Category: NEJM Highlights

Recon takes an analytical look behind select developments in healthcare

An opinionated take on NEJM highlights for July 2017

Taking stock: two decades of progress in heart failure: Here comes a clever study using existing clinical trial data to assess progress in standard of care over time for heart failure. For each trial, the authors assessed the rate of sudden cardiac death during the early part of the study (excluding patients with ICDs), and it appears that between 1995 and 2014, it decreased by nearly half.  As always, in observational retrospective studies, one has to worry about systematic biases around the population that are included (i.e. are they really

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June was negative-to-ambiguous: an opinionated take on NEJM highlights for June 2017

Stent news First there was angioplasty, then bare stents, then drug-eluting stents, and now the next generation: bioresorbable stents: each generation commanding a significant price premium for the manufacturers (but only for a few years). But, while bare stents and drug eluting stents were clear improvements on the previous standard of care, the case is not at all obvious for bioresorbable stents.  Now the latest news is that the Absorb stent (Abbott), instead of showing a benefit over the previous standard of care, appears to lead to a higher rate

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An opinionated take on NEJM highlights for May 2017

A hammer finds new nails (which happen to be eyeballs) The insulin growth factor receptor 1 (IGF-1R) was once upon a time a popular cancer target pursued by multiple biopharmas each with their own humanized antibody, and each without much success. In 2013, River Vision licensed the Roche compound teprotumumab, to treat Graves’ ophthalmopathy, a condition in which hyperactivity of the thyroid gland causes (among many other issues) bulging eyeballs with esthetic, comfort, and sometimes severe visual implications for which treatment options are limited. Nobody quite knows why the ocular

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April was a light month: an opinionated take on NEJM highlights for April 2017

Calendaring care The length of our sidereal year is an accident – we happen to be circling a G2 star from which the habitable zone where free surface liquid water can exist lies at around 150,000,000 km; by Newton’s laws this in turn corresponds to an orbital period that is our year.  Even if it is not particularly strongly connected to the underlying human biology, a lot of healthcare cycles are aligned to the Earth Year for convenience but is it effective and efficient? Individuals with diabetes are at risk

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Regeneration and mitigation: an opinionated take on NEJM highlights for March 2017

Gene therapy for sickle cell disease Typical diseases targeted by gene therapy are those for which there is a defect that prevents the production of a functional protein needed for normal life; remediation is achieved by inserting functioning copies of the gene, and fortunately, it is usually the case that expression at a low level is sufficient to greatly improve outcomes. The situation is different in sickle cell where the defective hemoglobin is actually harmful, and where success of gene therapy requires not only production normal hemoglobin, but replacement of

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It’s in the blood: an opinionated take on NEJM highlights for February 2017

A knock at the door of a monster franchise Adalimumab (Humira, Abbvie) is the best-selling drug on the planet with the bulk of sales coming from patients suffering from rheumatoid arthritis (RA). It is therefore quite a coup for Lilly/Incyte to have shown in a double blind controlled study that baricitinib, an inhibitor of JAK (an important intracellular signaling molecule), performed better in relieving the symptoms of patients with RA than adalimumab. It was all the more surprising given that another JAK inhibitor, tofacitinib (Xeljanz, Pfizer, now also approved for

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Keeping the pipes clean and the wires intact: an opinionated take on NEJM highlights for January 2017

An innovative modality to suppress PCSK9 Antisense technology relies on the concept that it is possible to interfere with the cellular genetic machinery in very specific ways by deploying short RNA sequences that are complementary to the message that one wants to suppress. The idea has been around for a while, but has only achieved limited success in very niche indications (see here for the two latest). This is what makes the publication of phase 1 trial of the antisense agent inclisiran (Alnylam and the Medicines Company) targeting the synthesis

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A strong close to a banner year for progress against cancer: an opinionated take on NEJM highlights for December 2016

Successful use of CAR-T therapy in a solid tumor Chimeric Antigen Reception T-cells (CAR-T) are immune cells molecularly engineered to seek out and destroy cancer cells; the push to develop them into a scalable generally usable treatment is likely the most exciting challenge in cancer right now.  Successful CAR-T use has so far been generally confined to hematological tumors.  In a brief report, a group from City of Hope reports on the use of CAR-T in a patient who was dying from an advanced, aggressive form of brain cancer, which

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We may figure out cancer before we figure out the healthcare system: an opinionated take on NEJM highlights for November 2016

“My name is T-Cell…, James T-Cell” Immune T-cells are licensed to kill other cells through a quick molecular kiss of death, and as such are potentially powerful allies in controlling a tumor. For obvious reasons this killing power is under strict regulatory control and in particular T-cells display PD-1 proteins on their surface, which when engaged by the ligand PD-L1 on another cell, protects that cell from being killed. Tumors often display high levels of PD-L1 so that disrupting the interaction between PD-L1 and PD-1 can enhance the effectiveness of

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An ad page in the NEJM and the future of cancer care

I am not sure how many docs continue to do this, but I still read the actual hard copy of my NEJM, and that means I flip past ad pages with smiling grandfathers playing with grandchildren thanks to supercalifragilistic products on my way to scholarly papers with tables and figures.  But this time, I stopped in puzzlement when I came across exhibit 1; Intermountain is a health system based in Utah, very highly respected for its sound approach to quality and cost control[1], but not broadly well known for cancer care

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An opinionated take on NEJM highlights for October 2016

Continued progress in multiple myeloma About 25,000 patients are diagnosed with multiple myeloma yearly in the US. Despite being initially treatable, typically this disease is ultimately lethal. Following a highly successful phase 1-2 study a monoclonal antibody against a marker of myeloma cells (daratumumab, Janssen) underwent phase 3 studies in combinations with established mainstays of therapy (the proteasome inhibitor bortezomib and the immune modulator lenalinomide) in a patient population several years out from their initial diagnosis.  Results were stellar, with the inclusion of daratumumab decreasing the disease progression rate by

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An opinionated take on NEJM highlights for September 2016

Taking a page from HIV to build a response to opioid abuse A couple of perspectives on the challenges of treating individuals who suffer from opioid dependence. The first highlights the importance of integrating medication assisted treatment (e.g. methadone or buprenorphine) into hospital and post-hospital care – plausibly an ED visit or a hospital stay for an event triggered by opioid abuse (such as an overdose) is a significant opportunity to go beyond treating the acute issue and starting patients on long term treatments. In the second, the author recalls

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An opinionated take on NEJM highlights for August 2016: cleanliness is not next to healthiness, testing before thinking, a long slog for precision medicine

There is such a thing as too much hygiene The prevalence of asthma in children has increased dramatically over the last few decades. Observational studies have shown that children in “dirty” environments such as farms seem to be relatively protected from asthma.  A theory is that the lack of exposure to microbes leads to higher sensitivity to allergens, but this causality has been hard to show. Amish and Hutterite farm communities are genetically similar, but Amish rely on animals instead of machinery, and Amish children have much lower incidence of

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NEJM Highlights for July 2016: Bayesians vs. frequentists, PCPs vs. specialists, SGLT-2 vs. GFR

Adaptive clinical trials slowly coming of age In an adaptive clinical trial, the protocol of the trial is allowed to change in a pre-specified manner during the study based on on-going study events.  In this issue of the NEJM, two research papers, one perspective, and one editorial are devoted to the I-SPY 2 trials which dynamically changed randomization procedures for neo-adjuvant (pre-surgery) chemotherapy for stage II and III breast cancer and allowed accelerated identification of subgroups that benefit from a novel tyrosine kinase inhibitor (neratinib – Puma Biotechnology) and a

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NEJM Highlights for June 2016: Improving care delivery is just plain #%^*! hard

Disappointing interim results from two ACA experiments Two papers reporting results from ACA experiments – the Comprehensive Primary Care (CPC) Initiative in which primary practices were incentivized with fairly generous payments to strengthen care management activities such as management of chronic conditions, or coordination of care – and the ACO initiatives (2012 cohort) described elsewhere in many reviews. Both papers provide a view on the early impact of these initiatives (2 years out) on costs and outcomes by using well controlled no-intervention comparison groups. The upshot is that so far,

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NEJM Highlights for May 2016: Referral for surgery, and a miscellany of interesting biochemistry

Surgical volume and referral for surgery: The impact of surgical volume on outcomes has been well documented, but is it top of mind with physicians referring patients to surgery? Readers of the Journal were polled on a hypothetical scenario whereby a community physician would be referring a patient in need of a major surgical procedure to either a nearby community hospital with a well-respected general surgeon doing approximately 5 of these cases a year versus a tertiary medical center 40 miles away. The great majority of readers chose the option

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NEJM Highlights April 2016: Value and values: RBRVS, ACA and readmissions, E-cigs

RBRVS: an acronym we ought to think more about RBRVS stands for the Resource Based Relative Value Scale, and codifies the time and effort involved for a comprehensive set of physician activities on which Medicare payments are based. In this perspective, the authors highlight that most value-based payment (VBP) systems currently under development are essentially built as modifiers on top of the RBRVS. But the RBRVS has two major issues with it: it is “downward sticky” and has not evolved to take into account increased efficiency (e.g. automation), and it

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NEJM Highlights March 2016: Getting value for money in healthcare, Zika bad news, linking the microbiome to the metabolic syndrome

Could Uber happen to healthcare? A Perspective article that points out that the success of Uber is rooted in the flaws of an industry where customer convenience and value for money took the backseat to the interest of a set of service providers highly protected by regulation. Sounds familiar?  Obviously, the regulatory moats of healthcare are much wider and deeper, but in a curious mix of warning (watch out!) and encouragement (this will be good for you if you embrace it!) the authors argue that the medical profession should not

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NEJM Highlights Feb 2016: metrics for all, ROI perversion, less memory loss, the value of a kinder gentler residency

Defining success in health care A perspective advertising yeoman’s work of the International Consortium for Health Outcomes Measurement (ICHOM) which has defined specific metrics for dozens of diseases for which there are no widely accepted standards defined so far. If followed broadly, this will greatly facilitate performance comparisons across systems, improvement of processes of care delivery, and the implementation of value based contracting. Standardizing Patient Outcomes Measurement (free access)   Public health gets no respect A lament on how population health interventions tend to be beholden to positive ROI standards

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NEJM Highlights January 2016: a medley of social service, OB, data mining, obesity, and ESRD

Leveraging community services for health In poor individuals, a lot of health issues are intimately connected to their socioeconomic circumstances. However, at the system level, there has been a chronic lack of integration between social and health services. Several efforts have tried to remedy this, notably through integration of the Medicare and Medicaid components for duals in the financial alignment demonstration projects sponsored by CMS. But a there are a lot of social services that are not part of Medicaid; and recognizing the need to ensure awareness, and access, CMS

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