COVID: Schools & Age-Related Morbidity and Mortality

JF Ludvigsson et al NEJM 2021; 384: 669-671. Full text: Open Schools, Covid-19, and Child and Teacher Morbidity in Sweden In this letter to the editor, the authors report on outcomes in Sweden, which kept schools open during the pandemic; time period: from March 1-June 30, 2020 (schools end around June 10th). Key findings:

  • Among 1-16 years of age (~1.95 million in total), 15 required ICU admission; there were no deaths in this age group
  • “Fewer than 10 pre-school teachers [1-6 years] and 20 schoolteachers received ICU care up to June 30, 2020.” Excluding health care workers, the occupational risk was similar to other occupations, with relative risk of 1.10 (0.49-2.49, 95% CI) and 0.43 (0.28-0.68, 95% CI) for preschool and school teachers respectively.

My take: This study suggests that school teachers are at similar risk for COVID-19 infection as other essential workers. In Sweden, during this timeframe, distancing but not masking was recommended. Thus, transmission rates could be lowered further.

Related article: SR Kadire et al. NEJM 2021; 384: DOI: 10.1056/NEJMclde2101987. Full text: Delayed Second Dose versus Standard Regimen for Covid-19 Vaccination This article provides rationale for both vaccine options.

Related blog posts:

Excess Deaths From COVID-19 and Other Causes

For musical fans: 2020: The Musical YouTube Link (~8 minutes) with Jimmy Fallon and Andrew Rannells


SH Woolf et al.. JAMA 2020; 324: 510-513. Excess Deaths From COVID-19 and Other Causes, March-July 2020

The authors compared deaths from 2014-2020 using data from the National Center for Health Statistics and US Census Bureau.

Key findings:

  • Between March 1 and August 1, 2020, 1 336 561 deaths occurred in the US, a 20% increase over expected deaths (1 111 031 [95% CI, 1 110 364 to 1 111 697]). 
  • Of the 225 530 excess deaths, 150 541 (67%) were attributed to COVID-19
  • The authors conclude that the excess deaths attributed to causes other than COVID-19 could reflect deaths from unrecognized or undocumented infection with severe acute respiratory syndrome coronavirus 2 or deaths among uninfected patients resulting from disruptions produced by the pandemic

My take: The COVID-19 situation has worsened considerably in the past 2 months and the final toll from this infection will be truly staggering; this unfortunately will include its indirect effects due to deferral of care

Phase 3 Trial of Budesonide for Eosinophilic Esophagitis & COVID-19 Deaths in U.S.

NY Times article:  U.S. Coronavirus Cases Are Rising Sharply, but Deaths Are Still Down

This article explains why deaths from COVID-19 have not increased despite increasing number of infections.  Three main reasons: increased testing -detects many with less severe symptoms, younger population are being infected, and new treatment approaches may be helping.  However, “the dip in coronavirus mortality will not necessarily last. As more people socialize, those with milder infections might end up ferrying the pathogen to vulnerable individuals…Recent upswings in coronavirus case numbers leave experts apprehensive of what’s to come. Death, when it occurs, tends to trail infection by about two to four weeks.”


The Budesonide Oral Suspension (BOS) resulted in 62% of BOS patients meeting the threshold of < 15 eos/hpf compared to 1% of placebo patients. From lead author, Ikuo Hirano: “the results of the BOS trial showed that BOS successfully treated both the symptoms and signs of EoE. The positive results will hopefully lead to an approved, safe and effective therapy for EoE.”

Abstract from ACG Meeting October 2019:

Abstract: Efficacy of Budesonide Oral Suspension for Eosinophilic Esophagitis in Adolescents and Adults: Results From a Phase 3, Randomized, Placebo-Controlled Trial

Introduction: Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease for which there is an unmet clinical need for new therapies. The safety and efficacy of budesonide oral suspension (BOS) for the treatment of EoE has been demonstrated in a previous phase 2 study. The current phase 3 study evaluated the efficacy and safety of BOS in a large cohort of patients with EoE. 

Methods: This randomized, double-blind, placebo-controlled trial (SHP621-301; NCT02605837) investigated the safety and efficacy of BOS in patients (11–55 years) with EoE and dysphagia. Patients were randomized 2:1 to 2.0 mg BOS or placebo twice daily (b.i.d.) for 12 weeks (Figure 1). Co-primary endpoints were histologic (peak eosinophil count ≤6 eosinophils/high-powered field [eos/hpf]) and dysphagia symptom (≥30% decrease in symptoms as measured by the Dysphagia Symptom Questionnaire [DSQ]) responses after 12 weeks of therapy. Secondary endpoints included change in DSQ score and change in EoE Endoscopic Reference Score (EREFS) from baseline to final treatment period. Safety was also assessed.

Results: A total of 322 patients were randomized (BOS, n=215; placebo, n=107), of whom 318 patients received at least one dose of double-blind therapy (BOS, n=213; placebo, n=105) (Table). The primary outcomes were achieved, with significantly more histologic and symptom responders in the BOS-treated than the placebo-treated group (53.1% vs 1.0%, p< 0.001; 52.6% vs 39.1%, p=0.024, respectively; Figure 2). Improvements in mean DSQ score from baseline to week 12 were significantly greater in the BOS group (n=197) than the placebo group (n=89) (−13.0 vs −9.1; p=0.015). Similarly, improvements in mean EREFS scores were significantly greater with BOS (n=202) than placebo (n=93) (−4.0 vs −2.2; p< 0.001). In total, 61.0% of patients reported a treatment-emergent adverse event (TEAE) (BOS, 61.0%; placebo, 61.0%). Only 2.5% of patients experienced a TEAE leading to dose discontinuation (BOS, 1.4%; placebo, 4.8%). Few patients had severe or serious TEAEs on BOS or placebo.  No life-threatening TEAEs were reported.

Discussion: This phase 3 trial demonstrated the efficacy of BOS as induction therapy for EoE. BOS resulted in significant improvements in histologic, symptomatic and endoscopic endpoints compared with placebo. The majority of TEAEs were mild to moderate and comparable between placebo and BOS. A double-blind, placebo-controlled maintenance study (SHP621-302) is ongoing.

Related blog posts:

Island Ford, Sandy Springs

 

 

 

PPI and Poor Outcomes

A large observation study provides some bad publicity for proton pump inhibitors (PPI):

BMJ Open Access: Risk of death among users of Proton Pump Inhibitors: a longitudinal
observational cohort study of United States veterans (Y Xie et al BMJ Open
2017;7:e015735. doi:10.1136/bmjopen-2016-01573) Thanks to Ben Enav for this reference.

This study selected ~350,000 patients from a database which identified more than 1.7 million PPI users. These patients were ‘new’ PPI users.

Key finding:  Over a median follow-up of 5.71 years, PPI use was associated with increased risk of death compared with H2 blockers use (HR 1.25, CI 1.23 to 1.28).

The authors note the limitations of this observational study; however, they suggest that the findings cannot be fully explained by residual confounders.  They recommend limiting PPI use to “instances and durations where it is medically indicated.”

My take: As noted in a recent post (see below), some risks attributed to PPIs in observational studies do not pan out.  Yet, PPI therapies need to be better-targeted to those who will truly benefit from them.

Related blog posts:

The Battery, Charleston, SC

 

Trends in Non-medical Opiod Use and Heroin Addiction

Almost all physicians use opiods in their practice and need to keep up with the challenges of pain management and addiction.  An update on the problem of non-medical opiod use and heroin addiction from NEJM:

Full article link: Relationship between Nonmedical Prescription-Opiod Use and Heroin Use

An excerpt:

The transition from nonmedical use of prescription opioids to heroin use appears to be part of the progression of addiction in a subgroup of nonmedical users of prescription opioids, primarily among persons with frequent nonmedical use and those with prescription opioid abuse or dependence. Although some authors suggest that there is an association between policy-driven reductions in the availability of prescription opioids and increases in the rates of heroin use,16,18 the timing of these shifts, many of which began before policies were robustly implemented, makes a causal link unlikely…

In the majority of studies, the increase in the rates of heroin use preceded changes in prescription-opioid policies, and there is no consistent evidence of an association between the implementation of policies related to prescription opioids and increases in the rates of heroin use or deaths, although the data are relatively sparse. Alternatively, heroin market forces, including increased accessibility, reduced price, and high purity of heroin appear to be major drivers of the recent increases in rates of heroin use…

Fundamentally, prescription opioids and heroin are each elements of a larger epidemic of opioid-related disorders and death. Viewing them from a unified perspective is essential to improving public health. The perniciousness of this epidemic requires a multipronged interventional approach that engages all sectors of society.

Related blog posts:

 

Screen Shot 2016-01-14 at 8.01.08 PM

 

Causes of Death with Hepatitis B in U.S.

A recent study followed 6,689 patients with hepatitis B virus (HBV) between 1996-2005 and analyzed causes of death (Hepatology 2013; 58: 21-30, editorial pg 6). This study used a large prospectively-collected database.

The patients were all part of Kaiser Permanente Northern California health plan.  Patients were not eligible if they were coinfected with HIV or HCV.  Causes of death were divided into HBV-related (eg. decompensated cirrhosis [DCC], hepatocellular carcinoma [HCC]) and other causes, including cancer and cardiovascular.

Among this cohort, 68.3% were Asian-Pacific Islander (API) descent, and 11.8% were white (non-hispanic); the remainder were other or unknown descent.  The cohort had a mean age of 41 years.

Findings:

  • Males had higher overall 10-year death rates than females for total deaths (8.9% versus 4.1%) and for HBV-related deaths (4.8% versus 1.2%).
  • 46.7% of all deaths were HBV-related.
  • Death rate rose with increasing age; approximately 40% of deaths after age 40 were HBV-related.
  • Among HBV-related deaths, the death rate from HCC was twice the rate of DCC
  • “We did not find that subjects of API descent origin were at higher risk of death from HBV-related complications.”  This was unexpected because presumably “they are often infected in childhood and therefore have disease of longer duration.”
  • Limitations included absence of data on alcohol, cigarettes and coffee.  In addition, the study period occurred when treatment options for HBV were more limited.

The accompanying editorial notes wide variability in mortality outcome data depending on the study setting.   “Studies in patients with incidentally detected HBV infection, mostly conducted in blood donors in Western countries, tend to portray a benign course…with…their incidence of complications of chronic liver disease, HCC, or liver-related mortality is not significantly higher than that in hepatitis B surface antigen-negative healthy controls.”  In China, the lifetime risk for an infected patient to die from an HBV-related cause “has been estimated to be up to 50% in men and 15% in women.”

Related blog posts: