Distribution of Solid Lung Nodules Presence and Size by Age and Sex in a Northern European Nonsmoking Population

Cai J, Vonder M, Pelgrim GJ, Rook M, Kramer G, Groen HJM, de Bock GH, Vliegenthart R.. Radiology. 2024 Aug;312(2):e231436. [CrossRef] [PubMed]

Background

Most of the data regarding prevalence and size distribution of solid lung nodules originates from lung cancer screening studies that target high-risk populations or from Asian general cohorts. In recent years, the identification of lung nodules in non-high-risk populations, scanned for clinical indications, has increased. However, little is known about the presence of solid lung nodules in the Northern European nonsmoking population. Purpose To study the prevalence and size distribution of solid lung nodules by age and sex in a nonsmoking population.

Materials and Methods

Participants included nonsmokers (never or former smokers) from the population-based Imaging in Lifelines study conducted in the Northern Netherlands. Participants (age ≥ 45 years) with completed lung function tests underwent chest low-dose CT scans. Seven trained readers registered the presence and size of solid lung nodules measuring 30 mm³ or greater using semiautomated software. The prevalence and size of lung nodules (≥30 mm³), clinically relevant lung nodules (≥100 mm³), and actionable nodules (≥300 mm³) are presented by 5-year categories and by sex.

Results

A total of 10 431 participants (median age, 60.4 years [IQR, 53.8-70.8 years]; 56.6% [n = 5908] female participants; 46.1% [n = 4812] never smokers and 53.9% [n = 5619] former smokers) were included. Of these, 42.0% (n = 4377) had at least one lung nodule (male participants, 47.5% [2149 of 4523]; female participants, 37.7% [2228 of 5908]). The prevalence of lung nodules increased from age 45-49.9 years (male participants, 39.4% [219 of 556]; female participants, 27.7% [236 of 851]) to age 80 years or older (male participants, 60.7% [246 of 405]; female participants, 50.9% [163 of 320]). Clinically relevant lung nodules were present in 11.1% (1155 of 10 431) of participants, with prevalence increasing with age (male participants, 8.5%-24.4%; female participants, 3.7%-15.6%), whereas actionable nodules were present in 1.1%-6.4% of male participants and 0.6%-4.9% of female participants.

Conclusion

Lung nodules were present in a substantial proportion of all age groups in the Northern European nonsmoking population, with slightly higher prevalence for male participants than female participants.

Mandibular Advancement vs CPAP for Blood Pressure Reduction in Patients with Obstructive Sleep Apnea

Ou Y-H, Colpani JT, Cheong CS, et al. Am J Cardiol. 2024 (Accepted). [CrossRef]

Background: Hypertension guidelines recommend diagnosis and treatment of obstructive sleep apnea (OSA) in patients with hypertension. The mandibular advancement device (MAD) is an oral appliance therapy for patients who decline or cannot tolerate CPAP.

Objective: We compared the relative effectiveness of MAD versus CPAP in reducing 24-hour ambulatory BP.

Methods: In an investigator-initiated, randomized, non-inferiority trial (pre-specified margin 1.5 mmHg), 321 participants, aged over 40, with hypertension and increased cardiovascular risk were recruited at 3 public hospitals for polysomnography. Of these, 220 participants with moderate-to-severe OSA (apnea–hypopnea index (AHI) ≥15 events/hour) were randomized to either MAD or CPAP (1:1). The primary outcome was the difference between the 24-hour mean arterial BP at baseline and 6 months.

Results: Compared to baseline, the 24-hour mean arterial BP decreased by 2.5 mmHg (P = 0.003) at 6 months in the MAD group, whereas no change was observed in the CPAP group (P = 0.374). The between-group difference was -1.6 mmHg (95% confidence interval: -3.51 to 0.24, non-inferiority P < 0.001). The MAD group demonstrated a larger between-group reduction in all secondary ambulatory BP parameters compared to the CPAP group, with the most pronounced effects observed in the asleep BP parameters. Both the MAD and CPAP improved daytime sleepiness, with the between-group difference similar (P = 0.384). There were no between-group differences in cardiovascular biomarkers.

Conclusion: MAD is non-inferior to CPAP for reducing 24-hour mean arterial BP in participants with hypertension and increased cardiovascular risk.

Telemedicine Critical Care Availability and Outcomes Among Mechanically Ventilated Patients

Graves JM, Krings JG, Buss JL, Kallogjeri D, Ofoma UR. J Crit Care. 2024 Mar 23;82:154782. [CrossRef] [PubMed]

Telemedicine Critical Care (TCC) improves adherence to evidence based protocols associated with improved mortality among patients receiving invasive mechanical ventilation (IMV).  The authors performed a cross-sectional study of 66,522 adults who received IMV for non-postoperative acute respiratory failure at 318 non-federal hospitals in New York, Massachusetts, Maryland, and Florida in 2018. Hospital-level TCC availability was ascertained from the 2018 American Hospital Association Annual Survey. The primary outcome was in-hospital mortality. Secondary outcomes included the composite of tracheostomy or reintubation and duration of IMV. We used two-level hierarchical multivariable regression models to investigate the association between TCC availability and outcomes. 20,270 (30.5%) patients were admitted into 89 TCC-available hospitals. There was no difference between TCC and non-TCC-available hospitals in mortality (odds ratio [OR] 0.94, 99% confidence interval [CI] 0.84–1.05), composite of tracheostomy or reintubation (OR 0.95 [0.82–1.11], or duration of IMV (OR 0.95 [0.83–1.09]). There was no difference in outcomes among the subgroup of patients with acute respiratory distress syndrome. The authors conclude that hospital TCC availability was not associated with improved outcomes among patients receiving IMV. 

Impact of Ambient Ultrafine Particles on Cause-Specific Mortality in Three German Cities

Schwarz M, Schneider A, Cyrys J, Bastian S, Breitner S, Peters A. Am J Respir Crit Care Med. 2023 May 15;207(10):1334-1344. [CrossRef] [PubMed]

Rationale: Exposure to ambient air pollution has been associated with adverse effects on morbidity and mortality. Ambient ultrafine particles (UFPs) result from combustion of combustion of gas, coal or hydrocarbons, biomass burning (i.e. agricultural burning, forest fires and waste disposal), vehicular traffic and industrial emissions, tire wear and tear from car brakes, air traffic, seaport, maritime transportation, restoration and concrete processing, domestic wood stoves, outdoor burning, kitchen, and cigarette smoke. However, the evidence of the impact of UHFs on morbidity and mortality based on epidemiological studies remains scarce and inconsistent. Objectives: The authors examined associations between short-term exposures to UFPs and total particle number concentrations (PNCs; 10–800 nm) and cause-specific mortality in three German cities: Dresden, Leipzig, and Augsburg. Methods: We obtained daily counts of natural, cardiovascular, and respiratory mortality between 2010 and 2017. UFPs and PNCs were measured at six sites, and measurements of fine particulate matter (PM2.5; ⩽2.5 μm in aerodynamic diameter) and nitrogen dioxide were collected from routine monitoring. We applied station-specific confounder-adjusted Poisson regression models. We investigated air pollutant effects at aggregated lags (0–1, 2–4, 5–7, and 0–7 d after UFP exposure) and used a novel multilevel meta-analytical method to pool the results. Additionally, we assessed interdependencies between pollutants using two-pollutant models. Measurements and Main Results: For respiratory mortality, we found a delayed increase in relative risk of 4.46% (95% confidence interval, 1.52 to 7.48%) per 3,223-particles/cm3 increment 5–7 days after UFP exposure. Effects for PNCs showed smaller but comparable estimates consistent with the observation that the smallest UFP fractions showed the largest effects. No clear associations were found for cardiovascular or natural mortality. UFP effects were independent of PM2.5 in two-pollutant models. Conclusions: The authors found delayed effects for respiratory mortality within 1 week after exposure to UFPs and PNCs but no associations for natural or cardiovascular mortality.

Video versus Direct Laryngoscopy for Tracheal Intubation of Critically Ill Adults

M.E. Prekker ME, B.E. Driver BE, S.A. Trent, D. Resnick‑Ault TD, et al. N Engl J Med. 2023 Jun 16. [CrossRef] [PubMed]

Whether video laryngoscopy as compared with direct laryngoscopy increases the likelihood of successful tracheal intubation on the first attempt among critically ill adults is uncertain. In a multicenter, randomized trial conducted at 17 emergency departments and intensive care units (ICUs), critically ill adults undergoing tracheal intubation were randomly assigned to the video-laryngoscope group or the direct-laryngoscope group. The trial was stopped for efficacy at the time of the single preplanned interim analysis. Among 1417 patients who were included in the final analysis (91.5% of whom underwent intubation that was performed by an emergency medicine resident or a critical care fellow), successful intubation on the first attempt occurred in 600 of the 705 patients (85.1%) in the video-laryngoscope group and in 504 of the 712 patients (70.8%) in the direct-laryngoscope group (absolute risk difference, 14.3 percentage points; 95% confidence interval [CI], 9.9 to 18.7; P<0.001). 

Both groups had similar rates of severe complications (peripheral oxygen saturation, <80%, systolic blood pressure <65 mm Hg, new or increased use of vasopressors, cardiac arrest, or death): 21.4% vs 20.9%. The median time of an intubation attempt was 38 seconds and 46 seconds respectively. Safety outcomes, including esophageal intubation, injury to the teeth, and aspiration, were similar in the two groups. 

This trial has several strengths including randomization, an independent observer to prevent observer bias, and low numbers of missing data. However, there were also limitations. The video laryngoscope and the shape of the blade were not standardized, neither were the stylets and bougies utilized. Because 97% of the operators had performed fewer than 250 previous tracheal intubations, the findings may not apply to operators with more experience. 

Additional considerations include the patient’s airway anatomy, positioning, and anticipation of hemoptysis and emesis that will distort the view of the glottis. The COVID-19 pandemic showed us that speed may also be important especially in those very critically ill patients who cannot tolerate more than 20 seconds while attempting to secure the airway. Being familiar with your institution's airway tools is also important because not all hospitals have the same laryngoscopes, stylets or bougies.

Reviewed by Evan D Schmitz MD

Changes in Practice of Controlled Hypothermia after Cardiac Arrest in the Past 20 Years

Nielsen N, Friberg H. Am J Respir Crit Care Med. 2023 Apr 27. doi: 10.1164/rccm.202211-2142CP. Epub ahead of print. [CrossRef] [PubMed]

For 20 years, induced hypothermia and targeted temperaturemanagement have been recommended to mitigate brain injuryand increase survival after cardiac arrest. On the basis of animalresearch and small clinical trials, the International LiaisonCommittee on Resuscitation strongly advocated hypothermia at32–34C for 12–24 hours for comatose patients with out-of-hospital cardiac arrest with initial rhythm of ventricularfibrillation or nonperfusing ventricular tachycardia. Theintervention was implemented worldwide. In the past decade,hypothermia and targeted temperature management have beeninvestigated in larger clinical randomized trials focusing ontarget temperature depth, target temperature duration,prehospital versus in-hospital initiation, nonshockable rhythms,and in-hospital cardiac arrest. Systematic reviews suggest littleor no effect of delivering the intervention on the basis of thesummary of evidence, and the International Liaison Committeeon Resuscitation today recommends only to treat fever and keepbody temperature below 37.5C (weak recommendation,low-certainty evidence). Here we describe the evolution oftemperature management for patients with cardiac arrestduring the past 20 years and how the accrued evidence hasinfluenced not only the recommendations but also the guidelineprocess. We also discuss possible paths forward in this field,bringing up both whether fever management is at allbeneficial for patients with cardiac arrest and which knowledgegaps future clinical trials in temperature management should address. 

There is also an additional review in PulmCCM. Unfortunately, both require subscriptions in order to view the content. 

Habitual Fish Oil Supplementation and Incident Chronic Obstructive Pulmonary Disease: Data from a Prospective Cohort Study

Li ZH, Song WQ, Shen D, Zhang PD, et al. Clin Nutr. 2022 Oct 8;41(12):2651-2658. [CrossRef] [PubMed]

Background: Fish oil is one of the most popular supplements in the UK and other developed countries. However, the relationship between fish oil use and chronic obstructive pulmonary disease (COPD) is unclear.

Objective: To prospectively examine the association of habitual fish oil supplementation with incident COPD risk and to evaluate potential effect modification by genetic predisposition.

Methods: This study included 484,414 participants (mean and standard deviation [SD] age: 56.5 [8.1] years) from the UK Biobank who completed a touchscreen questionnaire on habitual fish oil supplement use between 2006 and 2010 and were followed up through 2018. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for sociodemographic and lifestyle behaviours, health conditions, and other potential confounding factors. A weighted genetic risk score (GRS) for COPD was derived from 112 validated single nucleotide polymorphisms.

Results: During a median follow-up of 9.0 years, 8860 incident COPD events were recorded. A total of 31.4% (152,230) of the study participants reported habitual fish oil supplementation at baseline. Habitual fish oil supplementation was significantly associated with a lower risk of incident COPD (adjusted HR: 0.88; 95% CI: 0.84-0.93). The association with COPD did not differ by GRS strata (P for interaction = 0.880). The results from subgroup and sensitivity analyses supported the robustness of our findings.

Conclusions: Our findings suggest that habitual fish oil supplementation is associated with a lower risk of incident COPD, irrespective of genetic predisposition.

Novel Bronchoscopic Interventions Appear Promising for Patients with COPD

Bowser AD. Chest Physician, November 3, 2022. Available at: https://www.mdedge.com/chestphysician/article/248210/copd/novel-bronchoscopic-interventions-appear-promising-patients-copd?channel=39313

Dr. Christian Ghattas reported on several emerging bronchoscopic treatments for patients with chronic obstructive pulmonary disease at the annual meeting of the American College of Chest Physicians (1).

Targeted Lung Denervation

Targeted lung denervation is one promising novel therapeutic option that is safe and may improve clinical outcomes. The targeted lung denervation system under study (dNerva®, Nuvaira Inc.) which involves the use of a radiofrequency catheter to ablate the peribronchial branches of the vagus nerve. The goal of disrupting pulmonary nerve input is to achieve sustained bronchodilation and reduce mucous secretion, thereby simulating the effect of anticholinergic drugs. AIRFLOW-1 demonstrated the safety and procedural success of bronchoscopic lung denervation (2). In AIRFLOW-2, a randomized, sham-controlled trial enrolling patients with symptomatic COPD targeted lung denervation plus optimal drug treatment led to fewer respiratory adverse events of interest, including hospitalizations for COPD exacerbation(3). Respiratory adverse events occurred in 32% of treated patients versus 71% of sham-treated patients in a predefined 3- to 6.5-month postprocedure window. Currently underway is AIRFLOW-3, a randomized study of targeted lung denervation versus sham procedure in patients with COPD. The study has a primary outcome measure of moderate or severe COPD exacerbations over 12 months and is slated to enroll 480 patients.

Metered Cryospray

One novel intervention with the potential to benefit patients with chronic bronchitis is metered cryospray (RejuvenAir), which works by delivering liquid nitrogen to the tracheobronchial airways. This targeted delivery ablates abnormal epithelium, facilitating the regeneration of healthy mucosa. In the study, 34 of 35 participants received three treatments 4-6 weeks apart. Investigators reported that at 3 months there were significant reductions in the COPD Assessment Test that were durable to 6 months, and changes in the St. George's Respiratory Questionnaire and the Leicester Cough Questionnaire that were durable to 9 months (4).

An ongoing randomized study called SPRAY-CB is comparing metered cryospray to sham procedure in an anticipated 210 patients with COPD with chronic bronchitis.

Bronchial Rheoplasty

Bronchial rheoplasty (RheOx, Gala Therapeutics), is another promising intervention under investigation for the treatment of chronic bronchitis.

This system delivers nonthermal pulsed electrical energy with the intention of ablating goblet cells in the airways. In 12-month results of multicenter clinical trial, bronchial rheoplasty was technically feasible and safe, with reductions in goblet cell hyperplasia and changes in patient-reported quality of life seen following the procedure (5).

A larger randomized, double-blind prospective trial with a sham control arm is underway and will include 270 patients.

References

1. Novel bronchoscopic interventions appear promising for patients with COPD Bowser AD. Chest Physician, November 3, 2022. Available at: https://www.mdedge.com/chestphysician/article/248210/copd/novel-bronchoscopic-interventions-appear-promising-patients-copd?channel=39313
2. Pison C, Shah PL, Slebos DJ, et al. Safety of denervation following targeted lung denervation therapy for COPD: AIRFLOW-1 3-year outcomes. Respir Res. 2021 Feb 19;22(1):62. [CrossRef] [PubMed]
3. Slebos DJ, Shah PL, Herth FJF, et al. Safety and Adverse Events after Targeted Lung Denervation for Symptomatic Moderate to Severe Chronic Obstructive Pulmonary Disease (AIRFLOW). A Multicenter Randomized Controlled Clinical Trial. Am J Respir Crit Care Med. 2019 Dec 15;200(12):1477-1486. [CrossRef] [PubMed]
4. Garner JL, Shaipanich T, Hartman JE, et al. A prospective safety and feasibility study of metered cryospray for patients with chronic bronchitis in COPD. Eur Respir J. 2020 Dec 17;56(6):2000556. [CrossRef] [PubMed]
5. Valipour A, Fernandez-Bussy S, Ing AJ, et al. Bronchial Rheoplasty for Treatment of Chronic Bronchitis. Twelve-Month Results from a Multicenter Clinical Trial. Am J Respir Crit Care Med. 2020 Sep 1;202(5):681-689. [CrossRef] [PubMed]

Sleep Apnea and Incident Unprovoked Venous Thromboembolism: Data from the French Pays de la Loire Sleep Cohort

Trzepizur W, Gervès-Pinquié C, Heude B, et al. ERS 2022 Congress. Presented Sept. 5, 2022. Abstract available at: https://k4.ersnet.org/prod/v2/Front/Program/Session?e=377&session=14833

Medscape is reporting that you can add unprovoked venous thromboembolic events to the list of potential consequences of severe obstructive sleep apnea (1). That conclusion comes from a study showing that patients with obstructive sleep apnea (OSA) who had the longest nocturnal hypoxemia episodes had a twofold risk for venous thromboembolic events. The association between nocturnal hypoxemia and VTE was strongest among patients who did not use continuous positive airway pressure (CPAP) systems, reported Wojciech Trzepizur, MD, from Angers University Hospital in Angers, France. "We found that those who spent more than 6% of their nighttime with levels of oxygen in their blood below 90% of normal had an almost twofold risk of developing VTEs as compared to patients without oxygen deprivation," he said. Trzepizur and colleagues conducted a retrospective study linking cohort data to an administrative health database. They identified unprovoked VTE in patients with a suspicion for OSA and no previous VTE. They created Cox proportional hazard models to assess the association of unprovoked VTE with apnea hypopnea index (AHI) measures and nocturnal hypoxemia markers, including the time patients spent below 90% oxygen saturation (T90), oxygen desaturation index (ODI), and hypoxic burden, defined as the total area under the respiratory event-related desaturation curve. They found that after a median follow-up of 6.3 years, 104 out of 7355 patients had an unprovoked VTE. In an unadjusted hazard model, there were significant associations between VTE and T90, as well as with hypoxic burden, but not with either AHI or ODI. However, in an analysis adjusted for age, gender, body mass index, alcohol intake,  hypertension, depression, history of cardiovascular disease, statin use, type of sleep study, study site and CPAP adherence, the investigators found that only T90 remained a significant independent predictor of VTE, with a hazard ratio (HR) of 1.06, P = .02. The association between T90 and VTE strengthened as the time spent below 90% saturation increased. Patients in the highest tercile, who spent more than 6% of the time undersaturated, had an HR for VTE of 1.95 (P = .02) compared with patients with a T90 less than 1%. There were no significant differences in VTE risk between patients who used CPAP for more than 4 hours per night compared with those who either used the devices for less than 4 hours or refused CPAP.

Reference

1. Osterweil N. Obstructive Sleep Apnea Linked to Unprovoked VTE. Medscape. September 8, 2022. Available at: https://www.medscape.com/viewarticle/980453 (accessed 9/13/2022).

Dopamine Use and Its Consequences in the Intensive Care Unit: A Cohort Study Utilizing the Japanese Intensive Care Patient Database

Suzuki R, Uchino S, Sasabuchi Y, Kawarai Lefor A, Sanui M.. Crit Care. 2022 Apr 2;26(1):90. [CrossRef] [PubMed]

Background: Dopamine is used to treat patients with shock in intensive care units (ICU) throughout the world, despite recent evidence against its use. The aim of this study was to explore the consequences of dopamine use in Japan.

Methods: The authors retrospectively searched the Japanese Intensive Care PAtient Database (JIPAD). Inclusion criteria included patients: 1) age 18 years or older, 2) admission to the ICU for reasons other than procedures, 3) ICU length of stay of 24 h or more, and 4) treatment with either dopamine or noradrenaline within 24 h of admission. The primary outcome was in-hospital mortality. Multivariable regression analysis was performed, followed by a propensity score-matched analysis.

Results: Dopamine was administered to 4,653 patients and noradrenaline to 11,844. There was no statistically significant difference in facility characteristics between frequent dopamine users (N = 28) and infrequent users (N = 28). Patients receiving dopamine had more cardiovascular diagnosis codes (70% vs. 42%; p < 0.01), more post-elective surgery status (60% vs. 31%), and lower APACHE III scores compared to patients given noradrenaline alone (70.7 vs. 83.0; p < 0.01). Multivariable analysis
showed an odds ratio for in-hospital mortality of 0.86 [95% CI: 0.71–1.04] in the dopamine ≤ 5 μg/kg/min group, 1.46 [95% CI: 1.18–1.82] in the 5–15 μg/kg/min group, and 3.30 [95% CI: 1.19–9.19] in the > 15 μg/kg/min group. In a 1:1 propensity score matching for dopamine use as a vasopressor (570 pairs), both in-hospital mortality and ICU mortality were significantly higher in the dopamine group compared to no dopamine group (22.5% vs. 17.4%, p = 0.038; 13.3%
vs. 8.8%, p = 0.018), as well as ICU length of stay (mean 9.3 days vs. 7.4 days, p = 0.004).

Conclusion: Dopamine is still widely used in Japan. The results of this study suggest detrimental effects of dopamine use specifically at a high dose. 

Reduction Of Dietary Sodium to Less Than 100 Mmol in Heart Failure (SODIUM-HF): An International, Open-Label, Randomised, Controlled Trial

Ezekowitz JA, Colin-Ramirez E, Ross H, et al. Lancet. 2022 Apr 1:S0140-6736(22)00369-5. [CrossRef] [PubMed]

Dietary restriction of sodium has been a standard of care to prevent fluid overload and adverse outcomes for patients with heart failure. To test this hypothesis, the authors conducted the SODIUM-HF study which is an international, open-label, randomized, controlled trial that enrolled patients with chronic heart failure (New York Heart Association [NYHA] functional class 2-3), and receiving optimally tolerated guideline-directed medical treatment. Patients were randomly assigned to either usual care according to local guidelines or a low sodium diet of less than 100 mmol (ie, <1500 mg/day). The primary outcome was the composite of cardiovascular-related admission to hospital, cardiovascular-related emergency department visit, or all-cause death within 12 months in the intention-to-treat (ITT) population (ie, all randomly assigned patients). 806 patients were enrolled and randomly assigned to a low sodium diet (n=397) or usual care (n=409). There was no statistical difference in mortality, hospitalizations, or emergency room visits (p>0.05 all comparisons). In ambulatory patients with heart failure, a dietary intervention to reduce sodium intake did not reduce clinical events.

Reduction Of Dietary Sodium to Less Than 100 Mmol in Heart Failure (SODIUM-HF): An International, Open-Label, Randomised, Controlled Trial

Ezekowitz JA, Colin-Ramirez E, Ross H, et al. Lancet. 2022 Apr 1:S0140-6736(22)00369-5. [CrossRef] [PubMed]

Dietary restriction of sodium has been a standard of care to prevent fluid overload and adverse outcomes for patients with heart failure. To test this hypothesis, the authors conducted the SODIUM-HF study which is an international, open-label, randomized, controlled trial that enrolled patients with chronic heart failure (New York Heart Association [NYHA] functional class 2-3), and receiving optimally tolerated guideline-directed medical treatment. Patients were randomly assigned to either usual care according to local guidelines or a low sodium diet of less than 100 mmol (ie, <1500 mg/day). The primary outcome was the composite of cardiovascular-related admission to hospital, cardiovascular-related emergency department visit, or all-cause death within 12 months in the intention-to-treat (ITT) population (ie, all randomly assigned patients). 806 patients were enrolled and randomly assigned to a low sodium diet (n=397) or usual care (n=409). There was no statistical difference in mortality, hospitalizations, or emergency room visits (p>0.05 all comparisons). In ambulatory patients with heart failure, a dietary intervention to reduce sodium intake did not reduce clinical events.

Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

REMAP-CAP Writing Committee for the REMAP-CAP Investigators, Bradbury CA, Lawler PR, Stanworth SJ, et al. JAMA. 2022 Mar 22. [CrossRef] [PubMed]

Anticoagulation has been proposed to benefit patients with COVID-19. The authors asked the question, “Does antiplatelet therapy administered to critically ill patients with COVID-19 improve organ support–free days (a composite end point of in-hospital mortality and duration of intensive care unit–based respiratory or cardiovascular support) up to day 21? In this bayesian randomized clinical trial that included 1557 patients, antiplatelet therapy with either aspirin or a P2Y12 inhibitor, compared with no antiplatelet therapy, resulted in a 95.7% posterior probability of futility with regard to the odds of improvement in organ support–free days within 21 days. The authors conclude that among critically ill patients with COVID-19, there was a low likelihood that treatment with an antiplatelet agent provided improvement in organ support–free days within 21 days.

Association Between Dexamethasone Treatment After Hospital Discharge for Patients With COVID-19 Infection and Rates of Hospital Readmission and Mortality

Huang CW, Yu AS, Song H, Park JS, Wu SS, Khang VK, Subject CC, Shen E. JAMA Netw Open. 2022 Mar 1;5(3):e221455. [CrossRef] [PubMed]

Current guidelines recommend use of dexamethasone, 6 mg/d, up to 10 days or until discharge for patients hospitalized with COVID-19. Whether patients who received less than 10 days of corticosteroids during hospitalization for COVID-19 benefit from continuing treatment at discharge has not been determined. The authors performed a retrospective cohort study at 15 medical centers within Kaiser Permanente Southern California. The population included adults who received less than 10 days of dexamethasone, 6 mg/d, until discharge during hospitalization for COVID-19 and were discharged alive between May 1 and September 30, 2020. A total of 1164 patients with a median age of 55 (IQR, 44-66) years were identified. Most patients were of Hispanic ethnicity (822 [70.6%]) and male (674 [57.9%]) and required oxygen support during hospitalization (1048 [90.0%]). Of the 1164 patients, 692 (59.5%) continued dexamethasone, 6 mg/d, at discharge. The adjusted odds ratio (OR) for readmissions or mortality within 14 days was 0.87 (95% CI, 0.58-1.30) for patients who continued dexamethasone therapy at discharge compared with those who did not. This finding suggests that dexamethasone should not be routinely prescribed beyond discharge for individuals with COVID-19.

Aspirin Use Is Associated with Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients with Coronavirus Disease 2019

Chow JH, Khanna AK, Kethireddy S, et al. Anesth Analg. 2021 Apr 1;132(4):930-941. [CrossRef] [PubMed]

Coronavirus disease-2019 (COVID-19) is associated with hypercoagulability and increased thrombotic risk in critically ill patients. The authors conducted a retrospective, observational cohort study of adult patients admitted with COVID-19 to multiple hospitals in the United States between March 2020 and July 2020 was performed. The primary outcome was the need for mechanical ventilation. Secondary outcomes were ICU admission and in-hospital mortality. Adjusted hazard ratios (HRs) for study outcomes were calculated using Cox-proportional hazards models after adjustment for the effects of demographics and comorbid conditions. Four hundred twelve patients were included in the study. Three hundred fourteen patients (76.3%) did not receive aspirin, while 98 patients (23.7%) received aspirin within 24 hours of admission or 7 days before admission. Aspirin use had a crude association with less mechanical ventilation (35.7% aspirin versus 48.4% nonaspirin, P = .03) and ICU admission (38.8% aspirin versus 51.0% nonaspirin, P = .04), but no crude association with in-hospital mortality (26.5% aspirin versus 23.2% nonaspirin, P = .51). After adjusting for 8 confounding variables, aspirin use was independently associated with decreased risk of mechanical ventilation (adjusted HR, 0.56, 95% confidence interval [CI], 0.37-0.85, P = .007), ICU admission (adjusted HR, 0.57, 95% CI, 0.38-0.85, P = .005), and in-hospital mortality (adjusted HR, 0.53, 95% CI, 0.31-0.90, P = .02). There were no differences in major bleeding (P = .69) or overt thrombosis (P = .82) between aspirin users and nonaspirin users. A sufficiently powered randomized controlled trial is needed to assess whether a causal relationship exists between aspirin use and reduced lung injury and mortality in COVID-19 patients.

Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants

Oskotsky T, Maric I, Tang A, Oskotsky B, Wong RJ, Aghaeepour N, Sirota M, Stevenson DK. JAMA Netw Open. 2021 Nov 1;4(11):e2133090. [CrossRef] [PubMed]

Importance: Antidepressant use may be associated with reduced levels of several proinflammatory cytokines suggested to be involved with the development of severe COVID-19. An association between the use of selective serotonin reuptake inhibitors (SSRIs)—specifically fluoxetine hydrochloride and fluvoxamine maleate—with decreased mortality among patients with COVID-19 has been reported in recent studies; however, these studies had limited power due to their small size.

Objective: The authors investigated the association of SSRIs with outcomes in patients with COVID-19 by analyzing electronic health records (EHRs).

Design, setting, and participants: This retrospective cohort study used propensity score matching by demographic characteristics, comorbidities, and medication indication to compare SSRI-treated patients with matched control patients not treated with SSRIs within a large EHR database representing a diverse population of 83 584 patients diagnosed with COVID-19 from January to September 2020 and with a duration of follow-up of as long as 8 months in 87 health care centers across the US. A total of 3401 adult patients with COVID-19 prescribed SSRIs were identified. When compared with matched untreated control patients, relative risk (RR) of mortality was reduced among patients prescribed any SSRI (497 of 3401 [14.6%] vs 1130 of 6802 [16.6%]; RR, 0.92 [95% CI, 0.85-0.99]; adjusted P = .03); fluoxetine (46 of 470 [9.8%] vs 937 of 7050 [13.3%]; RR, 0.72 [95% CI, 0.54-0.97]; adjusted P = .03); and fluoxetine or fluvoxamine (48 of 481 [10.0%] vs 956 of 7215 [13.3%]; RR, 0.74 [95% CI, 0.55-0.99]; adjusted P = .04). The association between receiving any SSRI that is not fluoxetine or fluvoxamine and risk of death was not statistically significant (447 of 2898 [15.4%] vs 1474 of 8694 [17.0%]; RR, 0.92 [95% CI, 0.84-1.00]; adjusted P = .06).

Conclusions and Relevance:  These results support evidence that SSRIs may be associated with reduced severity of COVID-19 reflected in the reduced RR of mortality. Further research and randomized clinical trials are needed to elucidate the effect of SSRIs generally, or more specifically of fluoxetine and fluvoxamine, on the severity of COVID-19 outcomes.

Effectiveness of Covid-19 Vaccines against the B.1.617.2 (Delta) Variant

Lopez Bernal J, Andrews N, Gower C, et al. N Engl J Med. 2021 Jul 21. [CrossRef] [PubMed] [Epub ahead of print.] 

The Pfizer-BioNTech and AstraZeneca vaccines — the primary vaccine options in the United Kingdom — were less effective against symptomatic COVID-19 when people were exposed to the Delta variant of SARS-CoV-2 compared with the Alpha variant (known as B.1.1.7, or the UK variant), according to a study published online today in the New England Journal of Medicine. The Indian investigators used a test-negative case–control design to estimate the effectiveness of vaccination against symptomatic disease caused by the delta variant or the predominant strain (B.1.1.7, or alpha variant) over the period that the delta variant began circulating. Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations.

Azithromycin for Community Treatment of Suspected COVID-19 in People at Increased Risk of an Adverse Clinical Course in the UK (PRINCIPLE): A Randomised, Controlled, Open-Label, Adaptive Platform Trial

PRINCIPLE Trial Collaborative Group. Lancet. 2021 Mar 4:S0140-6736(21)00461-X. [CrossRef] [PubMed]

Azithromycin, an antibiotic with anti-inflammatory and potential antiviral properties, has been used to treat COVID-19, but evidence from community randomised trials is lacking. We aimed to assess the effectiveness of azithromycin to treat suspected COVID-19 among people in the community who had an increased risk of complications.

In this UK-based, primary care, open-label, multi-arm, adaptive platform randomized trial of interventions against COVID-19 in people at increased risk of an adverse clinical course (PRINCIPLE), we randomly assigned people aged 65 years and older, or 50 years and older with at least one comorbidity, who had been unwell for 14 days or less with suspected COVID-19, to usual care plus azithromycin 500 mg daily for three days, usual care plus other interventions, or usual care alone. The trial had two coprimary endpoints measured within 28 days from randomization: time to first self-reported recovery, analysed using a Bayesian piecewise exponential, and hospital admission or death related to COVID-19, analyzed using a Bayesian logistic regression model. Eligible participants with outcome data were included in the primary analysis, and those who received the allocated treatment were included in the safety analysis.

Participants were enrolled between May 22 and Nov 30, 2020. 2265 participants were randomly assigned, 540 to azithromycin plus usual care, 875 to usual care alone, and 850 to other interventions. 2120 (94%) of 2265 participants provided follow-up data and were included in the Bayesian primary analysis, 500 participants in the azithromycin plus usual care group, 823 in the usual care alone group, and 797 in other intervention groups. 402 (80%) of 500 participants in the azithromycin plus usual care group and 631 (77%) of 823 participants in the usual care alone group reported feeling recovered within 28 days. We found little evidence of a meaningful benefit in the azithromycin plus usual care group in time to first reported recovery versus usual care alone (hazard ratio 1·08, 95% Bayesian credibility interval [BCI] 0·95 to 1·23), equating to an estimated benefit in median time to first recovery of 0·94 days (95% BCI −0·56 to 2·43). The probability that there was a clinically meaningful benefit of at least 1·5 days in time to recovery was 0·23. 16 (3%) of 500 participants in the azithromycin plus usual care group and 28 (3%) of 823 participants in the usual care alone group were hospitalised (absolute benefit in percentage 0·3%, 95% BCI −1·7 to 2·2). There were no deaths in either study group. Safety outcomes were similar in both groups. Two (1%) of 455 participants in the azithromycin plus usual care group and four (1%) of 668 participants in the usual care alone group reported admission to hospital during the trial, not related to COVID-19.

These findings do not justify the routine use of azithromycin for reducing time to recovery or risk of hospitalization for people with suspected COVID-19 in the community.

The Lancet Commission on Public Policy and Health in the Trump Era

Himmelstein DU, Woolhandler S, Cooney R, McKee M, Horton R.. Lancet. 2018 Sep 22;392(10152):993-995. [CrossRef] [PubMed]

The article is lengthy at 49 pages and has no abstract available. The executive summary runs about 2 pages. The key messages listed in the article are below. Links to the executive summary and the whole article are at the end of this summary.

Key messages

• Politicised and repudiated science, leaving the USA unprepared and exposed to the COVID-19 pandemic
• Eviscerated environmental regulation, hastening global warming
• Incited racial, nativist, and religious hatred, provoking vigilante and police violence
• Denied refuge to migrants fleeing violence and oppression, and abused immigrant detainees
• Undermined health coverage
• Weakened food assistance programmes
• Curtailed reproductive rights
• Undermined global cooperation for health, and triggered trade wars
• Shifted resources from social programmes to military spending and tax windfalls for corporations and the wealthy
• Subverted democracy both nationally and internationally
• Although the Trump administration policies posed a uniquely urgent threat to health,
• damaging neoliberal policies predated and abetted his ascendance:
• Life expectancy in the USA has lagged behind other wealthy nations since 1980 and
• began falling in 2014
• The chronically high mortality of Native Americans started rising in 1999, while
• yawning disparities between Black and white people persisted and progress on racial
• equity in other domains (eg, education, housing, income and policing) halted or
• reversed
• Substance abuse deaths greatly increased
• Income and wealth inequality widened
• Incarceration increased four-fold, initiated by President Nixon’s racially motivated war
• on drugs and compounded by harsh laws enacted under Presidents Reagan and Clinton
• Welfare eligibility restrictions implemented by President Clinton removed benefits from millions
• Deindustrialisation spurred by trade agreements that favoured corporate interests
• over labour protections reduced economic opportunity in many regions of the USA,
• damaging health and increasing receptivity to racist and xenophobic appeals
• Market-based reforms commercialised and bureaucratised medical care, raised costs, and shifted care toward high-income US residents
• Despite the Affordable Care Act, nearly 30 million people in the USA remained
• uninsured and many more were covered but still unable to afford care
• Funding cuts reduced the front-line public health workforce by 20%
• The Biden administration must cancel Trump’s actions and also address the healthdamaging structural problems that were present before Trump’s presidency:
• Raise taxes on high-income people and use the proceeds to bolster social, educational, and health programmes, and address urgent environmental problems
• Mobilise against the structural racism and police violence that shorten the lives of
• people of colour
• Replace means-tested programmes such as Medicaid that segregate low-income
• people, with unified programmes such as national health insurance that serve all
• US residents, aligning the interests of the middle class and the poor in maintaining excellence
• Reclaim the US Government’s role in delivering health and social services, and stop channelling public funds through private firms whose profit-seeking skews priorities
• Redirect public investments from militarism, corporate subsidies, and distorted
• medical priorities to domestic and global fairness, environmental protection,
• and neglected public health and social interventions
• Reinvigorate US democracy by reforming campaign financing, reinforcing voting,
• immigration, and labour rights, and restoring oversight of presidential prerogatives

Full Text and Executive Summary

The Lancet Commission on Public Policy and Health in the Trump Era

Himmelstein DU, Woolhandler S, Cooney R, McKee M, Horton R. Lancet. 2018 Sep 22;392(10152):993-995. [CrossRef] [PubMed]

The article is lengthy at 49 pages and has not abstract available. The executive summary runs about 2 pages. The key messages listed in the article are below. Links to the executive summary and the whole article are at the end the key messages.

Key messages

• Politicised and repudiated science, leaving the USA unprepared and exposed to the COVID-19 pandemic
• Eviscerated environmental regulation, hastening global warming
• Incited racial, nativist, and religious hatred, provoking vigilante and police violence
• Denied refuge to migrants fleeing violence and oppression, and abused immigrant detainees
• Undermined health coverage
• Weakened food assistance programmes
• Curtailed reproductive rights
• Undermined global cooperation for health, and triggered trade wars
• Shifted resources from social programmes to military spending and tax windfalls for corporations and the wealthy
• Subverted democracy both nationally and internationally
• Although the Trump administration policies posed a uniquely urgent threat to health,
• damaging neoliberal policies predated and abetted his ascendance:
• Life expectancy in the USA has lagged behind other wealthy nations since 1980 and
• began falling in 2014
• The chronically high mortality of Native Americans started rising in 1999, while
• yawning disparities between Black and white people persisted and progress on racial
• equity in other domains (eg, education, housing, income and policing) halted or
• reversed
• Substance abuse deaths greatly increased
• Income and wealth inequality widened
• Incarceration increased four-fold, initiated by President Nixon’s racially motivated war
• on drugs and compounded by harsh laws enacted under Presidents Reagan and Clinton
• Welfare eligibility restrictions implemented by President Clinton removed benefits from millions
• Deindustrialisation spurred by trade agreements that favoured corporate interests
• over labour protections reduced economic opportunity in many regions of the USA,
• damaging health and increasing receptivity to racist and xenophobic appeals
• Market-based reforms commercialised and bureaucratised medical care, raised costs, and shifted care toward high-income US residents
• Despite the Affordable Care Act, nearly 30 million people in the USA remained
• uninsured and many more were covered but still unable to afford care
• Funding cuts reduced the front-line public health workforce by 20%
• The Biden administration must cancel Trump’s actions and also address the healthdamaging structural problems that were present before Trump’s presidency:
• Raise taxes on high-income people and use the proceeds to bolster social, educational, and health programmes, and address urgent environmental problems
• Mobilise against the structural racism and police violence that shorten the lives of
• people of colour
• Replace means-tested programmes such as Medicaid that segregate low-income
• people, with unified programmes such as national health insurance that serve all
• US residents, aligning the interests of the middle class and the poor in maintaining excellence
• Reclaim the US Government’s role in delivering health and social services, and stop channelling public funds through private firms whose profit-seeking skews priorities
• Redirect public investments from militarism, corporate subsidies, and distorted
• medical priorities to domestic and global fairness, environmental protection,
• and neglected public health and social interventions
• Reinvigorate US democracy by reforming campaign financing, reinforcing voting,
• immigration, and labour rights, and restoring oversight of presidential prerogatives

Full Text and Executive Summary