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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.)

will.i.am on personal data ownership

Personal data needs to be regarded as a human right, just as access to water is a human right. The ability for people to own and control their data should be considered a central human value. The data itself should be treated like property and people should be fairly compensated for it.

WillIAm-on-consumer-health-data-services

Today, my gadgets may count my steps, but they aren’t seeing the big picture: what I ate, how I felt, what my blood pressure is. New services, built from the point of view of the consumer, will benefit me by sharing and interconnecting my own data, rather than selling it on. When more trust is established, my personal “agent” or “assistant” should merge relevant things together that are currently just disconnected data points.

BARBARIANS AT THE GATE: CONSUMER-DRIVEN HEALTH DATA COMMONS AND THE TRANSFORMATION OF CITIZEN SCIENCE

A few state court cases have found patients own their medical records under specific circumstances.118 Unfortunately, the pertinent body of state medical records law generally applies in traditional healthcare settings and seemingly does not govern commercial providers of PHD devices and services, such as purveyors of medical and fitness devices. Courts do not recognize an individual property right in personal information such as one’s name, address, and social security number.119 Commercial databases that hold such information are generally treated as the property of the companies that compiled them.120 In a famous case121 where plaintiffs sought to block a company from disclosing their personal information by selling its mailing lists, Vera Bergelson notes an implicit judicial bias “that, to the extent personal information may be viewed as property, that property belongs to the one who collects it.”122 This bias— if it exists—is reminiscent of the ancient res nullius doctrine from natural resource law, which treated assets such as subsurface mineral deposits and wild animals as unowned until somebody discovers and captures (takes possession of) them.123 “Rarely used today, it let private owners stake claims as in the Klondike gold rush.”124

BARBARIANS AT THE GATE: CONSUMER-DRIVEN HEALTH DATA COMMONS AND THE TRANSFORMATION OF CITIZEN SCIENCE

This article explores how these mechanisms, imbedded in major federal research and privacy regulations, enshrine institutional data holders—entities such as hospitals, research institutions, and insurers that store people’s health data—as the prime movers in assembling large-scale data resources for research and public health. They rely on approaches—such as de-identification of data and waivers of informed consent—that are increasingly unworkable going forward. They shower individuals with unwanted, paternalistic protections—such as barriers to access to their own research results—while denying them a voice in what will be done with their data.

BARBARIANS AT THE GATE: CONSUMER-DRIVEN HEALTH DATA COMMONS AND THE TRANSFORMATION OF CITIZEN SCIENCE

Data resources are a central currency of twenty-first-century science, and the question is, “Who will control them?”

Genetic risk for ADHD manifest in brain structure in childhood -- ScienceDaily

The analysis showed that morphological differences in the caudate nucleus could, in part, explain the association between genetic risk for ADHD and attention problems in boys; however, this association was not observed in girls. "ADHD is more prevalent among boys than girls and the reasons for this difference are still being investigated," explains Silvia Alemany. "And our findings suggest that the genetic variants associated with ADHD may act differently in the brains of boys and girls."

Privacy in the age of medical big data | Nature Medicine

For instance, once a patient requests their own health data—which HIPAA gives them the right to do, and some concerted efforts encourage patients to do35,36—if the patient then gives those data to another individual, HIPAA does not restrict use or disclosure of those data (unless the recipient is another covered entity or a business associate)24. But the more fundamental problem is that the majority of health data is not covered by HIPAA at all (Fig. 2).

Privacy in the age of medical big data | Nature Medicine

Big data is often defined by ‘three Vs’: volume (large amounts of data), velocity (high speed of access and analysis), and variety (substantial data heterogeneity across individuals and data types), all of which appear in medical data2.

All of Us enrollees can now share health data from their Fitbit accounts with researchers | MobiHealthNews

“Collecting real-world, real-time data through digital technologies will become a fundamental part of the program,” Eric Dishman, director of the All of Us Research Program, said in a statement. “This information in combination with many other data types will give us an unprecedented ability to better understand the impact of lifestyle and environment on health outcomes and, ultimately, develop better strategies for keeping people healthy in a very precise, individualized way.”

The F.D.A. vs. Personal Genetic Testing | The New Yorker

A fifty-five-year-old who is confused and depressed and learns that he carries two copies of the risk gene and stands an eighty-per-cent chance of getting Alzheimer’s might reach for a gun, which is the kind of scenario that some genetic counsellors worry about.

23andMe Is Sharing Genetic Data with Drug Giant - Scientific American

Only about 10,000 of the 1 million Americans with Parkinson’s disease have the disease because of LRRK2. So, GlaxoSmithKline has to test about 100 Parkinson’s patients to find just one potential candidate. However, 23andMe has already provided 250 Parkinson’s patients who have agreed to be re-contacted for GlaxoSmithKline’s clinical trials, which may help the pharmaceutical company develop the drug much faster, Forbes reported.

Full transcript: 23andMe CEO Anne Wojcicki answers genetics and privacy questions on Too Embarrassed to Ask - Recode

It’s hard because health care is spectacularly fragmented. An oncology team at Stanford doesn’t do the same things as an oncology team at Memorial Sloan Kettering and to protect it under the Practice of Medicine, and they have different ways that they engage with their patients. Everything is spectacularly fragmented. For us, one of the things that I’m really proud of that we saw is I have millions of people now on a single platform that I know are all interested in their DNA and their health. I think there’s a huge potential for us to help, again, engage all of our customers and potentially work with all of the innovative tech companies out here and give them a platform.

Brains of people with schizophrenia-related disorders aren't all the same: New study supports the use of a data-driven approach to identify novel biomarkers -- ScienceDaily

"We know that, on average, people with schizophrenia have more social impairment than people in the general population," says senior author Dr. Aristotle Voineskos in the Campbell Family Mental Health Research Institute at the Centre for Addiction and Mental Health (CAMH) in Toronto. "But we needed to take an agnostic approach and let the data tell us what the brain-behavioural profiles of our study participants looked like. It turned out that the relationship between brain function and social behaviour had nothing to do with conventional diagnostic categories in the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders)." Most brain research in the mental health field compares a disease group to a non-disease or "healthy" group to search for biomarkers, a biological measure of mental health symptoms. This search for biomarkers has been elusive. This multi-site research study -- which included 179 participants recruited at CAMH in Toronto, Zucker Hillside Hospital in New York and the Maryland Psychiatric Research Center in Baltimore -- calls that paradigm into question because people with the same mental illness may not show the same biological patterns. The study, which involved participants completing a facial imitation task while undergoing functional MRI brain scans, found three "activation profiles," says first author Dr. Colin Hawco, also of CAMH. These can be described as typical, over-activated and de-activated profiles.

The cumulative effect of reporting and citation biases on the apparent efficacy of treatments: the case of depression

Figure 1 demonstrates the cumulative impact of reporting and citation biases. Of 105 antidepressant trials, 53 (50%) trials were considered positive by the FDA and 52 (50%) were considered negative or questionable (Fig. 1a). While all but one of the positive trials (98%) were published, only 25 (48%) of the negative trials were published. Hence, 77 trials were published, of which 25 (32%) were negative (Fig. 1b). Ten negative trials, however, became ‘positive’ in the published literature, by omitting unfavorable outcomes or switching the status of the primary and secondary outcomes (Fig. 1c). Without access to the FDA reviews, it would not have been possible to conclude that these trials, when analyzed according to protocol, were not positive. Among the remaining 15 (19%) negative trials, five were published with spin in the abstract (i.e. concluding that the treatment was effective). For instance, one article reported non-significant results for the primary outcome (p = 0.10), yet concluded that the trial ‘demonstrates an antidepressant effect for fluoxetine that is significantly more marked than the effect produced by placebo’ (Rickels et al., 1986). Five additional articles contained mild spin (e.g. suggesting the treatment is at least numerically better than placebo). One article lacked an abstract, but the discussion section concluded that there was a ‘trend for efficacy’. Hence, only four (5%) of 77 published trials unambiguously reported that the treatment was not more effective than placebo in that particular trial (Fig. 1d). Compounding the problem, positive trials were cited three times as frequently as negative trials (92 v. 32 citations in Web of Science, January 2016, p < 0.001, see online Supplementary material for further details) (Fig. 1e). Among negative trials, those with (mild) spin in the abstract received an average of 36 citations, while those with a clearly negative abstract received 25 citations. While this might suggest a synergistic effect between spin and citation biases, where negatively presented negative studies receive especially few citations (de Vries et al., 2016), this difference was not statistically significant (p = 0.50), likely due to the small sample size. Altogether, these results show that the effects of different biases accumulate to hide non-significant results from view.

Infections (or Dr-philia?) correlate with mental disturbances

The study showed that children who had been hospitalised with an infection had an 84 per cent increased risk of suffering a mental disorder and a 42 per cent increased risk of being prescribed medicine to treat mental disorders. Furthermore, the risk for a range of specific mental disorders was also higher, including psychotic disorders, OCD, tics, personality disorders, autism and ADHD.

Pear Therapeutics, Novartis announce commercial launch of reSET | MobiHealthNews

reSET — a substance use disorder treatment that was the first software-only therapeutic cleared by the FDA — is now commercially available for clinicians to prescribe to their patients, according to a release from Pear Therapeutics and Sandoz, a division of Novartis with which Pear partnered back in April. But while physical prescription drugs are usually handled through a pharmacy, the process is a bit different for the digital therapeutic, Dr. Yuri Maricich, Pear’s chief medical officer and head of clinical development, told MobiHealthNews. Prescribing physicians will write a script that is sent to Pear’s reSET Connect Patient Service Center, which staffs specialists who guide the patient through downloading and using the app. Outside of that wrinkle, though, Maricich said that disseminating the treatment to care centers has been “very similar” to how a pharmaceutical company might put a novel treatment into the wild. “We have a team of salespeople who are going out and educating clinicians about the product, its data, how to use it; and we also have a set of services that support dispensing, but they aren’t selling to the clinicians,” he said. “Also, that dispensing and fulfillment process allows the physician to access the dashboard and the therapeutic for their patient as well. And in the background we [Pear and Sandoz] work with payers around coverage and contracts. So, really, what we’re focusing on now is getting the therapeutic in the hands of patients who need it and helping clinicians understand how to use it, who’s the right patient for it, how do I prescribe it and interact with it as part of standard care.” Still, Pear and Sandoz seem to be playing it safe with the new treatment modality — beyond general distribution and sales, the Patient Service Center is also equipped talk patients and providers through any questions or troubles they might be having. “How a patient gets access to [reSET] and how it’s prescribed is new, so we really wanted to try to provide bespoke services to the clinician and the patient,” Maricich explained. “The Patient Service Center is available to help with troubleshooting, they have clinical staff available if there’s clinical questions, and then they also are available if there are complaints or adverse events. So they are, basically, the central node for all of those activities to help clinicians and patients get access to therapeutic and to use it.” reSET is a 12-week digital cognitive behavioral therapy program accessed through an app and designed to accompany outpatient care delivered by a physician. According to Maricich, it is the only treatment authorized by the FDA for patients aged 18 years and older experiencing addiction to and dependency on stimulants, cannabis and cocaine (as well as alcohol).

Brain signature of depressed mood unveiled in new study: Direct recordings of human brain activity link memory, emotion, and anxiety during bouts of low mood -- ScienceDaily

Then, to compare results across the unique brains and distinct electrode placements of all 21 research participants, the researchers mapped each subject's ICNs onto neural connectivity diagrams. Comparing these standardized records of network activity across subjects revealed several "cliques" -- groups of brain regions that repeatedly became synchronized at specific frequencies, and were therefore likely to represent functional brain networks. One such clique was highly active and coordinated in 13 research participants, all of whom had also scored high on a psychological assessment of baseline anxiety conducted prior to the start of the study. In these same individuals, changes in the activity of this brain network were also highly correlated with day-to-day bouts of low or depressed mood. This mood-related network was characterized by so-called beta waves -- synchronized oscillations between 13 and 30 cycles per second -- in the hippocampus and amygdala, two deep brain regions which have long been linked, respectively, to memory and to negative emotion. Sohal said the research team was at first taken aback by the clarity of the finding. "We were quite surprised to identify a single signal that almost completely accounted for bouts of depressed mood in such a large set of people," said Sohal. "Finding such a powerfully informative biomarker was more than what we'd expected at this stage of the project." Surprisingly, this powerful link between of mood-associated beta waves in the amygdala and hippocampus was entirely absent from eight other research participants, all of whom had comparatively low preexisting anxiety, suggesting new questions about how the brains of people prone to anxiety may differ from others in how they process emotional situations.