Recent quotes:

A Missed Opportunity to Address a National Shame: The Case of Sickle Cell Disease in the United States | Hematology | JAMA Pediatrics | JAMA Network

There are more than 100 000 persons in the United States with SCD, and 1:365 African American individuals are born with SCD.2 Although there have been limited, yet infrequent, local points of progress, at a national level the quality of care for children with SCD is shameful. Fundamental preventive care is not provided to most of these children despite overwhelming evidence of its effectiveness. For example, daily antibiotic prophylaxis for children younger than 5 years has been shown to markedly decrease the risk of sepsis and has been recommended by national authorities for more than 20 years.3 Yet, studies across several states have shown that less than 20% of children reliably receive such care, and rates have not improved significantly during the past decade.4 Similarly, annual transcranial Doppler screening is a proven effective mechanism to help prevent stroke in patients with SCD. However, only 22% to 44% of eligible children are screened each year,5 and no improvements have been seen in at least the past 5 years.

Or was it the "speed"?

The rates of traffic and moving violations were also significantly higher among young drivers with ADHD as compared to those without ADHD. Among these drivers, nearly 37 percent were issued a traffic violation and nearly 27 percent a moving violation within their first year of driving, compared to 25 percent and 18 percent respectively among their peers without ADHD. Drivers with ADHD had higher rates of alcohol or drug violations and moving violations (including speeding, nonuse of seat belts, and electronic equipment use). Their rate was 3.5 times that of young drivers without ADHD in the first year of driving and 1.5 times that of young drivers without ADHD in the first four years of driving.

Apixaban: Evaluation of the Inclusion of Studies Identified by the FDA as Having Falsified Data in the Results of Meta-analyses: The Example of the Apixaban Trials | Research, Methods, Statistics | JAMA Internal Medicine | JAMA Network

In our reanalysis of the 22 meta-analyses, we found that 10 (46%) yielded results that would change the initial meta-analysis findings. Each affected meta-analysis had a median of 9.5 publications (range, 2-17), and the median meta-analysis publication InCite journal impact factor was 5.830 (range, 3.154-17.202). The median weight of publications with falsified data was 55.7% (range, 13.1%-99.6%). From our reanalysis of the 22 meta-analyses, we found that 32 of 99 analyses (32%) yielded results that would change the conclusions of the initial analysis (Table). Of the 32 affected estimates, 31 (97%) no longer favored apixaban for the prevention of serious medical issues, and 1 (3%) favored the control.

The Lab Coat Is on the Hook in the Fight Against Germs - The New York Times

This change took place in part because doctors wanted to spruce up their dubious reputation. Until the advent of such medical reformers as Abraham Flexner and Sir William Osler about 100 years ago, medical training in the United States was notoriously lax. Lectures, not clinical experience, were the norm. It was the age of horse sense and the quack. So to more closely associate themselves in the public mind with sound science, physicians began donning the lab coats that were being worn by chemists and other laboratory types. These coats were generally beige. But white soon became the standard. “Our notion since the 1880s, when the germ theory of disease began to take hold, is that microbes hide in dark, dirty places, and that white stands for purity, both material and moral,” said Guenter Risse, a physician and author of “Mending Bodies, Saving Souls: A History of Hospitals” (Oxford, 1999). “Wearing white coats was a symbol that you were clean.”

ICER chastises J&J for overpricing depression drug esketamine ‘where there is such need for treatment’ – Endpoints News

Us­ing the es­ke­t­a­mine list price of $295 per 28 mg in­tranasal de­vice, the treat­ment’s use re­sults in an in­cre­men­tal cost-​effectiveness ra­tio of ap­prox­i­mately $198,000 per QALY com­pared to no ad­di­tional treat­ment, ex­ceed­ing the com­monly cited cost-​effectiveness thresh­olds of be­tween $50,000-​$150,000 per QALY. Mean­while, es­ke­t­a­mine is es­ti­mated to cost ap­prox­i­mately $2.6 mil­lion per life year gained, ICER found. Es­ke­t­a­mine’s ap­proval was also meant to en­hance ac­cess to treat­ment — since ke­t­a­mine is not cov­ered by health in­sur­ers — al­though there is a con­cern that there may still be high out-​of-pocket ex­penses through de­ductibles or non-​coverage poli­cies. In­deed, “the place for es­ke­t­a­mine may de­pend on the com­par­a­tive ben­e­fits be­tween es­ke­t­a­mine and other avail­able treat­ments, such as ke­t­a­mine. Un­for­tu­nately, such in­for­ma­tion is not avail­able at this time,” ICER said.

This Is How You Kill a Profession - The Chronicle of Higher Education

We discarded college faculty in the same way that we discarded medical general practitioners: through providing insane rewards to specialists and leaving most care in the hands of paraprofessionals. We discarded college faculty in the same way that we discarded cab drivers: by leveling the profession and allowing anyone to participate, as long as they had a minimum credential and didn’t need much money. We discarded college faculty in the same way that we discarded magazine and newspaper writers: by relabeling the work “content” and its workers “content providers.” We discarded college faculty in the same way that we discarded local auto mechanics: by making all of the systems and regulations so sophisticated that they now require an army of technicians and specialized equipment. We discarded college faculty in the same way that we discarded bookkeepers: by finally letting women do it after decades of declaring that impossible, and then immediately reducing the status of the work once it became evident that women could, in fact, do it well.

Many leading universities still failing to report clinical trial results - STAT

Specifically, findings were not posted for 31 percent — or 140 —of 450 studies that were to have been disclosed in public registries as a result of transparency requirements in the FDA Amendments Act, according to Universities Allied for Essential Medicines, a student-led organization concerned with access to medicines, and TranspariMED, a nonprofit research advocacy group. Moreover, only 15 of 40 universities previously found to have lax reporting are in full compliance. For instance, MD Anderson Cancer Center, which sponsored the largest number of applicable trials, disclosed only 77 percent of the findings. Similarly, the Mayo Clinic divulged 42 percent of studies. Columbia University had the worst track record, reporting 17 percent of trials, according to the analysis.

Time to say goodbye to “statistically significant” and embrace uncertainty, say statisticians – Retraction Watch

The bright-line thinking that is emblematic of declaring some results “statistically significant” (p<0.05) and others “not statistically significant” (p>0.05) obscures that uncertainty, and leads us to believe that our findings are on more solid ground than they actually are. We think that the time has come to fully acknowledge these facts and to adjust our statistical thinking accordingly.

Note 'average' number of treatments?!

The 16 participants in the FORSEE-II study had suffered from severe depression for 8 to 22 years and had previously undergone an average of 18 drug therapies, 20 electroconvulsive therapies, and 70 hours of psychotherapy -- without success. Prof. Dr. Volker A. Coenen, first author of the study and director of the Stereotactic and Functional Neurosurgery Unit at the Department of Neurosurgery of the Medical Center -- University of Freiburg, and his team implanted the deep brain stimulation systems in the patients medial forebrain bundle of the brain and used them to stimulate the medial forebrain bundle. This brain region is involved in the perception and regulation of pleasure and reward and is thus also significant for motivation and the perceived quality of life. Clear Relief Often within Days The doctors evaluated the success of the therapy monthly with the help of the established Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS scores of ten study participants already decreased significantly within the first week and remained at a low level. All study participants reacted to the stimulation in the course of the study. Eight of the 16 patients had a MADRS score of under 10 points at the end of the study and thus were regarded as non-depressive. "Our patients had struggled with severe depression for years with no signs of improvement. Deep brain stimulation brought most of them significant relief within days, which lasted throughout the course of the therapy. Other forms of treatment like medication and psychotherapy often lose their effectiveness over the course of time. Absolutely sensational about the study data is that the effect seems to be long lasting, with the positive effects continuing for years," says Prof. Schläpfer. "We know from a pilot study that the stimulation of this brain region is very promising and we are delighted about the replication of these significant effects," says Prof. Coenen.

Fast-acting psychedelic associated with improvements in depression/anxiety -- ScienceDaily

One of the unique properties of 5-MeO-DMT is the fast action and short duration of the psychedelic effects when compared to other psychedelics. "Research has shown that psychedelics given alongside psychotherapy help people with depression and anxiety. However, psychedelic sessions usually require 7 -- 8 hours per session because psychedelics typically have a long duration of action," says Alan K. Davis, Ph.D., a postdoctoral research fellow in the Behavioral Research Unit, at the Johns Hopkins University School of Medicine. "Because 5-MeO-DMT is short-acting and lasts approximately 30-90 minutes, it could be much easier to use as an adjunct to therapy because current therapies usually involve a 60 -- 90 minute session."

Drug Companies and Doctors Battle Over the Future of Fecal Transplants - The New York Times

Mark Smith, a microbiologist at M.I.T., was halfway through his pitch with a group of pharmaceutical executives when one of them interrupted to ask if the meeting was a prank. “I can’t believe you wasted my time with this crazy idea,” the man said, Dr. Smith later recalled. That was 2012. Later that year he helped found OpenBiome, the nonprofit stool bank that now supplies most of the fecal matter for transplants in the United States. Three years ago, he started his own drug company, Finch Therapeutics, which has raised $77 million. Over the past decade, tens of thousands of Americans with C. diff have been cured through fecal transplants, often with a single dose that can bring patients back from the brink of death. The treatment has more than an 80 percent success rate, according to several studies, and many patients feel better within hours of receiving the procedure, which is usually administered through colonoscopy or capsules containing desiccated fecal matter. The F.D.A. has not formally approved the therapy but it has suspended enforcement of its rules for patients who have failed on antibiotics while it figures out the best way to regulate a regimen that, until recently, was sometimes performed at home by desperate patients using an enema, saline and a relative’s stool. Ms. Duff, the head of the C. diff patients group, credits her own recovery from the disease to a homemade concoction her husband created with his own stool in the kitchen blender.

Medical Device Makers Report Malfunctions And Patient Injuries In FDA Database Hidden From Public ViewKaiser Health News

Agency records provided to KHN show that more than 480,000 injuries or malfunctions were reported through the alternative summary reporting program in 2017 alone. Alison Hunt, another FDA spokeswoman, said the majority of device makers’ “exemptions” were revoked that year as a program took shape that requires a summary report to be filed publicly. More than a million reports of malfunctions or harm spanning about 15 years remain in a database accessible only to the FDA. But with the agency’s new transparency push, the public may find a public report and submit a Freedom of Information Act request to get information about incidents. A response can take up to two years. The long-standing exemption program “has allowed the FDA to more efficiently review adverse events … and take action when warranted without sacrificing the quality of our review or the information we receive,” Hunt said in an email. Madris Tomes(Courtesy of Madris Tomes) To those outside the agency, though, the exceptions to the reporting rules are troubling. They strike Madris Tomes, a former FDA manager, as the agency surrendering some of the strongest oversight and transparency powers it wields. “The FDA is basically giving away its authority over device manufacturers,” said Tomes, who now runs Device Events, a website that makes FDA device data user-friendly. “If they’ve given that up, they’ve handed over their ability to oversee the safety and effectiveness of these devices.”

Applying a network perspective to human physiology: Physicist describes 'network physiology,' which looks at different organ systems and how they relate to each other -- ScienceDaily

"We need to show how the different systems communicate with each other and adjust, coordinate and stay in sync," said Ivanov. The human body, according to this view, can be thought of as a network, with each organ serving as a node connected to other organs and other nodes. "The nodes are not just dots," he said. "They're dynamical systems, constantly changing in time, as are the connections between them." Today's best hospitals aren't equipped to monitor the inter-organ interactions. "Separate devices keep track of separate functions, but no single monitor can observe a multitude of functions," he said. To improve health monitoring techniques, Ivanov and his colleagues have spent the past decade developing the computational tools and biomedical devices needed to capture data streams from different organ systems and see how they relate to each other.

Psychiatry: Case notes indicate impending seclusion -- ScienceDaily

The retrospective examination encompassed the records of 26 adult patients who ultimately required seclusion. A patient group of equal size with identical diagnoses, for whom coercive measures were not required, was used as a comparison. The basis for the qualitative and quantitative text analysis was the notes from the three days preceding an escalation. The results showed that the case notes before seclusion were more extensive, meaning they contained a significantly higher number of words. "It seems that the attending staff describe problematic behavior more comprehensively in order to improve information transfer between different shifts, justify upcoming coercive measures and ensure that they are legally protected," says Dr. Clara Stepanow, author of the study.

Health data tools to rapidly detect sepsis in newborns: Study uses automated models to identify sepsis before clinical recognition -- ScienceDaily

"Because early detection and rapid intervention is essential in cases of sepsis, machine-learning tools like this offer the potential to improve clinical outcomes in these infants," said first author Aaron J. Masino, PhD, who led the study team's machine-learning efforts. Masino is an assistant professor in the Department of Anesthesiology and Critical Care Medicine and a member of the Department of Biomedical and Health Informatics at Children's Hospital of Philadelphia (CHOP). "Follow-up clinical studies will allow researchers to evaluate how well such systems perform in a hospital setting."

Worldwide estimates suggest that nearly 1 in 2 children with cancer are left undiagnosed and untreated -- ScienceDaily

"Our model suggests that nearly one in two children with cancer are never diagnosed and may die untreated," says study author Zachary Ward from the Harvard T.H. Chan School of Public Health, USA. "Accurate estimates of childhood cancer incidence are critical for policy makers to help them set healthcare priorities and to plan for effective diagnosis and treatment of all children with cancer. While under-diagnosis has been acknowledged as a problem, this model provides specific estimates that have been lacking."

Could we soon be able to detect cancer in 10 minutes? | Science | The Guardian

Looking for ctDNA has become a viable proposition in recent years because of improvements in DNA sequencing technologies that make it possible to scan fragments and find those few with alterations that may indicate cancer. While other blood-based biomarkers are being investigated, the advantage of ctDNA is that, because it has a direct link to the tumour, it can be very specific at identifying cancer. For that reason, ctDNA is also showing promise as a way to profile and monitor advanced stage cancers, a “liquid biopsy”. Early detection is a harder problem. Early on, when the tumour is small, there is not as much ctDNA to detect. The women Illumina identified as having cancer were all late, not early stage.

The shifting model in clinical diagnostics: how next-generation sequencing and families are altering the way rare diseases are discovered, studied, and treated | Genetics in Medicine

Until very recently, the fragmented distribution of patients across institutions hindered the discovery of new rare diseases. Clinicians working with a single, isolated patient could steadily eliminate known disorders but do little more. Families would seek clinicians with the longest history and largest clinic volume to increase their chances of finding a second case, but what does a physician do when N = 1 or if the phenotype is inconsistent across patients? These challenges are driving an increase in the use of NGS. Yet this technological advance presents new challenges of its own. Perhaps the most daunting, in our opinion, is the inability to share sequencing data quickly and universally. Standards and bioinformatic tools are needed that allow for a national repository where families or scientists can bring clinical results and NGS data for comparison. This challenge can be circumvented by tools already created for and by the Internet and social media.

Open-science model for drug discovery expands to neurodegenerative diseases -- ScienceDaily

Open science is a way for researchers to share their data and knowledge quickly and publicly, unencumbered by patents and the peer review publishing process, with the aim of speeding up scientific discovery. The movement gathered force in the life sciences in the 1990s with the Human Genome Project, and spread to protein structures and then early-stage drug discovery through the Structural Genomics Consortium (SGC).

Side-effects not fully reported in more than 30 percent of healthcare reviews -- ScienceDaily

The new study looked at the reporting of adverse events in 187 systematic reviews published between 2017 and 2018. Systematic reviews in health research aim to summarise the results of controlled healthcare interventions and provide evidence of the effectiveness of a healthcare intervention. Research showed that 35 per cent of reviewers did not fully report the side-effects of the medical intervention under review. Dr Su Golder, from the University of York's Department of Health Sciences, said: "Despite reviewers stating in their own protocols that adverse events should be included in the review, 65 per cent fully reported the event as intended by the protocol, eight per cent entirely excluded them, and the remaining 27 per cent either partially reported or changed the adverse event outcomes." "Just over 60 per cent, however, didn't even include adverse events in their protocols, which suggests that a more proactive approach is needed to prompt reviewers to report on potential harmful side-effects in their reporting of healthcare interventions."

Myriad Genetics to Acquire Counsyl for $375M | GenomeWeb

Myriad will merge Counsyl's reproductive health tests with its existing preventive care business unit into a new business unit called Myriad Women's Health, which will focus solely on OB-Gyns and reproductive healthcare providers. Myriad will also combine its women's health sales force of approximately 225 representatives with Counsyl's 80 sales professionals, enabling a threefold increase in physician reach for reproductive testing, according to Myriad.

An Expanded View of Complex Traits: From Polygenic to Omnigenic: Cell

In summary, many complex traits are driven by enormously large numbers of variants of small effects, potentially implicating most regulatory variants that are active in disease-relevant tissues. To explain these observations, we propose that disease risk is largely driven by genes with no direct relevance to disease and is propagated through regulatory networks to a much smaller number of core genes with direct effects. If this model is correct, then it implies that detailed mapping of cell-specific regulatory networks will be an essential task for fully understanding human disease biology.

An Expanded View of Complex Traits: From Polygenic to Omnigenic: Cell

core genes generally contribute just a small part of the total heritability and how most genes expressed in relevant cell types could make non-zero contributions to heritability. To resolve this, we propose that cell regulatory networks are highly interconnected to the extent that any expressed gene is likely to affect the regulation or function of core genes.

Peter Thiel vs. the FDA - Vox

Thiel, a libertarian iconoclast, has repeatedly made the case that the FDA gets in the way of drug innovation by making it too difficult for new medicines to get to the market. Some of the FDA candidates he’s identified — including Silicon Valley’s Jim O’Neill and Balaji Srinivasan — have similarly argued that the agency should dump its requirement that drugs be proven effective before reaching the market, and that we’d be better off if the FDA operated more like a “Yelp for drugs.” In other words, bringing the same speedy and disruptive approach to medical regulation that Silicon Valley brought to the taxi and hotel industries, for example, will unlock cures — fast.

FDA Plans To Modernize 510(k) Program - Covering the specialized field of orthopedic product development and manufacturing

Importantly, we’ve increased expectations for the quality and quantity of information required in 510(k) submissions, resulting in a more than doubling of the size of submissions—now, an average of 1,185 pages, compared to 475 pages in 2009. And while our reviewers have spent more time reviewing applications during this same period—an increase of about 32 percent—the average total time for the agency to reach a decision has decreased, reflecting a more robust and efficient program. These metrics reflect not only the strengthening of the medical device review program, but also the dedication of the talented CDRH career staff in carrying out our public health mission and continuing to drive forward critical program enhancements.

‘Omnigenic’ Model Suggests That All Genes Affect Every Complex Trait | Quanta Magazine

Starting about 15 years ago, geneticists began to collect DNA from thousands of people who shared traits, to look for clues to each trait’s cause in commonalities between their genomes, a kind of analysis called a genome-wide association study (GWAS). What they found, first, was that you need an enormous number of people to get statistically significant results — one recent GWAS seeking correlations between genetics and insomnia, for instance, included more than a million people. Second, in study after study, even the most significant genetic connections turned out to have surprisingly small effects. The conclusion, sometimes called the polygenic hypothesis, was that multiple loci, or positions in the genome, were likely to be involved in every trait, with each contributing just a small part. (A single large gene can contain several loci, each representing a distinct part of the DNA where mutations make a detectable difference.)