Preempting severe genetic disease
Around 2% of births come with a genetic disease, often with devastating impact. While some appear de novo (either from germplasm dominant mutations or from chromosoma…
The new Humira?
It’s not that often that you see industry-sponsored head-to-head studies of one biologic vs. another, but Abbvie took the plunge comparing risankizumab (Skyrizi) to ustekinumab (Stela…
The quest for solid tumor CAR-T
For all their success in hematological cancers, the track record of CAR-Ts against solid tumors has been disappointing (though see here for an exception). One key obsta…
Hitting reset for the immune system
Every time I get into a new issue of the NEJM, I have a sense of anticipation as in “will this one have an article that blows my mind?” It doesn’t happen very often…
A Chinese study uncovers a new use for an old drug
Bleeding in the small intestine is often due to vascular malformations and is difficult to diagnose and manage because 1) the area is hard to reach w…
How the US taxpayer saved 25M+ people
A short piece celebrating the 20th anniversary of PEPFAR, a program that few outside of the field of Global Health are aware of. The world is not always nasty and…
Preparing for the next pandemic: don’t waste the value of waste
During the Covid-19 pandemic, I got in the habit of checking weekly the Boston sewage report, as a reliable, unbiased way of monitoring …
Hypertension?!
Antihypertensive drugs are so 80s and 90s (well, except for pulmonary hypertension) to the point that I cannot recall when I last read research in the NEJM about a new blood pressure dr…
An unusual article on road safety
Motor vehicle accidents are a major share of morbidity and mortality in the young, and as such prevention has long been considered a medically adjacent area (e.g. wit…
A psychedelic for refractory depression
While major depression is awful, treatment-resistant depression (as defined not responding to at least two different courses of therapy) is worse with sufferers…
Is Parkinson’s α-synuclein going to be as elusive a target as β-amyloid has been for Alzheimer’s?
Alpha-synuclein aggregates are characteristic of Parkinson’s disease and genetic variants of this prot…
Tirzepatide in pole position
As previously described in this blog, GLP-1 agonists initially designed to treat glycemia in Type-2 diabetes are emerging as powerful weight loss agents in obesity indepen…
A cell therapy success against a solid tumor
In CAR-T therapies, T-cells are transformed to express an antibody on their surface that allows them to home in on cancer cells and effect killing. This ap…
A step forward for kidney xenotransplantation
A report on the recent, well-publicized, temporary transplantation of kidneys from genetically modified pigs in two deceased individuals at NYU. The kidne…
The opioid crisis and patient abandonment
A perspective from a February issue that I originally missed highlighting the plight of patients who have been on a long-term opioid regimen for chronic pain.…
Gene therapy in beta-thalassemia and sickle cell anemia
Beta-thalassemia and sickle cell anemia are common genetic diseases of hemoglobin (Hb) which manifest themselves in the former through transfusi…
In search of a diagnosis: deploying genomics at scale
A substantial number of children have a disease identified as “rare” without having any kind of causative diagnosis (autism is not a causative dia…
What makes an indication especially tough? The combination of a lack of understanding about the mechanism of disease and a lack of clarity on what endpoints would be sufficient for approval of a thera…
The weird world of synthetic biology
In biology 101, one learns about the alphabet that translates DNA/RNA code into amino acids sequences ultimately resulting in proteins. Given that there are 64 pos…
Cancer and mutational complexity
Probably the biggest news in cancer treatment this year is the approval of sotorasib (Lumkras, Amgen) which received accelerated approval in lung cancer with mutated K…
Remodeling to health?
Chronic disease progression is often due to a maladaptive tissue response which leads to remodeling – such as cardiac hypertrophy with hypertension. While most therapeutics focu…
A new approach to schizophrenia
Antipsychotic agents treat schizophrenia by manipulating the dopaminergic system. While they are effective at treating psychosis, they can have major side effects and t…
We can cure Hep C but not immunize against it
Sovaldi and other drugs have made curing chronic Hepatitis C a routine, if expensive, proposition. Still, given how common Hep C infection is, and how it …
Incremental progress in the fight to treat heart failure
After a decade or more of relative quiescence in the 2000s, a volley of new therapies have come to the forefront in the pages of the NEJM: sacu…
Cardiovascular health – go big or go narrow?
A follow up on the development of evinacumab (Regeneron), an inhibitor of ANGPLT3 (see this opinionated take from 2017), confirming the safety and LDL red…
Small but real progress in ALS:
Despite enormous public attention and significant effort, ALS remains a disease for which the development of new therapies has been challenging. Animal models showed po…
A cheap, low tech intervention for a common Achilles’ heel
When I am out and about, for instance at the grocery store, I am always surprised at the number of people I see with swollen legs. About half…
Stunting and the microbiome
Stunting (low growth for age) affects > 20% of children across the globe and has major impact on the brain, on health, and on opportunities for success in life. The prec…
What’s your blood type?
The first report of a genome wide association study of Covid-19 severity on approximately 4000 patients and controls conducted in Spain and Italy identifies a locus on the 3rd…
Remdesivir works… but not enough to change the public health perspective
The eagerly awaited results of the remdesivir NIH trial are out, and it’s solid but not smashing, although this is a partial re…
Hydroxychloroquine does not seem to help much in Covid-19 (with caveat)
There has been significant attention to the use of the antimalarial hydroxychloroquine in Covid-19, but data on impact has been …
A first Covid-19 interventional study – unfortunately negative
The first of what promises to be a series of many interventional studies for acute Covid-19 disease to appear in the Journal. Lopinavir i…
Keeping up with COVID-19
It’s not easy for a refereed weekly print periodical to keep up with an epidemic that evolves on a daily basis, but the NEJM is doing its best and all articles are free on-lin…
The loneliness of the patent-less drug
Colchicine is a very old drug commonly used in gout with an anti-inflammatory mechanism of action that is not well defined. It is a generic (although in the US, …
A triumph for cystic fibrosis patients (and for Vertex)
Phase 3 confirmation that the benefits seen in early trials from triple-combination therapy of elexacaftor, tezacaftor, and ivacaftor, are susta…
Genomic applications and scalability
Two very different papers about applications of genomics, one for a very common clinical scenario, the other for an ultra-rare disease.
It is well known that while…
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 …
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 h…
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 …
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 qu…
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 c…
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 cholestero…
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 tu…
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 metr…
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…
Peanut medicine that won’t cost peanuts
Allergy to peanuts is a major issue and though prevention is now possible in infants there is a huge population for whom actual survival is connected to vigilan…
One century after the use of convalescent serum, convalescent T-cells
The use of tailored T-cells (e.g. CAR-T) is transforming our approach to (blood) cancers, but what about using T-cells against the…
Primary care organizations are better ACOs when it comes to achieving savings
Initial results from the Medicare Shared Savings Program ACO have been disappointing pointing to small to negligible net e…
Transthyretin heats up
Last month saw a couple landmark papers about the use of parenteral RNA drugs (from Alnylam and Ionis) in hereditary transthyretin amyloidosis with a focus mainly on mitigating …
RNA drugs coming of age
Hereditary Transthyretin Amyloidosis (ATTR) is a genetic disease in which one of the alleles of Transthyretin (TTR), a protein produced by the liver and with a role in thyroid …
It’s hard to quit (and E-cigs don’t help)
A large trial (6000 participants) comparing free cessation support, e-cigarettes, and a $600 cash incentive for sustained abstinence shows that none of these …
One more on the chin for Alzheimer’s
A report of a large phase 3 study of the highly potent oral BACE inhibitor verubecestat (Merck) with yet again a lack of therapeutic effect, despite a dramatic red…
Are we nearing an asymptote with implantable cardiac pumps?
Severe heart failure is common, and spare hearts for transplant are rare, which has led to the development of implantable mechanical alterna…
GWAS, Regeneron and Geisinger, and liver disease
Genome wide association studies (GWAS) look at broad populations for gene variants associated with a particular phenotype. Often, like in Type II diabe…
A-fib in heart failure – time to be aggressive
Over the last 15 years, there has been a growing body of evidence for the effectiveness of catheter ablation to treat atrial fibrillation (a-fib), a cond…
Playing chess against cancer
Tumors are not intelligent, but, because they have escaped mutational control, they constantly probe for mutations that will allow them to escape chemotherapeutic suppress…
Successes in gene therapy for hemophilia B and A
Hemophilia A and B are X-linked genetic diseases which prevents the formation of functional coagulant factors VII and IX respectively and cause a prope…
Two new therapies against a horrible congenital disease – but trouble ahead on pricing…
Spinal Muscular Atrophy (SMA) is a genetic disease that declares itself at a few months of age, and typically le…
Between the very common and the very rare – An opinionated take on NEJM highlights for October 2017
Another tool for prevention in cardiovascular disease
Taking aspirin daily has been standard of ca…
A new drug to address hard-to-treat severe asthma
In ~10% of people with asthma, traditional therapies do not work well and they have recurrent exacerbations leading them to the ED. Over the past few …
At last, drug prices influence physician usage patterns
Association of Reference Pricing with Drug Selection and Spending (subscriber access); Nitroprusside and Isoproterenol Use after Major Price Inc…
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,…
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 m…
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 hum…
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 …
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; remedi…
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 i…
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 se…
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 …
“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 obvi…
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 su…
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. Follo…
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 …
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” environme…
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. …
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 …
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 Journa…
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 wh…
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 …
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 disease…
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 chron…
A new focus on the diagnostic reliability of clinicians
Two perspectives highlighting the recent report from the National Academy of Medicine (formerly IOM) entitled “Improving Diagnosis in Health Car…
Systems biology finally gets real: an unexpected use for a diabetes drug
Chronic Myelogenous Leukemia (CML) has been the poster child first for a disease with a precise genetic cause (the Philadelphia…
What are annual physicals for?
Annual physicals are costly (~$10 billion annually) and have never been shown to improve outcomes, but people value them. In this dichotomy lies a lot of the inner tensi…
Promise for systemic amyloidosis (and beyond?)
Systemic amyloidosis is an uncommon disease in which abnormal cells (typically antibody-producing B cells) produce large amounts of protein that deposit …
The emergence of a new approach to drug development in cancer
Cancers are classified by the organ or tissue from which they arise, but as our molecular understanding increases, another level of categ…
Palbociclib – first to target cyclin dependent kinases – breast cancer
As all biology majors know, cyclin dependent kinases are critical elements controlling the machinery of cell proliferation. They…
Interventionalist treatment for stroke:
In the 80s and 90s, treatment of myocardial infraction was greatly advanced by the introduction of systemic clot busting drugs (t-PA and others); further advanc…
Early results of the ACO experiment: directionally right, but impact is still small
In this study, the authors compare metrics for Medicare beneficiaries assigned to the 32 ACOs part of the Pioneer pr…
The rise, fall, and rebirth of the Chinese healthcare system
A fascinating account of the evolution of the Chinese healthcare system which almost seems to be an upside-down picture of the rest of the …
A promising agent for Crohn’s Disease, a miserable illness
Crohn’s is an inflammatory bowel disease that is notoriously unpredictable; flares can affect any part of the digestive tract and lead to gra…
Our selection from a month with relatively few exciting articles - perhaps this long Boston winter has us all down.
Precious metals and health plan buying:
The implementation of the ACA has placed …
A vaccine for dengue finally nears the market
Dengue is a mosquito transmitted viral infection that is often severe and occasionally fatal, and that has been identified as a growing public health thre…
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