Body

The combination of cancer therapy lenalidomide plus the steroid dexamethasone (together called Rd) is considered standard treatment for elderly patients with multiple myeloma. However, prolonged steroid use can be harmful for some older adults.

A new study published in Blood found that switching select older patients to a lower dose of lenalidomide and discontinuing dexamethasone after nine months was not only safe, but it also yielded similar outcomes as compared with patients who received continuous Rd.

Multiple myeloma, a cancer affecting the blood plasma cells (a type of white blood cell in the bone marrow), most commonly occurs in people over 60. Because of patients' older age, they are generally more susceptible to adverse events due to a higher likelihood of having other health conditions or functional impairments, and some treatments affect the body differently as we age.

This phase III clinical trial involved 33 medical centers in Italy and is the first to evaluate an adapted Rd treatment schedule that spares steroid use in older patients. Participants included people with newly diagnosed multiple myeloma (median age 76) who were deemed intermediate fitness for treatment, either because of their age or deficits in their ability to perform activities of daily living, such as bathing or dressing.

"Myeloma patients are a very diverse population, including fit patients who may tolerate full-dose treatments, and intermediate-fit and frail patients who are more susceptible to adverse events that may negatively affect the duration and outcome of treatment due to the presence of comorbidities and functional impairments, thus requiring an adapted therapy," said lead author Alessandra Larocca, MD, PhD of the University of Turin in Italy. "Our study shows, for the first time, that reducing the dose or intensity of treatment is a feasible option and produces similar outcomes as standard dose treatments for intermediate-fit patients."

Nowadays, multiple myeloma patients usually receive continuous treatment including steroids, which are typically given until a patient's disease progresses or they are unable to tolerate the therapy, according to Dr. Larocca. But as she explained, "Prolonged steroid use is scarcely tolerated in the long term, even in younger patients, and patients may often require dose reduction or interruption."

In fact, long-term use of dexamethasone-based regimens have been associated with insomnia, anxiety, agitation, weight gain, and swelling (edema) in the legs.

Finding ways to adapt treatments for older patients and those with functional deficits to allow them to remain on treatment longer and maintain disease control is critically important. As such, researchers wanted to evaluate whether stopping dexamethasone early, after initial therapy, and tapering the dose of lenalidomide (to 10 mg/day) would still benefit older intermediate-fit patients with newly diagnosed multiple myeloma who were not eligible for transplantation.

A total of 199 patients were enrolled and randomized to one of two study groups between October 2014 and October 2017. Only individuals deemed intermediate-fit were eligible for the study; patients were excluded if they were considered to be either fit or frail based on the International Myeloma Working Group frailty scale. Of these participants, 98 were randomized to receive continuous Rd and 101 received the adjusted dose and schedule after nine Rd induction cycles (called induction therapy).

After a median follow-up of 37 months, those who were no longer taking dexamethasone experienced a significantly longer period without an adverse event or relapse compared with those who continued on the standard Rd therapy (event-free survival of 10.4 months vs. 6.9 months, respectively). The tailored approach was also better tolerated, resulting in fewer adverse effects. Of the adverse events observed on the tailored approach, most were minor, including low white blood cell counts, infections, and skin disorders. The groups showed similar response rates, as well as similar chances of staying free of disease progression.

The findings could have important implications for practice. Dr. Larocca estimates that about one-third of myeloma patients not eligible for stem cell transplantation, a risky but common and effective treatment approach, fit the criteria used in this study.

"We expect the results of this study may help to improve and optimize the treatment of elderly patients who may be at greater risk of treatment toxicity and poor survival due to their age or comorbidities," she said, adding that ongoing trials are now evaluating steroid sparing in combination with monoclonal antibody or the role of frailty-guided treatment.

A growing number of studies show that the environmental factors and lifestyle habits of pregnant women play an important role in the health of their child. But how about the semen quality of young men? Researchers at the University of Geneva (UNIGE), Switzerland, showed two years ago that only 38% of Swiss men had semne parameters above the thresholds set by the World Health Organisation (WHO) for fertile men. Epidemiologists from the Institut de recherche en santé, environnement et travail (IRSET, Rennes, France), in collaboration with the UNIGE team analyzed the potential impact of endocrine disruptors on semen quality of men whose mothers were working at the early stages of their pregnancy. Their results, published in the journal Human Reproduction, show that men who have been exposed in utero to products known to contain endocrine disruptors are twice more likely to have semen volume and total sperm count per ejaculation below the reference values set by the WHO.

Endocrine disrupters are chemical substances of natural or synthetic origin which can interfere with the endocrine system and causes adverse health effects in an organism, or its progeny, according to the World Health Organization (WHO). "Several animal studies have already shown that gestational exposure to certain endocrine disruptors can influence the development of the male reproductive system, as well as the sperm production and semen quality in adulthood," explains Ronan Garlantézec, a researcher at the IRSET, the Rennes University Hospital Centre (CHU) and University of Rennes 1. "In view of the results obtained by Serge Nef's team on the semen quality of young Swiss men, we were interested in studying the potential effect of exposure to endocrine disruptors during pregnancy as one out of many possible reasons behind the observed trends", he continues.

The semen of more than 1000 conscripts analysed

The team of Serge Nef, professor at the Department of Genetic Medicine and Development of the UNIGE Faculty of Medicine, has evaluated semen quality of around 3000 conscripts, 1045 out of which had their mother working during pregnancy. "For each of them, a semen quality analysis was carried out to determine the semen volume, as well as the sperm concentration, motility and morphology," explains the Serge Nef. "A detailed questionnaire was also sent to the parents before the semen analysis was carried out, covering in particular the maternal jobs exerted during the conscripts' pregnancy period."

This allowed for the analysis of semen parameters of men whose mothers were employed during their pregnancy. "The maternal jobs were classified according to the International Classification of Occupations (ISCO-88 of the International Labour Office of the WHO)," explains Luc Multigner, research director at the IRSET. "Exposure to products containing endocrine disruptors during pregnancy has been defined using a job-exposure matrix, which makes it possible to attribute the maternal exposure a probability score." This has enabled epidemiologists to establish probabilities of exposure to one or more categories of products that may contain endocrine disruptors according to the mother's occupation.

Endocrine disruptors associated with poorer sperm quality

The results of this study show that young men exposed in utero to endocrine disruptors are twice as likely to have values below the reference values established by the WHO, both in terms of the semen volume (threshold at 2 ml) and the total number of spermatozoa per ejaculation (40 million). "In our study, the products most associated with these anomalies were pesticides, phthalates and heavy metals", notes Ronan Garlantézec.

"These observations do not determine the future fertility of young men, and only a follow-up over time will make it possible to assess the consequences. Nevertheless, the results could explain, at least in part, the low semen quality of some young Swiss men", Serge Nef continues. An additional study is already planned in this same population to study the link between maternal occupational exposure to endocrine disruptors and changes in sexual hormones during adulthood.

Preventing exposure to endocrine disruptors

The results of this study suggest an association between the mother's occupational exposure to endocrine disruptors and a decrease in several semen parameters in their children during adulthood. "It therefore appears necessary to inform women planning to conceive and during their early stages of pregnancy of the potential hazards of exposure to these substances, which could alter their children's fertility", underlines Luc Multigner. "Similarly, it would be interesting to carry out a similar study in women, in order to evaluate whether the impact of endocrine disruptors is the same on the female reproductive system, although this is much more complex to carry out", explains Ronan Garlantézec. Finally, the data concerns mothers 25 years ago. Since then, the professions exerted by women have greatly evolved, as has the presence of endocrine disruptors in the products used. "Hence the crucial preventive role of this study", concludes Serge Nef.

Approximately 8 out of every 10 health professionals in Spain are willing to be vaccinated against COVID-19, according to a study led by researchers from the Universitat Oberta de Catalunya (UOC). Published in the open-access journal Vaccines, the study assessed for the first time this population segment's willingness to be vaccinated against SARS-CoV-2 and concluded that the level of acceptance is higher among physicians than among nursing staff. Among the reasons given by health personnel for not wanting to be immunized, fears about the vaccines' safety and the potential side effects stood out.

Although vaccination is considered to the most effective method for preventing and eradicating viral infections and stopping their transmission, a significant percentage of the population is sceptical about the role played by these preventive drugs in immunity. One of the consequences of this has been a drop in the number of vaccinated people, leading to outbreaks of diseases that were controlled or even eradicated, such as measles. In fact, the growth of anti-vaccine groups led the World Health Organization (WHO) to include resistance to vaccination as one of the 10 global threats of 2019.

One of the main channels for propagating fake or scientifically unfounded information against vaccines are social media, including Instagram, Facebook, TikTok, Telegram and Twitter. In view of this, the researchers, led by Hans Eguia, a doctoral student enrolled on the UOC's doctoral programme in Health and Psychology, recruited 1,002 volunteers from Twitter between 10 September and 23 November 2020, most of them healthcare workers, and asked them to complete a questionnaire in which they were asked whether or not they would accept the vaccine and why.

Of the 731 people who were Spanish, 164 answered that they would not receive the vaccine. Of these, 17.5% were physicians, 35% were nursing staff and 31.5% were other healthcare professionals. Among the main reasons given for not vaccinating, they mentioned concerns about a possible lack of effectiveness, a lack of safety and possible adverse side effects.

"It is an extraordinary thing that the vaccines have been developed in less than a year. This has never happened before and it may give grounds for scepticism, even among some health professionals," explained Francesc Saigí, professor of Health Sciences at the UOC and a researcher at the I2TIC research group, which led the study.

"However, we can be sure that all the approved vaccines are safe. The fact that they been developed in such a short time is because they have received an enormous amount of resources. The criteria applied by the regulatory agencies in approving medicines are very strict," he added.

The results were obtained when the second wave was just starting in Spain and the vaccines' phase III clinical trials had not yet been completed. "There were no data and this perhaps might explain why some health professionals preferred to wait until more information was available. Perhaps if we repeated the survey today, the results would be different," suggested Marina Bosque, a researcher at the GRESP research group (University of Manresa, UOC).

The paper's authors consider that the fact that twice as many nursing staff as medical staff were unwilling to be vaccinated is worrying, because "they are the people who are closest to the patients and, therefore, more likely to influence their opinion, as is already the case in the flu vaccination campaigns," Saigí observed.

Although the study was carried out with a small sample before vaccination started, the authors believe that the results are a warning bell that shows that more interventions are needed to improve communication with the public in general and with health professionals in particular. Previous studies have shown that when people have doubts about vaccines, the reluctance diminishes and tends to disappear if they are given clear, powerful messages. A second study is in progress to determine the opinion and willingness to be vaccinated among the general population and health professionals, now that the vaccination process is in full swing.

"By understanding the reasons why people do not want to be vaccinated, especially health personnel, it will be possible to design communication and education strategies and even use social media to settle doubts, improve the vaccination rate and, ultimately, achieve the desired herd immunity effect," the authors concluded.

Stay tuned for the hottest science in the prevention of heart disease at ESC Preventive Cardiology 2021, an online scientific congress of the European Society of Cardiology (ESC). The annual congress of the European Association of Preventive Cardiology (EAPC), a branch of the ESC, takes place 15 to 17 April online.

Preventive cardiology covers how to avoid first and subsequent heart attacks and strokes. It also includes sports cardiology, primary care, epidemiology and population science, basic and translational research, and rehabilitation after an event. Explore the scientific programme.

Novel research will be presented including new insights into the connections between diet, exercise, and cardiovascular health. How does shift work affect the body? And are there links between climate change and heart disease? Find out how the COVID-19 lockdown affected lifestyle behaviours. And much more.

Featuring debate and discussion during live sessions covering the entire scope of preventive cardiology. Among them: how to keep active during the pandemic, with leading experts from Europe and the US. Professor Ana Abreu, congress chairperson said: "Social isolation and home working have led to sedentary lifestyles with increased consumption of high calorie foods and drinks, alongside anxiety, stress and uncertainty. What are the possible strategies to maintain physical and emotional balance and prevent disease? How should we raise activity levels during lockdown? These questions and more will be discussed, with exchange of ideas between the speakers and audience."

Activity monitors on phones, bracelets, rings, and T-shirts could get society moving - but which technologies are the best motivators? Dr. Nicolle Kraenkel, congress co-chairperson said: "Physical activity should be done every day, rather than moving little during the week and going for long runs at the weekend. Wearables may help users keep track of daily movement, but devices vary in their accuracy and usefulness for different activities. We will hear the most up-to-date experience and discuss potential solutions."

Childhood is a good time to adopt healthy lifestyle habits that will last a lifetime. Dr. Kraenkel said: "A dedicated session will explore whether it is best to focus first on body weight or not. Also, what is the most effective way to teach children how to take care of their own health - is school the best environment? And how might digital technology be used to reach a young audience?"

The optimal diet for cardiovascular health is controversial. An "essentials of nutrition" session goes beyond calories, fat, carbs, and salt and delves into contemporary topics. Are the health benefits of fasting, veganism, and paleo (caveman) diets only a myth or are they based on science? Should wine, chocolate and coffee be considered forbidden joys? Professor Abreu said: "All of these issues are affected by culture, religion, age, and so on. We will also discuss how to create a healthy food environment and the affordability of nutritious food for lower income groups."

Up-to-the-minute scientific evidence on electronic cigarettes will be highlighted including effects on cardiovascular and respiratory function, prevalence of usage, and legislation. Dr. Kraenkel said: "We will discuss the targeting of adolescents to take up vaping and what became of the promise that e-cigarettes would make it easier to quit smoking."

Also on the agenda: contemporary data on how heart disease and cancer intersect, the role of exercise in preventing cardiac side effects of cancer treatment, and managing cardiovascular disease in cancer patients and survivors. Plus: genetic testing to assess individual cardiovascular risk, guide lifestyle and choose treatment - how does it work and is it for everyone?

ESC Preventive Cardiology 2021 is designed for allied health professionals, cardiologists, general practitioners, policymakers, and researchers. Register as Press now and receive news releases from the leading international congress on preventive cardiology.

We all feel physical pain in different ways, but people with nerve injuries often have a dysfunctional pain suppression system, making them particularly prone to discomfort.

Now researchers have uncovered that virtual reality (VR) can reduce types of pain typically seen in patients with nerve injuries - and that VR can boost the dysfunctional pain suppression system, giving people with chronic pain a possible game-changing hope.

Dr Sam Hughes, Lecturer in Psychology at the University of Plymouth, led the study focusing on conditioned pain modulation (CPM) - a pain inhibitory pathway in humans.

He and colleagues at Imperial College London had previously published work showing that watching soothing 360-degree scenes of the Arctic in virtual reality can help to ease pain symptoms similar to those experienced during sunburn.

In the current study they showed that VR can also reduce pain symptoms such as prickling and pain following touch, that are often seen in patients with nerve injury.

They have also gone one step further and measured VR's direct effects on CPM. CPM is dysfunctional in patients with nerve injury, so by knowing what can enhance its action, scientists can help to stimulate the body's natural pain inhibiting process.

The study, published in The Journal of Pain, showed that 360-degree scenes of the Arctic in virtual reality had an effect on the CPM efficiency, while the 2D versions of the same scenes (described as 'sham VR') reduced CPM efficiency.

Dr Hughes said: "It's brilliant that we've seen these results as it shows more evidence that virtual reality can not only reduce pain perception in human models of chronic pain, but also gives us insight into the mechanisms behind this effect. The next step of course is to conduct the study with people who experience chronic pain to see if it works for them.

"If it does work, it could be a really helpful in forming part of ongoing pain management by helping to target the dysfunctions in the brain that underpin chronic pain."

Boston, Mass. - In a paper published in the Journal of General Internal Medicine, physician-researchers at Beth Israel Deaconess Medical Center (BIDMC) assessed the relative impact of COVID-19 on patients hospitalized with the viral infection in March and April 2020, versus patients hospitalized with influenza during the last five flu seasons at the medical center. Overall, the team demonstrated that COVID-19 cases resulted in significantly more weekly hospitalizations, more use of mechanical ventilation and higher mortality rates than influenza.

COVID-19 and influenza are both contagious respiratory viral diseases that can lead to pneumonia and acute respiratory failure in severe cases. However, detailed comparison of the epidemiology and clinical characteristics of COVID-19 and those of influenza are lacking.

"COVID-19 has been compared to influenza both by health care professionals and the lay public, but there's really limited detailed objective data available for comparing and contrasting the impact of these two diseases on patients and hospitals," said corresponding author Michael Donnino, MD, Critical Care and Emergency Medicine physician at BIDMC. "We compared patients admitted to BIDMC with COVID-19 in spring 2020 to patients admitted to BIDMC with influenza during the last five flu seasons. We found that COVID-19 causes more severe disease and is more lethal than influenza."

Donnino and colleagues included a total of 1,634 hospitalized patients in their study, 582 of whom had laboratory-confirmed COVID-19 and 1,052 of whom had confirmed influenza. The team found that, on average, 210 patients were admitted to BIDMC during each eight-month flu season, compared to the 582 patients with COVID-19 admitted in March and April 2020. While 174 patients with COVID-19 (or 30 percent) received mechanical ventilation during the two-month period, just 84 patients with influenza (or 8 percent) were placed on ventilation over all five seasons of influenza. Likewise, the proportion of patients who died was much higher for COVID-19 than for influenza; 20 percent of admitted patients with COVID-19 died in the two-month period, compared to three percent of patients with influenza over five seasons.

Further analysis revealed that hospitalized patients with COVID-19 tended to be younger than those hospitalized with influenza. Among patients requiring mechanical ventilation, patients with COVID-19 were on ventilation much longer -- a median duration of two weeks -- compared to just over three days for patients with influenza. Moreover, among patients requiring mechanical ventilation, patients with COVID-19 were far less likely to have had pre-existing medical conditions.

"Our data illustrate that 98 percent of deaths of patients hospitalized with COVID-19 were directly or indirectly related to their COVID-19 illness, illustrating that patients did not die with COVID but rather from COVID pneumonia or a complication," said Donnino.

The authors note that the stringent social distancing guidance in effect last spring may have impacted these findings by limiting the incidence and lethality of COVID-19 toward the end of April 2020. Conversely, some treatment practices have evolved over the course of the pandemic, potentially improving outcomes for patients with COVID-19.

COVID-19 vaccines being rolled out in the UK are effective in preventing severe disease, but the extent to which they prevent against infection is still unclear.

First modelling study looking at relaxing control measures (eg, mask wearing, physical distancing, and lockdown measures) and planned vaccination rollout in the UK suggests that vaccination alone may not be enough to prevent the spread of infection - with the R number estimated to be 1.58 even if the vaccine prevents 85% of new infections occurring, after vaccine rollout is complete and all other control measures are removed.

Relaxing control measures is highly likely to lead to another wave of infection, but gradual reopening, high vaccine uptake, and a vaccine with high protection against infection can minimise the scale of infections, hospitalisations, and deaths.

As restrictions are eased and infections grow, although vaccination will reduce the total number of COVID-19 deaths significantly, there are likely to be deaths in people who have been vaccinated, as no vaccine offers 100% protection.

Vaccinating all adults in the UK is unlikely to achieve herd immunity and fully contain the virus, according to a modelling study published in The Lancet Infectious Diseases journal. Therefore, the gradual release of control measures, high vaccine uptake, and a vaccine with high protection against infection is essential to minimise future waves of infection.

This analysis was done before early real-world data from vaccination rollout studies. Preliminary findings suggest that the vaccine does offer a level of protection against infection, but the exact level is still unclear - for this reason the authors examine a range of levels of protection against infection.

The authors note that their model does not account for the emergence of new variants, to which the vaccine might offer less protection, nor for the effects of waning immunity, which might necessitate additional vaccination. They also note that they are unable to look at the effects of relaxing individual control measures.

Professor Matt Keeling, from University of Warwick, UK, says "Our modelling suggests that vaccination rollout in adults alone is unlikely to completely stop COVID-19 cases spreading in the UK. We also found that early sudden release of restrictions is likely to lead to a large wave of infection, whereas gradually easing measures over a period of many months could reduce the peak of future waves. The huge success of the UK's vaccine programme so far coupled with the government's gradual roadmap for easing restrictions are a cause for optimism. However, some measures, such as test, trace, and isolate, good hand hygiene, mask-wearing in high-risk settings, and tracing from super-spreader events, may also be necessary for some time." [1]

Vaccination may offer a potential exit strategy for the pandemic and the UK currently ranks third globally for the total number of vaccine doses administered. [2] This study modelled the combined interaction of the UK vaccination rollout with different scenarios of relaxing control measures, to predict the R number and deaths and hospital admissions due to COVID-19 from January 2021 to January 2024.

The model assumed vaccine uptake would be 95% in those aged 80 years and older, 85% in those aged 50-79 years, and 75% in those aged 18-49 years, as well as looking at a more optimistic uptake scenario (95%, 90%, and 85%, respectively), and a more pessimistic scenario (90%, 80%, and 70%, respectively). Vaccine protection against symptomatic disease was assumed to be 88% based on phase 3 trial data from the Pfizer-BioNTech and Oxford-AstraZeneca vaccines being administered in the UK (the analysis was done before early real-world data from vaccination rollout studies). Since the vaccines' protection against infection is still uncertain, it was varied in four scenarios (0%, 35%, 60%, and 85%).

The findings suggest that although vaccination can substantially reduce R, it may not be enough to drive R below 1 without other control measures. Under the most optimistic scenario for protection against infection (85%), the R number is estimated to be 1.58 without other controls. [3]

As vaccination alone is not expected to drive R below 1, removing all restrictions after the vaccination rollout is complete is predicted to lead to another wave of infections with a substantial number of deaths. The scale of future waves and the number of deaths is influenced by how early and over what time-scales measures are relaxed, the vaccine's level of protection against infection, and vaccine uptake.

Even small relaxations of measures if done abruptly were predicted to lead to large waves of infection. The authors consider abrupt releases of some measures (from current restrictions to a situation comparable to September 2020) with a vaccine that offers 85% protection against infection and calculate the number of deaths from Jan 2021 until January 2024. A partial release in February 2021 was estimated to lead to 130,100 deaths by January 2024, whereas partial release in April 2021 lowers this to 61,400 deaths and partial release in June 2021 to 53,900 deaths (see Table 1), highlighting the impact of the vaccination programme rollout. It should be noted that these estimates all include the 49,300 deaths that have already occurred this year. [4]

If all control measures are removed in January 2022 (after complete rollout of the vaccine), 21,400 COVID-19 deaths are estimated, if the vaccine prevents 85% of infections. This increases to 96,700 if the vaccine only prevents 60% of infections (see Table 2). The only scenario where case numbers remain low is if all control measures are removed in January 2022 with the optimistic vaccine uptake scenario (95%, 90%, and 85%, in those over 80, 50-79 and 18-49 respectively) and a vaccine that offers 85% protection against infection, which reduces deaths to an estimated 1,030.

Gradual relaxation, as opposed to immediate release of control measures, may reduce future waves of infection. For example, partial release of control measures in February, 2021, was predicted to lead to a wave of infection that peaks at 1,670 deaths per day, but gradual release of measures over the course of 5 months or 10 months leads to waves that peak at 430 and 46 deaths per day, respectively.

Although vaccination substantially decreases overall deaths, because no vaccine's protection against symptomatic disease is 100%, the authors note that some people who have been vaccinated will still die of COVID-19. If the vaccine offers 60% protection against infection, the authors predict that 48% and 16% of deaths may be in individuals who have received one or two doses of the vaccine, respectively.

Dr Sam Moore, from University of Warwick, UK, says "We're rapidly learning more about vaccine efficacy as vaccination programmes are rolled out across the world. Since we conducted this study, new evidence suggests there may be a higher level of protection against severe disease offered by both the Pfizer-BioNTech and Oxford-AstraZeneca vaccines than the level we assumed. This may reduce the size of future hospital admissions and deaths we estimated, making future waves more manageable for the health service. As for protection against infection, some preliminary findings have suggested that the vaccine does offer a level of protection against infection, but the exact level of protection offered by vaccines is still unclear. We will continue to update our predictions as new data on vaccine efficacy becomes available." [1]

The authors caution that vaccine uptake is likely to be uneven (clustering among certain households and socioeconomic groups), potentially giving rise to pockets of infection, as control measures are relaxed. They stress the importance of intensive test, trace, and isolate capabilities to target these pockets of infection.

Writing in a linked Comment, Dr Viola Priesemann (who was not involved in the study), from Max Planck Institute for Dynamics and Self-Organization, Germany, comments on the importance of using the protection from vaccines wisely to prevent further waves of infection, "The advantage of avoiding another pandemic wave is clear: less so-called long COVID-19, less quarantine, fewer deaths, and reducing the impact of the pandemic on societies and economies. Finally, more infections mean more scope for the spread and evolution of escape variants, which risk a major setback for any vaccination strategy, so avoiding this eventuality will be crucial."

Researchers who simulated early stages of the SARS-CoV-2 outbreak in Wuhan, China, conclude that the virus was likely circulating earlier than has been described, possibly even in mid-October 2019. The findings do not reveal whether the virus that first emerged was less "fit" than the virus that spread throughout China, say the authors, but the estimates do further distance the first ("index") case from the outbreak at the Huanan Seafood Wholesale Market, which has received much attention. A concerted effort has been made to determine when the SARS-CoV-2 virus first began transmitting among humans. Research suggests the first described cluster of COVID-19 - associated with the Huanan Seafood Wholesale Market in late-December 2019 - is unlikely to have marked the beginning of the pandemic, as COVID-19 cases from early December lacked connections to the market. What's more, newspaper reports by the Chinese government detail daily retrospective COVID-19 diagnoses going back through November. To better estimate the timing of the first SARS-CoV-2 case, presumably in Hubei, China, Jonathan Pekar and colleagues used a combined approach. They first applied Bayesian molecular clock phylogenetics to estimate the timing of most recent common ancestor of sampled strains of the virus. Using an epidemiological model, the researchers then ran forward simulations. Critically, their simulations considered the possibility that the variant of SARS-CoV-2 that first emerged was less fit than the variant that spread widely; the authors thus simulated two-phase epidemics wherein the first case was infected with a less fit variant that went extinct, but not before giving rise to a mutant strain that persisted. In this approach, about two-third of SARS-CoV-2 events died off without igniting a pandemic. Based on their simulations, the authors predict SARS-CoV-2 was circulating in Hubei province at low levels in early-November 2019, and possibly as early as mid-October 2019. The inferred prevalence of this virus was too low to permit its discovery for weeks or months, they say. By the time COVID-19 was first identified, the virus had established itself in Wuhan. The delay highlights the difficulty in surveillance for novel zoonotic pathogens with high transmissibility and moderate mortality rates.

Oncotarget published "Quantitative proteome profiling stratifies fibroepithelial lesions of the breast" which reported that the current grading system remains unreliable in differentiating these tumors due to histological heterogeneity and lack of appropriate markers to monitor the sudden and unpredictable malignant transformation of PTs.

The high- throughput quantitative proteomic analysis suggested that FAD and PTs form distinct clusters away from borderline and malignant though there exist marked differences between them.

Interestingly, over-expression of extracellular matrices related proteins and epithelial-mesenchymal transition markers in borderline PTs led these authors to hypothesize a model of deposition and degradation leading to ECM remodeling and EMT acquisition triggering its malignant transformation.

They also identified three candidate biomarkers such as MUCL1, HTRA1, and VEGDF uniquely expressed in FAD, borderline, and malignant PTs, respectively, which were further validated using immunohistochemistry.

The present Oncotarget work shed light on a brief mechanistic framework of PTs aggressive nature and present potential biomarkers to differentiate overlapping FELs that would be of practical utility in augmenting existing diagnosis and disease management for this rare tumor.

The present Oncotarget work shed light on a brief mechanistic framework of PTs aggressive nature and present potential biomarkers to differentiate overlapping FELs that would be of practical utility in augmenting existing diagnosis and disease management for this rare tumor

Dr. Lekha Dinesh Kumar and Dr. Prashant Kumar both from The CSIR-Centre for Cellular and Molecular Biology said, "Fibroepithelial lesions (FELs) of the breast are a group of biphasic tumors that are highly heterogeneous in terms of their morphological as well as biological features."

FADs are widespread tumors accounting for 68% of all breast masses and 44–94% of biopsied breast lesions.

A commonly encountered complication in diagnosis is the differentiation of FADs and benign PTs primarily contributed by the overlapping histologic and morphological characteristics between these lesions.

Several recurrently mutated genes unique to FAD and PTs, and several protein markers have also been investigated previously for their diagnostic utility and association with histological grade in FELs.

However, not much effort has been made to identify potential diagnostic biomarkers that could improve the diagnostic practice to classify PTs and differentiate them from FADs.

To this end, the authors employed iTRAQ based quantitative proteomics of FELs to extensively characterize the proteomic alterations across these tumors in order to identify potential biomarkers and distinctly stratify these overlapping tumors.

The Kumar/Kumar Research Team concluded in their Oncotarget Research Output, "this study provided a comprehensive profile of differentially regulated proteins across various subtypes of FELs. The presence of extensive ECM proteins and EMT markers led us to hypothesize a model of deposition and degradation of these proteins thus triggering ECM remodeling and EMT acquisition in borderline PTs leading to its malignant state. Enrichment of platelet degranulation factors in malignant PT indicates active angiogenesis during this transformation. Herein, our initial findings suggest that MUCL1, HTRA1, and VEGFD can be used as potential proteomic markers that could augment existing diagnosis, and help in monitoring the progression of the disease. Further characterization of FELs using different omics platforms would help in better understanding of the cellular and molecular events that would help in understanding the disease dynamics and thus better management of the disease."

WASHINGTON--Nearly one-third of adults age 65 and older who take thyroid hormone also take medications that are known to interfere with thyroid function tests, according to a study presented virtually at ENDO 2021, the Endocrine Society's annual meeting.

"Our findings highlight the complexity of managing thyroid hormone replacement in older adults, many of whom take medications for other medical conditions," said first author Rachel Beeson, M.D., of the University of Michigan in Ann Arbor, Mich. "Until now, the prevalence of concurrent use of thyroid hormone and interfering medications in older adults, and patient characteristics associated with this practice, has been unknown."

Thyroid hormone use is very common in older adults. Levothyroxine, used to treat hypothyroidism (low thyroid hormone), is one of the most frequently prescribed medications in the United States. Thyroid function tests are used to determine the dose and effectiveness of treatment. The results of these tests can be altered by a variety of medications.

Beeson and colleagues analyzed data from 538,137 adults age 65 and older who used thyroid hormone. They looked at how many patients concurrently took thyroid hormone and medications that commonly interfere with thyroid function tests, such as prednisone, prednisolone, carbamazepine, phenytoin, phenobarbital, amiodarone, lithium, interferon-alpha and tamoxifen.

Overall, 31.6% of patients were taking medications that have been known to interfere with thyroid function tests.

"When we examined patient characteristics associated with concurrent use of thyroid hormone and at least one interfering medication, this was more likely to be seen in patients who were female, non-white and of Hispanic ethnicity," Beeson said. The researchers also found people who had other chronic medical conditions were more likely to concurrently use thyroid hormone and medications that interfere with thyroid tests.

WASHINGTON--Less than one in 10 commercially insured patients in the United States who broke a hip, a major complication of osteoporosis, receive any osteoporosis medical treatment within two calendar quarters of their fracture, according to a study whose results will be presented at ENDO 2021, the Endocrine Society's annual meeting.

Rates of treatment with osteoporosis, or bone loss, medicines dropped dramatically over the past decade from 15 percent to 8 percent, a new analysis of a large nationwide private insurance database found. The decrease comes despite fractures often being the first sign of osteoporosis, said the study's lead author, Sara Cromer, M.D., an endocrinology fellow at Massachusetts General Hospital in Boston, Mass.

"This very low rate of treatment with bone-directed medications to prevent future fractures is concerning," Cromer said. "This is analogous to providing no therapy to lower blood pressure or cholesterol after a heart attack."

Medical associations recommend osteoporosis evaluation and treatment after a hip fracture. Osteoporosis medications, also called bone-directed or bone-modifying drugs, prevent bones from getting weaker by slowing the natural breakdown of bone or by stimulating new bone to form.

Some 54 million Americans--primarily women--have osteoporosis or are at risk of the bone-weakening disease, putting them at increased danger of broken bones, according to the Hormone Health Network. Each year, more than 300,000 older adults nationwide sustain a hip fracture requiring hospitalization, according to the U.S. Centers for Disease Control and Prevention.

The new study involved more than 15 million prescription claims and reviewed trends in U.S. prescribing of bone-directed therapies from 2009 to 2020. Although the study data do not address possible reasons for the decrease in bone-directed treatment of hip fractures, Cromer said the diagnosis of osteoporosis is often overlooked, even in patients who experience disease-defining fractures.

Another reason could be public concerns about the side effects of some common osteoporosis drugs, including bisphosphonates, she suggested. These include the very rare chance of either osteonecrosis of the jaw, which is a severe breakdown of bone in the jaw, or of fractures of the thigh bone.

The Society's Clinical Practice Guideline on osteoporosis treatment in postmenopausal women state that the benefits of bone-directed medications outweigh their risk for women at high risk of breaking a bone, especially those who recently experienced a fracture.

"The risk of second fracture is higher without osteoporosis medications," Cromer said. "Also, a hip fracture can be deadly, with approximately 20-30 percent of people dying within a year after a hip fracture, and studies show that some medications for osteoporosis can even lower this risk of death."

Another trend that their study identified that Cromer said seems out of proportion to the Society's guideline recommendations is the rapid rise in use of denosumab, which became available in 2010. This medicine, which is given twice a year as an injection in the doctor's office, is a monoclonal antibody that works similar to bisphosphonates. The guidelines recommend denosumab as an alternative to bisphosphonates for the initial treatment of osteoporosis if they cannot take bisphosphonates or are at high risk of osteoporotic fractures.

By 2017, use of denosumab surpassed all other bone-directed drugs except the bisphosphonate alendronate for the treatment of osteoporosis, the study data showed. Furthermore, Cromer said by 2013 denosumab became the most commonly used drug for the prevention of fractures related to cancers that have, or are likely to, spread to the bone.

"While denosumab is highly effective at improving bone density and preventing fracture, it has also been known for several years that there is an increase in spinal fractures if denosumab is discontinued without follow-up treatment, and sometimes even with follow-up treatment," Cromer said. "This safety concern does not seem to be reflected in medication use as of early 2020, the end of our study."

Cromer hypothesized that the popularity of denosumab over other effective medications may be because its form of administration--twice-a-year injections--is more convenient than that of oral bisphosphonates that patients take once a week. However, she said denosumab was used more often than zoledronic acid, an intravenous bisphosphonate that requires only once-yearly dosing. The reasons for the rapid increase in use of denosumab remain unclear, she noted.

She encouraged patients with osteopenia or osteoporosis to discuss their risks and benefits of treatment with their doctor and to ask which medicine is best for them.

Leesburg, VA, March 18, 2021--According to ARRS' American Journal of Roentgenology (AJR), contrast-enhanced mammography (CEM) showed concordance with MRI in women with newly diagnosed breast cancer and breast augmentation.

Noting that CEM has not been investigated in women with breast augmentation, Molly Carnahan and her Mayo Clinic team in Phoenix, AZ, concluded, "the findings suggest a possible role of CEM for staging in women with breast augmentation and contraindication or limited access to MRI."

From an institutional database of 2,215 women who underwent CEM between January 2015 and March 2020, the researchers identified breast implants in 67 women: 42 without corresponding MRI, 3 without breast cancer, 1 with axillary disease only, and 6 with neoadjuvant chemotherapy before CEM or MRI--leaving a final sample of 17 women (mean age 52 years; 6 with non-dense breasts, 11 with dense breasts).

The index cancer histology was invasive ductal carcinoma (IDC) in 15 (88%) women, invasive lobular carcinoma (ILC) in 1 (6%), and ductal carcinoma in situ in 1 (6%). Median index cancer size was 2 cm, and 2 (12%) index cancers were mammographically occult. Ultimately, CEM and MRI were concordant for the index cancer in all 17 women.

Six additional lesions were demonstrated by CEM and confirmed by MRI in 6 (35%) women: 3 multifocal, 1 multicentric, 2 contralateral. Two of these lesions revealed malignant histopathology: 1 IDC, 1 ILC.

"MRI did not identify any additional cancers not identified on CEM," the authors of this AJR article added.

Research from the University of Kent's School of Biosciences has revealed that a molecule produced by the human immune system can severely diminish the potency of certain antibiotics.

This may explain why antibiotics effective in laboratory settings can be less effective at clearing infections in humans.

The research findings, which have been published in the journal Archives of Microbiology, reveal that nitric oxide, a molecule produced by our immune systems, can render aminoglycoside antibiotics ineffective when used against E. coli strains isolated from human infections.

E. coli causes life-threatening infections including sepsis, bladder infections, kidney failure, and dysentery. Whilst the human immune system produces nitric oxide to kill invading bacteria, this study reports that nitric oxide can also undermine the function of antibiotics that are used as first-line agents to treat infections caused by drug-resistant E. coli.

It is expected that these findings will greatly influence the choice and dose of antibiotic treatments prescribed by medical professionals.

Corresponding author Dr Mark Shepherd, Senior Lecturer in Microbial Biochemistry at Kent, said: 'This work highlights the urgent need for a better understanding of how the human immune system can profoundly affect the activity of antibiotics, which is of great importance for future therapies to treat multidrug-resistant bacterial infections.'

Google Trends reveal how searches related to family and relationship behaviors, such as weddings, contraception, and abortions, changed during lockdowns in the US and Europe.

A new study involving UCLA researchers finds that mobile stroke units (MSUs) - state-of-the-art ambulances built to provide stroke patients with emergency neurological diagnosis and treatment prior to hospital arrival -- improve patient outcomes and lessen the chance for disability by delivering care faster than standard stroke care.

The UCLA Mobile Stroke Unit serves as a shared regional resource of LA County EMS Provider Agencies, taking patients to 15 different stroke center hospitals within 3 regions in Los Angeles County. The MSU carries a CT scanner that can directly image the brain and blood vessels in the field. UCLA was one of seven national mobile stroke unit programs to participate in the clinical trial, which was presented March 17 at the International Stroke Conference.

Dr. May Nour, the UCLA MSU program's medical director and a lead author on the study, said that she is very pleased that the study findings reflect the positive experience that she and her colleagues have been witnessing while treating patients in the field.

"Stroke is one of the golden-hour emergencies in which the swift timing of conclusive diagnosis and treatment dramatically impacts patient outcome and their chances of meaningful recovery," Dr. Nour said. "We set out a few years ago to quantify the magnitude of benefit of mobile stroke unit pre-hospital care for our patients. We are proud to have participated in this pivotal trial. Today is a momentous day for the citizens of Los Angeles County."

In October, Stephanie Wimberly, 40, of South Los Angeles, was at her dentist in Hawthorne when she experienced a stroke.

"I honestly believe that if it wasn't for the UCLA Mobile Stroke Unit, I wouldn't be alive today," she said. "Dr. Nour saved my life."

UCLA's was the first mobile stroke unit launched in the California and in the western third of the United States. There are 20 mobile stroke unit sites throughout the United States. Clinical operations began in September of 2017 and have been supported by the Arline and Henry Gluck Foundation as well as Measure B funds from the Los Angeles County Board of Supervisors, which Supervisor Janice Hahn was instrumental in making available.

"The (UCLA) Mobile Stroke Unit is saving lives and preventing patients from experiencing debilitating brain damage after a stroke," said Supervisor Hahn. "Mobile stroke units are the future of stroke treatment and I envision a day when we have enough of these units on the road to treat every stroke patient in LA County."

The program currently provides hyper acute stroke care in the field for patients 6 days per week, 12 hours per day.

The study compared tissue plasminogen activator (tPA)-eligible patients managed by MSUs vs standard ambulance/emergency room care. It enrolled 1,517 patients with suspected acute ischemic stroke within 4.5 hours of experiencing symptoms. This included 617 patients in the MSU group and 430 in the standard care group who qualified for tPA. Of the tPA eligible patients, 97% received it in the MSU versus 80% with standard care.

Time from onset of symptoms until tPA treatment was shorter in the MSU group with a median time of 72 minutes versus 108 minutes in the standard treatment group. Thirty-three percent of MSU patients were treated within 60 minutes, compared to just 3% of SM patients.

The research concluded that the MSU patients had better outcomes and experienced much less disability, likely because the MSU patients received treatment faster.

"This convincing demonstration of the benefits of MSU care will support the incorporation of mobile stroke units into emergency medical systems throughout the country," said Jeffrey Saver, MD, the director of the UCLA Comprehensive Stroke and Vascular Neurology Program. He added, "A new era in acute stroke has arrived."

Research from UCLA has shown that 2 million brain cells are injured every minute in a stroke, supporting the American Heart/Stroke Association's public message that, "Time lost is brain lost in acute stroke,'' Dr. Saver said.

"The study results demonstrate that for every 100 patients treated with a mobile stroke unit rather than standard care later in the emergency department, 27 will have less final disability, including 11 more who will be disability free," Dr. Nour added. "With these results, and keeping our patients and their families in the forefront of our minds, we are hopeful that this data provides initiative for expanding the mobile stroke unit pilot in our county to include a fleet of MSUs to serve all of the citizens of Los Angeles County in their greatest time of need."