Body

New research shows how second-degree burns cause hard-to-treat chronic pain, and this understanding may be key to treating these complications, common in war veterans This research, published in Physiological Reports, suggests that burns cause changes to neurons in multiple parts of the spinal cord, even far from the injury site, which can contribute to chronic pain and other long-term complications.

Second degree burns initially only affects layers of the skin, specifically the top and second layers. More than 11 million individuals per year around the world suffer burn injuries severe enough to require hospitalization and long-term care (1).

Treatment of burns normally entails localised treatment at the site of the burn, but this doesn't address problems that the burn may cause in other parts of the body, such as the central nervous system (brain and spinal cord), which is crucial for fully treating the burn and possible neurological complications, such as neuropathic pain.

Siraj Patwa and his colleagues at Yale University and the US Department of Veterans Affairs studied spinal cord neurons in a burn injury mouse animal model and found that the skin injury affected the structural connections between neurons. They also identified an important molecule in this problem called PAK1, which is involved with regulating these changes in the spinal cord.

An exciting discovery from this work was the identification of an existing clinical drug targeting PAK1, called Romidepsin, which is already used in cancer treatment. One promising avenue of study is looking at "re-purposing" this drug for targeting chronic pain associated with burn injuries.

Andrew Tan, senior author on the study said:

"This research has exciting potential to provide a new avenue for speeding up the development of new treatments for long-lasting complications that often follow burn injury. Having a treatment that would not only treat the acute injury, but long-lasting complications could have a big impact on clinicians' treatment of burns, including battlefield injured-veterans."

With a global shortage of both blood and organ donors, QUT researchers are suggesting language used to attract donors be changed, especially for organ donor donation.

They say focussing on a sense of social obligation rather than 'gift of life term' terminology may have better cut-through with non-donors.

QUT behavioural economists Dr Stephen Whyte, Dr Ho Fai Chan and Professor Benno Torgler, along with Dr Karin Hammarberg from Monash University, compared responses from more than 1,000 people who participated in an online survey looking at the reasons given for the donation decision given by blood and/or registered organ donors versus non-donors.

The study - Exploring the impact of terminology differences in blood and organ donor decision making - has just been published online by PLOS ONE.

"We categorised the responses based on five dimensions of language choice: egocentric (referring to self), social, moral, positively emotional, and negatively emotional," said Dr Whyte.

"The spirit of philanthropy is stronger than ever in the very trying times society faces at present, whether in Australia or overseas, and there are many people making a variety of donations.

"While we know a lot about what has motivated people to donate blood or register as an organ donor, we don't know a lot about why individuals continue to choose not to. Yet most people do not and never will donate.

"There's no doubt that donation (whether its blood or organ donation) saves lives. What's interesting about our study though is that it appears motivating people by telling them their donation saves lives only seems to work in increasing blood donor numbers, not organ donors.

"While many not-for-profit organisations regularly use the term 'the gift of life' as an emotional hook, the impact on potential blood donors is much more positive than potential organ donors.

"In fact, there is significant debate on whether altruism is the major motive underlying any donation. Individuals may instead be driven by a more general preference for morality and 'doing the right thing' in the eyes of others."

Dr Whyte said blood and organ donation were very different in their medical, psychological, and socio-cultural implications, especially in relation to how individuals give consent and supply their donation, the level of time and physical investment required for donation, the timing of when a donation can be given (or taken), and, most significantly, the before and after physical and psychological costs.

"The only immediately quantifiable similarity between blood and organ donation is that they continue to be under-supplied in developed economies," Dr Whyte said.

"It also appears from our survey that blood or organ donor campaigns based on altruistic terminology are ineffective at targeting non-donors.

"In Australia organ donation registration is as costless as ticking a box during driver's license renewal or completing tax return. Consent to be an organ and tissue donor is recorded on the Australian Organ Donor Register, which can be altered at any time. Blood donation takes more effort as it requires individuals to attend a blood donation facility for an extended period.

"Yet blood donors have been shown to be higher in primary prosocial characteristics like altruism, empathy and social responsibility, all traits thought to be key drivers in motivating donations.

"Organ donation is impacted by more complex factors. Some respondents admit to the fact that it 'freaks them out' and also creates an ethical dilemma. Others want to leave it to their family to decide.

"Asking people why they do not donate blood or register as an organ donor may provide more valuable insights into how to increase donor numbers than simply asking self-selected donors to explain why they do.

"Understanding key egocentric, social, moral, and emotional factors that impact and drive individual decisions to (not) participate in medical donation can provide vital insights into how to foster, support, and motivate increased donation and altruistic or prosocial behaviour across blood and organ donation markets both now and in the future."

The anonymous data for the study was collected via a survey promoted by Australian donation organisations including Zaidee's Rainbow Foundation, Kidney Health Australia, and Transplant Australia.

Sophia Antipolis, 9 January 2020: Drinking tea at least three times a week is linked with a longer and healthier life, according to a study published today in the European Journal of Preventive Cardiology, a journal of the European Society of Cardiology (ESC).1

"Habitual tea consumption is associated with lower risks of cardiovascular disease and all-cause death," said first author Dr. Xinyan Wang, Chinese Academy of Medical Sciences, Beijing, China. "The favourable health effects are the most robust for green tea and for long-term habitual tea drinkers."

The analysis included 100,902 participants of the China-PAR project2 with no history of heart attack, stroke, or cancer. Participants were classified into two groups: habitual tea drinkers (three or more times a week) and never or non-habitual tea drinkers (less than three times a week) and followed-up for a median of 7.3 years.

Habitual tea consumption was associated with more healthy years of life and longer life expectancy.

For example, the analyses estimated that 50-year-old habitual tea drinkers would develop coronary heart disease and stroke 1.41 years later and live 1.26 years longer than those who never or seldom drank tea.

Compared with never or non-habitual tea drinkers, habitual tea consumers had a 20% lower risk of incident heart disease and stroke, 22% lower risk of fatal heart disease and stroke, and 15% decreased risk of all-cause death.

The potential influence of changes in tea drinking behaviour were analysed in a subset of 14,081 participants with assessments at two time points. The average duration between the two surveys was 8.2 years, and the median follow-up after the second survey was 5.3 years.

Habitual tea drinkers who maintained their habit in both surveys had a 39% lower risk of incident heart disease and stroke, 56% lower risk of fatal heart disease and stroke, and 29% decreased risk of all-cause death compared to consistent never or non-habitual tea drinkers.

Senior author Dr. Dongfeng Gu, Chinese Academy of Medical Sciences, said: "The protective effects of tea were most pronounced among the consistent habitual tea drinking group. Mechanism studies have suggested that the main bioactive compounds in tea, namely polyphenols, are not stored in the body long-term. Thus, frequent tea intake over an extended period may be necessary for the cardioprotective effect."

In a subanalysis by type of tea, drinking green tea was linked with approximately 25% lower risks for incident heart disease and stroke, fatal heart disease and stroke, and all-cause death. However, no significant associations were observed for black tea.

Dr. Gu noted that a preference for green tea is unique to East Asia. "In our study population, 49% of habitual tea drinkers consumed green tea most frequently, while only 8% preferred black tea. The small proportion of habitual black tea drinkers might make it more difficult to observe robust associations, but our findings hint at a differential effect between tea types."

Two factors may be at play. First, green tea is a rich source of polyphenols which protect against cardiovascular disease and its risk factors including high blood pressure and dyslipidaemia. Black tea is fully fermented and during this process polyphenols are oxidised into pigments and may lose their antioxidant effects. Second, black tea is often served with milk, which previous research has shown may counteract the favourable health effects of tea on vascular function.

Gender-specific analyses showed that the protective effects of habitual tea consumption were pronounced and robust across different outcomes for men, but only modest for women. Dr. Wang said: "One reason might be that 48% of men were habitual tea consumers compared to just 20% of women. Secondly, women had much lower incidence of, and mortality from, heart disease and stroke. These differences made it more likely to find statistically significant results among men."

She added: "The China-PAR project is ongoing, and with more person-years of follow-up among women the associations may become more pronounced."

The authors concluded that randomised trials are warranted to confirm the findings and provide evidence for dietary guidelines and lifestyle recommendations.

An existing drug can be used to improve the womb for pregnancy, study led by University of Warwick finds

Sitagliptin is first drug of its kind shown to increase stem cells in the lining of the womb

Stem cells have been shown to improve renewal of the womb lining and to reduce inflammation in early pregnancy

Researchers are now looking to test the treatment in a large scale clinical trial

A drug designed to tackle diabetes could also be repurposed as the first treatment to prevent miscarriage by targeting the lining of the womb itself, according to a clinical trial led by the University of Warwick.

The treatment works by increasing the amount of stem cells in the lining of the womb, improving conditions in the womb to support pregnancy.

The research by Warwick Medical School is reported today (9 January) in the journal EBioMedicine from research conducted with University Hospitals Coventry and Warwickshire and supported by the NIHR Coventry and Warwickshire Clinical Research Facility. The research was funded by and took place at Tommy's National Miscarriage Research Centre.

Recurrent miscarriage is defined as the loss of two or more consecutive pregnancies, with additional miscarriages decreasing the likelihood of a successful pregnancy. Previous research by the Warwick team revealed that a lack of stem cells in the womb lining is causing thousands of women to suffer from recurrent miscarriages. The team also demonstrated that stem cells protect specialised cells, called decidual cells, from excessive stress and inflammation. Decidual cells surround the implanting embryo and excessive stress can cause breakdown of the womb lining in pregnancy.

A new class of diabetes drugs called gliptins targets an enzyme involved in the recruitment of circulating stem cells to the womb. The researchers investigated whether inhibiting this enzyme, called DPP4, using a particular drug, sitagliptin, would improve conditions in the womb for pregnancy.

In a pilot clinical trial, thirty-eight women aged 18 to 42 who had experienced a large number of recurrent miscarriages (average five) were given either an oral course of sitagliptin or a placebo for three menstrual cycles. Biopsies of the womb were taken at the start of the course of treatment and afterwards to determine the number of stem cells present before and after the course.

They found an average increase in stem cell count of 68% in those women who took the full course of sitagliptin. This compares to no significant increase in those in the control group receiving an identical placebo pill. They also saw a 50% decrease in the number of 'stressed' cells present in the lining of the womb. There were minimal side effects for the participants.

The researchers now hope to take the treatment to clinical trial and, if successful, it would be the first targeted specifically at the lining of the womb to prevent miscarriage.

Professor Jan Brosens, of Warwick Medical School and Consultant in Reproductive Health at University Hospitals Coventry and Warwickshire NHS Trust, said: "There are currently very few effective treatments for miscarriage and this is the first that aims at normalising the womb before pregnancy. Although miscarriages can be caused by genetic errors in the embryo, an abnormal womb lining causes the loss of chromosomal normal pregnancies. We hope that this new treatment will prevent such losses and reduce both the physical and psychological burden of recurrent miscarriage."

Professor Siobhan Quenby from Warwick Clinical Trials Unit and an Honorary Consultant at University Hospital Coventry and Warwickshire NHS Trust, said: "We have improved the environment that an embryo develops in and in doing so we hope to improve the chances of a successful pregnancy. Although this research was specifically designed to test whether we could increase the presence of stem cells in the womb, follow-up of participants found that there were no further losses of normal pregnancies in those who took sitagliptin. These are very early results and the treatment now needs to be further tested in a large-scale clinical trial."

Jane Brewin, Chief Executive at Tommy's said: "For far too long it has often been said by many health professionals that miscarriage is not preventable, and parents have been left with little hope given the paucity of treatment options available. This situation prompted Tommy's to invest in the Tommy's National Centre for Miscarriage Research and this breakthrough research by the world leading team at Warwick shows great promise for an effective treatment which will reduce miscarriage and possibly later pregnancy loss too. A large-scale trial is needed to verify the findings and we hope that this will get underway quickly."

Stem cells play a key role in creating the decidual cells in the womb lining which support the placenta throughout pregnancy. Insufficient stem cells in the womb lining leads to an excess of stressed and inflammatory decidual cells, which in turn may cause placental bleeding and miscarriage. Sitagliptin was effective not only in increasing stem cells in the womb lining but also decreasing the abundance of stressed decidual cells.

New Haven, Conn. -- A new study suggests that state-mandated notifications on mammogram reports intended to inform women of the health risks related to breast density are not worded effectively.

The study, conducted by researchers at Yale and New York University, found that although dense breast notification (DBN) laws did help some women understand they had increased breast density, those women were not more likely to know that breast density is associated with a higher risk of breast cancer or that dense breasts limit the ability of mammograms to detect cancer. The finding was particularly pronounced for women with a high school education or less.

The study appears in the Journal of General Internal Medicine.

"We know that women with less education are less likely to receive high-quality breast cancer screening and treatment," said senior author Cary Gross, M.D., a Yale professor of medicine and member of the Yale Cancer Center. "Our study underscores one potential mechanism for this disparity. Ensuring that notifications are written in simple language may help improve understanding of breast density for all women."

Thirty-eight states have enacted DBN laws. Critics of the laws have raised concerns that they might increase women's anxiety about getting breast cancer. There have also been concerns about the readability of language used in the notifications. The U.S. Food and Drug Administration recently announced a proposal to extend DBN requirements to all mammogram facilities.

For the new study, researchers surveyed 1,928 women across the country. They found no difference in breast cancer-related anxiety between women in DBN and non-DBN states. Women in DBN states were more likely to know if they have increased breast density, but only when those women had higher than a high school level of education.

"The goal for these state laws is not being met," said NYU's Kelly Kyanko, M.D., first author of the study. "Women who lived in states with DBN laws were not more likely to understand the implications of breast density -- that having dense breasts meant they were at increased risk of breast cancer or that the radiologist would have a harder time seeing a cancer on their mammogram."

The cover for issue 1 of Oncotarget features Figure 5, "APLN overexpression correlates with worsened prognosis in ovarian cancer patients treated with bevacizumab," by Jaiprasart, et al.

To establish a molecular signature of this resistance in ovarian cancer, the authors developed preclinical tumor models of adaptive resistance to chronic anti-VEGF treatment.

These findings link signature gene expressions with anti-VEGF response, and may thus provide novel targetable mechanisms of clinical resistance to anti-VEGF therapies.

Dr. Sukyung Woo from the Department of Pharmaceutical Sciences, College of Pharmacy, the University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA as well as the Gynecologic Cancers Research Program, Peggy and Charles Stephenson Cancer Center, the University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA said, "Ovarian cancer is the principal cause of gynecological-cancer-related deaths in women in the United States"

Figure 5: APLN overexpression correlates with worsened prognosis in ovarian cancer patients treated with bevacizumab. (A) APLN expression in patients in APLN-low and APLN-high groups. (B) Kaplan-Meier analysis of disease-free survival (DFS) in patients in APLN-low and APLN-high groups (Median DFS of 14.1 vs. 41.2 months; P = 0.05). (C) APLNR expression in patients in APLNR-low and APLNR-high groups (P

Increased tumor angiogenesis in ovarian cancer is also critical to ovarian cancer metastasis and ascites development.

Several studies have shown that a high level of vascular endothelial growth factor, a key regulator of tumor angiogenesis, is associated with poor prognosis in patients with ovarian cancer.

In the present study, the scientists developed preclinical xenograft models of ovarian cancer that acquire adaptive resistance to anti-VEGF therapeutics.

Using these tumors, they utilized unbiased approaches to identify not only a distinct gene signature associated with resistance development, but also the source of resistance.

The Woo Research Team concluded, "we have used in vivo tumor models that gain adaptive resistance to VEGF-targeting therapeutics to discover a unique molecular signature associated with the anti-VEGF resistance phenotype. These pathways may function as important alternative angiogenic signaling pathways in the presence of VEGF blockade. The present study has thus paved the way for the development of new combination or sequential treatment strategies that may help to counteract the resistance mechanisms."

A new Boston University School of Public Health (BUSPH) study characterizes how Twitter users discuss miscarriage and preterm birth. Published in Paediatric and Perinatal Epidemiology, the study finds that miscarriage disclosures by Michelle Obama and other public figures prompted spikes in discussion, and in other people sharing their own experiences of miscarriage. The study also gathered thousands of individuals' tweeted experiences with miscarriage, showing gaps in knowledge and support.

"Most individuals who self-disclosed a miscarriage in our data did not appear to have been offered any type of mental health support as part of medical management of their miscarriage," says Dr. Elaine Nsoesie, the study's senior author and an assistant professor of global health at BUSPH. "The need for emotional and psychological support seems to drive individuals to seek information and community online."

Dr. Nsoesie points to a quote from the former First Lady's disclosure: "What nobody tells you is that miscarriage happens all the time, to more women than you'd ever guess, given the relative silence around it." In fact, 15-20% of known pregnancies end in a miscarriage.

Dr. Nsoesie and colleagues obtained and analyzed 291,443 tweets on miscarriages and preterm births from January 2017 through December 2018, including 7,282 personal miscarriage disclosure tweets, and categorized them into eight topics: Michelle Obama (8.4% of tweets), other celebrity disclosures (23.0%), preterm birth (10.9%), politics (17.6%), loss and anxiety (10.1%), ectopic pregnancy (7.50%), healthcare (10.7%) and misconceptions about the influenza vaccine (11.7%). Celebrity miscarriage disclosures prompted disclosures by Twitter users, and the most common emotions expressed about users' own miscarriages were grief (50.64%) and annoyance (16.19%).

The study also found increases in discussion of miscarriage around events related to reproductive rights, including legislation passed in Texas in 2017 requiring burial or cremation of fetal tissue associated with miscarriages, ectopic pregnancies, and abortions, and a pharmacist refusing to fill a prescription for misoprostol to end a Michigan woman's failed pregnancy in 2018. Preterm birth tweets spiked around reports of the high rate of preterm birth in the U.S., expressing frustration and calling for action. The researchers also found significant misinformation on the causes of miscarriage and preterm birth.

"Social media data provides a lens into the physical, emotional, and psychological impacts of miscarriages," says Dr. Nsoesie, explaining that this information can inform care and support for people who have experienced miscarriages, and help identify knowledge gaps and misinformation in the public.

Researchers at Caltech have demonstrated that machine-learning algorithms can monitor online social media conversations as they evolve, which could one day lead to an effective and automated way to spot online trolling.

The project unites the labs of artificial intelligence (AI) researcher Anima Anandkumar, Bren Professor of Computing and Mathematical Sciences, and Michael Alvarez, professor of political science. Their work was presented on December 14 at the AI for Social Good workshop at the 2019 Conference on Neural Information Processing Systems in Vancouver, Canada. Their research team includes Anqi Liu, postdoctoral scholar; Maya Srikanth, a junior at Caltech; and Nicholas Adams-Cohen (MS '16, PhD '19) of Stanford University.

"This is one of the things I love about Caltech: the ability to bridge boundaries, developing synergies between social science and, in this case, computer science," Alvarez says.

Prevention of online harassment requires rapid detection of offensive, harassing, and negative social media posts, which in turn requires monitoring online interactions. Current methods to obtain such social media data are either fully automated and not interpretable or rely on a static set of keywords, which can quickly become outdated. Neither method is very effective, according to Srikanth.

"It isn't scalable to have humans try to do this work by hand, and those humans are potentially biased," she says. "On the other hand, keyword searching suffers from the speed at which online conversations evolve. New terms crop up and old terms change meaning, so a keyword that was used sincerely one day might be meant sarcastically the next."

Instead, the team used a GloVe (Global Vectors for Word Representation) model to discover new and relevant keywords. GloVe is a word-embedding model, meaning that it represents words in a vector space, where the "distance" between two words is a measure of their linguistic or semantic similarity. Starting with one keyword, this model can be used to find others that are closely related to that word to reveal clusters of relevant terms that are actually in use. For example, searching Twitter for uses of "MeToo" in conversations yielded clusters of related hashtags like "SupportSurvivors," "ImWithHer," and "NotSilent." This approach gives researchers a dynamic and ever-evolving keyword set to search.

But it is not enough just to know whether a certain conversation is related to the topic of interest; context matters. For that, GloVe shows the extent to which certain keywords are related, providing input on how they are being used. For example, in an online Reddit forum dedicated to misogyny, the word "female" was used in close association with the words "sexual," "negative," and "intercourse." In Twitter posts about the #MeToo movement, the word "female" was more likely to be associated with the terms "companies," "desire," and "victims."

The project was a proof-of-concept aimed at one day giving social media platforms a more powerful tool to spot online harassment. Anandkumar's interest in the topic was intensified by her involvement in the campaign to change the shorthand name of the Neural Information Processing Systems conference from its original acronym, "NIPS," to "NeurIPS."

"The field of AI research is becoming more inclusive, but there are always people who resist change," says Anandkumar, who in 2018 found herself the target of harassment and threats online because of her successful effort to switch to an acronym without potentially offensive connotations. "It was an eye-opening experience about just how ugly trolling can get. Hopefully, the tools we're developing now will help fight all kinds of harassment in the future."

DURHAM, N.H. - Researchers at the University of New Hampshire have reported the first structural model for a key enzyme, and its activating protein, that can play a role in some genetically inherited eye diseases like retinitis pigmentosa and night blindness.

"There has been substantial research on the biochemical pathway involving this enzyme, known as PDE6, but defining atomic-level models is important for locating PDE6 mutations in order to understand why they cause disease and how we can develop new therapeutic interventions to manage retinal diseases," said Rick Cote, director of Center of Integrated Biomedical and Bioengineering Research and principal investigator on the study.

Vision starts in the photoreceptor cells of the retina which contains rods, responsible for low light vision, and cones, which are active in brighter light and capable of color vision. When light is absorbed by the rods and cones, it triggers a pathway which activates the enzyme phosphodiesterase 6, or PDE6. This generates a nerve impulse to the brain that ultimately results in visual perception. Some genetically inherited eye diseases are caused by mutations to PDE6, or its activating protein, transducin, that can lead to disruptions of normal vision or even total blindness.

In the study, recently published in the Journal of Biological Chemistry, researchers reported how they were able to use chemical cross-linking combined with mass spectrometric analysis to resolve the structure of PDE6 in its nonactivated and transducin-activated states. This approach permitted visualization of flexible regions of individual PDE6 catalytic and inhibitory subunits that were poorly resolved in previous work as well as the overall molecular architecture of the activated protein complex.

"Determining the structure of these visual signaling proteins has always been a challenge because of their complexity," said Michael Irwin, doctoral student in biochemistry and lead author. "Having detailed structural information about how PDE6 is activated by transducin will help us understand the molecular causes of visual disorders and blinding diseases resulting from mutations in these proteins."

Current medical treatment for such genetically inherited retina diseases may include gene therapy or drugs meant to inhibit the disease process. However, they are not always successful in restoring the balance of PDE6 and preventing blindness. Scientists believe that knowing the molecular structures of these visual signaling proteins and how they interact with each other can offer clues for the development of new drugs to both restore vision and prevent blindness.

The research was funded by the National Eye Institute, the National Institute of General Medical Sciences, the National Institute of Child Health and Human Development, the National Science Foundation, and the UNH Research Office.

The University of New Hampshire inspires innovation and transforms lives in our state, nation and world. More than 16,000 students from all 50 states and 71 countries engage with an award-winning faculty in top-ranked programs in business, engineering, law, health and human services, liberal arts and the sciences across more than 200 programs of study. As one of the nation's highest-performing research universities, UNH partners with NASA, NOAA, NSF and NIH, and receives more than $110 million in competitive external funding every year to further explore and define the frontiers of land, sea and space.

For the 20 percent of Americans who suffer from chronic pain, prescription opioids may bring relief, but also risks. An estimated 21 to 29 percent of patients who receive chronic opioid treatment will misuse their medications, and 8 to 12 percent will develop an opioid use disorder.

Tufts researchers believe that changing the way clinics and their staff approach opioids—upending old attitudes and systems—could improve those statistics. At a family medicine clinic in the Boston area, a team led by faculty from Tufts University School of Medicine conducted a five-year case study where they found medical facilities can help physicians to treat chronic pain in a way that will deter opioid misuse, while creating better processes to identify and treat patients who develop an opioid use disorder (OUD).

The team explains their process in a new paper published this month in the Journal of the American Board of Family Medicine.

The study was led by family medicine faculty Randi Sokol, a pain and addiction physician and educator, and Allen Shaughnessy, a clinical pharmacist and educator who conducts research on evidence-based medicine and clinical decision-making. Both practice and teach family medicine at Cambridge Health Alliance, an affiliate of Tufts School of Medicine.

“Oftentimes primary care teams want to make changes around pain and addiction management, particularly with respect to safe opioid prescribing and helping patients with OUD, but they need the work culture and infrastructure support to do so. A culture shift could have a big impact on how clinicians are able to care for their patients,” said Shaughnessy, senior and corresponding author. “For ourselves and for other clinicians, we designed a case study to see what support this might be and what it might look like.”

Of the 249 million opioid prescriptions written in the United States in 2013, nearly half came from primary care clinicians. But often those clinicians run into barriers to care, from having trouble communicating with other prescribers to create a treatment plan to not having training in medications that treat opioid dependence, such as buprenorphine-naloxone.

The researchers started the project by making the medical facility and its clinicians aware of the need, developing broad institutional support to address the opioid epidemic. A resident made a presentation on the community’s opioid epidemic and the value of OUD treatment. Sokol then sparked conversation about the scope of the epidemic by posting a map of local overdose rates.

Next, the researchers introduced new systems, structures, and staff support at the clinic, including:

clinic-wide guidelines for managing chronic pain, based on evidence and best practices
routine monitoring of patients on opioids through a prescription tracking program, questionnaires and toxicology tests
using shared electronic health records to promote collaborative care around safe prescribing, monitoring, and responding to aberrant patient behaviors
developing quality improvement metrics and tracking measures
helping chronic pain patients through behavioral strategies, such as stress reduction, cognitive restructuring, and routines that promote good sleep
developing a consultation service to support primary care providers with complex pain and addiction related cases
using a team-based approach with group visits to treat patients with OUD
providing all staff with education and training around pain and addiction
sponsoring a clinic-wide training on opioid overdose reversal
certifying all primary care providers to prescribe buprenorphine-naloxone
using staff meetings to share patient stories and promote a culture that destigmatizes addiction, viewing it as a chronic disease rather than a moral failing

Recognizing the need, the clinic readily adopted all these changes over the course of the study time, essentially changing the clinic culture around managing chronic pain and addressing opioid use disorder.

“Our case study highlights the importance of addressing aspects of clinical care that are not typically considered when addressing complex patient populations. We focused on changing the underlying structure and culture of a clinic to provide collaborative, interdisciplinary, team-based, and evidence-based care that will hopefully help our patients with chronic pain and addiction,” said Sokol, first author on the study. “We hope other clinics will use this case series as an example for how they can support safe prescribing practices and play a role in responding to the devastating opioid epidemic.”

Lisa LaPoint can be reached at lisa.lapoint@tufts.edu

Journal

The Journal of the American Board of Family Medicine

DOI

10.3122/jabfm.2020.01.190223

TALLAHASSEE, Fla. -- A discovery by Florida State University College of Medicine researchers is expected to open the door for new and more potent treatment options for many of the more than 36 million people worldwide infected with the HIV virus and for others chronically ill with hepatitis B.

Their work has established for the first time the mechanism responsible for how two widely used antiviral drugs inhibit viruses.

In a paper published by Communications Biology, an open-access journal from Nature Research, Professor Zucai Suo and colleagues also provide the key to understanding how a single HIV-1 mutation can inactivate the anti-HIV drugs emtricitabine and lamivudine. Those drugs are worth billions in annual sales for the companies that make them, and the frequency of patients who develop resistance creates serious and dangerous obstacles to controlling the disease.

Emtricitabine also is approved for use in patients with hepatitis B, which afflicts 270 million people worldwide, according to the World Health Organization.

The paper suggests new pathways for developing drugs able to avoid specific virus mutations that can render these two blockbuster L-nucleoside drug treatments ineffective for many patients.

It's not unusual for patients undergoing treatment to develop a resistance to their prescribed anti-HIV medications, leaving physicians with three options: adjust the treatment regimen, temporarily interrupt therapy or continue with an only partially effective regimen.

For patients who have failed their first treatment regimen, or even a second, doctors typically try to salvage the current course of treatment by adjusting the combination of drugs. But for patients who have failed multiple treatment regimens, there are limited options to suppress the incurable virus.

The number of drug choices available when one combination fails is limited. More than a million of those infected with HIV live in the U.S.

"In our paper, we suggest new chemical possibilities for more potent L-nucleoside analog drugs, which may possess different drug-resistance mutation profiles from the most widely used current anti-HIV drugs," said Suo, the study's co-lead author, and an Eminent Professor and the Dorian and John Blackmon Chair in Biomedical Science at the FSU College of Medicine. Eric Lansdon of Gilead Sciences Inc. is the co-lead author.

"Right now, there are a limited number of FDA-approved drugs available," Suo said. "New drugs need to be developed if doctors are to have other options when treating so many patients who may have developed resistance to most of the FDA-approved anti-HIV drugs."

The drugs remain highly effective in keeping the disease under control for most patients, but some patients develop a resistance due to mutations within the HIV virus.

Suo's paper explains how the class of HIV drugs known as L-nucleoside reverse transcriptase inhibitors (L-NRTIs) work. L-NRTIs block an enzyme that HIV needs to replicate, but they were discovered through blind trials. Important details about the underlying mechanism triggering L-NRTIs have remained a mystery, as well as a source of controversy among the scientists who study them.

"The enzyme has a unique pocket and supposedly recognizes NRTIs, but not their structural mirror images -- L-NRTIs," said Suo, who grew curious about the mechanism behind L-NRTI drugs as a graduate student. He's been motivated since then to understand and explain the mechanism involved, which he does in his paper -- one of six he has published involving L-NRTI research.

Suo's current paper also explains how a mutation found in some patient populations leads to developing resistance to antiviral L-NRTI drugs.

"Patients, HIV scientists and medical doctors all will benefit from this," Suo said. "HIV scientists and drug companies will now know how it works and will be able to design better drugs in the same class of medications. They will be able to build on the mechanism described in this paper to make slight adjustments for better and more powerful treatment options."

DALLAS, Jan. 8, 2020 -- One-year survival was similar for adults with severe heart failure who received a heart transplant from a donor with hepatitis C compared to those who received hearts from donors who did not have hepatitis C, according to new research published today in the Journal of the American Heart Association, the open access journal of the American Heart Association.

In the United States, more than 6 million people have heart failure and more than 900,000 new cases are diagnosed each year, according to the American Heart Association. The disorder occurs when other types of heart disease weaken the heart until it is unable to pump blood effectively throughout the body. Lifestyle changes and medications can help manage mild heart failure; however, severe cases may require a heart transplant.

Hepatitis C is a viral infection of the liver that spreads through contact with contaminated blood. The infection is spread through use of shared needles, from mother to infant during pregnancy and delivery, or through an organ transplant from someone infected with hepatitis C. If left untreated, hepatitis C can damage the liver, however, with the recent advent of new, direct-acting, antiviral drugs, hepatitis C is much more manageable than it was in the past. In many cases, hepatitis C is curable, which has led to increased use of organs from donors with hepatitis C as the need for heart transplants continues to exceed the supply.

In this study, nearly all patients survived one year after heart transplant, regardless of whether they received a heart from a donor with or without hepatitis C. Specifically, 90% of patients whose donors had hepatitis C survived, compared to a survival rate of 91% for the patients whose donors did not have the infection. Similarly, the rates of drug-treated organ rejection, kidney dialysis to remove toxins from the blood and stroke were similar between the two groups of patients.

"We are encouraged by these results and believe this is a landmark change in our ability to better meet the demand for heart transplantation by increasing the donor supply," said Arman Kilic, M.D., lead study author, assistant professor of cardiothoracic surgery, director of surgery quality and analytics, and co-director of the Center for Cardiovascular Outcomes and Innovation at the University of Pittsburgh Medical Center in Pennsylvania. "It is our hope that more centers will use hepatitis C-positive donors for heart transplantation."

The study included 7,889 U.S. patients at 128 medical centers, aged 18 years and older, who received a heart transplant between January 1, 2016 and December 31, 2018. Researchers compared one-year survival, organ rejection, dialysis and stroke among heart-transplant recipients from donors with hepatitis C to those from donors without hepatitis C. Slightly more than 4% of patients, or 343, received heart transplants from donors with hepatitis C.

Some limitations of the study are that the researchers did not have information about the donors' type of hepatitis C infection, past treatment and whether the heart-transplant recipients later developed the infection. Also, this study examined one-year survival only and included a relatively small number of patients with heart transplants from donors with hepatitis C.

Researchers note broadened implementation of protocols for using organs from donors with hepatitis C and an assessment of longer-term outcomes will be important to help reduce national organ donor shortages.

The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported. The news comes from Cancer Statistics, 2020, the latest edition of the American Cancer Society's annual report on cancer rates and trends.

The steady 26-year decline in overall cancer mortality is driven by long-term drops in death rates for the four major cancers - lung, colorectal, breast, and prostate, although recent trends are mixed. The pace of mortality reductions for lung cancer - the leading cause of cancer death - accelerated in recent years (from 2% per year to 4% overall) spurring the record one-year drop in overall cancer mortality. In contrast, progress slowed for colorectal, breast, and prostate cancers. The article appears early online in CA: A Cancer Journal for Clinicians, and is accompanied by a consumer version, Cancer Facts & Figures 2020.

Overall cancer death rates dropped by an average of 1.5% per year during the most recent decade of data (2008-2017), continuing a trend that began in the early 1990s and resulting in the 29% drop in cancer mortality in that time. The drop translates to approximately 2.9 million fewer cancer deaths than would have occurred had mortality rates remained at their peak. Continuing declines in cancer mortality contrast with a stable trend for all other causes of death combined, reflecting a slowing decline for heart disease, stabilizing rates for cerebrovascular disease, and an increasing trend for accidents and Alzheimer disease.

Lung cancer death rates have dropped by 51% (since 1990) in men and by 26% (since 2002) in women, with the most rapid progress in recent years. For example, reductions in mortality accelerated from 3% per year during 2008-2013 to 5% per year during 2013-2017 in men and from 2% to almost 4% in women. However, lung cancer still accounts for almost one-quarter of all cancer deaths, more than breast, prostate, and colorectal cancers combined.

The most rapid declines in mortality occurred for melanoma of the skin, on the heels of breakthrough treatments approved in 2011 that pushed one-year survival for patients diagnosed with metastatic disease from 42% during 2008-2010 to 55% during 2013-2015. This progress is likewise reflected in the overall melanoma death rate, which dropped by 7% per year during 2013-2017 in people ages 20 to 64, compared to declines during 2006-2010 (prior to FDA approval of ipilimumab and vemurafenib) of 2%-3% per year in those ages 20 to 49 and 1% per year in those ages 50 to 64. Even more striking are the mortality declines of 5% to 6% in individuals 65 and older, among whom rates were previously increasing.

"The news this year is mixed," said Rebecca Siegel, MPH, lead author of the report. "The exciting gains in reducing mortality for melanoma and lung cancer are tempered by slowing progress for colorectal, breast, and prostate cancers, which are amenable to early detection. It's a reminder that increasing our investment in the equitable application of existing cancer control interventions, as well as basic and clinical research to further advance treatment, would undoubtedly accelerate progress against cancer."

Highlights from the report:

The death rate for breast cancer dropped by 40% from 1989 to 2017.

The death rate for prostate cancer dropped by 52% from 1993 to 2017.

The death rate for colorectal cancer dropped by 53% from 1980 to 2017 among males and by 57% from 1969 to 2017 among females.

Decades-long rapid increases in liver cancer mortality appear to be abating in both men and women.

Cervical cancer, which is almost completely preventable, caused ten premature deaths per week in women ages 20-39 in 2017.

Other highlights:

In 2020, 1,806,590 new cancer cases and 606,520 cancer deaths are projected to occur in the United States.*

Progress for hematopoietic and lymphoid malignancies (leukemias and lymphomas) has been especially rapid due to improvements in treatment protocols, including the development of targeted therapies. The 5-year relative survival rate for chronic myeloid leukemia increased from 22% in the mid-1970s to 70% for those diagnosed during 2009 through 2015, and most patients treated with tyrosine kinase inhibitors now experience nearly normal life expectancy.

The overall cancer incidence rate in men declined rapidly from 2007 to 2014, but stabilized through 2016, reflecting slowing declines for colorectal cancer and stabilizing rates for prostate cancer.

The overall cancer incidence rate in women has remained generally stable over the past few decades because lung cancer declines have been offset by a tapering decline for colorectal cancer and increasing or stable rates for other common cancers in women.

The slight rise in breast cancer incidence rates (by approximately 0.3% per year) since 2004 has been attributed at least in part to continued declines in the fertility rate and increased obesity, factors that may also contribute to increasing incidence for uterine cancer (1.3% per year from 2007-2016).

Lung cancer incidence continues to decline twice as fast in men as in women, reflecting historical differences in tobacco uptake and cessation.

In contrast, colorectal cancer incidence patterns are generally similar in men and women, with the rapid declines noted during the 2000s in the wake of widespread colonoscopy uptake appearing to taper in more recent years.

Incidence continues to increase for cancers of the kidney, pancreas, liver, and oral cavity and pharynx (among non-Hispanic whites) and melanoma of the skin. Liver cancer is increasing most rapidly, by 2% to 3% annually during 2007 through 2016, although the pace has slowed from previous years.

The 5-year relative survival rate for all cancers combined diagnosed during 2009 through 2015 was 67% overall, 68% in whites, and 62% in blacks.

Cancer survival has improved since the mid-1970s for all of the most common cancers except cervical and uterine cancers. Stagnant survival rates for these cancers largely reflect a lack of major treatment advances for patients with recurrent and metastatic disease.

"The accelerated drops in lung cancer mortality as well as in melanoma that we're seeing are likely due at least in part to advances in cancer treatment over the past decade, such as immunotherapy," said William G. Cance, M.D., chief medical and scientific officer for the American Cancer Society. "They are a profound reminder of how rapidly this area of research is expanding, and now leading to real hope for cancer patients."

Fatal overdoses involving stimulants (cocaine and other psychostimulants, primarily methamphetamine) have been increasing over the past few years. A recent analysis published in Addiction found that in 2016, 27% of overdose visits to U.S. emergency departments involving cocaine and 14% involving psychostimulants also involved an opioid. Also, in 2017, almost 75% of overdose deaths involving cocaine and half involving psychostimulants involved at least one opioid.

The study also found that since 2006, rates of overdose emergency departments visits involving cocaine and psychostimulants with an opioid increased in recent years, as did those involving psychostimulants without opioids. Overdose deaths involving cocaine and psychostimulants increased in the past several years with and without opioids.

These increases occurred across a broad range of demographic groups and geographic areas, underscoring the escalating nature of the overdose crisis in the United States.

"Since opioids are driving increases in some stimulant overdoses, expanding opioid overdose prevention and reversal efforts through risk reduction services and access to medication-assisted treatment is critical for people who use stimulants," said lead author Brooke Hoots, PhD, MSPH, epidemiologist at the Centers for Disease Control and Prevention's National Center for Injury Prevention and Control. "Increases in stimulant overdoses without opioids also draws attention to the need for new, evidence-based interventions to address the evolving drug overdose crisis."

Pregnant women with inflammatory bowel disease (IBD) are more likely to undergo delivery by Caesarean section and face certain risks during pregnancy, according to an analysis of published studies.

The analysis, which is published in Alimentary Pharmacology & Therapeutics, found that one-third of all pregnancies in women with IBD were delivered by Caesarean section, reflecting almost a two-fold increase compared with women without IBD.

The analysis also demonstrated increased risks of gestational diabetes and preterm prelabour rupture of membranes in women with IBD. Placental-related disorders, such as pre-eclampsia, placental abruption, and placenta previa, did not appear to be increased in women with IBD.