Kate is nothing short of a marvel, wrote Alexander Gelbard, MD, associate professor and director of Clinical Trials and Translational Research in the department, in his nomination letter.

The clinical trials she has helped manage have restored hearing (new cochlear implant designs), restored speech (new vocal cord pacer for the paralyzed larynx) and led to approval of several new reagents for chronic sinusitis, Gelbard wrote.

In his nomination letter, Eben Rosenthal, MD, the Carol and John Odess Professor of Facial, Plastic and Reconstructive Surgery, and chair of the department, noted that Von Wahlde and her team significantly contributed to the rise in the departments ranking in total NIH funding, from 11th place in 2010 to 2nd in 2021.

Von Wahlde, who has been at VUMC since 2004, also is a role model for efficient and successful clinical investigation, universally applauded by medical students, residents, fellows and faculty alike, added Justin Turner, MD, PhD, the departments vice chair for Research.

Von Wahldes award is named for the late Vivien T. Thomas, the pioneering surgical technician who began his career at Vanderbilt in the 1930s.

Stevens joined the lab of Mark Denison, MD, in 2017. With the emergence of COVID-19 in early 2020, she contributed to the first laboratory demonstration that human antibodies to the Moderna vaccine neutralized the COVID-19 virus, SARS-CoV-2. She also aided preclinical development of the antiviral drugs remdesivir and molnupiravir.

It is hard to imagine another bench investigator in the entire world who has performed experiments that directly supported a vaccine and two antivirals against SARS-CoV-2, and that are preventing illness and saving lives, Denison, the Edward Claiborne Stahlman Professor of Pediatric Physiology and Cell Metabolism, wrote in his nomination letter.

Barney Graham, MD, PhD, whose team at the NIH Vaccine Research Center led development of the Moderna vaccine, noted that Stevens, with VUMC colleagues Jim Chappell, MD, PhD, and Andrea Pruijssers, PhD, worked courageously with this then frightening and clearly lethal virus, with capabilities we didnt have at the NIH.

Her research contributions have been foundational to development of countermeasures against SARS-CoV-2, wrote Chappell, research professor of Pediatrics.

We all leaned on Laura to get it done right, added Pruijssers, who now works for Merck. Lauras basic science skills, her servitude attitude, and her grit have saved the lives of thousands of people.

Stevens award is named for the late Edward E. Price Jr., an internationally known research assistant in the Department of Biochemistry and Cardiovascular Physiology Core.

Gottleib is a registered diagnostic medical sonographer and registered diagnostic cardiac sonographer who first joined the VICTR Clinical Research Center in 2011. During the past five years, she has contributed to 27 clinical studies.

Her skills are recognized at a national level. Her expertise is central to the success of many of these projects, Kevin Niswender, MD, PhD, and James Luther, MD, MSCI, CRC medical director and associate medical director, respectively, wrote in their nomination letter.

Gottlieb produces the best echo images I have seen in my 15-plus years of reading echocardiograms, noted Deepak Gupta, MD, MSCI, associate professor of Medicine and director of the Vanderbilt Translational and Clinical Cardiovascular Research Center.

Her contributions have not only enabled publications and preliminary data for new grant applications, but also have facilitated obtaining more than $1.5 million in extramural research funding for my program alone, he wrote.

High quality echocardiography is a key endpoint for translational studies of pulmonary vascular disease and right heart failure. Gottlieb consistently delivers high quality images even under the most difficult circumstances, wrote VUMC physician-scientists Anna Hemnes, MD, and Evan Brittain, MD, MSCI.

Its safe to say that we could not be where we are today without JoAnn Gottlieb, they added.

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Research Staff Awards honor contributions to discovery | VUMC ... - VUMC Reporter

Physiology

Rady grad students shine at Three Minute Thesis final – UM Today

April 5, 2023

Three minutes isnt much time to explain complex research and novel ideas, but a trio of Rady Faculty of Health Sciences graduate students excelled at presenting their work clearly and concisely in just 180 seconds.

The students took home three of the four prizes at the University of Manitobas annual Three Minute Thesis (3MT) final on March 30.

Keshav Narayan Alagarsamy, a PhD student in physiology and pathophysiology at the Max Rady College of Medicine, won this years Dr. Archie McNicol Prize for First Place and $2,500.

Akshi Malik, also a PhD student in physiology and pathophysiology, received the UM Retirees Association Prize for Second Place and $1,250.

Dr. Olubukola Olatosi, a PhD student in oral biology at the Dr. Gerald Niznick College of Dentistry, clinched the Peoples Choice Award and $200.

Congratulations to the students, who did an outstanding job of representing the Rady Faculty of Health Sciences at the 3MT final, said Dr. Peter Nickerson, vice-provost (health sciences), dean, Max Rady College of Medicine, and dean, Rady Faculty of Health Sciences.

They showcased the valuable research our graduate students are working on and showed the importance of being able to explain their complicated work in plain language to reach a larger audience.

3MT competitors must summarize their research and its importance without using any notes or props. They are allowed to use a single slide to illustrate their topic.

Alagarsamy has mixed feelings about beating out the other 11 UM graduate students who made the final from an initial field of 34 competitors. Hes happy he was victorious, but hes anxious about having to represent UM at the Western Regional 3MT Competition on May 25.

I have very good presentation skills, but Im always nervous, he said. Im a very nervous guy. I have great stage fear. If I can do it, then anyone can do it.

In front of the audience on the Fort Garry campus, Alagarsamy calmed his nerves and presented his thesis project on the capacity to use stem cells and nanomaterials to regenerate a damaged heart after a heart attack. The goal of the research is to allow more heart disease patients to lead normal lives.

I congratulate Keshav on this wonderful achievement, said Dr. Sanjiv Dhingra, a professor of physiology and pathophysiology who is Alagarsamys advisor. I think winning the 3MT competition will further help him to achieve his career goals.

It was Dhingra who motivated Alagarsamy to take part in the competition. With his advisors encouragement, and his labmates suggestions on how to improve his presentation, Alagarsamy practised his performance over and over. To get ready for the Western Regional 3MT Competition at the University of Saskatchewan, hes going to do more of the same.

Im grateful for what happened today, and Ill try my best in the future as well, Alagarsamy said.

Akshi Malik

Like Alagarsamy, Malik put in a lot of practice to fine-tune her presentation. She recited her performance whenever she could from the shower to lunchtime.

I felt really, really amazing while I was presenting, so I think it was a well-earned place, said Malik, whose advisor is Dr. Pawan Singal, a professor of physiology and pathophysiology.

Maliks research is seeking to understand how the chemotherapy drug doxorubicin affects the hearts of cancer patients, as well as looking for a cardioprotective agent that can prevent doxorubicin-induced heart failure.

Dr. Olubukola Olatosi

While the judges were wowed by Alagarsamy and Maliks performances, Olatosi was voted by the audience as its favourite.

Olatosi was thankful for the people who voted for her and said shes no longer afraid to speak in public.

Getting to the finals and getting the Peoples Choice Award is quite an amazing feeling, she said. I feel so happy and so glad.

Olatosis research focuses on determining the strategies to implement the novel Canadian Caries Risk Assessment Tool and to provide guidelines for implementation to improve the oral health of Indigenous children. Her advisor is Dr. Robert Schroth, professor of preventive dental science at the Dr. Gerald Niznick College of Dentistry.

Daniel Schwade Araujo, a PhD student in applied health sciences, a joint program between the College of Rehabilitation Sciences and the Faculty of Kinesiology and Recreation Management, and Michelle Morello, a masters student in genetic counselling at the Max Rady College of Medicine, also took part in the 3MT final.

Watch the participants 3MT presentations.

Matthew Kruchak

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Rady grad students shine at Three Minute Thesis final - UM Today

Physiology

The Physical and Mental Benefits of Stretching Regularly – Laughing Squid

In a limberTED-Ed lessonwritten byMalachy McHugh and directed bySofia Pashaei,narratorAddison Anderson explains the physiology of stretching, how varied stretching is important for different exercises, how long and often stretching should be done, and how stretching is beneficial to both brain and body.

Typically, athletes stretch before physical activity to avoid injuries like muscle strains and tears. But does stretching actually prevent these issues?And if so, how long do the benefits of stretching last? To answer these questions, we need to know whats actually happening in the body when we stretch.

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The Physical and Mental Benefits of Stretching Regularly - Laughing Squid

Physiology

Olympic silver medalist calls for Nike boycott after retail giant makes Dylan Mulvaney paid ambassador – Fox News

Nike continues to receive backlash after transgender influencer Dylan Muvaney posted multiple photos to social media modeling its sports bras and leggings.

Mulvaney, whose face was recently put on honorary cans of Bud Light by beer maker Anheuser-Busch, posted the photos to Instagram on Wednesday.

Anheuser-Busch set social media ablaze when beer juggernaut Bud Light celebrated transgender activist Dylan Mulvaneys "365 Days of Girlhood" with a polarizing promotion. (Instagram)

On Thursday, Olympian Caitlin Jenner announced the launch of the "Fairness First PAC" in order to "fight the radical gender ideology, put parental rights at the forefront of education, and keep boys out of womens sports."

TRANSGENDER FEMALE GOLFER BREANNA GILL WINS WOMEN'S TOURNAMENT IN AUSTRALIA

Sharron Davies, the winner of a silver medal in swimming at the 1980 Olympics, called for the public to boycott companies such as Nike on Thursday.

"Nobody really seems really to be listening to the general public," Davies said on GB News.

"And thats what seems to be incredibly frustrating. So, the only way we can actually make these companies and make governments listen is to boycott with our wallet."

English former competitive swimmer Sharron Davies, right, interviews Chloe Tutton of Great Britain following her Women's 100m Breaststroke heat on Day 2 of the Rio 2016 Olympic Games at the Olympic Aquatics Stadium on Aug. 7, 2016 in Rio de Janeiro. (Julian Finney/Getty Images)

Davies pointed out that Mulvaney is promoting a sports bra, an item of clothing that "doesnt apply" to Mulvaney.

CLICK HERE FOR MORE SPORTS COVERAGE ON FOXNEWS.COM

"Like you said, sports bras when there was nothing to put in the sports bra, when its really important that all women get proper support when they do sport. It just doesnt make sense," Davies said.

"For a long time, they [Nike] sponsored Allyson Felix, one of the world's most incredible track athletes. And then when Allyson got pregnant, they reduced her sponsorship by 70% when she had something happen to her that happens only to women.

"Its just this total disdain that women are being treated to at the moment, particularly in the world of sport where physiology makes so much difference." Davies continued.

Nikes latest campaign comes as transgender participation in sport has become a major political issue.

On Thursday, former NCAA swimmer Riley Gaines was physically assaulted following a speech at San Francisco State University to students about saving women's sports at a Turning Point USA and Leadership Institute event on the campus.

University of Kentucky swimmer Riley Gaines reacts after finishing tied for 5th in the 200 Freestyle finals at the NCAA Swimming and Diving Championships on March 18, 2022 at the McAuley Aquatic Center in Atlanta. (Rich von Biberstein/Icon Sportswire via Getty Images)

"The prisoners are running the asylum at SFSU...I was ambushed and physically hit twice by a man," Gaines wrote in the tweet. "This is proof that women need sex-protected spaces. Still only further assures me I'm doing something right. When they want you silent, speak louder."

Fox News Kyle Morris contributed to this report

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Olympic silver medalist calls for Nike boycott after retail giant makes Dylan Mulvaney paid ambassador - Fox News

Physiology

Ethylene transcriptionally regulates cold stress in grapevine leaves – Phys.org

This article has been reviewed according to ScienceX's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility:

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Low temperature can affect the development of plants and the yield of crops. Ethylene (ETH) is known to positively regulate cold tolerance. However, the role of ETH in transcriptional regulation of grapevine leaves subjected to low temperature stress remains poorly understood.

Researchers from the Wuhan Botanical Garden of the Chinese Academy of Sciences selected leaves of V. amurensis, a wild grape variety that is extremely cold-tolerant in winter, as experimental material. They investigated changes in the transcriptome and phytohormones of grapevine leaves under low temperature stress, identified genes regulated by ETH under low temperature stress and discussed possible interactions between ETH and other low temperature-induced phytohormones.

The researchers found that two highly enriched transcription factors families, APETALA2/ETHYLENE RESPONSIVE FACTOR (AP2/ERF) and WRKY, exhibited consistent up-regulation in response to cold stress, but inhibited by aminoethoxyvinylglycine (AVG, an inhibitor of ETH synthesis) treatment. The study was published in Plant Physiology and Biochemistry on March 10.

The inhibition of ETH synthesis (using AVG) enables the identification of genes positively and negatively regulated by ETH that participates in a wide range of biological processes, such as, solute transport, protein biosynthesis, phytohormone action, antioxidant and carbohydrate metabolism.

Beyond their potential roles in regulating many aspects of cellular metabolism, transcriptone and phytohormone analysis also indicates that ETH may regulate the abscisic acid (ABA) and indole-3-acetic acid (IAA) synthesis-related genes, thus contributing to respective phytohormone accumulation and potential downstream signals.

This work provides new insight into the ETH signaling pathways and ETH-regulated genes under cold stress, and presents candidate gene resource for breeding cold-resilient grapevines.

More information: Yujun Hou et al, Dissecting the effect of ethylene in the transcriptional regulation of chilling treatment in grapevine leaves, Plant Physiology and Biochemistry (2023). DOI: 10.1016/j.plaphy.2023.03.015

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Physiology

Middletown’s Libretti inducted into Biology Honor Society at Scranton – themonmouthjournaleastern.com

MIDDLETOWN Victoria Libretti of Middletown was among the 54 University of Scranton students inducted into Beta Beta Beta, the national honor society for biology. For induction into the honor society, students must have completed at least three biology courses, maintained at least a 3.0 grade point average in biology, and be in good academic standing at the University. The honor society encourages undergraduate biological research through presentations at conventions, publication in the journal BIOS, and research/travel grants. The University's chapter of the honor society was established in 1994.

Libretti is a sophomore physiology major at the Jesuit university located in Northeastern Pennsylvania.

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Middletown's Libretti inducted into Biology Honor Society at Scranton - themonmouthjournaleastern.com

Physiology

Physical therapist assistant students learn compassion as … – Pennsylvania State University

HAZLETON, Pa. Each year, students enrolled in the Clinical Reasoning for the PTA course in Penn State Hazletons Physical Therapist Assistant program head out into the community to volunteer their time for those in need. Each year, their experiences are the same.

The word we always hear is rewarding, said Gina Tarud, associate teaching professor of Physical Therapy and instructor for the course. Ive never had anyone who said they didnt enjoy it.

Madi Entz and Raven Van Gogh are no different. Both are in their final semester of the two-year PTA program and are among the PTA students enrolled in the course for spring 2023.

Each is part of a three-member group charged with helping others not with the physical skills theyve learned, but instead by utilizing their compassion, care, service, social responsibility and other qualities critical to a successful physical therapist assistant.

In the physical therapy profession, were very involved in community outreach, especially time spent volunteering, Tarud said. Part of our duty to the profession is getting students to realize that we play a role not just in helping people with physical ailments but getting out there and helping those in need in our communities as well.

Groups are given guidelines but largely have free reign over how they conduct their projects, including where they would like to volunteer. They spend about eight weeks working with their chosen organization.

Van Goghs group volunteers at AGAPE in Bloomsburg, a community organization that provides food, clothing, home goods and other essentials to people in need. His group helps log inventory and sort donations that come into AGAPEs 100,000-square-foot warehouse.

It was really awesome to be able to get out in the community and work with people, he said. It just makes you want to do more and more of it.

Entz and her group chose Brandons Forever Home, a nonprofit in Hazleton that offers services to children in foster care. Foster families can visit Brandons Forever Home to pick up food, clothing, toiletries, toys and more. Entz and her group also helped organize donations.

Its nice to experience a different way of helping people, Entz said. As PTAs, were getting them back to their normal lives physically, but this course gives us a chance to see the profession from a new perspective.

Tarud said she implemented the volunteerism aspect of the course into her curriculum about 13 years ago to give students the experience of working as part of a team.

These projects get them out there to experience being engaged in a community and working closely as a group, she said. It gets them to think on their own.

The PTA program has been offered at Penn State Hazleton for 40 years and has been accredited by the Commission on Accreditation in Physical Therapy Education (CAPTE) since 1983. Its comprehensive curriculum offers general education courses and major course work in topics including anatomy, physiology, kinesiology, therapy procedures, rehabilitation, human musculature and functional anatomy, and professional issues in clinical practice.

Both students spoke highly of the program, particularly their experiences in clinical experiences. Students must complete clinical learning experiences in acute, outpatient and inpatient care, ensuring they are capable of treating patients of all ages in various situations.

I started off not wanting to go into inpatient care but now Im starting to think that might be something I want to try, Entz said. Having that experience helps me decide where I might want to have a job.

Tarud said students in the Physical Therapist Assistant and Rehabilitation and Human Services programs will work together on service projects beginning in spring 2024.

Entz, Van Gogh and the rest of the PTA students in the course will conduct presentations on their service projects on April 13 at 8 a.m. in Room 7E of the Physical Education Building.

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Physical therapist assistant students learn compassion as ... - Pennsylvania State University

Physiology

Risk of ICU Admission and Related Mortality in Patients… : Critical … – LWW Journals

KEY POINTS

Questions: The efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors on clinical outcomes related to burden of critical illness has not been examined.

Findings: In this retrospective cohort study, 10,308 SGLT2 inhibitors users and 17,664 dipeptidyl peptidase-4 (DPP-4) inhibitors users were included in analysis after 1:2 propensity score matching. The use of SGLT2 inhibitors compared with DPP-4 inhibitors was significantly associated with lower rates of ICU admission (286 [2.8%] vs 645 [3.7%]) and all-cause mortality (315 [3.1%] vs 1,327 [7.5%]).

Meanings: SGLT2 inhibitors may be associated with benefits in clinical efficacy and cost-benefit ratios in the critical care setting that remains to be confirmed in prospective trials.

The global burden of critical illness has steadily increased especially with an aging population in the developed world (1). Despite modern advances in life support, mortality rates in the ICU has remained persistently high at over 15%, and even higher for patients admitted with sepsis (2,3). However, recent clinical trials have failed to identify therapies that effectively moderate overall ICU and sepsis-related mortality (4,5). In large cohort studies, patients with diabetes contribute more than 15% of intensive care admissions and are at increased risks of adverse outcomes after intensive care (6).

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the occurrence rate of major adverse cardiovascular events (MACE) and adverse renal events among patients with type 2 diabetes in randomized controlled trials (711). At the same time, certain safety endpoints were more frequently observed in the groups assigned to SGLT2 inhibitors, including urinary tract infection, diabetic ketoacidosis (DKA), hypotension, volume depletion, and amputation (79,12). While there have been preliminary data on the reduced risks of pneumonia and sepsis-related morbidities with use of SGLT2 inhibitors (13,14), the effect on the overall burden of critical illnesses and their efficacy in reducing ICU-related mortality have not been studied.

The objective of the study was to determine whether SGLT2 inhibitors had any benefit to the overall burden of critical illness. We hypothesized that the use of SGLT2 inhibitors is associated with decreased risks of ICU admission and all-cause mortality. We compared the risks and causes of admission to the ICU, severity of illness, and mortality associated with the incidental use of SGLT2 inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes.

Data on new users of SGLT2 inhibitors or DPP-4 inhibitors between January 1, 2015, and December 31, 2019, from all public hospitals in Hong Kong were reviewed. Patients baseline characteristics, clinical information, and outcomes were retrieved from the Clinical Data and Analysis Reporting System of the Hospital Authority in Hong Kong. We included all adult patients (18 yr old or older) with type 2 diabetes who received SGLT2 inhibitors or DPP-4 inhibitors for the first time or had not received these drugs within 12 months prior to the index date. Type 2 diabetes was defined as having an International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code starting with 250, except those indicating type 1 diabetes; or having baseline hemoglobin A1c (HbA1c) greater than or equal to 6.5%; or using any anti-diabetic medications (i.e., insulins, glucagon-like peptide-1 [GLP-1] agonists, or oral hypoglycemic agents). Patients who received SGLT2 inhibitors or DPP-4 inhibitors for other indications and did not have diabetes were not included. Exclusion criteria were patients with estimated glomerular filtration rate (eGFR) less than 25mL/min/1.73 m2 or patients who were started on both SGLT2 inhibitors and DPP-4 inhibitors on the index date. This study was approved by the Institutional Review Board of The University of Hong Kong/Hospital Authority of Hong Kong West Cluster with a waiver of informed consent on July 28, 2022 (Institutional Review Board reference number: UW 22-561, study title Association of SGLT2 Inhibitors and ICU Outcomes In a Territory Wide Longitudinal Cohort). All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki Declaration of 1975 and its later amendments.

We defined the index date as the first date of dispensing SGLT2 inhibitors or DPP-4 inhibitors. SGLT2 inhibitors included canagliflozin, dapagliflozin, and empagliflozin. DPP-4 inhibitors included alogliptin, linagliptin, linagliptin/metformin, saxagliptin, sitagliptin, sitagliptin/metformin, vildagliptin, and vildagliptin/metformin. Patients were assigned to either the SGLT2 inhibitors group or DPP-4 inhibitors group and followed up according to their assigned drug group. Patients who were prescribed medication from the alternative drug group were censored on the dispense date of the alternative drug.

The co-primary outcomes were any admission to the ICU and all-cause mortality. Secondary outcomes were duration of ICU stay, severity of illness upon ICU admission, mortality due to cardiovascular, renal, and infectious causes, any emergent ICU admission, and any nonoperative ICU admission. The severity of illness upon ICU admission was measured by the Acute Physiology and Chronic Health Evaluation (APACHE) IV-predicted mortality (15). Safety outcomes including DKA, lower limb amputation, new requirement for dialysis, acute pulmonary edema, and urinary tract infection were also examined. DKA was defined using ICD-9-CM code or an elevated beta-hydroxybutyrate level. All outcome events were recorded until the date of censoring or death, or the data cutoff date of March 31, 2022, whichever occurred first. Detailed ICD-9-CM codes for clinical outcomes are listed in eTable 1 (https://links.lww.com/CCM/H330).

Patients baseline characteristics including age, sex, HbA1c, eGFR, comorbidities, and previous ICU admissions were collected. Detailed ICD-9-CM codes for comorbidities, that is, malignancy, hypertension, cerebrovascular disease, coronary artery disease, and congestive heart failure (CHF) are listed in the eTable 1 (https://links.lww.com/CCM/H330). Concomitant cardiovascular medications, including aspirin, statins, beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs); laboratory results were also obtained. Baseline laboratory results were defined as results closest to the index date.

All analyses were performed with prespecified outcome and statistical methods. Based on data in published literature and biological plausibility, we constructed a logistic regression model that predicted the likelihood of receiving SGLT2 inhibitors or DPP-4 inhibitors. These included age, sex, baseline HbA1c, duration of diabetes, eGFR, previous ICU admission, underlying malignancy, hypertension, cerebrovascular disease, coronary artery disease, CHF, use of metformin, insulins, sulfonylureas, GLP-1 agonists, thiazolidinedione, ACEIs or ARBs, beta-blockers, statins and ezetimibe, calendar year of index medication initiation, risk for amputation, risk for fractures, and risk for genitourinary infections. Risk for amputation was defined using history of peripheral vascular disease or lower limb amputation. Risk for fractures was defined using history of osteoporosis or fractures, and risk for genitourinary infections was defined using history of urinary tract infections or positive urine cultures. The final study cohort consisted of two comparison groupsSGLT2 inhibitors and DPP-4 inhibitorsgenerated by 1:2 propensity score matching using a caliper of 0.2 times sd of the logit of propensity score.

Unadjusted analyses were made using chi-square tests for categorical variables and Student t test or Wilcoxon rank-sum tests for continuous variables. Cox proportional hazards regression was performed to evaluate the relationship between use of SGLT2 inhibitors or DPP-4 inhibitors and clinical outcomes in a time-to-first-event analysis.

First, we performed sensitivity analysis by including all complete cases before propensity score matching. A multivariable Cox proportional hazards model adjusting for the same variables in the propensity score model was used to examine the association between study groups and the co-primary outcomes. Next, we repeated the analysis in all complete cases before propensity score matching using inverse probability treatment weighting to adjust for the same set of confounders. An on-treatment analysis was performed to account for possible differences in treatment duration.

Since the complete case method was adopted to address missing data in the primary statistical analysis, we tested the robustness of our results by repeating the multivariable Cox regression analysis with the entire cohort using the technique of multiple imputations by chained equations to account for missing data. We calculated E-values to quantify the association that a confounder would need to have with clinical outcomes to nullify the primary analyses (16). Finally, to better ensure that the observed association between medication groups and clinical outcomes was not due to some underlying cause unrelated to the mechanistic hypothesis, falsification testing was performed with two clinical outcomes, trauma and acute cholecystitis. These outcomes were selected based on unlikely causal relationships with the medication groups, and detailed ICD-9-CM codes are listed in eTable 1 (https://links.lww.com/CCM/H330).

Subgroup analyses were performed according to the following seven dichotomized subgroups: age greater than 65 years, sex, HbA1c greater than 8%, eGFR less than 60mL/min/1.73 m2, previous heart failure, number of oral hypoglycemic agents greater than or equal to 2, and index medication initiation during or after 2018.

All analyses were performed using Stata MP software, Version 16.1 (StataCorp, College Station, TX). A two-tailed p value of less than 0.05 was considered statistically significant.

Between January 2015 and December 2019, a total of 73,111 patients were considered for inclusion: 4,053 (5.5%) were excluded after application of exclusion criteria. Of the remaining 69,058 patients, a total of 6,674 (9.7%) were excluded from complete case analysis due to missing values in any of the variables used in the propensity score matching model. After 1:2 propensity score matching, a total of 10,308 SGLT2 inhibitors users and 17,664 DPP-4 inhibitors users were included in the final analysis, representing 44.8% of the complete case cohort (eFig. 1, https://links.lww.com/CCM/H330). The mean age of the cohort was 5911 years, and 17,416 (62.3%) were male. Baseline characteristics and medications prescribed of the propensity score matched cohort and the complete case cohort are shown in Table 1 and eTable 2 (https://links.lww.com/CCM/H330), respectively. All variables in Table 1 were included in the propensity score model, and apart from certain oral anti-diabetic agents were well-balanced between groups with standardized difference less than 0.1. The median follow-up period was 2.9 years (2.34.0 yr).

aLipid-lowering medications included atorvastatin, fluvastatin, rosuvastatin, simvastatin, and ezetimibe.

bRisk for amputation was defined using history of peripheral vascular disease or lower limb amputation.

cRisk for fractures was defined using history of osteoporosis or fractures.

dRisk for genitourinary infections was defined using history of urinary tract infections or positive urine cultures.

All results were presented with frequency (percentage) or mean sd.

Table 2 describes the primary and secondary outcomes in SGLT2 inhibitors users and DPP-4 inhibitors users. Critical illness requiring ICU admission occurred in 286 patients (2.8%) in the SGLT2 inhibitor group and 645 patients (3.7%) in the DPP-4 inhibitor group. The risk of ICU admission was lower in SGLT2 inhibitors users compared with DPP-4 inhibitors users (hazard ratio [HR], 0.79; 95% CI, 0.690.91; p = 0.001), translating to an absolute between-group difference of 0.9 percentage points (95% CI, 0.51.3) and a number needed to treat of 114. The severity of illness upon ICU admission was lower in SGLT2 inhibitors users compared with DPP-4 inhibitors users (median APACHE IV-predicted risk of death 0.08 [0.030.25] vs 0.14 [0.050.36]; p < 0.001). The ICU length of stay was similar between the two groups. The risk of emergency ICU admission was lower in SGLT2 inhibitors users (208 [2.0%] vs 496 [2.8%]; HR, 0.75; 95% CI, 0.640.89; p = 0.001), as was the risk of nonoperative ICU admission (151 [1.5%] vs 415 [2.4%]; HR, 0.66; 95% CI, 0.540.79; p < 0.001). Kaplan-Meier survival curves showed that the use of SGLT2 inhibitors was associated with lower risks of critical illness requiring any ICU admission, emergent ICU admission, and nonoperative ICU admission (Fig. 1). Admissions for sepsis were fewer in SGLT2 inhibitors users compared with DPP-4 inhibitors users (45 [0.4%] vs 134 [0.8%]; HR, 0.61; 95% CI, 0.430.85; p = 0.004). Data for other causes of ICU admission are presented in eTable 3 (https://links.lww.com/CCM/H330).

DPP-4 = dipeptidyl peptidase-4, SGLT2 = sodium-glucose cotransporter 2.

aResults are presented as rate per 100 patient year (95% CI).

bResults are presented as median (interquartile range).

cAmong 931 people required ICU admission, two patients (0.2%) had missing Acute Physiology and Chronic Health Evaluation IV predicted values, therefore, n = 929.

Estimated probabilities of ICU admission stratified by sodium-glucose cotransporter 2 (SGLT2) inhibitor group and dipeptidyl peptidase-4 (DPP-4) inhibitor group. Use of SGLT2 inhibitors was associated with lower risks of critical illness requiring any ICU admission (hazard ratio [HR], 0.79; 95% CI, 0.690.91; p = 0.001) (A), emergent ICU admission (HR, 0.75; 95% CI, 0.640.89; p = 0.001) (B), and nonoperative ICU admission (HR, 0.66; 95% CI, 0.540.79; p < 0.001) (C) compared with use of DPP-4 inhibitors.

The co-primary outcome of all-cause mortality occurred in 315 patients (3.1%) in the SGLT2 inhibitor group and 1,327 patients (7.5%) in the DPP-4 inhibitor group. The risk of death was lower in SGLT2 inhibitors users compared with DPP-4 inhibitors users (HR, 0.44; 95% CI, 0.380.49; p < 0.001), translating to an absolute between-group difference of 4.5 percentage points (95% CI, 3.95.0) and a number needed to treat of 22 (Table 2). The risk of mortality due to infectious causes was lower in SGLT2 inhibitors users compared with DPP-4 inhibitors users (59 [0.6%] vs 414 [2.3%]; HR, 0.26; 95% CI, 0.200.34; p < 0.001). The risk of cardiovascular death was lower in SGLT2 inhibitors users (105 [1.0%] vs 332 [1.9%]; HR, 0.58; 95% CI, 0.460.72; p < 0.001), as was the risk of renal-related mortality (3 [0.03%] vs 25 [0.14%]; HR, 0.22; 95% CI, 0.070.73; p = 0.014). Kaplan-Meier survival curves demonstrated that the use of SGLT2 inhibitors was associated with lower risks of all-cause mortality, mortality due to infectious, cardiovascular, and renal causes, compared with use of DPP-4 inhibitors (Fig. 2).

Estimated probabilities of all-cause mortality stratified by sodium-glucose cotransporter 2 (SGLT2) inhibitor group and dipeptidyl peptidase-4 (DPP-4) inhibitor group. Use of SGLT2 inhibitors was associated with lower risks of all-cause mortality (hazard ratio [HR], 0.44; 95% CI, 0.380.49; p < 0.001) (A), mortality due to infectious causes (HR, 0.26; 95% CI, 0.200.34; p < 0.001) (B), cardiovascular mortality (HR, 0.58; 95% CI, 0.460.72; p < 0.001) (C), and renal mortality (HR, 0.22; 95% CI, 0.070.73; p = 0.014) (D) compared with use of DPP-4 inhibitors.

After adjustment by multivariable Cox regression, the risk of ICU admission was lower in SGLT2 inhibitors users compared with DPP-4 inhibitors users (HR, 0.85; 95% CI, 0.740.97; p = 0.016) in the complete case cohort (n = 62,384), as was the risk of all-cause mortality (HR, 0.53; 95% CI, 0.470.60; p < 0.001), which were consistent with the primary analysis. These associations remained significant after adjustment by inverse probability treatment weighting as determined by the propensity score (ICU admission: HR, 0.76; 95% CI, 0.710.81; p < 0.001 and all-cause mortality: HR, 0.43; 95% CI, 0.410.45; p < 0.001). The median duration of treatment were similar in the two medication groups (SGLT2 inhibitors: 953 d [4031,367 d] and DPP-4 inhibitors: 967 d [4001,351 d]; p = 0.70), and results in the on-treatment analysis were similar to the intention-to-treat analysis.

A total of two variables, baseline HbA1c and eGFR, in the propensity score model had missing data. Multiple imputation was conducted, and the imputed cohort included all 6,674 patients (9.7%) who were excluded due to missing values in any of the variables used in the propensity score model. The association between SGLT2 inhibitors and ICU admission in the imputed dataset remained significant (adjusted HR, 0.79; 95% CI, 0.69 to 0.90; p < 0.001), as was the association with all-cause mortality (adjusted HR, 0.52; 95% CI, 0.460.58; p < 0.001). The E-value for the HR for new ICU admission is 1.63, while the E-value for the HR for all-cause mortality is 2.94, suggesting that for an unmeasured confounder to render the primary results statistically insignificant, it would need to be very strongly associated with ICU admission and all-cause mortality (> 60% difference in prevalence between SGLT2 inhibitors users and DPP-4 inhibitors users, and a HR > 1.6 or < 0.6 on ICU admission). Finally, falsification testing showed that the clinical outcomes of trauma and acute cholecystitis were not significantly associated with medication group. Detailed results of sensitivity analyses are presented in Table 2.

The effect of SGLT2 inhibitors on the outcomes of ICU admission and all-cause mortality was modified by eGFR (p for interaction < 0.001 and 0.004, respectively), with patients with eGFR less than 60mL/min/1.73 m2 deriving more clinical benefit than those with eGFR greater than or equal to 60mL/min/1.73 m2. The benefit of SGLT2 inhibitors on ICU admission was greater in patients on less than two oral hypoglycemic agents (p for interaction = 0.042) and the benefit of SGLT2 inhibitors on all-cause mortality was greater in patients who were initiated on index medication before 2018 (p for interaction = 0.025). The associations between SGLT2 inhibitors and outcomes were not modified by age, sex, HbA1c level, or previous CHF (p for interaction > 0.05 for all) (eTable 4, https://links.lww.com/CCM/H330; and Fig. 3).

Forest plots for subgroups analyses. The effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the outcomes of ICU admission and all-cause mortality was modified by estimated glomerular filtration rate (eGFR) (p for interaction < 0.001 and 0.004, respectively). Patients who were on less than two oral hypoglycemic agents and patients who were initiated on index medication before 2018 also derived greater clinical benefit. There was no effect modification in other predefined subgroups for the two co-primary outcomescritical illness requiring any ICU admission (A) and all-cause mortality (B). DDP4i = dipeptidyl peptidase-4 inhibitor, HbA1c = hemoglobin A1c.

Safety outcomes are reported in Table 3. The risks of lower limb amputation, new requirement for dialysis, acute pulmonary edema, and urinary tract infection were significantly lower in SGLT2 inhibitors users compared with DPP-4 inhibitors users (p < 0.05 for all). The risk of DKA was similar between the SGLT2 inhibitor users and DPP-4 inhibitor users (160 [1.6%] vs 297 [1.7%]; p = 0.41).

aDiabetic ketoacidosis was defined as using International Classification of Diseases, 9th Revision, Clinical Modification code or an elevated beta-hydroxybutyrate level.

bNew requirement for dialysis refers to patients who were started and maintained on dialysis with no record of receiving dialysis prior to the index date.

In this cohort of 69,058 adult patients with type 2 diabetes, initiation of SGLT2 inhibitors compared with DPP-4 inhibitors were associated with lower risks of critical illness, decreased disease severity, and lower all-cause mortality over a median follow-up of 2.9 years. We identified that infections- and sepsis-related admissions to ICU and mortality were concurrently mitigated by the use of SGLT2 inhibitors. The beneficial effects of SGLT2 inhibitors were seen across various subgroups of age and underlying comorbid conditions, and the protection appeared to be more pronounced in patients with chronic renal impairment.

SGLT2 inhibitors have been shown to effectively reduce MACE and renal events among patients with type 2 diabetes (710). Since hospitalizations secondary to decompensated heart failure and decline in renal function are clearly reduced with the use of SGLT2 inhibitors, it would be reasonable to extrapolate a reduction in burden of critical illnesses and admissions to ICU. However, SGLT2 inhibitors have been associated with a two- to 10-fold risk of DKA (8,17), along with other safety concerns including a doubling in risk of severe urinary tract infection (18), hospital admission for infections (19), volume depletion (8,20), hypotension (21), or even amputation (9). Taken together, the net effect of SGLT2 inhibitors on critical illness and the utilization of ICU resources remains to be clarified. To our knowledge, this topic has never been evaluated in any randomized trials or observational studies.

In the current study including a large representative cohort of patients with type 2 diabetes, we observed that the risk of critical illness requiring admission to ICU was reduced by approximately 20% with the use of SGLT2 inhibitors. The biological mechanisms underlying the protective effects of SGLT2 inhibitors against critical illnesses are multidimensional, among which benefits in cardiac and renal function are two of the most important. SGLT2 inhibitors can improve cell life programming (22), arterial stiffness (23), cardiac structure and function (24,25), and reduce cardiorenal effects and albuminuria (26,27); hence, the strong cardiorenal efficacy observed in clinical trials (28). In our cohort, the absolute differences in mortality due to cardiovascular and renal causes were 0.9% and 0.1%, respectively.

More specific to acute and critical illnesses, SGLT2 inhibitors have been associated with protective effects against pneumonia, sepsis, and infection-related mortality (13). This may be related to the anti-inflammatory properties of SGLT2 inhibitors, mediated through down-regulation of cytokine production by macrophages and inflammasomes (29). Alternative mechanisms such as counteracting lipopolysaccharide (LPS)-induced vascular hyperpermeability and improving intestinal barrier function have also been demonstrated in animal models (30,31). The beneficial effects of SGLT2 inhibitors were observed across all categories of ICU admission but were most evident in reducing nonoperative ICU admissions, which in our cohort referred to emergency admissions due to nonsurgical causes. When further stratified by disease category, the reduction in ICU admission due to sepsis was the most striking, with a 40% reduction in risk for SGLT2 inhibitors users. The milder severity of illness upon ICU admission may be partially explained by pathophysiological mechanisms such as damping of LPS-induced acute renal injury in animal models (14), possibly undermining the greater benefit derived in patients with renal impairment and eGFR less than 60mL/min/1.73 m2. The reduction of sepsis-related complications in chronic users of SGLT2 inhibitors, if confirmed in follow-up prospective trials, could have significant implications for the population with diabetes, to whom up to 6% of infection-related hospitalizations and 12% of infection-related deaths had been attributed (32). It remains to be examined whether users of SGLT2 inhibitors for reasons other than diabetes would derive similar clinical benefits.

The significant reduction in all-cause mortality of SGLT2 inhibitors that has been demonstrated in randomized trials was further validated in our cohort (9,11), as were reductions in death due to cardiovascular, renal, and infection-related causes, with a number needed to treat of 22. Recent studies have shown that the clinical benefit derived from SGLT2 inhibitors begins to manifest as early as 13 days (33). The potential cost-efficiency of SGLT2 inhibitors in decreasing healthcare utilization and morbidities across broad populations of patients with cardiovascular risk factors, risks for progressive renal injury, and even immunosuppressed or infection-prone individuals could amount to significant cost-benefit ratios across hospital intensive care systems (34).

The current study had some limitations. First, the observational nature of the study conferred risks of unmeasured confounding and bias, but the large cohort size with complete longitudinal electronic healthcare records and incident new user design minimized selection, information, and recall biases (35). We used rigorous propensity score matching, and the findings were consistent in many sensitivity analyses. The utilization of an active comparator of DPP-4 inhibitors allowed evaluation of SGLT2 inhibitors in a typical decision bifurcation during escalation of diabetes care. Second, we only collected prescription data and could not ascertain drug adherence, which could have biased the results toward the null. Third, patients were censored if they crossed over to or added on the other drug class, and the effect of continuing both drug classes is unclear.

In conclusion, we showed that patients with type 2 diabetes who were on SGLT2 inhibitors were independently associated with reduction in admission to the ICU, milder disease severity, and lower all-cause mortality compared with patients on DPP-4 inhibitors. The use of SGLT2 inhibitors in the critical care setting remains to be clarified in future prospective trials.

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