Posted by on in NEJM Highlights

Best care vs. good care In wealthy countries, the recommended standard of care can often lead to complex medication regimens requiring frequent follow-ups: this can be very challenging for people who though they live in wealthy countries but are poor themselves. In developing countries, efforts have been made to prioritize simplicity and population level impact through one-size fits all polypill interventions, but that has not been tested in the US. Here the authors report on a randomized study including 303 individuals living in poverty and at risk for cardiovascular disease. The active arm was provided with a daily polypill combining… Read More

Posted by on in NEJM Highlights

Is the lack of new (non-viral) antibiotics a market failure? A lament about the lack of success in getting the biopharma industry to invest sustainably in the development of new antibiotics against highly-resistant organisms, and a recommendation “it is time to seriously consider the establishment of nonprofit organizations for developing these lifesavings drugs”.  Let’s be clear; the reason economic viability of this therapeutic area is problematic is due to three confluent factors: (1) treatment is curative – i.e. does not provide recurrent revenues (2) the targeted population is small (3) unmet need is unpredictable. On its face, the risk-reward… Read More

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Huntington’s disease: light at the end of the tunnel? The awful thing about Huntington’s is that in most cases, people know they are going progressively lose their mind at an early age, but there is absolutely nothing they can do about it.  Recently there has been tremendous excitement around suppressing toxic huntingtin production in the brain by using antisense oligonucleotides (ASOs) administered intrathecally (i.e. in the cerebrospinal fluid through the spine). Two ASOs are in full blown clinical testing: HTTRx (Ionis and Roche) which does not discriminate between mutant and normal huntingtin, and WVE-120101/2 (Wave Therapeutics and Takeda) which… Read More

Posted by on in Population Health, Providers

A clinical vignette: the cases of Jane and Joe Imagine if you will two individuals both at age 50. Jane is a project manager whose recent health care has focused on managing menopausal symptoms, a knee injury sustained while skiing, and moderate episodic depression, with a medication list of one chronic medication, and one medication as needed.  Joe is a bus driver whose recent health care has focused on managing Type II diabetes, hypertension, and low back pain, with a regimen of 4 chronic medications, and 2 medications as needed.  Jane is highly informed and engaged in her care. Read More

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TAVR for all? TAVR has become the standard of care for patients who need an aortic value replacement but are at high/medium surgical risk.  But what about those at low-risk? Two studies answer that question, one with the Edwards device and the other with Medtronics. Both show that TAVR is superior along a number of end-points (stroke, hospitalization duration, atrial fibrillation) both at 30 days and at 1-2 year. Long-term outcomes remain a question though. Low-risk patients are younger (mean age 73-74) and will live with their valves longer, which means that in contrast with the mechanical valves that can… Read More

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He’s dead, Jim As previously widely advertised, the BACE-1 inhibitor verubecestat (Merck) (and in journal correspondence atabecestat, Janssen) has now failed in a population with very early signs of cognitive impairment (this after a failure of those agents in mild-moderate Alzheimer’s). Target engagement clearly occurred with a decline of the amyloid detected through PET imaging in the treatment arms and an increase in the placebo arm. However, if anything, cognition declined more in the treatment arm than in the placebo arm after 2 years on study. A silver lining is that the study does show the feasibility to execute… Read More

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Target assessment with genetic polymorphisms Please bear with me for a long (but interesting!) story. Bempedoic acid (Esperion) is an inhibitor of ATP citrate lyase (ACLY), an enzyme in the cholesterol synthesis pathway (upstream of HMG-CoA reductase, the target of statins). In a study of 2,230 patients at high risk for cardiovascular events, on maximum statin therapy, and LDL > 70 (basically the PCSK9 target population), bempedoic acid was well tolerated and lowered the LDL by around 16% – a substantial effect. This would potentially position bempedoic acid, an oral drug, to take on the parenteral PCSK9 inhibitors as main… Read More

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Targeted conjugated cancer therapeutics – so few, but may be more soon The idea that one could combine the precision of a targeted biologic with the potency of a traditional cytotoxic to demolish a tumor has been around for decades, but with very rare exceptions, has not had the level of traction one would have expected.  But this month, the journal has two studies reporting on these types of therapies, both in breast cancer. One shows that in a group of heavily pre-treated triple-negative breast cancer patients, sacituzumab govitecan-hziy (Immunomedics) induced a respectable 33% response rate. The other shows that… Read More

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The bundle Unlike many other CMMI experiments, the Comprehensive Care for Joint Replacement (CJR) program was a true randomized control trial in that participation was mandatory in a selection of metropolitan areas and not allowed anywhere else, which allows for an analysis untainted by self-selection bias. In brief the question to be answered was does a 90-day bundled payment for a joint replacement (knee/hip) get better value (improved care and/or lower costs) than the traditional FFS approach? A differences of differences analysis comparing the bundled vs. control arms before and after the intervention finds that the most significant divergence between… Read More

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Genetic trade secrets In 2012, the US Supreme Court decided a case known as “Prometheus” establishing that therapeutic methods based on biomarkers were not patentable – this essentially blocked one of the two main avenues to monetizing intellectual property from the very hard clinical work of figuring out personalized medicine, i.e. what works for whom. The other avenue that would remain is that of trade secrets, and I for one, have been waiting for the other shoe to drop.  A hint comes from a study on ovarian cancer just published in the NEJM: patients were selected on the basis… Read More