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In the US, there are no effective regulations controlling how much the price of a medication can increase. A patchwork of studies examining the reasons for soaring prices has focused on medications that have received considerable media attention, like insulin, epinephrine, and colchicine. To identify the 50 medications with the greatest increase in average spending per beneficiary and the 50 medications with the greatest decrease in average spending per beneficiary, and to identify the factors associated with spending increases. This cross-sectional study used publicly available data from the Medicare Part D Prescription Drug Program from 2014 to 2020. We included drugs dispensed to > 1000 beneficiaries in each study year and excluded those primarily administered intravenously. Percentage change in average spending per beneficiary from 2014 to 2020 was calculated for each drug. For each drug, we extracted the number of beneficiaries, the number of manufacturers, and the drug-specific total annual spending reported in the Medicare Part D data set. An online database search was conducted to identify the primary clinical indication, the availability of any generic versions, and the date of FDA approval for each drug. The 50 medications with the greatest increase in spending per beneficiary had a median increase of 362.4% (interquartile range [IQR]: 286.6%-563.0%), with a cumulative spending of almost $5 billion in 2020 alone. Most drugs with the greatest increases in spending per beneficiary had generic versions available (68%) and were approved by the FDA over 10 years ago (66%). Medications with the greatest increase in spending per beneficiary had a median of 1 manufacturer (IQR: 1-2), while medications with the greatest decrease in spending per beneficiary had a median of 9.5 manufacturers (IQR: 5-14). This study identified rapidly increasing costs of medications under Medicare Part D. Our findings demonstrate that off-patent medications can skyrocket in price, especially when there are few manufacturers of a given medication.

The failure of solanezumab offers a window into the U.S. drug regulatory system, particularly in the context of the 21st Century Cures Act and the national debate about the role of the FDA. The solanezumab story is an important case of a regulatory system that worked. The November 2016 announcement that Eli Lilly’s investigational drug solanezumab failed in a phase 3 clinical trial dashed hopes that it would be a long-anticipated disease-modifying treatment for Alzheimer’s disease. 1 For people living with Alzheimer’s — along with their relatives and caregivers, whose lives are also transformed by the disease — there is real urgency for new treatments. Additional details from this trial may ultimately provide insights about pathophysiology or potential treatment pathways for future study. But the failure of solanezumab also offers a window into the U.S. drug regulatory system, particularly in the context of the recently signed 21st . . .

Isolation guidelines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are largely derived from data collected prior to the emergence of the delta variant. We followed a cohort of ambulatory patients with postvaccination breakthrough SARS-CoV-2 infections with longitudinal collection of nasal swabs for SARS-CoV-2 viral load quantification, whole-genome sequencing, and viral culture. All delta variant infections in our cohort were symptomatic, compared with 64% of non-delta variant infections. Symptomatic delta variant breakthrough infections were characterized by higher initial viral load, longer duration of virologic shedding by PCR, greater likelihood of replication-competent virus at early stages of infection, and longer duration of culturable virus compared with non-delta variants. The duration of time since vaccination was also correlated with both duration of PCR positivity and duration of detection of replication-competent virus. Nonetheless, no individuals with symptomatic delta variant infections had replication-competent virus by day 10 after symptom onset or 24 hours after resolution of symptoms. These data support US CDC isolation guidelines as of November 2021, which recommend isolation for 10 days or until symptom resolution and reinforce the importance of prompt testing and isolation among symptomatic individuals with delta breakthrough infections. Additional data are needed to evaluate these relationships among asymptomatic and more severe delta variant breakthrough infections.

Despite formidable barriers to designing, implementing, and completing clinical trials in the midst of a pandemic, there are ways to ensure that the selected trials are structured to maximize the chance that the key research questions will be definitively answered.

Clinicians should remain sceptical until peer reviewed findings are published in full

In March 2020, as the coronavirus pandemic spread throughout the United States, Americans bought nearly 2 million guns — the second highest monthly total in the decades since such records have been kept. Previous spikes in U.S. firearm sales have followed widely publicized mass shootings and the attendant national calls for regulations regarding the prevention of gun violence. (January 2013, the month after the massacre at Sandy Hook Elementary School in Newtown, Connecticut, holds the record for the highest number.) 1 That so many Americans started or added to their personal arsenal when faced with deeply uncertain times suggests the extent . . .

At the moment that Daniel was shot, I had just fallen asleep after a night on call in the cardiac intensive care unit. My attending during that rotation was Robert Gerszten, who offered us insights from the burgeoning field of metabolomics and cardiovascular disease: that alterations in levels of blood metabolites may precede chronic illnesses by decades — knowledge that might someday enable us to identify people at risk for diseases years before the first clinical manifestation. Contemplating the possibilities of this concept, caring for critically sick patents, and studying the vast cardiology literature, I found my mind filled with . . .

As we enter a new era of treatment for heart failure with reduced ejection fraction, historical perspective is provided in a timeline (at NEJM.org) of 26 randomized, controlled trials in heart-failure treatment that have been published in the Journal since 1986. With the publication of the PARADIGM-HF trial in the Journal (pages 993–1004) we may be entering a new era of treatment for heart failure with reduced ejection fraction. To provide a historical perspective on the beginning of this new epoch, we constructed an interactive timeline (available with the full text of this article at NEJM.org) of 26 randomized, controlled trials in heart-failure treatment that have been published in the Journal since 1986. Each of these articles — some demonstrating successes and others documenting disappointments — represents a critical step in the effort to reduce mortality from heart failure with reduced . . .

In a claims-based study involving 3790 affected youths, parental firearm injury was associated with increases in psychiatric diagnoses — especially trauma-related disorders — and in mental health visits among children.