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The results of a study to be presented at the Annual European Congress of Rheumatology (EULAR 2018) suggest childhood and adult obesity increase the risk of developing hip osteoarthritis (OA) and knee OA but not hand OA.1

Obesity and OA are two interconnected health care problems affecting a large proportion of the adult population worldwide, however studying causality in this association is difficult due to confounding factors. To test the hypothesis that the association between obesity and OA is causal, investigators used a method know as 'mendelian randomization', which uses genetic variants to investigate whether a biomarker has an effect on the risk of developing disease.

"Obesity in both childhood and adulthood is an important public health issue," said Professor Johannes W. Bijlsma, EULAR President. "These data showing a causal relationship with osteoarthritis should add further impetus to tackle the issue of obesity and reduce related disability."

Results of the study indicated that adult body mass index (BMI) significantly increased the prevalence of self-reported OA, knee OA or hip OA by 2.7%, 1.3%, and 0.4% per unit (1 kg/m2) increase in BMI respectively. Childhood BMI significantly increased the prevalence of self-reported OA, knee OA or hip OA by 1.7%, 0.6%, and 0.6% per BMI unit respectively. No associations were found between either adult or child BMI and hand OA, which contradicts previous cohorts. Investigators suggest that this could be explained by the impact of various confounding factors such as manual work or related socio-economic factors. Finally, no relationship was found with traumatic eye injury which was used in the study as a negative control.1

"Our results suggest the effect of adult BMI seems to be stronger on knees, whilst childhood BMI might impact both knee and hip osteoarthritis risk similarly," said Professor Prieto-Alhambra (senior study author). "Interestingly our findings contradict previous studies that found an association between obesity and hand osteoarthritis."

Investigators used data from two genome wide association studies (GWAS) which identified 15 and 97 specific gene changes, known as SNPs (single nucleotide polymorphism), associated with childhood and adulthood BMI respectively. They then used a separate GWAS of 337,000 unrelated individuals in the UK BioBank. Within this data they identified 13/15 childhood obesity SNPs and 68/97 adulthood obesity SNPs and then analysed the association between these SNPs and self-reported osteoarthritis, as well as hospital data for knee, hip and hand osteoarthritis. Associations with negative controls (myopia, left-handedness, and traumatic eye injury) were all inexistent as expected.

Abstract number: SAT0681

The results of a study to be presented at the Annual European Congress of Rheumatology (EULAR 2018) suggest that rates of anxiety and depression in patients with rheumatoid arthritis correlate with measures of disease activity over the first year following diagnosis.1

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects a person's joints, causing pain and disability. It can also affect internal organs. RA is more common in older people, but there is also a high prevalence in young adults and adolescents. It affects women more frequently than men. High rates of depression and anxiety have been shown in patients with RA.2

"These results confirm both depression and anxiety as significant comorbidities at the time of rheumatoid arthritis diagnosis," said Professor Thomas Dörner, Chairperson of the Abstract Selection Committee, EULAR. "It is interesting to see the changes in anxiety and depression scores appear in tandem with disease activity over time, which requires further investigation."

The study included data from 848 patients and results showed significant reductions in anxiety from 19.0% to 13.4% (p=0.004) and depression from 12.2% to 8.2% (p=0.01) one year after RA diagnosis, this was in line with observed decrease in disease activity. Both depression and anxiety scores demonstrated significant correlation with disease activity scores (DAS28*) at baseline, six months and at 12 months (p

"Our results demonstrate a number of interesting associations with socioeconomic and other variables," said Dr George Fragoulis, honorary research fellow at the University of Glasgow (study author). "Most interestingly c-reactive protein, which is a blood test marker for inflammation, was highly associated with depression but not anxiety at all time points. This provides further support to compelling data linking inflammation and depression."

Investigators conducted statistical analysis to highlight potential associations between depression and anxiety scores and multiple variables at each time point. When looking at anxiety scores, statistically significant associations were found with female gender, younger age, and patient global assessment score (PGA) at baseline. At six months and 12 months, significant association was demonstrated between anxiety scores and low body mass index (BMI), PGA and baseline anxiety scores. When looking at depression scores, significant associations were found with PGA at baseline. At six months and 12 months, depression score was significantly associated with PGA, c-reactive protein (CRP) levels as well as baseline depression and anxiety scores.

The study used data from patients in the Scottish Early Rheumatoid Arthritis (SERA) cohort of newly diagnosed patients with RA. Patients had been followed-up every six months following diagnosis and tested for pre-specified clinical, laboratory and psychosocial features. This included anxiety and depression which was measured using the hospital anxiety and depression score.

Glenview, IL, June 15, 2018 - Only a minority of intensive care units (ICUs) in smaller, community, and regional ICUs in the United States hire intensivists to provide advanced critical care, but many employ ICU telemedicine (Tele-ICU) to help fill the gap. The Veteran's Administration (VA) has implemented a Tele-ICU program to provide remote access to comprehensive acute care expertise for smaller, community, and regional ICUs in its health system. A new study in the journal CHEST® examined transfers of ICU patients to acute care centers before and after the VA implemented its Tele-ICU program. Investigators found that hospitals using Tele-ICU support experienced a greater reduction in transfers of ICU patients to other facilities than hospitals that did not use the services. Additionally, mortality did not change when more patients were treated locally through Tele-ICU.

"Tele-ICU provides acute care expertise remotely to help local ICUs treat critically ill patients. Our study validates that it prevents transfers to other facilities without increasing the risk of mortality," explained lead investigator, Spyridon Fortis, MD, Pulmonary, Critical Care and Occupation Medicine, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA, USA. Tele-intensivists collaborate with local staff to co-manage patient care at the bedside, using cameras and sharing vital signs and equipment, and in many cases, preventing the need to triage patients to centers with more enhanced capabilities. "The on-site treatment helps to lower the cost of care and improves patient, family, and staff satisfaction."

The study tracked 553,523 patients admitted to VA hospital ICUs (97,256 with access to Tele-ICU services, and 456,267 without). Data were retrieved for all patients admitted to 306 VA ICUs in 117 acute care facilities from October 2009 through September 2015, excluding those for whom vital data were missing. During this period, the VA implemented Tele-ICU at 52 ICUs in 23 facilities in nine states.

Overall, interhospital transfers decreased by 1.47 percent (from 3.46 percent to 1.99 percent) in the facilities with available Tele-ICU and 0.34 percent (from 2.03 percent to 1.68 percent) in facilities without the services, between pre- and post-implementation periods. After adjusting for demographics, illness severity, admission diagnosis, and facility, Tele-ICU was associated with overall reduced transfers; the reduction occurred in patients with moderate, moderate-to-high, and high illness severity and in nonsurgical patients. The findings were not affected by the day of admission or ICU patient volume levels. The decrease in transfers was seen in all patient groups except those presenting with mild illness severity. Tele-ICU did not change overall adjusted or unadjusted 30-day mortality.

More than a million neonatal deaths worldwide each year are estimated to be due to sepsis1. In the UK there are approximately 90,000 admissions to neonatal intensive care units per year. Nearly all these patients receive antibiotic therapy during their hospital stay, but babies with a specific genetic change can suffer irreversible hearing loss as a result. Now, in a collaboration between Manchester-based geneticists and a molecular diagnostics company, a rapid test for distinguishing those infants who will have this adverse reaction to the antibiotic gentamicin has been developed.

Dr John McDermott, from the Manchester Centre for Genomic Medicine, Manchester, UK, will tell the annual conference of the European Society of Human Genetics tomorrow (Saturday) that their simple test for bedside use can produce a result in around 40 minutes. « In the absence of a point of care testing approach we are reliant on core hospital testing facilities, which can take up to three days to provide a result. This is inadequate, considering that life-saving antibiotics need to be given in the first hour of admission, » he says. « Our test, developed together with Genedrive plc, uses a cheek swab and can allow tailored prescribing. We are thus able to avoid the antibiotic-related deafness that can occur in infants with this genetic mutation. »

Although there are several antibiotics that can be used to treat sepsis, the UK National Institute for Health and Care Excellence (NICE) recommends a combination of penicillin and gentamicin because the combination has a narrow spectrum of activity and hence a lower risk that the patient might develop antibiotic resistance. But, in new-borns, a particular mutation in mitochondrial DNA2 that is present in one in every 500 of the population, means that a single dose of gentamicin can cause profound and irreversible hearing loss.

"The development of our test has provided us with an exciting opportunity to explore how genetic information can be used in acutely unwell patients, » says Dr McDermott. « As genomic data become ever more prevalent in the population, studies like this will be essential in establishing how patients, clinicians and healthcare systems respond to genetic information being used to personalise treatment as part of everyday healthcare. »

The collaboration plan to undertake a multi-centre feasibility study introducing the test into several neonatal centres around the UK3. All children admitted to these centres will be tested for the genetic change and antibiotics tailored accordingly. « This represents the first example of a point of care genetic test being used in the acute setting, » Dr McDermott will say. « Acute neonatal disease is hugely distressing for all concerned, and we are delighted to be able to contribute to the safety and efficacy of its treatment. »

Chair of the ESHG conference, Professor Joris Veltman, Director of the Institute of Genetic Medicine at Newcastle University in Newcastle, United Kingdom, said: "This study shows us the importance of rapid genetic tests to prevent severe side effects from the use of antibiotics in a small group of sepsis patients who carry a mutation in their DNA. Identifying those patients within an hour can now allow doctors to prescribe alternative drugs in this group of patients, whereas the majority of patients can safely use the standard antibiotics."

CHAPEL HILL, N.C. - A study published today in the American Journal of Preventive Medicine shows the effectiveness of the Tdap (tetanus, diphtheria, acellular pertussis) vaccine for infants whose mothers receive the vaccine during pregnancy. The "Effectiveness of Prenatal Tetanus, Diphtheria, Acellular Pertussis Vaccination in the Prevention of Infant Pertussis in the U.S." study led by Sylvia Becker-Dreps, MD, MPH, associate professor in the departments of family medicine in the UNC School of Medicine and epidemiology in the UNC Gillings School of Global Public Health, is the first to look at clinical outcomes of the vaccine in infants over the first 18 months of life.

Pertussis, also known as whooping cough, is a severe respiratory infection that is especially dangerous for infants and can result in hospitalization or death. It has been increasing in occurrence in the U.S. since 2000. The CDC has long-recommended that children under the age of seven receive doses of the DTaP (diphtheria, tetanus, acellular pertussis) vaccination through a series of shots. The current series of shots are given at the ages of two, four and six months, followed by two booster doses later in childhood. In 2013, the CDC started recommending that all women receive the Tdap vaccine during every pregnancy in order to pass immunity on to the fetus. That recommendation was based on immunological data showing that maternal anti-pertussis antibodies are transferred to the fetus through the placenta, but not on true clinical outcomes, such as pertussis cases.

Becker-Dreps' study reviewed more than 675,000 pregnancies in the U.S. from 2010-2014 and analyzed insurance claims data to identify the receipt of Tdap during pregnancy. Researchers also looked at hospitalizations and outpatient visits for pertussis in the infants through 18 months of age. The clinical outcomes show that the immunity passed from mother to fetus during pregnancy protected the infant during the first six months of life, before the infant completes the full course of the pertussis vaccine themselves.

The study found that in the first six months of life for infants whose mothers were immunized during pregnancy, there was a 75 percent reduction of pertussis hospitalizations and a 46 percent reduction of any pertussis cases. Further, the study did not find that infants whose mothers received the vaccine had a less effective response to their own pertussis vaccine series, as has been suggested by some immunological studies.

"This just adds more fuel to the fire for encouraging women to get Tdap during pregnancy," said Becker-Dreps. "A lot of women are concerned about vaccines in general, but you really might be harming your baby by not getting this vaccine."

Becker-Dreps says they also looked at the timing of immunization during pregnancy, and whether or not that played a role in the effectiveness of the Tdap vaccine in infants.

"Our results showed that getting it during the third trimester, but at least two weeks before delivery, is best to optimize the benefits of the vaccine," Becker-Dreps said.

The study found that infants whose mothers received the immunization during the third trimester had a reduction in pertussis, while no benefits of the vaccine were observed when mothers received it earlier in the pregnancy. These findings further reinforce the CDC's currently recommended "optimal timing" of the Tdap vaccine between 27 and 36 weeks of pregnancy.

This is the third and final study in a series by UNC investigators looking at how many women get the Tdap vaccine during pregnancy, its safety and its effectiveness. Becker-Dreps also says that because the Advisory Committee on Immunization Practices (ACIP) recommends the Tdap vaccine during pregnancy, it is covered by most insurance policies with a copay.

The international Consortium for Refractive Error and Myopia (CREAM) recently published the worldwide largest genetic study of myopia in Nature Genetics. Researchers from the Gutenberg Health Study at the Medical Center of Johannes Gutenberg University Mainz participated in this study, which identified 161 genetic factors for myopia. This quadruples the number of known genetic risk factors playing a role in all retinal cell types. Most of them are involved in processing light. This supports the assumption that insufficient sunlight is an important trigger in the development of myopia.

Myopia, also known as short-sightedness or near-sightedness, is the most common disorder affecting the eyesight and it is on the increase. This is particularly worrying for severely short-sighted people as it increases their risk of developing eyesight complications. The causes are both genetic and environmental.

The international research group CREAM, which includes scientists from the Gutenberg Health Study of the Mainz University Medical Center, has now made important progress towards understanding the mechanisms behind the development of the condition. They evaluated the data of more than 250,000 people from Europe, Asia, and North America in cooperation with gene test provider 23andme.

The study established 161 genetic factors for spherical equivalent and myopia, most of which were previously unknown. It became clear that all retinal cell types play a role in the development of myopia alongside their primary role as light processors. This supports the theory that the internal layer of the eye communicates with the external layer to increase the length of the eye, which is a decisive factor in the development of myopia.

"We have known for some time that education-related behavior is a major environmental factor in developing short-sightedness", said co-author Professor Norbert Pfeiffer, Head of the Department of Ophthalmology at the Mainz University Medical Center. It was unclear which role close-up work during reading plays in the process, or if lack of sunlight is responsible. The new results provide important insights into the underlying biological mechanisms. They also support the most important advice Pfeiffer can give to concerned parents as a preventive measure against myopia: "Send your kids to play outside for two hours every day. And it's not just their eyes that will benefit."

The spread of short-sightedness is a worldwide phenomenon, particularly in South East Asia, where the incidence of myopia in school children has increased notably over the last decades. This is likely due to rising levels of education. People who read a great deal also perform a lot of close-up work, usually in poor levels of daylight. The eye adjusts to these visual habits and the eyeball becomes more elongated than normal as a result. But if it becomes too elongated, the cornea and lens focus the image just in front of the retina instead of on it, making distant objects appear blurry.

CHAPEL HILL - Parents ranked cancer prevention as the most compelling reason health care providers can give for recommending the human papillomavirus (HPV) vaccine, according to a survey led by University of North Carolina Lineberger Comprehensive Cancer Center researchers.

The findings, published in the journal Cancer Epidemiology, Biomarkers and Prevention, offer guidance as to what doctors and other health care providers should be emphasizing to parents when discussing vaccination for their children against HPV, a sexually transmitted virus that can cause oral, head and neck, genital and cervical cancers.

"Parents confirmed the advice from the CDC and other professional organizations, which is cancer prevention is the most important reason for HPV vaccination," said UNC Lineberger's Melissa B. Gilkey, PhD, assistant professor in the UNC Gillings School of Global Public Health. "Providers report giving a wide variety of reasons to vaccinate, but this study suggests what parents really want to hear about is cancer prevention. This was true even for parents who had relatively low confidence in adolescent vaccination."

The U.S. Centers for Disease Control and Prevention estimates 41,000 people are diagnosed with HPV-associated cancer in the United States each year. HPV vaccination could prevent most HPV-linked cancers, which include cancers of the throat, the cervix, and genitals. However, just 43 percent of adolescents were up-to-date on the HPV vaccine in the United States in 2016, according to the CDC. Studies have shown that a provider's recommendation is highly influential.

"Research has shown that a provider's recommendation is the single most important factor in whether parents decide to get their kids vaccinated," Gilkey said. "Public health organizations, including the Centers for Disease Control and Prevention, are leading large-scale campaigns to improve provider communication about HPV vaccination. We're working to understand what the most powerful messages are to inform those ongoing interventions."

The researchers drew their findings from a survey of 1,177 adults in the United States with children between the ages 11 and 17. The parents were asked to rank, from best to worst, a list of reasons a doctor commonly use to encourage parents to consider vaccinating their child against HPV.

Parents said cancer prevention was the most persuasive reason for HPV vaccination. The prevention of a common infection, the vaccine's lasting benefits and its safety also scored high. Reasons that received low rankings included "it is a scientific breakthrough," and "I got it for my own child."

When the researchers compared the responses from parents who had low confidence in adolescent vaccines at the outset, they found these parents ranked messages very similarly to parents who had high confidence. "This should give providers confidence that leading with the idea of cancer prevention doesn't have to be targeted toward a particular type of parent," Gilkey said. "Cancer prevention is likely to be your best bet no matter who you're talking to."

The results of a population study presented today at the Annual European Congress of Rheumatology (EULAR 2018) demonstrate a significantly increased rate of self-harm attempts in inflammatory arthritis (IA), particularly following a diagnosis of Ankylosing Spondylitis (AS).1

Results of the study showed that individuals with AS were almost twice as likely to self-harm as their comparators (adjusted hazard ratio of 1.59 (95% CI 1.16 to 2.21). Deliberate self-harm was also increased in individuals with rheumatoid arthritis (RA) but only before adjustment for baseline characteristics. The most frequent method of self-harm was poisoning (64% of attempts in AS, 81% in RA) or self-mutilation (36% in AS, 18% in RA).

"Our study is one of the first to document the risk of serious mental health outcomes following a RA or AS diagnosis and highlights the need for routine evaluation of self-harm behaviour as part of the management of patients," said Dr. Nigil Haroon, senior study author, University of Toronto.

Physical aspects of AS include pain, joint stiffness, and a gradual loss of spinal mobility, however, there is also considerable impact on mental health.2 Although a higher prevalence of psychiatric comorbidities, including depressive disorder, has been proven in patients with AS,3 until now there is limited data on the risk of serious mental health outcomes following diagnosis.

"This study is important because understanding the mechanisms that contribute to deliberate self-harm attempts will help tailor future preventative strategies to reduce morbidity associated with this serious mental health outcome," said Professor Thomas Dörner, Chairperson of the Abstract Selection Committee, EULAR.

The study evaluated population-based cohorts of RA (N=53,240) and AS (N=13,964), each matched 1:4 by age, sex, and calendar year (at diagnosis) with non-IA comparator cohorts in Ontario, Canada. Individuals with a history of mental illness or prior episode of deliberate self-harm were excluded. The outcome was a first emergency room presentation for deliberate self-harm, subsequent to RA or AS diagnosis, between April 1, 2002 and March 31, 2016. Hazard ratios were adjusted for demographic, clinical and health service utilisation variables.

This study suggests there is a link between inflammatory arthritis and the development of serious mental health consequences. These findings highlight the need for routine evaluation of self-harm behaviour as part of the management of chronic inflammatory arthritis. Understanding the mechanisms contributing to deliberate self-harm attempts will help inform risk-reduction strategies among individuals living with inflammatory arthritis.

Abstract number: OP0296

Minneapolis, June 14, 2018 - A thorough, terminal cleaning of hospital rooms between patients is essential for eliminating environmental contamination, and a checklist is a standard tool to guide the cleaning staff. But new research presented at the 45th Annual Conference of the Association for Professionals in Infection Control and Epidemiology (APIC) offers an important reminder that the checklist is only as good as the list itself.

The environmental services team at Summit Health, a hospital in rural Pennsylvania, used a 175-item checklist in 2017 to guide terminal room cleaning. The list included the dry-erase white boards used for communications. However, it did not include the markers or the erasers.

In an inspection of 55 cleaned and prepared patient rooms, 39 markers and 52 erasers were identified and tested for the presence of Adenosine triphosphate (ATP), an indicator for the presence of biological residues. Not a single marker and only two erasers passed the test.

This was in stark contrast to the more than 95 percent of checklist surfaces that passed.

"Although they are just small writing instruments, both the markers and erasers tested at 40 times the threshold," said Ericka Kalp, PhD, MPH, CIC, FAPIC, lead study author and director of epidemiology and infection prevention at Summit Health. "Because these are a main communication tool for nurses, cleaning them properly is of great significance to improving infection prevention."

The ATP testing was performed with environmental services staff in attendance. If results were over the threshold, the infection preventionist conducting the test then demonstrated how to properly clean and retest.

"Environmental cleaning is essential to preventing the spread of infection," said 2018 APIC President Janet Haas, PhD, RN, CIC, FSHEA, FAPIC. "This study emphasizes the importance of not only using a checklist as a reminder of what needs to be cleaned, but also making sure the list includes all frequently touched items."

Summit Health has utilized the 175-item checklist since 2012. Both the markers and the erasers have since been added to the checklist.

A study has estimated that around three million Britons - or 7.6 % of the country - believe they have experienced a harmful or potentially harmful but preventable problem in primary healthcare.

The research by University of Manchester epidemiologists and patient collaborators, also estimates that 1.5 million people believe their health has been made worse by a problem which could have been prevented.

The findings revealed a large divide between the opinions of patients and clinicians: of the 7.6% of preventable-problems reported by patients, clinicians said only a small percentage might be potentially harmful.

The figures are based on a representative survey of 4000 people which looked at the experience of respondents over the previous 12 months. The survey was carried out in England, Scotland and Wales, and was designed and analysed by the Manchester team, which includes patients.

It is published in BMJ Open and funded by the NIHR Greater Manchester Patient Safety Translational Research Centre..

Problems reported by patients which could have been avoided included:

A patient prescribed medication without necessary blood tests resulting in hospital admission and cardiac arrest

Dentists extracting the wrong teeth.

A GP failing to spot the dangers of chronic nose bleeding over several months, which turned out to be cancer

A GP failing to identify that a new mum had a retained placenta - a potentially life threatening condition.

Around 20% of the problems reported by patients involved prescribing of medicines and 12% involved late, and missed or wrong, diagnoses.

A further 15% were communications problems - such as apparent lack of interest, not listening to patients and not passing on important information.

Around 70% of the problems reported had occurred in general practice, and another 9% in dental surgeries.

Problems were also reported by the respondents in A&E, ambulance service, walk in clinics, pharmacy, community or district nursing, opticians and community mental health services.

Dr Jill Stocks from The University of Manchester, who led the study, said: "Our survey suggests there are probably a large number of patients in Great Britain who believe they have experienced a potentially-harmful preventable problem in primary care.

"Importantly, only around half of the patients discussed their concern with somebody working in primary care yet those that did retained a higher level of confidence and trust in their GP."

Patient research partner and study team member Ailsa Donnelly said: "Our respondents told us they want more patient centred care, more resources and better communication.

However, we need to develop ways for patients to raise problems in care easily and discuss them with clinicians, not only to make primary care safe but, crucially, to ensure it is felt to be safe by patients. Trust is an essential part of safe care.

Professor of General Practice Aneez Esmail from The University of Manchester, was also part of the research team.

He said: "This study shows that the views of patients are important when something goes wrong, irrespective of whether significant harm is caused.

"We also show that working with patients when something has gone wrong can help re-build trust with the GPs and other clinicians."

Bottom Line: With each decade of life, the likelihood of progression of melanoma after treatment with anti-PD1 immunotherapy decreased by 13 percent.

Journal in Which the Study was Published: Clinical Cancer Research, a journal of the American Association for Cancer Research.

Author: Ashani T. Weeraratna, PhD, the Ira Brind professor and co-program leader of the Immunology, Microenvironment and Metastasis Program at The Wistar Institute; and a member of Wistar's Melanoma Research Center in Philadelphia

Background: "We wanted to study how the aging microenvironment affects response to immunotherapy, and much to our surprise, the effect was exactly the opposite of what we learned with targeted therapy," said Weeraratna. Prior research by Weeraratna and colleagues had shown that the tumor microenvironment in older patients promoted melanoma metastasis and resistance to targeted therapy with a BRAF inhibitor.

How the Study Was Conducted and Results: In this multinational study, the researchers analyzed data from 538 patients with melanoma treated with the anti-PD1 therapy pembrolizumab (Keytruda) at eight different institutes worldwide. Of the patients, 238 were younger than 62 years. They found that 50 percent of patients younger than 62 years, compared with only 37 percent of patients 62 years or older, had poor response to the treatment. This finding was independent of gender or prior treatment with MAPK inhibitor (MAPKi) therapies.

"Interestingly, younger patients who had prior MAPKi therapy had a much lower rate of complete response to anti-PD1 than older patients who had prior MAPKi therapy (4 percent versus 15 percent)," Weeraratna said.

Weeraratna and colleagues conducted further experiments using mice bearing melanoma to understand the relationship between the aging microenvironment and response to anti-PD1 immunotherapy. The results from the studies with mice were in agreement with those from human patients: Young mice were more resistant to anti-PD1 therapies than aged mice. The results were also independent of tumor mutational burden, because both young and aged mice were implanted with genetically identical tumors but had different outcomes.

Further research revealed differences in the immune microenvironment of the two groups of mice. A subpopulation of T cells that are known to be immunosupressive, FOXP3-positive Tregs, were fewer in older mice compared with younger mice.

The team analyzed primary and metastatic melanoma samples from another cohort of 268 patients for the presence of the protein FOXP3 in T cells and found that the FOXP3-positivity of intratumoral T cells decreased in patients over 50 years of age. The researchers also observed age-related differences in the T-cell subpopulations within the tumors of these patients.

Her team found that in young mice, combining anti-PD1 with an anti-CD25 antibody therapy, which depletes Tregs, yielded response rates comparable to those seen in older mice.

Author's Comments: "Our current study showed that for each decade of life, patients with melanoma had a 13 percent lower chance of having a negative outcome following anti-PD1 immunotherapy," Weeraratna noted.

"Our results suggest that preconditioning the tumor microenvironment in younger patients by depleting Tregs could make them respond to anti-PD1 immunotherapies better," she said. "Our studies suggest that in designing therapies for melanoma, age should be considered as a factor in both preclinical and clinical models."

"Age has a huge impact on patients' response to therapy and tumor progression," Weeraratna noted. "Researchers conducting preclinical studies should ensure that the age of the mice reflects the age of the patients the treatments are intended for, as these studies form the basis for drug development and human clinical trials."

Study Limitations: As limitations to the study, the researchers were unable to perform multivariate analyses and could not control for tumor mutational burden in their studies with melanoma patients, Weeraratna said.

---Treatment changes including the advent of targeted and immune therapies have dramatically improved survival for blood cancers, but new report calls for improved evaluation of poorly understood side effects that may develop over time.---

Survival rates for blood cancers - including lymphoma, myeloma and some types of leukaemia - have dramatically increased over the past decade, due in great part to novel treatment approaches including molecularly-targeted therapies and immunotherapies.

In contrast to traditional forms of treatment which were largely episodic and finite (ie, a set number of cycles of intravenous chemotherapy), therapy for some haematological cancers may now be given continuously over years, or in some cases indefinitely.

However, a new Commission by The Lancet Haematology shows how current methods of reporting adverse events, focused on assessing a drug or regimen's safety, often fail to also appropriately identify important delayed, chronic or cumulative effects that can affect patients substantially.

In particular, the toxicity over time and tolerability to the patient of new chronic or continuously administered therapies are not well defined, and are poorly captured by existing reporting mechanisms.

The Commission brings together 40 leading clinicians, clinical investigators, regulators, biostatisticians and patient advocates to analyse the evidence and propose recommendations to policy makers, researchers, industry and regulators, and will be launched at the European Haematological Association meeting in Stockholm.

"The success in outcomes and survival in many haematological malignancies is historically unparalleled and fuelled by scientific discovery and implementation. Patients are now living with the challenge of managing not just their haematological malignancy, but also managing chronic therapy for their illness, with new types of acute, chronic, cumulative and late toxicities. Measures to address the broad facets of toxicity assessment must be prioritised and further developed to ultimately enhance accurate, comprehensive, patient-centred toxicity reporting that will meaningfully inform the care of patients with blood cancers," says Commission Chair Dr. Gita Thanarajasingam, Mayo Clinic, Rochester (MN), USA. [1]

The authors propose new approaches to evaluating and reporting adverse events to complement the current methods. These include expanding reporting beyond high grade, acute toxic side-effects, and capturing less severe but chronic side effects, and cumulative and late effects in a more standardized manner. While short term side effects with some regimens might include nausea and vomiting occurring over a few days in a cycle, long term effects might include neuropathy which worsens over time with ongoing drug exposure and can persist even after therapy is complete, for example.

Additionally, the authors emphasize that changes to clinical trial design to accommodate delayed adverse events, and incorporating patient reported outcomes into trials to assess and improve tolerability, adherence and quality of life are essential.

The Commission also examines streamlined approaches to identify unexpected side effects from stem cell transplantation and improved evaluation of late and long term side effects in survivors. As newer treatments in haematological malignancies are offered more widely, capturing data from population studies will be essential to understand side effects outside of clinical trial settings. Additionally, post-marketing surveillance by regulatory agencies should adapt to include relevant data on long-term adverse events in a real world patient population.

DALLAS, June 11, 2018 -- Erectile dysfunction (ED) indicates greater cardiovascular risk, regardless of other risk factors, such as cholesterol, smoking and high blood pressure, according new research published in the American Heart Association's journal Circulation.

In the study, which followed more than 1,900 men, ages 60 to 78, over 4 years, those who reported ED were twice as likely to experience heart attacks, cardiac arrests, sudden cardiac death and fatal or non-fatal strokes.

The findings, the research team says, suggest that ED is an important telltale sign that can help physicians gauge cardiovascular risk among middle-aged men--an indicator the United Kingdom formally incorporated last year in the risk-scoring algorithm used by clinicians to assess a patient's 10-year risk for suffering an adverse cardiovascular event.1

Erectile dysfunction (ED) -- defined as the inability to achieve or maintain an erection for satisfactory sexual intercourse -- affects nearly 20 percent of men over age 20, according to research. Cardiovascular disease and ED share common risk factors, including obesity, hypertension, smoking, diabetes and metabolic syndrome -- a condition marked by a cluster of features such as elevated blood sugar, hypertension and excess abdominal fat.

"Our results reveal that erectile dysfunction is, in and of itself, a potent predictor of cardiovascular risk," says study senior investigator Michael Blaha, M.D., M.P.H., associate professor of medicine at the Johns Hopkins School of Medicine in Baltimore, Maryland. "Our findings suggest that clinicians should perform further targeted screening in men with erectile dysfunction, regardless of other cardiac risk factors and should consider managing any other risk factors -- such as high blood pressure or cholesterol -- that much more aggressively."

Limited evidence of a link between ED and cardiovascular disease has emerged over the last several years, but results of this latest study provide what researchers say is the strongest indication to date that sexual dysfunction indicates heightened cardiovascular risk.

During the four-year follow-up, there were a total of 115 fatal and non-fatal heart attacks, fatal and non-fatal strokes, cardiac arrests and sudden cardiac deaths. A greater proportion of men who reported ED (6.3 percent) suffered heart attacks, cardiac arrests or strokes than men who didn't report ED (2.6 percent). When the investigators adjusted their analysis to eliminate the potential influence of other risk factors, that risk was somewhat lessened but still markedly higher: Men with ED were nearly twice as likely to suffer cardiovascular events than men without ED.

Participants in the research are part of the ongoing Multi-Ethnic Study of Atherosclerosis, which is following more than 6,000 people of various ethnic and racial backgrounds at several cities across the United States.

Men seeking treatment and evaluation for ED should be a signal to conduct a comprehensive cardiovascular evaluation, said Blaha. Additionally, the researchers say, men should be aware that ED places them at elevated risk for cardiovascular disease.

"The onset of ED should prompt men to seek comprehensive cardiovascular risk evaluation from a preventive cardiologist," Blaha noted. "It is incredible how many men avoid the doctor and ignore early signs of cardiovascular disease, but present for the first time with a chief complaint of ED. This is a wonderful opportunity to identify otherwise undetected high-risk cases."

Childhood deaths from two leading bacterial causes of pneumonia and meningitis, pneumococcus and Hib, declined sharply during the period 2000 to 2015, especially as vaccines against these pathogens were introduced in high-burden countries, according to new estimates from a team led by scientists at Johns Hopkins Bloomberg School of Public Health.

The findings, published in The Lancet Global Health on June 11, highlight the success of the global fight against these illnesses, and also provide a clear picture of the remaining disease burden, now largely concentrated in South Asia and Africa.

"Further progress against these diseases will depend on efforts in a few large countries," says study lead author Brian Wahl, PhD, an assistant scientist at the International Vaccine Access Center in the Bloomberg School's Department of International Health. "These bacteria still cause far too many child deaths."

Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (pneumococcus) are bacteria that can cause meningitis, pneumonia, sepsis and other serious complications, especially in children. They have been major causes of child mortality in developing countries. Estimates for the year 2000 showed about 2.1 million severe infections and 299,000 child deaths from Hib, and 6.6 million severe infections and 600,000 child deaths from pneumococcus--not including cases of opportunistic infection in children with HIV.

Conjugate vaccines against Hib have been used in the U.S., Europe and some other countries for almost three decades. They virtually eliminated Hib as a significant public health threat in areas of high and sustained coverage. However, children in several developing countries with high disease burdens have only started to receive Hib vaccine in the past decade. A vaccine against pneumococcus, known as the pneumococcal conjugate vaccine (PCV), began to be used in many low-income countries, where much of the disease burden is found, in 2009.

Wahl and colleagues developed updated estimates--on a country-by-country basis, for each year from 2000 to 2015--of the numbers of Hib and pneumococcal disease cases and deaths in children. They used country-specific figures of children who died of pneumonia and meningitis, along with field-based evidence on the fraction of those deaths caused by pneumococcus and Hib, and WHO/UNICEF estimates of vaccine coverage to estimate the burden of pneumococcal and Hib deaths and cases.

Their primary findings were that both Hib and pneumococcus caused far fewer cases of severe disease and death in children ages one to 59 months in 2015 compared to 2000. For Hib in 2015, there were approximately 29,500 child deaths, and for pneumococcus an estimated 294,000 child deaths. These figures suggest declines of 90 percent and 51 percent, respectively, from the estimated deaths in the year 2000.

The researchers estimated that Hib and pneumococcal deaths among children with HIV/AIDS also declined sharply--75 percent--from about 95,000 in 2000 to about 23,000 in 2015.

The sharp declines in child mortality from Hib and pneumococcus were due not just to the introduction of vaccines but also to general factors that have reduced pneumonia and meningitis deaths from all causes, such as better hygiene and access to health care. "In 2015 compared to 2000 fewer children died from all causes, not just Hib and pneumococcus," Wahl notes.

However, there was evidence that vaccines were specifically responsible for a considerable reduction in mortality. "The estimated average annual decline in child deaths from pneumococcus jumped from 3 percent during 2000-2010 to 8 percent after 2010 when many high-burden countries began widespread immunizations with PCV," Wahl says.

The researchers estimated that during 2000-2015 PCV prevented a total of about 250,000 child deaths--mostly after 2010--while Hib vaccines prevented 1.2 million child deaths. These figures do not include the prevented cases of pneumococcal and Hib deaths among children who were HIV-infected.

The new estimates will guide ongoing efforts to reduce the burdens of Hib and pneumococcal diseases, which together still kill approximately 900 children per day around the world. The estimates suggest, for example, that about half of the pneumococcal child deaths in 2015 occurred in just four countries: India, Nigeria, Democratic Republic of the Congo and Pakistan. "The pneumoccocal disease burden is now limited to a small number of countries that have not introduced the vaccine or have not yet fully scaled the vaccines," Wahl says.

The introduction of Hib vaccine and PCV into high-burden, low-income countries since 2009 has occurred with the support of Gavi, the Vaccine Alliance, a public-private partnership of countries, WHO, UNICEF and other partners.

Missense mutations occur when there is a change in one gene's DNA base pair, and the change results in the substitution of one amino acid for another in the gene's protein. Mutations that disrupt the function of proteins are widely recognized as a risk source for development disorders such as intellectual disability, congenital heart defects and autism spectrum disorder (ASD).

A new study published in Nature Genetics established a computationally integrated approach to investigate the functional impact of missense mutations. The team, which includes Carnegie Mellon University's Kathyrn Roeder, tested the approach by analyzing genetic structures of individuals with ASD who also had mutations as well as their siblings who did not have the mutations. They found that the framework successfully identified and prioritized missense mutations that contribute to disease or disorder risk.

"Identifying genetic mutations that increase the likelihood of disease is a major challenge to progress for personalized medicine. Using a machine learning model that predicts which mutations are likely to perturb the human interactome network, we showed that these mutations are much more likely to occur in autistic children than their siblings," said Roeder, the UPMC Professor of Statistics and Life Sciences in the Dietrich College of Humanities and Social Sciences. "This result extends to several other mental disorders suggesting that our finding may have even broader applicability."