Pfizer announced that it has started a Phase 1/2 trial of its respiratory syncytial virus, or RSV, vaccine candidate in healthy adult volunteers. RSV is a common respiratory virus that affects the lungs and airways, with significant impact on young children and older adults. The highest risk of severe outcome from RSV occurs in the first months of life. Currently available prophylactic treatments for RSV are limited for use in high risk young children and infants, including very premature infants. If successful, Pfizer’s investigational RSV vaccine could help protect young infants through the immunity created following vaccination of pregnant women. The maternal vaccine candidate is intended to raise RSV neutralizing antibody levels in pregnant women who then pass these protective antibodies to their unborn child and provide immunity during the early months of an infant’s life. Pfizer is also advancing a maternal vaccine candidate against Group B streptococcus, or GBS, currently in Phase 1/2 trials. For older adults, RSV is the second leading cause of moderate to severe respiratory illness, following influenza. The risk of serious infection increases with age and for those with chronic heart or lung disease or a weakened immune system. There is no specific treatment for RSV and currently no licensed vaccine to prevent the disease. The trial is designed as a Phase 1/2 randomized, placebo-controlled, observer-blind, dose-ranging study with two age groups enrolled in parallel to support both the maternal and older adult indications. One age group includes males and females 18-49 years of age; the other includes males and females 50-85 years of age. The study’s primary endpoints are safety and tolerability, and its secondary endpoint is immunogenicity
Tuesday, May 22, 2018
FDA to review Sanofi potential treatment for type 1 diabetes
The U.S. Food and Drug Administration has accepted Sanofi’s (SNY) regulatory filing for Zynquista. The investigational oral treatment would be used in addition to insulin therapy to improve blood sugar control in adults with type 1 diabetes. Developed in partnership with Lexicon Pharmaceuticals (LXRX), Zynquista is an investigational oral dual inhibitor of SGLT-1 and SGLT-2, proteins that influence how the intestines and kidneys absorb and eliminate sugar resulting in improved glucose control and additional clinical benefits. The FDA New Drug Application for sotagliflozin is based on data from the inTandem clinical trial program which includes three Phase 3 clinical trials assessing the safety and efficacy of Zynquista in approximately 3,000 adults with inadequately controlled type 1 diabetes. The safety and efficacy data have not yet been evaluated by any regulatory authority. The target FDA action date under the Prescription Drug User Fee Act is anticipated to be March 22, 2019. Sanofi also submitted a regulatory application to the European Medicines Agency earlier this year.
BioMarin updates on gene therapy for hemophilia
BioMarin Pharmaceutical Inc. (NASDAQ: BMRN) announced today an update to its previously reported results of an open-label Phase 1/2 study of valoctocogene roxaparvovec (formerly BMN 270), an investigational gene therapy treatment for severe hemophilia A. The updated results were presented during an oral presentation at the World Federation of Hemophilia (WFH) 2018 World Congress in Glasgow, Scotland by John Pasi, M.B., Ch.B., Ph.D., from Barts and the London School of Medicine and Dentistry and primary investigator for this Phase 1/2 study.
Previously, the Company provided updated data on the 4e13 vg/kg dose cohort and 6e13 vg/kg dose cohort on Dec. 9, 2017 at the American Society of Hematology (ASH) Annual Meeting.
The data presented at WFH is the most current data (Apr. 16, 2018 cut off) and includes 104 weeks of data for the 6e13 vg/kg cohort and 52 weeks of data for the 4e13 vg/kg cohort.
In the 6e13 vg/kg cohort, the data showed continued and substantial reductions in bleeding requiring Factor VIII infusions with a 97% reduction in mean Annualized Bleed Rate (ABR), with no spontaneous bleeds and elimination of all bleeds in target joints in the second year. 71% and 86% of participants had zero bleeds requiring Factor VIII infusions in years 1 and 2 respectively compared to 14%, who had zero bleeds requiring Factor VIII infusions for a year at baseline. There was a 96% reduction in mean FVIII usage through week 104. Quality of life as measured by the six-domain Haemo-QoL-A instrument rapidly improved across all domains by up to 17.3 points in mean over baseline through the second year. This is well above the 5.2 point increase considered to be the minimal clinically important difference.
The 4e13 vg/kg cohort also showed a substantial reduction in bleeding requiring Factor VIII infusions with a 92% reduction in ABR. 83% of participants had zero bleeds requiring Factor VIII infusions following treatment for a year compared to 17%, who had zero bleeds requiring Factor VIII infusions for a year at baseline. Mean Factor VIII usage decreased by 98%. Consistent with the reduction in ABR and FVIII usage, quality of life showed mean improvement by 3.8 to 6.3 points.
For the 6e13 vg/kg cohort, mean Factor VIII activity levels from week 20 through 104 have been consistently within the normal or near normal range and no participant was above the upper limit of normal at week 104, expressed as a percentage of normal factor activity in blood. At 104 weeks post-infusion, mean Factor VIII activity level of the 6e13 vg/kg cohort is within the normal range at 59%, and the median is near normal at 46%.
For the 4e13 vg/kg cohort, mean Factor VIII activity levels from week 20 through 52 have been consistently within the mild range, expressed as a percentage of normal factor activity in blood. At 52 weeks post-infusion, mean and median Factor VIII activity levels of the 4e13 vg/kg cohort are 32%.
The Company will be updating the protocol for the GENEr8-1 study evaluating the 6e13 vg/kg dose and will power the study to evaluate superiority to the current standard of care, Factor VIII prophylaxis. The study will now include 130 participants (an increase of 90 from the original 40).
“In order to make this option available with the urgency and data support that people with severe hemophilia A deserve, we plan to raise the sample size of our registrational study, Gener8-1 with the 6e13 dose to demonstrate benefits well beyond prophylactic factor use,” said Hank Fuchs, M.D., President, Worldwide Research and Development at BioMarin.
Monday, May 21, 2018
Robots can now grow human organs
Is there anything robots can’t do? They can perform our jobs, get periods and now . . . grow human organs.
Scientists at the University of Washington School of Medicine have developed an automated system that uses robots to produce human mini-organs from stem cells. According to Science Daily, the ability to mass produce “organoids” promises to expand the use of mini-organs in basic research and drug discovery.
“This is a new ‘secret weapon’ in our fight against disease,” the university’s Benjamin Freedman tells Science Daily.
Before, scientists would grow cells for biomedical research by culturing them into flat sheets. But these were too simplistic to truly mimic the ways true cells behaved. More recently, researchers have had some success growing these cells into more complex, and three-dimensional, structures called mini-organs.
This new development, however, allows them to produce these organoids at a rapid pace. It’s the first time researchers have been able to mass-produce these mini-organs from stem cells.
“Ordinarily, just setting up an experiment of this magnitude would take a researcher all day, while the robot can do it in 20 minutes,” Freedman tells Science Daily. “On top of that, the robot doesn’t get tired and make mistakes. . . . There’s no question — for repetitive, tedious tasks like this, robots do a better job than humans.”
Soldiers may soon get implantable health monitors, remote robotic surgeries
Soldiers may soon be carrying monitoring devices that can alert doctors thousands of miles away to medical emergencies and the need for treatment.
The devices may even be implanted in soldiers and continuously monitor their status, the Army’s top doctor said in describing the near future of Army medicine.
“We should be monitoring all soldiers, all the time, looking for patterns of injury or other signs for early detection,” said Lt. Gen. Nadja West, the Army’s surgeon general, during a talk May 8 at the Association of the U.S. Army in Arlington, Virginia. “We can do better when every soldier is a sensor, and we can continuously monitor information culled from them.”
The monitors would send out streams of detailed data on a soldier’s health. For example, a device could measure blood sugar levels and a doctor or nurse hundreds or thousands of miles away can check on a soldier’s diabetes and recommend treatment or calibrate insulin.
“There is an explosion of wearable and soon to be implantable peripheral monitors,” West said. “It completely revolutionizes how we can follow and impact a soldier’s health and a patient’s health.”
Soldiers face environments where the threat may be unknown, and such devices will make a difference, she said. U.S. diplomats in Havana, Cuba, became ill last year from a mysterious cause, possibly a type of sound wave, that remains unknown, she added as an example. Monitoring them and their environment could have led to early detection and potentially better understanding of what happened.
Commanders can use this kind of technology to decide who to send on the next mission, West said.
“Just imagine a commander having that information, where that person is and how they’re doing,” she said.
The commander would see not just “are they deployable or not,” but their state of health.
“If you had a pilot getting into a cockpit, wouldn’t you want to know if they’re sleepy or not?” West said. “If you have the tools to predict, it’s amazing what you can prevent. “
Monitoring devices are available now, and Army medicine is working through how to scale the capability and secure the information flow, she said.
The device is one of many innovations in medical care, which is changing dramatically, and the Army is changing with it, West said.
Austere environments
The realization that the military may no longer count on having the “golden hour” for treatment of illness or injury is driving the thinking on what is next in medical care.
Troops will be forward deployed in units with a smaller footprint and often without the luxury of uncontested air space, West said.
The ambush and killings in October of four American soldiers in Niger bring to the forefront the danger troops face in remote locations.
“We might not have the life-saving golden hour evacuation system we’ve been accustomed to for the last 17 years. Our soldiers may be isolated for 72 hours or more, requiring prolonged field care when injured in an austere environment,” West said. “Our medics will be faced with doing more, with less, for longer. That means no easy access to emergency departments or operating suites or trauma surgeons. “
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This the reality facing Army medics. This new environment requires significant changes in how medics and soldiers are trained and equipped, West said, and the changes are taking place now.
Command posts in the near future will have medical capabilities integrated within them, so patients can be monitored and calls made to a surgeon to recommend life-saving procedures.
Robotic surgeries are another technology in development. It’s a question now of “how quickly we can scale it throughout our enterprise,” West said.
Such surgery has been tested at Fort Campbell, Kentucky, for example, with doctors there and a satellite hookup with soldiers in a remote area.
Technology used around the world today allows surgeons to operate virtually, West said.
The Army has invested in its first virtual medical center at Brooke Army Medical Center, Texas, which she said will expand capacity and capabilities and save more lives.
A change in mindset is needed now, West said, “one that opens our minds to completely new possibilities as to the how, when, where and by whom health care is delivered.”
London hospitals to replace doctors and nurses with AI for some tasks
UCLH aims to bring ‘game-changing’ benefits of artificial intelligence to NHS patients, from cancer diagnosis to reducing wait times
One of the country’s biggest hospitals has unveiled sweeping plans to use artificial intelligence to carry out tasks traditionally performed by doctors and nurses, from diagnosing cancer on CT scans to deciding which A&E patients are seen first.
The three-year partnership between University College London Hospitals(UCLH) and the Alan Turing Institute aims to bring the benefits of the machine learning revolution to the NHS on an unprecedented scale.
Prof Bryan Williams, director of research at University College London Hospitals NHS Foundation Trust, said that the move could have a major impact on patient outcomes, drawing parallels with the transformation of the consumer experience by companies such as Amazon and Google.
“It’s going to be a game-changer,” he said. “You can go on your phone and book an airline ticket, decide what movies you’re going to watch or order a pizza … it’s all about AI,” he said. “On the NHS, we’re nowhere near sophisticated enough. We’re still sending letters out, which is extraordinary.”
At the heart of the partnership, in which UCLH is investing a “substantial” but unnamed sum, is the belief that machine learning algorithms can provide new ways of diagnosing disease, identifying people at risk of illness and directing resources. In theory, doctors and nurses could be responsively deployed on wards, like Uber drivers gravitating to locations with the highest demand at certain times of day. But the move will also trigger concerns about privacy, cyber security and the shifting role of health professionals.
The first project will focus on improving the hospital’s accident and emergency department, which like many hospitals is failing to meet government waiting time targets.
“Our performance this year has fallen short of the four-hour wait, which is no reflection on the dedication and commitment of our staff,” said Prof Marcel Levi, UCLH chief executive. “[It’s] an indicator of some of the other things in the entire chain concerning the flow of acute patients in and out the hospital that are wrong.”
In March, just 76.4% of patients needing urgent care were treated within four hours at hospital A&E units in England in March – the lowest proportion since records began in 2010.
Using data taken from thousands of presentations, a machine learning algorithm might indicate, for instance, whether a patient with abdomen pain was likely to be suffering from a severe problem, like intestinal perforation or a systemic infection, and fast-track those patients preventing their condition from becoming critical.
“Machines will never replace doctors, but the use of data, expertise and technology can radically change how we manage our services – for the better,” said Levi.
Another project, already underway, aims to identify patients who are are likely to fail to attend appointments. A consultant neurologist at the hospital, Parashkev Nachev, has used data including factors such as age, address and weather conditions to predict with 85% accuracy whether a patient will turn up for outpatient clinics and MRI scans.
In the next phase, the department will trial interventions, such as sending reminder texts and allocating appointments to maximise chances of attendance.
“We’re going to test how well it goes,” said Williams. “Companies use this stuff to predict human behaviour all the time.”
Other projects include applying machine learning to the analysis of the CT scans of 25,000 former smokers who are being recruited as part of a research project and looking at whether the assessment of cervical smear tests can be automated. “There are people who have to look at those all day to see if it looks normal or abnormal,” said Williams.
Might staff resent ceding certain duties to computers – or even taking instructions from them? Prof Chris Holmes, director for health at the Alan Turing Institute, said the hope is that doctors and nurses will be freed up to spend more time with patients. “We want to take out the more mundane stuff which is purely information driven and allow time for things the human expert is best at,” he said.
When implementing new decision-making tools, the hospital will need to guard against “learned helplessness”, where people become so reliant on automated instructions that they abandon common sense. While an algorithm might be correct 99.9% of the time, according to Holmes, “once in a blue moon it makes a howler”. “You want to quantify the risk of that,” he added.
UCLH is aiming to circumvent privacy concerns that have overshadowed previous collaborations, including that of the Royal Free Hospital in London and Google’s DeepMind, in which the hospital inadvertently shared the health records of 1.6 million identifiable patients. Under the new partnership, algorithms will be trained on the hospital’s own servers to avoid any such breaches and private companies will not be involved, according to Holmes.
“We’re critically aware of patient sensitivity of data governance,” he said. “Any algorithms we develop will be purely in-house.”
Questions also remain about the day-to-day reality of integrating sophisticated AI software with hospital IT systems, which are already criticised for being clunky and outdated. And there will be concerns about whether the move to transfer decision-making powers to algorithms would make hospitals even more vulnerable to cyber attacks. Hospital IT systems were brought to a standstill last year after becoming victim to a global ransomware attack that resulted in operations being cancelled, ambulances being diverted and patient records being unavailable.
Williams acknowledged that adapting NHS IT systems would be a challenge, but added “if this works and we demonstrate we can dramatically change efficiency, the NHS will have to adapt.”
Interventions to Prevent Falls in Older Adults
Updated Evidence Report and Systematic Review for the US Preventive Services Task Force
Abstract
Importance Falls are the most common cause of injury-related morbidity and mortality among older adults.
Objective To systematically review literature on the effectiveness and harms of fall prevention interventions in community-dwelling older adults to inform the US Preventive Services Task Force.
Data Sources MEDLINE, PubMed, Cumulative Index for Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials for relevant English-language literature published through August 2016, with ongoing surveillance through February 7, 2018.
Study Selection Randomized clinical trials of interventions to prevent falls in community-dwelling adults 65 years and older.
Data Extraction and Synthesis Independent critical appraisal and data abstraction by 2 reviewers. Random-effects meta-analyses using the method of DerSimonian and Laird.
Main Outcomes and Measures Number of falls (number of unexpected events in which a person comes to rest on the ground, floor, or lower level), people experiencing 1 or more falls, injurious falls, people experiencing injurious falls, fractures, people experiencing fractures, mortality, hospitalizations, institutionalizations, changes in disability, and treatment harms.
Results Sixty-two randomized clinical trials (N = 35 058) examining 7 fall prevention intervention types were identified. This article focused on the 3 most commonly studied intervention types: multifactorial (customized interventions based on initial comprehensive individualized falls risk assessment) (26 trials [n = 15 506]), exercise (21 trials [n = 7297]), and vitamin D supplementation (7 trials [n = 7531]). Multifactorial intervention trials were associated with a reduction in falls (incidence rate ratio [IRR], 0.79 [95% CI, 0.68-0.91]) but were not associated with a reduction in other fall-related morbidity and mortality outcomes. Exercise trials were associated with statistically significant reductions in people experiencing a fall (relative risk, 0.89 [95% 13 CI, 0.81-0.97]) and injurious falls (IRR, 0.81 [95% CI, 0.73-0.90]) and with a statistically nonsignificant reduction in falls (IRR, 0.87 [95% CI, 0.75-1.00]) but showed no association with mortality. Few exercise trials reported fall-related fractures. Seven heterogeneous trials of vitamin D formulations (with or without calcium) showed mixed results. One trial of annual high-dose cholecalciferol (500 000 IU), which has not been replicated, showed an increase in falls, people experiencing a fall, and injuries, while 1 trial of calcitriol showed a reduction in falls and people experiencing a fall; the remaining 5 trials showed no significant difference in falls, people experiencing a fall, or injuries. Harms of multifactorial and exercise trials were rarely reported but generally included minor musculoskeletal injuries.
Conclusions and Relevance Multifactorial and exercise interventions were associated with fall-related benefit, but evidence was most consistent across multiple fall-related outcomes for exercise. Vitamin D supplementation interventions had mixed results, with a high dose being associated with higher rates of fall-related outcomes.
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