Body

New Rochelle, NY, April 18, 2019--Gene therapy offers the promise of a cure for beta-thalassemia and a new study has shown that it is associated with fewer complications and hospital admissions over 2 years than treatment by allogeneic hematopoietic stem cell transplantation (HSCT). The study, which analyzes and compares the effectiveness and cost of gene therapy versus (HSCT) in patients with major beta-thalassemia is published in Human Gene Therapy, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the Human Gene Therapy website through May 18, 2019.

Séverine Coquerelle, URC Eco-Assistance Publique Hôpitaux de Paris, Université Paris Diderot (Sorbonne Paris Cité), and CRESS, INSERM UMR (Paris), France led a team of French researchers in publishing the article entitled "Innovative Curative Treatment of Beta Thalassemia: Cost-Efficacy Analysis of Gene Therapy Versus Allogenic Hematopoietic Stem-Cell Transplantation." Patients treated with HSCT had 3 times more frequent infectious complications. Gene therapy was shown to be about 2.8 times more costly, with nearly half the cost of gene therapy accounted for by preparation of the delivery vector.

"There has been much discussion and controversy about the high cost of gene therapy, but what has been lacking is a direct comparison to alternative therapies, which them-selves are also often very costly and may produce suboptimal outcomes," says Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Med-ical School, Worcester, MA. "This study does a critical comparison of both cost and out-comes for patients with beta-thalassemia, whose primary alternative to gene therapy would be hematopoietic stem cell transplantation. These data may enable a more rational debate of the overall value of gene therapy for this relatively common genetic disease."

Reducing the sugar content of certain foods by 2020, in line with UK government policy targets, could cut child obesity and related illness, and save the NHS in England £286 million over 10 years, suggests a study published by The BMJ today.

But these benefits could be easily lost if the targets are not fully met, or if the programme leads to unintended changes in consumer or industry behaviour, warn the researchers.

Childhood obesity affects one in 10 children aged 4-5 years and one in 5 children aged 11-12 years, while the proportion of obese adults has risen from 15% in 1993 to 26% in 2016.

In 2016, the UK government set out plans to work with food manufacturers to reduce the sugar content of certain high-sugar products, such as cereals and confectionery, by 20% by 2020.

The strategy consists of three sugar reduction approaches: reformulating products to contain less sugar, reducing portion size, and shifting sales from high-sugar products to low-sugar alternatives.

But the potential health impacts of these measures have not been studied.

So a team of researchers, led by Ben Amies-Cull at Oxford University, set out to estimate the impact of this strategy on child and adult obesity, related diseases, and healthcare costs.

Data from the National Diet and Nutrition Survey (2012-13 and 2013-14) were used to simulate a scenario where the strategy had been successfully implemented in England. Changes to child and adult weight were then estimated, and their impact on disease burden and healthcare costs were modelled.

Several assumptions were made. For example, baseline diet would remain unchanged (apart from the portion size or sugar content of target food items), and there would be no unintended changes in eating patterns or products (e.g. individuals substituting foods due to differences in taste or manufacturers changing non-target nutrients like salt).

The results show that fully achieving the government's sugar reduction targets could reduce the number of obese 4-10 year olds by 5.5% of the obese population, 11-18 year olds by 2.2% and adults (19-80 year olds) by 5.5%.

Calorie intakes could be cut by 25 kcal/day for children and 19 kcal/day for adults.

In adults, this could lead to 155,000 fewer cases of type 2 diabetes, 3,500 cases of cardiovascular disease, 5,800 fewer cases of bowel (colorectal) cancer and a total NHS cost saving of £286m over 10 years.

However, they warn that the potential health benefits of the government's strategy could be lost if any of the three sugar reduction approaches fail to have the intended effect.

The limitations of this modelling study include the reliability of the survey data, which may have led to an under-estimate of the effect.

Nevertheless, the researchers say their findings remained largely unchanged after further analyses and conclude that the sugar reduction strategy "could be an effective means of reducing obesity-related illness and costs, although targets must be met."

In a linked editorial, Dr Annalijn Conklin from the University of British Columbia says the research makes "an important contribution to the current knowledge of the population benefits of public health collaborations."

Future studies could assess whether the government's programme is also an extension of 'business as usual', she writes, and thus whether the potential beneficial effects modelled by Amies-Cull and colleagues would be attributable to the programme or to a pre-programme trajectory.

Finally, although the programme may contribute, "a complete solution to the challenge of improving diets and reducing the burden of nutrition related chronic diseases requires a multi-sectoral package of policies which also includes the UK sugar tax, other fiscal tools, and hard regulation for improving public health," she concludes.

In the largest study of its kind, researchers from the Musculoskeletal Research Unit at the University of Bristol have identified the most important risk factors for developing severe infection after knee replacement. Patients who are under 60 years of age, males, those with chronic pulmonary disease, diabetes, liver disease, and a higher body mass index are at increased risk of having the joint replacement redone (known as revision) due to infection.

The research, which follows their work on hip replacement published last year [20 November 2018], also showed that some patients are at higher risk of early infection whilst others are more prone to late infection after knee replacement. The study analysed data from over 670,000 primary hip replacement patients, with 3,659 requiring revision for infection.

The study, published in The Lancet Infectious Diseases today [Wednesday 17 April], conducted as part of the INFORM research programme funded by the National Institute for Health Research (NIHR) and the NIHR Bristol Biomedical Research Centre (BRC), considered the risk of infection following first-time (primary) knee replacement. This study used data from the National Joint Registry (NJR) for England, Wales, Northern Ireland and the Isle of Man linked to the Hospital Episode Statistics database.

Knee replacement, used mainly to treat pain and disability caused by osteoarthritis, is a common procedure with around 110,000 operations performed annually in the UK. A rare but serious complication affecting about one per cent of patients is deep infection. This causes considerable distress and often requires long and protracted treatments including revision surgery.

This study showed the reason for surgery, the type of procedure performed and the type of prosthesis and its fixation, influenced the risk of needing revision surgery for infection. Surgery performed following trauma, inflammatory arthropathy or a history of previous infection in the operated joint were more likely to be revised for an infection. Cemented total knee replacements were more likely to be revised for infection compared to patients with an uncemented implant. Finally, the risk of revision was increased for patients with a posterior stabilised fixed-bearing implant or a constrained condylar (CC) implant compared to those with an unconstrained (or cruciate retaining) fixed-bearing implant. The experience of the surgeon and the size of the orthopaedic centre had no or only small effects on the risk of revision for infection.

Uniquely, the research identified that these important factors have a different effect depending on the post-operative period, with liver diseases or inflammatory arthropathy increasing the risk of revision for infection in the long-term but patients receiving a patellofemoral, unicondylar or uncemented total knee replacement had a lower risk of late revision for infection. This is an important factor to consider when conducting further research in this area as just considering overall risk or short-term risk may mean important effects are missed entirely.

Michael Whitehouse, Reader and Consultant in Trauma and Orthopaedic Surgery in the Musculoskeletal Research Unit of the Bristol Medical School: Translational Health Sciences (THS), said: "This work has identified key patient and surgical characteristics which influence the risk of revision for infection following knee replacement, and specifically the risk of further surgery for infection two years or more after the initial operation. This information provides me with the strong evidence I need to discuss the risk of infection with my patients undergoing knee replacement and helps us identify strategies to minimise that risk for them."

Dr Erik Lenguerrand, Research Fellow in the Musculoskeletal Research Unit, added: "These findings are consistent with the results of our infection after hip replacement study and could be applied to a wide range of patients undergoing different implant surgery. Most of the risk factors identified are generally associated with a complex initial knee replacement. This should be considered by surgeons when planning their surgery to minimise the risk for their patients. We now have strong evidence to develop new patient resources with better information to help them discuss with their surgeon and make decisions about their treatment."

The researchers found the risk of revision for infection following primary knee replacement is affected by many different factors but is mainly driven by patient and surgical factors. The possible issues identified in this study should be considered by clinicians when preparing patients for knee replacement surgery.

Further research should be carried out to find out if changes to the management of these conditions alters the risk of infection. It is equally important for clinicians to consider the issues that can't be changed and the factors that show time specific effects on the risk of prosthetic joint infection, to support patients appropriately in their decision making pre-operatively and after they have undergone knee replacement.

The research team will analyse further data from the NJR to look at the treatment of infection when it does occur to see what treatment has the best outcomes for patients.

CLEVELAND, Ohio (April 17, 2019)--Vaginal dryness and painful intercourse are some of the more common adverse events of post-breast cancer treatment therapies and often lead to sexual dissatisfaction and an overall lower quality of life (QOL). However, a new study finds that partnered women may fare better than those without a partner. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).

Breast cancer is the leading cancer diagnosis in women, with more than 266,000 new cases estimated in 2018. More than 70% of these cases occur in women aged older than 50 years. Adjuvant endocrine therapy (AET), such as tamoxifen, is often recommended for postmenopausal women for as long as 10 years after completion of breast cancer treatment as a means to limit the risk of cancer recurrence. Unfortunately, AET has many adverse effects, including sexual problems in the form of vaginal dryness, painful intercourse, and low sexual desire.

Previous studies have associated sexual problems with poor QOL, whereas others have shown that partnered survivors of breast cancer have better QOL than unpartnered survivors. However, this new study is the first known to examine how partner status influences the relationships between sexual problems and self-efficacy for managing sexual problems and QOL domains for postmenopausal survivors of breast cancer taking AET. Its findings suggest that unpartnered postmenopausal women with greater sexual problems or lower self-efficacy may be at a greater risk to experience decreased QOL than partnered women.

Study results appear in the article, "Partner status moderates the relationship between sexual problems and self-efficacy for managing sexual problems and psychosocial quality-of-life for postmenopausal breast cancer survivors taking adjuvant endocrine therapy."

"Survivors of breast cancer, particularly those on aromatase inhibitors, often have unaddressed sexual concerns, and healthcare providers aren't asking about them," says Dr. JoAnn Pinkerton, NAMS executive director. "In this study, postmenopausal, unpartnered women were the most vulnerable to having quality-of-life issues and also sense-of-self affected by unaddressed sexual problems."

The commonly used diabetes drug metformin could reverse the harmful thickening of heart muscle that leads to cardiovascular disease, according to a study at the University of Dundee.

Scientists led by Professor Chim Lang, Head of the Division of Molecular and Clinical Medicine at Dundee, discovered that metformin has the potential to be repurposed as a heart disease treatment in non-diabetic patients.

The MET-REMODEL Trial, published today in the prestigious European Heart Journal, showed that metformin, used to treat type 2 diabetes safely for the last six decades, reduced left ventricular hypertrophy (LVH) in patients with prediabetes and pre-existing heart disease. LVH is the thickening of the muscle wall in the heart's left pumping chamber and is a serious risk factor for future heart attack, stroke and heart failure.

LVH is often a silent symptom and most people do not know they have it prior to experiencing a heart attack or stroke. Large studies have previously shown that patients with LVH are at higher risk of adverse cardiovascular events and reducing LVH can substantially reduce mortality rates.

Professor Lang said, "Cardiovascular diseases are the leading cause of global mortality. We have previously shown that metformin can have beneficial effects in patients with cardiovascular diseases. But this is the first time anyone has looked specifically at the effects of metformin on LVH in nondiabetic patients with coronary artery disease in a clinical trial.

"The study involved treating prediabetic people with coronary artery disease with metformin or a placebo over a period of 12 months to see how the drug affected the heart muscle wall, using state-of-the-art MRI technology.

"The major causes of LVH are high blood pressure, obesity and insulin resistance, which are also thought to be key contributors of coronary artery disease. The dangerous thickening of the left ventricle was reduced by twice as much in those taking metformin compared to the placebo.

"We also found that metformin reduced blood pressure, oxidative stress and lost body weight - an average of 3.6 kg, compared to no changes in the placebo group. If the findings from this study are substantiated in a larger-scale study, metformin could offer hope for millions of patients across the globe."

The MET-REMODEL trial, funded by the British Heart Foundation (BHF), is the first clinical trial in the world to show that metformin could reverse harmful thickening heart muscle wall in a clinical trial. Repurposing cheap and readily available drugs, such as metformin, to treat other health conditions could potentially save the NHS billions of pounds every year.

Mohapradeep Mohan, lead author and principal investigator of the MET-REMODEL trial, said blood pressure medications were the standard treatment modalities for LVH but that this approach was not particularly effective as LVH can also be present in patients who have well-controlled blood pressure. This highlighted the need for new treatment strategies in these patients.

"In this context, we need non-blood pressure medication and we had good reason to suppose that metformin should help to reduce thickening of heart muscle wall," he said.

"The findings from our study reinforce the notion that metformin has the potential to improve cardiovascular health, offering the possibility of improving life expectancy of patients. From the standpoint of clinical practice, this drug is already approved and well tolerated with minimal side effects.

"If our findings are backed up by bigger studies, using metformin to target LVH presents a novel treatment option and unique opportunity for a quicker translation to the clinic. We are thankful to BHF for funding this study and extremely grateful to all the participants of this study."

Offering universal late pregnancy ultrasounds at 36 weeks would benefit mothers and babies and could be cost saving - according to research from the University of Cambridge and the University of East Anglia.

A new study shows that an additional routine ultrasound could eliminate undiagnosed breech presentation of babies, lower the rate of emergency caesarean sections, and improve the health of mothers and babies.

The study, led by the University of Cambridge in collaboration with UEA, is published today in the journal PLOS Medicine.

Undiagnosed breech presentation -- when a baby's buttocks or feet emerge first at birth -- increases risks for the mother and baby during childbirth. In current practice, midwives and doctors feel the pregnant mother's bump to assess the position of the baby. But the sensitivity of this approach varies by practitioner.

By routinely using ultrasound scanning, undiagnosed breech presentations in labour could be avoided, lowering the risk of complications, including death, for both mother and baby.

The research team performed screening ultrasounds at 36 weeks gestation in 3,879 women having first pregnancies in England.

A total of 179 women (4.6 per cent) were diagnosed with breech presentation by the scan. However, in over half of these cases (55 per cent) there was no prior suspicion that the baby was in the breech position.

Making the diagnosis at 36 weeks allowed women to opt for an attempt at turning the baby, called external cephalic version. For the women who declined this procedure, or where it was unsuccessful, a planned caesarean section was arranged.

None of the women opted to attempt a vaginal breech birth, which is known to be associated with an increased risk of complications, particularly in first pregnancies.

Dr Ed Wilson, from UEA's Health Economics Group in the Norwich Medical School, said: "We estimate that UK-wide routine scanning could prevent around 15,000 undiagnosed breech presentations, more than 4,000 emergency caesarean sections and between seven and eight baby deaths per year.

"We also looked into the costs of additional scans and found that if scans could be done for less than £12.90 each, it could be cost-saving to the NHS.

"If ultrasound screening could be provided at such a low cost, for example by making it a part of a standard midwife appointment, routinely offering ultrasound scans could well represent a good use of NHS resources."

Gordon Smith, Professor of Obstetrics and Gynaecology at the University of Cambridge and Chief Investigator of the study said: "We believe the study highlights an opportunity to identify women at increased risk of a complicated birth. It seems likely that screening for breech presentation near term could be introduced in a cost-effective manner and this should be considered by the NHS and other health systems."

Bioelectronic medicine scientists at The Feinstein Institute for Medical Research collaborated with counterparts from Academic Medical Center at University of Amsterdam in the Netherlands to carry out a series of pilot clinical studies to assess the effect of a novel bioelectronic stimulation. These studies show that non-invasive stimulation at the external ear improves disease symptoms in patients with rheumatoid arthritis (RA). These findings were first published today in Bioelectronic Medicine. An emerging field of science, bioelectronic medicine draws on neuroscience, focuses on molecular targets, and deploys bioengineering to tap into the nervous system to treat disease and injury without the use of pharmaceuticals.

RA is a chronic inflammatory disease, which is characterized by pain, swelling and stiffness of joints. It affects around 1.3 million people in the United States and costs tens of billions of dollars annually to treat. Commonly, signs and symptoms of this condition are treated using synthetic and biological antirheumatic drugs. However, these medications can result in side effects and may not be effective in all RA patients.

In this pilot study, Sangeeta S. Chavan, PhD, Feinstein Institute professor, along with Meghan E. Addorisio, BS, tested the efficacy of non-invasive vagus nerve stimulation to reduce inflammation and improve disease severity in RA patients. They found that bioelectronic medicine treatment was effective in inhibiting the production of cytokines, proteins that mediate inflammation and reduce the inflammatory responses in patients with rheumatoid arthritis.

"Our primary objective was to observe if a non-invasive treatment using an external device will be effective in improving disease severity of rheumatoid arthritis that continues to plague more than one million across the country each year," Dr. Chavan said. "We are pleased to observe that this novel bioelectronic treatment significantly reduces swelling and inflammation associated with RA."

"This clinical research suggests that non-invasive stimulation could suppress inflammation in rheumatoid arthritis patients," said Kevin J. Tracey, MD, president and CEO of the Feinstein Institute, and co-author on the paper.

Offering universal late pregnancy ultrasounds at 36 weeks' gestation eliminates undiagnosed breech presentation of babies, lowers the rate of emergency caesarean sections, and improves the health of mothers and babies. These are some of the conclusions of the Pregnancy Outcome Prediction (POP) study published this week in PLOS Medicine by David Wastlund of the University of Cambridge, UK, and colleagues.

Undiagnosed breech presentation--when a baby's buttocks or feet emerge first at birth--increases the risk of perinatal morbidity and mortality. In current practice, fetal presentation is assessed by palpation of the maternal abdomen, but the sensitivity of this approach varies by practitioner. By routinely using ultrasound screening, undiagnosed breech presentation in labour could be avoided, lowering the risk of morbidity and mortality for both mother and baby.

In the new study, researchers performed research screening ultrasounds at 36 weeks' gestation in 3879 women having first pregnancies in England. A total of 179 women (4.6%) were diagnosed with breech presentation by the research scan. However, in over half of these cases (55%) there was no prior suspicion that the baby was presenting in the breech position. Making the diagnosis at 36 weeks allowed women to opt for an attempt at turning the baby, called external cephalic version. For the women who declined this procedure, or where it was unsuccessful, a planned caesarean section was arranged. None of the women opted to attempt a vaginal breech birth, which is known to be associated with an increased risk of complications, particularly in first pregnancies.

Across the UK, the analysis estimated that routine scanning could prevent ~15,000 undiagnosed breech presentations, more than 4,000 emergency caesarean sections and 7 to 8 baby deaths per year. If a scan could be done for less than £12.90 then it could be cost-saving to the NHS. This could be possible once midwives are instructed how to perform the simple technique, using inexpensive portable equipment.

"Whether the health improvements are enough to justify the increased cost of ultrasound screening is still uncertain, mainly because the cost of ultrasound screening for presentation alone is unknown," the authors say. "If ultrasound screening could be provided at low cost, for example by making it a part of a standard midwife appointment, routinely offering ultrasound screening could well represent a good use of NHS resources."

Men and women are at differing risks of developing surgical site infections depending on the type of operation they undergo, according to new research being presented at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam, Netherlands (13-16 April).

The findings, generated from national surveillance data and involving over a million operations, indicate that women may be at greater risk than men for contracting surgical site infections following coronary bypass surgery, re-vascularization of arterial occlusion, and hernia repair; whilst men fared worse after orthopaedic and trauma procedures such as hip prosthesis following arthrosis, and minimally invasive arthroscopic knee procedures, as well as colon surgery, and thyroid surgery.

This differing risk suggests that there may be underlying biological responses in the way men and women respond to specific types of surgery that need to be better understood in order to prevent painful, costly, and potentially fatal surgical site infections, the researchers say.

Surgical site infections are among the most common healthcare-associated infections worldwide. Every year in the USA an estimated 300,000 patients develop surgical site infections, which are responsible for over 10,000 deaths, and cost the health care system billions of dollars. In NHS hospitals in England, surgery results in over 100,000 surgical site infections each year. [1] An estimated 40-60% of these infections are preventable.

Previous research has generally found men to be at higher risk of these postoperative complications. However, when focusing on specific procedures this does not always appear to be the case.

To explore this further, Dr Seven Aghdassi from Charité - Universitätsmedizin Berlin in Germany and colleagues analysed data from the German national hospital-acquired infection surveillance system to examine for which procedures gender may be a risk factor for surgical site infections, and what factors might explain these differences.

All surgical procedures conducted in German hospitals participating in the German national hospital-acquired infection surveillance system between 2008 and 2017 were included in the analyses. Procedures solely executed for one sex (e.g., mastectomy) and procedures with fewer than 20,000 operations were excluded.

In total, 16 procedure types with 1,266,782 individual operations and 18,824 surgical site infections were included in the analysis.

Researchers took into account and adjusted for other known risk factors for surgical site infections including the patient's age, physical state before surgery, wound contamination class, duration of surgery, and season.

Results showed that male patients undergoing orthopaedic and abdominal surgery were significantly more likely to develop a surgical site infection compared to female patients.

In contrast, surgical site infections-rates were substantially higher in women following heart and vascular surgery and general surgery (ie, hernia repair and thyroid surgery).

However, within these broad surgical groups individual procedures revealed mixed results (see figure 1). For instance, men were twice as likely to develop a surgical site infection following arthroscopic procedures than women, whereas the odds of acquiring a surgical site infection in patients undergoing hip replacement due to fracture did not differ significantly.

Conversely, women had a roughly doubled risk of contracting surgical site infections following coronary bypass surgery, and hernia repair than their male counterparts.

"A possible reason for the gender differences in surgical site infection rates for specific procedures may be due to differences in comorbidities, microbiome composition, and body constitution.", explains Dr Aghdassi.

Although the research does not establish a cause-and-effect relationship between gender and surgical site infections, the researchers say that the association between them is strong and should be investigated further.

"Our analysis considered a limited number of parameters, which were not sufficient to explain all the observed differences. By understanding the different factors that put men and women at risk for infections, we will hopefully be able to develop new prevention and surveillance strategies to improve infection rates and outcomes", says Dr Aghdassi.

The authors note several limitations including that the German national hospital-acquired infection surveillance system only collected a limited set of patient-based variables, therefore additional patient-based information, which could help interpret the results, is lacking. They also note that the data was collected from a large number of hospitals with heterogeneous data collection teams.

Venezuela's socioeconomic and political crisis has caused a huge upsurge in malaria cases, undoing years of progress in battling the disease and endangering neighbouring countries. The study, by Dr Adriana Tami (University Medical Center Groningen, Netherlands and University of Carabobo, Valencia, Venezuela) and Professor María Eugenia Grillet (Central University of Venezuela, Caracas, Venezuela) --together with an international network of scientists -- says that final estimates for 2018 could show more than 1 million cases of malaria in Venezuela alone. The data is being presented at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam, Netherlands (13-16 April).

Over the last two decades, Venezuela has transitioned into a deep socioeconomic and political crisis. Once recognised as a regional leader for public health and vector control policies and programming, Venezuela's healthcare has fallen into a state of collapse, creating a severe and ongoing humanitarian crisis. Economic and political mismanagement have precipitated hyperinflation rates above 1 million per cent, impoverishment of its people and long-term shortages of essential medicines and medical supplies.

In particular, public health provision has suffered with an exodus of trained medical professionals and long-term shortages in medicines and medical supplies. As a result, the country -- which was once a leader in public health policies and disease control in Latin America -- is now facing a re-emergence of many deadly diseases on a scale scientists describe as "an epidemic of unprecedented proportions". In this context, diseases that were previously well-controlled, such as malaria, are turning into epidemics of unprecedented magnitude.

In this new study, Venezuelan scientists and clinicians, and a global network of health scientists assessed the impact of Venezuela's healthcare crisis on malaria and other vector-borne diseases and the spillover to neighbouring countries. The researchers draw on new Venezuelan public health records, the health records of bordering states (Brazil, Colombia), The data show that between 2000-2015 Venezuela witnessed a 4.6 fold increase in malaria cases (from 29,736 cases in 2000 to 136,402 in 2015), followed by a 71% increase in 2017 (411 586 cases) compared with 2016 (240 613). These figures were reported earlier this year in The Lancet Infectious Diseases.

By 2017, malaria cases in Venezuela represented more than half of cases in the entire WHO region of the Americas: these updated numbers (from the latest World Malaria Report in 2018), show the proportion from Venezuela to be 53% (519,209/975,700). This is an increase of more than 20 times since the year 2000, when Venezuela accounted for only 2.5% (29,736/1,181,095) of the cases in the continent.

The most recent estimates come from the Alianza Venezolana por la Salud/ Red Defendamos la Epidemiologia Nacional: a group of recognised clinicians and epidemiologists, including 4 ex-Ministers of Health. These estimates, covering January to June 2018, show 600,000 new cases of malaria in Venezuela alone in just these six months, and latest estimates (as yet non-final) suggest the country will report over 1 million new cases of malaria for the whole of 2018.

The authors say that high malaria incidence in Venezuela is positively correlated with an increase in illegal mining activities and forest exploitation (which take place largely in mosquito endemic areas) which are in turn strongly linked to the ongoing socioeconomic crisis.

In response to Venezuela's rapidly decaying situation, a massive population exodus (more than 3 million people) is ongoing towards neighbouring countries including Brazil and Colombia, causing a spillover of cases. Brazil has reported an escalating trend of imported cases from Venezuela from 1,538 (2014) to 3,129 (2017) with some areas reporting up to 80% of imported cases from Venezuela. Colombian data is still to be verified to reveal the origin of imported cases, but it can be said with certainty that cases are being imported from Venezuela, it is just not possible to say exactly how many.

The authors conclude: "The continued upsurge of malaria in Venezuela is becoming uncontrollable jeopardising the hard-won gains of the malaria control programme in Latin America. We urge national, regional and global authorities to take immediate action to address this worsening epidemic and prevent its further expansion beyond Venezuelan borders."

Vaccine-preventable diseases have not just returned, but surged in crisis hit Venezuela, according to new research presented at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam, Netherlands (13-16 April). The study is by Dr Adriana Tami (University Medical Center Groningen, Netherlands and University of Carabobo, Venezuela) and Dr Alberto Paniz-Mondolfi (IDB Biomedical Research Institute, Barquisimeto, Venezuela), and colleagues.

Venezuela has plunged into a humanitarian, economic and health crisis of extraordinary proportions. This complex situation has progressed into a general collapse of Venezuela's health system, the dismantling of structures at the institutional, social and economic level affecting the life and wellbeing of the entire population. Some two thirds of the Venezuelan population currently live in extreme poverty, amid escalating violence. The country's crumbling healthcare infrastructure is now more typical of conflict zones or war-torn nations. More than 280,000 children are now perceived to be at risk of death from severe malnutrition.

In response, an ongoing exodus towards neighbouring countries has ensued. Emigrating individuals with infectious diseases may be unwillingly causing a spill-over of diseases beyond Venezuela's boundaries. This study provides new data on the resurgence and ongoing epidemics of measles and diphtheria and their disproportionate impact on indigenous populations.

The authors note that, since October 2014, there is a dire shortage of official epidemiological information in Venezuela; thus they did an active search of published and unpublished data. Data from the Americas were sourced from PAHO and from Venezuelan Health Observatory. Brazilian and Colombian data were accessed via their respective Ministries of Health.

In Venezuela, circulation of wild measles and diphtheria had not been reported since 2007 and 1992, respectively. Both diseases have recently re-emerged after a progressive interruption of the national immunisation program. Transmission is now present in most of the country. However, vulnerable indigenous populations such as the Yanomami inhabiting the Amazon region at the Venezuelan-Brazilian border, are mostly affected. There have been at least 100 cases and several deaths in this small population of 15.000 people, reported by a non-governmental agency that works with this vulnerable group.

"High morbidity and mortality rates are expected because these populations are immunologically naïve to measles," explains Dr Tami who has worked with these indigenous people in the Amazon forest. "Measles is presumed to have entered the Yanomami communities from Brazil after imported cases from Venezuela brought the disease to border populations of Brazil, before spreading back to Yanomami communities in Venezuela. Further spread of this epidemic wave could devastate the Yanomami people living in the Orinoco highlands of the Amazon, given that humanitarian aid to affected sites is limited or hard to deliver because of the seminomadic characteristics of these indigenous populations and the remoteness of the Yanomami territory."

The report provides data taken over a 16-month period (June 2017-October 2018) during which time a total of 7,524 suspected measles cases have been reported in Venezuela. Of these, 5,525 were confirmed representing 68% (5,525/8,091) of measles cases in the Americas reported, and also the most deaths from measles (73/85). The national coverage rate for the second dose of the measles vaccine was estimated at 52% according to the last reports from the Venezuela Ministry of Health. This estimate ranks Venezuela toward the bottom of vaccination coverage in the region, and estimates show measles vaccination is falling in all parts of the country.

Measles cases from Venezuela have been reported in Brazil, Colombia, Ecuador and Peru. Genetic analysis has confirmed that these cases have spread to these countries from Venezuela. Of all cases reported by Brazil's Ministry of Health in the state of Roraima (which borders Venezuela) through May 2018, a total of 68% corresponded to refugees from Venezuela, and 52.7% were in Warao Amerindians. The Colombia Ministry of Health has also reported 25 measles cases imported from Venezuela. Most cases were reported from bordering states that received a considerable migratory influx in 2018 and that also had received most of the 600,000 immigrants from Venezuela in 2017.

From January 2016 to October 2018, a total of 2,170 diphtheria cases have been reported to date with a lethality rate of 22%. In 2018, 96% (806/838) of diphtheria cases in the Americas region originate from Venezuela. Coverage of the minimum recommend 3 doses (although 4 is preferred) of diphtheria-tetanus-pertussis (DTP) vaccine has fallen from 84% in 2016 to 60% in 2017, and may not have reached 50% in 2018. Estimates suggest this could mean 3 million vulnerable Venezuelan children are now-exposed to this disease that should long have been consigned to the past.

Diptheria cases have also been reported in states of other countries that border Venezuela, and have been assumed to be transmitted from the many cases now occurring in Venezuela, though hard data to confirm this is not available at this time.

Although polio has not yet been reported in Venezuela, it is estimated that vaccination rates are now well below 80% and the authors believe it is only a matter of time before this disease, eliminated from the Americas in 1971, will make a comeback. The authors say: "The current reality in Venezuela is a conflux of plummeting vaccination coverages and ongoing outbreaks of other vaccine-preventable diseases. Combined with the weakening of surveillance programs, forced migrations, and a prolonged political, economic, and food crisis without foreseeable resolution, these factors have set the stage for potential re-emergence of poliomyelitis."

They conclude: "Action to halt the spread of vaccine-preventable diseases within Venezuela is a matter of urgency for the country and region. Global and regional health authorities should urge the Venezuelan government to allow establishing a humanitarian channel to bring relief efforts and adequate supplies for mass vaccination. Failure of timely action may bring a tsunami of new cases, not only in Venezuela but also other countries in the Americas."

PHILADELPHIA -- Nipah virus is a type of RNA virus transmitted from animals to humans. The infection causes severe respiratory illness and symptoms including cough, headache and fever, which can progress into encephalitis, seizure and coma. Currently, there is no approved vaccine against Nipah virus available on the market. In recent years, outbreaks, from bat-to-human or pig-to-human transmission, have been reported in Malaysia, Singapore, Bangladesh and India. The World Health Organization (WHO) therefore lists Nipah virus as a priority pathogen needing urgent action.

In order to reduce the risk of Nipah virus becoming a global danger, it's essential to develope a safe and effective vaccine against the virus for humans and animals. Matthias J. Schnell, PhD, Chair of the Department of Microbiology and Immunology and his team from Jefferson Vaccine Center at Jefferson (Philadelphia University + Thomas Jefferson University) developed a novel recombinant vaccine called NIPRAB that shows robust immunization against Nipah virus in animal models. They published their findings in npj Vaccines on April 15.

Dr. Schnell, together with the first author and graduate student Rohan Keshwara, took advantage of a modified rabies virus vector, and incorporated a gene from Nipah virus - creating a viral particle that displays components of both viruses on its surface. The rabies vector is a well-established vaccine strain with little capacity to cause diseases in the nervous system. Because the immune system interacts with both viral components, it develops a reaction that is specific and can defend against both viruses.

The researchers showed that the live vaccine was safe in mice, which had steady weight gain and no sign of neurological diseases. Dr. Schnell and colleagues demonstrated that one dose of vaccine elicited a strong antibodies response against Nipah virus and rabies virus. Those antibodies also react to a virus from the same family as Nipah, the Hendra virus, which causes similar symptoms.

In addition to the live version of the vaccine, which would be ideal for use in animals, the researchers also developed a chemically-killed version of the vaccine so that the viral replication was completely abolished. They found the inactivated vaccine induced as strong immunity as the live vaccine did, and would therefore be an ideal vaccine for immunocompromised individuals, such as HIV patients, pregnant women and children.

"We have a vaccine that is safe and effective against Nipah, Hendra, and Rabies virus in mice," says Dr. Schnell. "Future work will focus on testing the vaccine on different species and establishing the right dose of injection. We also used the same vaccine platform to develop vaccines against several other emerging viruses, including a vaccine against Ebola virus, which is close to entering into its first clinical trial."

Working with human colon cancer cells and mice, researchers led by experts at the Johns Hopkins Kimmel Cancer Center say they have successfully blocked the activity of portions of a protein known as UHRF1 and restored the function of hundreds of cancer-fighting genes that became "misregulated" by the disease.

In a report on the research, published online, April 4, 2019, in Cancer Cell, the investigators say the findings could lead to an entirely new strategy to fight a broad range of cancers.

Researchers have long known that gene mutations can cause cancers. However, it recently became clear that faulty gene regulation can also prompt and maintain cancers, explains study leader Stephen Baylin, M.D., Virginia and D. K. Ludwig Professor for Cancer Research and professor of oncology and medicine. This second phenomenon can occur through a process known as epigenetics, in which chemical tags settle onto genes to turn them on or off.

One type of chemical tag, called a methyl group, typically silences the function of genes once it's clipped on by cells. Cancers harness this type of epigenetic regulation, using it to broadly turn off genes that cells normally use to fight the onset or growth of cancer.

Researchers have attempted to adapt this strategy to the treatment of cancer by developing drugs that knock off methyl groups to turn cancer-fighting genes back on. However, Baylin says, it's been a challenge to develop drugs that robustly penetrate solid tumors and effectively remove methyl groups simultaneously. Consequently, drugs such as 5-azacytidine and entinostat haven't yet been as effective as researchers had hoped, particularly in solid tumors.

Looking for a new way to influence cancer epigenetics, Baylin and collaborators from the Van Andel Research Institute and Tongji Medical College in China turned to UHRF1. Although this protein was known to be responsible for adding and maintaining methyl groups, Baylin says it has never been fully explored as a way to block methylation and make it a potential drug target.

To better understand how UHRF1 operates, the researchers devised an experiment that allowed them to block discrete parts of this protein in human colon cancer cells with established abnormal methylation patterns. Their results showed that two distinct segments of the protein were pivotal in helping cells maintain these abnormal patterns: one called plant homeodomain (PHD) and another called SET and RING-associated domain (SRA).

When the researchers blocked these domains by inserting mutations in key regions, tests of how abnormal DNA methylation and gene expression were affected showed that hundreds of cancer-associated genes became demethylated, returning to normal levels of protective activity. As a result, Baylin says cells with blocked PHD and SRA were significantly impaired in their ability to divide and migrate, processes that are hallmarks of cancer.

Similarly, working with mice in which human colon cancer cells were implanted and grown, the researchers found that blocking PHD and SRA or the function of the entire protein consistently caused established tumors to shrink and blunted metastasis, the process by which cancer cells spread throughout the body.

Finally, to get a sense of how UHRF1 operates in people, the researchers looked at levels of this protein and the activity of genes that this protein suppresses through methylation in samples of human colon cancers obtained by the Chinese collaborators from more than 300 patients at the time of surgery. They found that tumors with higher levels of UHRF1 had lower levels of activity in cancer-fighting genes and vice versa.

Clinical records of the patients showed that the more UHRF1 is present at increased levels, the worse patients' outcomes were overall. That is, in over 150 patients whose tumors had high UHRF1--levels four to 10 times above levels in normal tissue--recurrence of tumors after surgery occurred 20 months earlier and led to an average of two years shorter overall survival compared with those with lower levels of this protein.

Together, Baylin says, the findings suggest that repressing those two key domains could offer a new way of controlling cancers. He and his team are working with a company to develop a drug to accomplish this goal, either alone or in combination with existing drugs. Because methylation patterns go awry nearly universally in cancer, he adds, such a drug could help fight a wide range of cancer types.

"By harnessing the power of UHRF1 we could fight cancers in a whole new way," says senior first author Xiangqian Kong, Ph.D.

New research examining influenza transmission in a tertiary hospital finds that a substantial proportion of patients and healthcare works shed the flu virus before the appearance of clinical symptoms. The findings, being presented at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam, Netherlands (13-16 April), raise the possibility that current influenza infection control measures may not be enough to protect healthcare workers and patients during routine care in hospitals.

The discovery came after Swiss researchers tracked almost 700 healthcare workers and inpatients over two consecutive influenza seasons at the University Hospital in Zurich. They uncovered several transmission clusters that were undetected by routine surveillance.

These results are consistent with previous research which suggests influenza may be spread to others by just breathing, and that coughing or sneezing are not required for transmission [1].

Knowing whether people are infectious in the absence of symptoms is a major concern for infection control in hospitals. While hospital acquired infection from asymptomatic individuals may occur, no prospective studies have investigated the transmission of influenza in the absence of symptoms in acute care.

To provide more evidence, Dr Stefan Kuster from the University Hospital and University of Zurich in Switzerland and colleagues conducted a prospective study of influenza virus transmission trajectories in 542 patients on medical wards and 152 acute care healthcare workers working on the same wards during the 2015/2016 and 2016/2017 influenza seasons.

The team tracked flu infection through nasal swabs collected daily, and performed diagnostic multiplex real-time PCR and RNA sequencing on specimens. Contacts between participants were traced, and participants were asked to completed daily diaries of any illnesses.

During the study, 16 (11%) healthcare workers and 19 (4%) inpatients tested were diagnosed with an influenza infection. Most of these 35 participants experienced influenza symptoms, particularly respiratory symptoms, when their tests were positive. However, several remained asymptomatic despite testing positive for influenza infection (2/16; 13% healthcare workers and 2/19; 11% inpatients).

Importantly, 17% (12/71) of influenza-positive swabs from healthcare workers and 8% (3/38) from patients were collected on days that they did not report flu symptoms.

Furthermore, among symptomatic individuals, 14% (2/14) of healthcare workers (but none of the 17 symptomatic inpatients) had a positive influenza test before symptoms developed.

Further analyses based on local and temporal proximity of healthcare workers and inpatients revealed at least seven clusters of potential transmission events among healthcare workers, among inpatients, or between healthcare workers and inpatients. However, evidence based on local and temporal proximity for one possible transmission from an asymptomatic healthcare worker to an inpatient was not supported by genetic analysis.

"Our findings suggest that influenza infection in acute care is common and a significant proportion of individuals appear to shed influenza virus without harbouring any symptoms, making the spread of flu very difficult to control even with self-diagnoses and current infection control practices", says Dr Kuster. "Influenza vaccination is not perfect but remains the best tool we have to protect healthcare workers and their patients from severe illness."

The authors note that more research on how influenza is transmitted in hospitals is needed before it can be firmly established whether people with no clinical symptoms may be contributing to the spread of the virus without realising.

The authors note several limitations including that the study was conducted in a single institution, and the total number of influenza events was moderate. They also note that because participating wards were alerted to the influenza problem, they may have paid more attention to prevention measures, and it is possible that transmission rates may generally be higher than seen in the study.

There is only a short window of opportunity to seek medical help before rabies becomes almost invariably fatal, but people wait an average of 10 days before seeking medical advice following exposure to potentially rabid animals overseas, according to new research being presented at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam, Netherlands (13-16 April). The average delay in seeking treatment following bat exposures in the UK was almost three days.

"The findings highlight the importance of raising public awareness around the risks of rabies, both for travellers visiting rabies-infected countries and from bat exposures in the UK", says co-author Dr Kevin Brown, Head of Rabies and Immunoglobulin Service for Public Health England.

Symptoms typically take 2 to 3 months to appear, but can develop in as little as a week (following severe bites to the head) or up to several years after exposure. "Preventive treatments are 100% effective if given promptly after exposure", says Dr Brown. "That's why seeking prompt care is so important, even if the wound or incident seems very trivial. If you are bitten, scratched, or licked by an animal you must wash the wound or site of exposure with plenty of soap and water and seek medical advice without delay. Travellers should not delay waiting for treatment until they return to the UK."

Rabies is a zoonotic infection (a disease that spreads from animals to humans) that can cause a rare but life-threatening infection of the brain and nervous system in humans. It usually results from a bite, scratch, or lick from an infected animal. The virus is estimated to kill around 59,000 people every year worldwide, most often as a result of a bite from a rabid dog in parts of Africa and Asia.

Rabies does not circulate in wild or domestic animals in the UK, although some species of bats can carry rabies-like viruses (European Bat Lyssavirus type 1 and type 2). Every year around 150 people in England are treated after being bitten by a bat.

People who believe they may have been exposed to rabies are advised to immediately seek treatment which involves a series of rabies vaccinations with or without immunoglobulin, an antibody treatment that gives immediate short-term protection while the vaccines start to work.

In England, national rabies advice, guidance and treatment is provided through the Rabies and Immunoglobulin Service within Public Health England, with ten issuing centres around the country.

In this study, medical staff from one of the issuing centres in Manchester, North West England conducted a review of all requests for rabies post-exposure treatment at their lab between June 2015 and June 2018.

In total, 200 patients (aged 0-77 years old) received post-exposure treatment through the virology laboratory. Over a third (69/200 patients) were aged 20-29 years old. The vast majority of patients (92%; 183/200) had not received any rabies vaccination in the past.

Results showed that over three-quarters (79% (157/200) of post-exposure treatment was given to travellers returning to the UK from 43 different countries.

However, 1 in 5 individuals (22%; 42/200) reported an exposure to a bat in the UK. "While the risk of catching rabies in the UK is extremely low, it is important that all potential bat bites are risk-assessed and treated as necessary. Bat bites in the UK often do not leave a mark, and are felt rather than seen", says Dr Brown.

In the UK, although prompt treatment is recommended, given the prolonged incubation time it is never considered too late to receive post-exposure treatment for an exposure.

In separate research, Public Health England doctors found a 7.5-fold increase in the number of risk assessments performed for rabies post-exposure in England since 2001--increasing from 390 in 2001 to 2949 in 2018--the majority as a result of dog bites in South and South East Asia, whilst around 1 in 10 were for bat bites in England.

Of the previously unimmunised individuals exposed to animals overseas, 40% did not seek rabies post-exposure treatment overseas, but waited until return to the UK. Similar to the results from Manchester, more than 60% of bat bites sought treatment within 2 days.

Nationally, in addition to the advice and guidance, Public Health England provides rabies vaccine and rabies immunoglobulin for all potential rabies exposures in England. In mid-2018, the guidance on post-exposure treatment for rabies was updated. The routine vaccine schedule for unimmunised individuals was reduced from 5 doses of vaccine to 4 doses. Additionally, a composite rabies risk (red, amber, or green) was calculated for each exposure, taking into account the country and animal risk; and the category of exposure. Rabies immunoglobulin was only recommended in cases with a 'Red' composite rabies risk, ie a category 3 exposure (bite or laceration) in a 'high risk' country/animal risk combination. Rabies immunoglobulin is also no longer given for bat bites in the UK, although still advised for non-UK bat bites.

Further analysis showed that in the first 6 months following the introduction of the new guidelines, there was a significant increase in the number of calls about possible cases of rabies compared to the same period in 2017 (1727 vs 1157). Nevertheless, there was a decrease in both the number of vaccines (2.4 vs 3) and vials of immunoglobulin (256 vs 575) issued as treatment.

"Those completing the risk assessment found the process easier to follow, and there was less risk of inappropriate treatment given", says Dr Brown. "The new guidance has led to a significant reduction in the costs of running the program, whilst still ensuring appropriate treatment for those at potential risk of rabies."