Acute Pulmonary Embolism and COVID-19

Poyiadji N, Cormier P, Patel PY, et al. Radiology. 2020 May 14:201955.  [CrossRef] [PubMed]

Patients with COVID-19 with a body mass index (BMI) >30 kg/m² have increased odds of developing pulmonary embolism (PE), according to an online research letter. The authors assessed the clinical characteristics of COVID-19 patients who developed PE in a retrospective analysis involving 328 COVID-19 patients who underwent pulmonary computed tomography (CT) angiography. Thy found that 22 percent of the patients had PE. Patients with a BMI >30 kg/m² were observed more often in the PE versus the non-PE group (58 versus 44 percent). Compared with the non-PE cohort, fewer patients with PE were on statin therapy prior to admission (27 versus 46 percent). In a multivariate model, patients taking statin therapy prior to admission had significantly reduced odds of developing PE (adjusted odds ratio, 0.4), while those with a BMI >30 kg/m² had an adjusted odds ratio of 2.7. The odds ratio was 4.8 for PE with a 6 µg/mL increase in D-dimer. The area under the receiver operating characteristic curve (AUC) was 0.86 for the multivariable model. A D-dimer of 3.11 µg/mL had sensitivity and specificity of 78 and 81 percent, respectively, for development of PE (AUC, 0.85). The authors advocate for early evaluation with pulmonary CT angiography in COVID-19 patients who are at increased risk for developing pulmonary embolism based on demographic, clinical, and laboratory variables.

Hydroxychloroquine or Chloroquine with or Without a Macrolide for Treatment of Covid-19: A Multinational Registry Analysis

Mehra MR, Desai SS, Ruschitzka F, Patel AN. Lancet. May 22, 2020. [Epub ahead of print]. [CrossRef]

Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19. The authors did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation). 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10 698 (11·1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%; hazard ratio 1·335, 95% CI 1·223–1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368–1·531), chloroquine (16·4%; 1·365, 1·218–1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273–1·469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935–2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106–5·983), chloroquine (4·3%; 3·561, 2·760–4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344–4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia. The authors were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19.

Remdesivir In Adults with Severe COVID-19: A Randomised, Double-Blind, Placebo-Controlled, Multicentre Trial

Wang Y, Zhang D, Du G, et al. Lancet. 2020; 395:1569-78. [CrossRef]

No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). The authors did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions) or the same volume of placebo infusions for 10 days. The primary endpoint was time to clinical improvement up to day 28. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87–1·75]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. The authors conclude that remdesivir was not associated with statistically significant clinical benefits.

Association of Treatment Dose Anticoagulation with In-Hospital Survival Among Hospitalized Patients with COVID-19

Paranjpe I, Fuster V, Lala A, et al. J Am Coll Cardiol. 2020 May 5. pii: S0735-1097(20)35218-9. [Epub ahead of print] [CrossRef] [PubMed] 

The novel coronavirus 2019 (COVID-19) has been associated with reports of increased thromboembolic events and anecdotal observations of improved outcomes with systemic anticoagulation (AC). The authors assessed the association between administration of in-hospital AC and survival in a large cohort of hospitalized patients with COVID-19. Between March 14 and April 11, 2020, 2,773 patients were hospitalized with laboratory\confirmed COVID-19 within the Mount Sinai Health System in New York City. The authors used a Cox proportional hazards model to evaluate the effect of treatment-dose systemic AC (including oral, subcutaneous, or intravenous forms) on in-hospital mortality. 786 (28%) received systemic AC during their hospital course. In-hospital mortality for patients treated with AC was 22.5% with a median survival of 21 days, compared to 22.8% and median survival of 14 days in patients who did not receive AC. In patients who required mechanical ventilation (N=395), in-hospital mortality was 29.1% with a median survival of 21 days for those treated with AC as compared to 62.7% with a median survival of 9 days in patients who did not receive AC. In a multivariate proportional hazards model, longer duration of AC treatment was associated with a reduced risk of mortality (adjusted HR of 0.86 per day, 95% confidence interval 0.82-0.89, p<0.001). Although limited by its observational nature, unobserved confounding, unknown indication for AC, lack of metrics to further classify illness severity in the mechanically ventilated subgroup, and indication bias, the findings suggest that systemic AC may be associated with improved outcomes among patients hospitalized with COVID-19. It should be noted that similar arguments were made for systemic anticoagulation in ARDS but when subjected to randomized trials, anticoagulation made no mortality difference.

Assessment of N95 Respirator Decontamination and Re-Use for SARS-Cov-2

Fischer RJ, Morris DJ, Doremalen N, et al. medRxiv. April 15, 2020. [CrossRef]

A shortage of N95 masks designed for single has forced many to reuse masks and attempt to sterilize the masks between uses. In a not as yet peer-reviewed preprint, the authors analyzed four different decontamination methods – UV radiation (260 – 285 nm), 70ºC heat, 70% ethanol and vaporized hydrogen peroxide (VHP) – for their ability to reduce contamination with infectious SARS-CoV-2 (COVID-19) and their effect on N95 respirator function. Vaporized hydrogen peroxide, ethanol and heat yielded extremely rapid inactivation but UV inactivated SARS-CoV-2 more slowly. Quantitative fit tests showed that the filtration performance of the N95 respirator was not markedly reduced after a single decontamination for any of the four decontamination methods. Subsequent rounds of decontamination caused sharp drops in filtration performance of the ethanol-treated masks, and to a slightly lesser degree, the heat-treated masks. The VHP- and UV-treated masks retained comparable filtration performance to the control group after two rounds of decontamination, and maintained acceptable performance after three rounds. The authors recommend VHP for decontamination based on their data that the VHP treatment exhibited the best combination of rapid inactivation of SARS-CoV-2 and preservation of N95 respirator integrity.

No Evidence of Clinical Efficacy of Hydroxychloroquine in Patients Hospitalized for COVID-19 Infection with Oxygen Requirement: Results of a Study Using Routinely Collected Data to Emulate a Target Trial

Mahevas M,  Tran V, Roumier M, et al. medRxiv. April 14, 2020. [CrossRef]

Treatments are urgently needed to prevent respiratory failure and deaths from coronavirus disease 2019 (COVID-19). Hydroxychloroquine (HCQ) has received worldwide attention because of positive results from small studies. The authors used data collected from routine care of all adults in 4 French hospitals with documented COVID-19 pneumonia and requiring oxygen ≥ 2 L/min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg/day. The composite primary endpoint was transfer to intensive care unit (ICU) within 7 days from inclusion and/or death from any cause. Analyses were adjusted for confounding factors by inverse probability of treatment weighting. The study included 181 patients with COVID-19 pneumonia; 84 received HCQ within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group). Initial severity was well balanced between the groups. In the weighted analysis, 20.2% patients in the HCQ group were transferred to the ICU or died within 7 days vs 22.1% in the no-HCQ group; 2.8% of the patients died within 7 days vs 4.6% in the no-HCQ group, and 27.4% and 24.1%, developed acute respiratory distress syndrome within 7 days. Eight patients receiving HCQ (9.5%) experienced electrocardiogram modifications requiring HCQ discontinuation. The authors state that the results do not support the use of HCQ in patients hospitalized for documented COVID-19 hypoxic pneumonia.

Compassionate Use of Remdesivir for Patients with Severe Covid-19

Grein J, Ohmagari N, Shin D, et al. N Engl J Med. 2020 Apr 10. [Epub ahead of print] [CrossRef] [PubMed]

Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. In article that is already being heavily criticized, the authors provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed. Of the 53 patients, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. The authors suggest that measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. The  paper has been criticized by a number of scientists but probably none as severe as Josh Farkas in his Pulmcrit blog. He was particularly critical of the lack of a control group and the lack of endpoints for the trial.

Forecasting COVID-19 impact on hospital bed-days, ICU-days, ventilator-days and deaths by US state in the next 4 months

IHME COVID-19 health service utilization forecasting team, Christopher JL Murray. MedRxiv. March 26. Available at: https://www.medrxiv.org/content/10.1101/2020.03.27.20043752v1 (accessed 4/2/20) [CrossRef]

The authors provide a preprint of their forecasting data for the COVID-19 epidemic. Using a statistical model, the authors predict excess demand in the US will be 64,175 (95% UI 7,977 to 251,059) total beds and 17,380 (95% UI 2,432 to 57,955) ICU beds at the peak of the COVID-19 epidemic. Peak ventilator use is predicted to be 19,481 (95% UI 9,767 to 39,674) ventilators. Peak demand will be in the second week of April. The authors estimate 81,114 (95% UI 38,242 to 162,106) deaths in the United States from COVID-19 over the next 4 months. In addition, they show their predictions include all beds, ICU beds, ventilators, deaths per day and total deaths at a separate website https://covid19.healthdata.org/projections for the US and each state. These estimates if accurate may help inform the development and implementation of strategies to deal with the COVID-19 epidemic.

Time Kinetics of Viral Clearance and Resolution of Symptoms in Novel Coronavirus Infection

Chang D, Mo G, Yuan X, Tao Y, Peng X, Wang F, Xie L, Sharma L, Dela Cruz CS, Qin E. Am J Respir Crit Care Med. 2020 Mar 23. [Epub ahead of print] [CrossRef] [PubMed]

The authors briefly describe the time kinetics of symptom onset, duration of symptoms and viral clearance is in 16 patients with COVID-19. The median age was 35.5 years (range 3-68 years), with 11/16 males. The major symptoms in these patients were fever (14/16), cough (11/16), pharyngalgia (5/16) and dyspnea (2/16). The mean  incubation period was 5 days (IQR 1-6 days). The mean duration of symptoms was estimated to be 8 days (IQR 6.25-11.5). Most importantly, half (8/16) of the patient remained viral positive (a surrogate marker of shedding) even after the resolution of symptoms (Median 2.5 days, range 1 to 8 days).

Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?

Fang L, Karakiulakis G2, Roth M3. Lancet Respir Med. 2020 Mar 11. pii: S2213-2600(20)30116-8. [CrossRef] [PubMed]

The most distinctive comorbidities of severe 32 novel coronavirus disease 2019 (COVID-19) hypertension, diabetes mellitus, coronary heart diseases, and cerebrovascular disease. Human pathogenic coronaviruses (severe acute respiratory syndrome coronavirus [SARS-CoV] and SARSCoV-2) bind to their target cells through angiotensin-converting enzyme 2 (ACE2), which is expressed by epithelial cells of the lung, intestine, kidney, and blood vessels. The expression of ACE2 is substantially increased in patients with type 1 or type 2 diabetes, who are treated with ACE inhibitors and angiotensin II type-I receptor blockers (ARBs). Hypertension is also treated with ACE inhibitors and ARBs, which results in an upregulation of ACE2. The authors hypothesize that the increased expression of ACE2 would facilitate infection with COVID-19 and that diabetes and hypertension treatment with ACE2-stimulating drugs would increase the risk of developing severe and fatal COVID-19.

CT Imaging Features of 2019 Novel Coronavirus (2019-nCoV)

Chung M, Bernheim A, Mei X, et al. Radiology. 2020 Feb 4:200230. [CrossRef] [PubMed]

In a retrospective case series, chest CT scans of 21 symptomatic patients from China infected with the 2019 novel coronavirus (2019-nCoV) were reviewed. Typical CT findings included bilateral pulmonary parenchymal ground-glass and consolidative pulmonary opacities, sometimes with a rounded morphology and a peripheral lung distribution. Notably, lung cavitation, discrete pulmonary nodules, pleural effusions, and lymphadenopathy were absent. Follow-up imaging in a subset of patients during the study time window often demonstrated mild or moderate progression of disease, as manifested by increasing extent and density of lung opacities. Although nonspecific, these manifestations are similar to many other viral pneumonias.

Effect of Obstructive Sleep Apnoea and Its Treatment with Continuous Positive Airway Pressure on the Prevalence of Cardiovascular Events in Patients with Acute Coronary Syndrome (ISAACC Study): A Randomised Controlled Trial

Sánchez-de-la-Torre M, Sánchez-de-la-Torre A, Bertran S, et al; on behalf of the Spanish Sleep Network. [published online December 12, 2019]. Lancet Respir Med. [CrossRef] [PubMed]

The authors evaluated the effect of obstructive sleep apnoea (OSA) and its treatment with continuous positive airway pressure (CPAP) on the clinical evolution of patients with acute coronary syndrome (ACS). A multicentre, open-label, parallel-group, randomised controlled trial of patients with ACS at 15 hospitals was conducted in Spain. Eligible non-sleepy patients were men and women aged 18 years and older, admitted to hospital for documented symptoms of ACS. All patients underwent respiratory polygraphy during the first 24–72 h after admission. OSA patients were randomly assigned (1:1) to CPAP treatment plus usual care (CPAP group) or usual care alone (UC group). The primary endpoint was the prevalence of a composite of cardiovascular events (cardiovascular death or non-fatal events [acute myocardial infarction, non-fatal stroke, hospital admission for heart failure, and new hospitalisations for unstable angina or transient ischaemic attack]) in patients followed up for a minimum of 1 year. A total of 2834 patients with ACS had respiratory polygraphy, of whom 2551 (90·01%) were recruited. The prevalence of cardiovascular events was similar in the CPAP and UC groups (98 events [16%] vs 108 events [17%]; hazard ratio [HR] 0·89 [95% CI 0·68–1·17]; p=0·40) during follow-up. The prevalence of cardiovascular events seems not to be related to CPAP compliance or OSA severity. The authors conclude that among non-sleepy patients with ACS, the presence of OSA was not associated with an increased prevalence of cardiovascular events and treatment with CPAP did not significantly reduce this prevalence. 

Changes in Quality of Care after Hospital Mergers and Acquisitions

Beaulieu ND, Dafny LS, Landon BE, Dalton JB, Kuye I, McWilliams JM. N Engl J Med. 2020 Jan 2;382(1):51-59. [CrossRef] [PubMed]

The hospital industry has consolidated substantially with multiple studies have shown that hospital mergers have led to higher prices for commercially insured patients, but research about effects on quality of care is limited. Using Medicare claims and Hospital Compare data from 2007 through 2016 on performance on four measures of quality of care (a composite of clinical-process measures, a composite of patient-experience measures, mortality, and the rate of readmission after discharge) and data on hospital mergers and acquisitions occurring from 2009 through 2013, we conducted difference-in-differences analyses comparing changes in the performance of acquired hospitals from the time before acquisition to the time after acquisition with concurrent changes for control hospitals that did not have a change in ownership. The study sample included 246 acquired hospitals and 1986 control hospitals. Being acquired was associated with a modest differential decline in performance on the patient-experience measure (adjusted differential change, −0.17 SD; 95% confidence interval [CI], −0.26 to −0.07; P=0.002; the change was analogous to a fall from the 50th to the 41st percentile) and no significant differential change in 30-day readmission rates (−0.10 percentage points; 95% CI, −0.53 to 0.34; P=0.72) or in 30-day mortality (−0.03 percentage points; 95% CI, −0.20 to 0.14; P=0.72). Acquired hospitals had a significant differential improvement in performance on the clinical-process measure (0.22 SD; 95% CI, 0.05 to 0.38; P=0.03), but this could not be attributed conclusively to a change in ownership because differential improvement occurred before acquisition. Hospital acquisition by another hospital or hospital system was associated with modestly worse patient experiences and no significant changes in readmission or mortality rates. Effects on process measures of quality were inconclusive.

Comparative Effectiveness of Combined Favipiravir A and Oseltamivir Therapy Versus Oseltamivir Monotherapy in Critically Ill Patients with Influenza Virus Infection

Wang Y, Fan G, Salam A, et al. J Infect Dis. 2019 Dec 11. pii: jiz656. [CrossRef] [PubMed]

A synergistic effect of combination therapy with favipiravir and oseltamivir has been reported in pre-clinical models of influenza. However, no data are available on the clinical effectiveness of combination therapy in severe influenza. Data from two separate prospective studies of influenza adults were used to compare outcomes between combination and oseltamivir monotherapy. Outcomes includes rate of clinical improvement, defined as a decrease of 2 categories on a 7-category ordinal scale, and viral RNA detectability over time. Forty patients were treated with combination therapy and 128 with oseltamivir alone. Clinical improvement on Day 14 occurred in the combination group was higher than in monotherapy group (62.5% vs 42.2%, p=0.0247). The proportion of undetectable viral RNA at day 10 was higher in the combination group than oseltamivir group (67.5% vs 21.9%, p<0.01). No significant differences were observed in mortality or other outcomes. The authors conclude that favipiravir and oseltamivir combination therapy may accelerate clinical recovery compared to oseltamivir monotherapy in severe influenza, and this strategy should be formally evaluated in a randomized controlled trial.

Balanced Crystalloids Versus Saline in Sepsis: A Secondary Analysis of the SMART Trial

Brown RM, Wang L, Coston TD, et al. Am J Respir Crit Care Med. 2019 Aug 27. [CrossRef] [PubMed]

Administration of intravenous crystalloid solutions is a fundamental therapy for sepsis, but the effect of crystalloid composition on patient outcomes remains unknown. The authors compared the effect of balanced crystalloids versus saline on 30-day in-hospital mortality among critically ill adults with sepsis. Of 15,802 patients enrolled in SMART, 1,641 patients were admitted to the medical intensive care unit with a diagnosis of sepsis. A total of 217 patients (26.3%) in the balanced crystalloids group experienced 30-day in-hospital morality, compared with 255 patients (31.2%) in the saline group (adjusted odds ratio, 0.74; 95% confidence interval, 0.59 - 0.93; P = 0.01) but the 60-day mortality did not significantly differ (aOR 0.80 [0.64 to 1.01]). Patients in the balanced group experienced a lower incidence of major adverse kidney events within 30 days (35.4% vs 40.1%; aOR 0.78; 95% CI 0.63 - 0.97) and a greater number of vasopressor-free days (20 ± 12 vs 19 ± 13; aOR 1.25; 95% CI 1.02 - 1.54) and renal replacement therapy-free days (20 ± 12 vs 19 ± 13; aOR 1.35 [1.08 - 1.69]), compared to the saline group. The authors conclude that amongst patients with sepsis in a large randomized trial, use of balanced crystalloids was associated with a lower 30-day in-hospital mortality compared to use of saline. The article is accompanied by a thoughtful editorial authored by Paul Young.

Association of Aspirin Use with Mortality Risk Among Older Adult Participants in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

Loomans-Kropp HA1, Pinsky P, Cao Y, Chan AT, Umar A. JAMA Netw Open. 2019 Dec 2;2(12):e1916729. [CrossRef] [PubMed]

Aspirin use has been associated with reduced risk of cancer mortality, particularly of the colorectum. However, aspirin efficacy may be influenced by biological characteristics, such as obesity and age. With the increasing prevalence of obesity and conflicting data regarding the effect of aspirin in older adults, the authors evaluated aspirin use among participants aged 65 years and older in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial at baseline (November 8, 1993, to July 2, 2001) and follow-up (2006-2008). The majority endpoints were all-cause, any cancer, GI cancer, or colorectal cancer (CRC) mortality. Multivariable hazard ratios (HRs) and 95% CIs were calculated using time-varying Cox proportional hazards regression modeling, adjusting for additional factors. Compared with no use, aspirin use 1 to 3 times per month was associated with reduced risk of all-cause mortality (HR, 0.84; 95% CI, 0.80-0.88; P < .001) and cancer mortality (HR, 0.87; 95% CI, 0.81-0.94; P < .001). Aspirin use 3 or more times per week was associated with decreased risk of mortality of all causes (HR, 0.81; 95% CI, 0.80-0.83; P < .001), any cancer (HR, 0.85; 95% CI, 0.81-0.88; P < .001), GI cancer (HR, 0.75; 95% CI, 0.66-0.84; P < .001), and CRC (HR, 0.71; 95% CI, 0.61-0.84; P < .001). When stratified by BMI (calculated as weight in kilograms divided by height in meters squared), aspirin use 3 or more times per week among individuals with BMI 20 to 24.9 was associated with reduced risk of all-cause mortality (HR, 0.82; 95% CI, 0.78-0.85; P < .001) and any cancer mortality (HR, 0.86; 95% CI, 0.79-0.82; P < .001). Among individuals with BMI 25 to 29.9, aspirin use 3 or more times per week was associated with reduced risk of all-cause mortality (HR, 0.82; 95% CI, 0.79-0.85; P < .001), any cancer mortality (HR, 0.86; 95% CI, 0.81-0.91; P < .001), GI cancer mortality (HR, 0.72; 95% CI, 0.60-0.86; P < .001), and CRC mortality (HR, 0.66; 95% CI, 0.51-0.85; P = .001). The authors conclude that aspirin use 3 or more times per week was associated with a reduction in all-cause, cancer, GI cancer and CRC mortality in older adults.

Dissecting Racial Bias in an Algorithm Used to Manage the Health of Populations

Obermeyer Z, Powers B, Vogeli C, Mullainathan S. Science. 2019;366:447-53. [CrossRef]

Insurance companies often use commercial algorithms to guide health decisions. The authors found evidence of racial bias in one widely used algorithm. At a given risk score, Black patients are considerably sicker than White patients, as evidenced by signs of uncontrolled illnesses. Remedying this disparity would increase the percentage of Black patients receiving additional help from 17.7 to 46.5%. The bias arises because the algorithm predicts health care costs rather than illness, but unequal access to care means that we spend less money caring for Black patients than for White patients. Thus, despite health care cost appearing to be an effective proxy for health by some measures of predictive accuracy, large racial biases arise. Reformulating the algorithm so that it no longer uses costs as a proxy for needs eliminates the racial bias in predicting who needs extra care.

Dog Ownership and Cardiovascular Health: Results from the Kardiovize 2030 Project

Maugeri A, Medina-Inojosa JR, Kunzova S, Barchitta M, Agodi A, Vinciguerra M, Lopez-Jimenez F. Mayo Clin Proc Innov Qual Outcomes. 2019 Aug 23;3(3):268-275. [CrossRef] [PubMed]

In Arizona an automobile license can be obtained which says, “Pets Enrich Our Lives”. This article suggests that pet ownership may have health benefits. The authors studied 1769 subjects (aged from 25 to 64 years; 44.3% males) with no history of cardiovascular disease and compared cardiovascular health (CVH) scores with nonpet owners. Approximately 42% of subjects owned a pet: 24.3% owned a dog and 17.9% owned another animal. Pet owners, and specifically dog owners, were more likely to report physical activity, diet, and blood glucose at ideal level which resulted in higher CVH score than nonpet owners (P=0.006). Compared with owners of other pets, dog owners were more likely to report physical activity and diet at ideal level. The comparison of dog owners with non-dog owners yielded similar results. After adjustment for covariates, dog owners exhibited higher CVH scores than non-pet owners (P=0.005), other pet-owners (0.309; P=0.041), and non-dog owners (P=0.004). The authors conclude that dog owners were more likely to achieve recommended level of behavioral CVH metrics (physical activity and diet) than non-dog owners, which likely translates into better cardiovascular health.

Analysis of Human Performance Deficiencies Associated with Surgical Adverse Events

Suliburk JW, Buck QM, Pirko CJ, Massarweh NN, Barshes NR, Singh H, Rosengart TK. JAMA Netw Open. 2019 Jul 3;2(7):e198067. [CrossRef] [PubMed]

Potentially preventable adverse events remain a formidable cause of patient harm and health care expenditure despite advances in systems-based risk-reduction strategies. The authors analyzed the incidence of human performance deficiencies (HPDs) during the provision of surgical care using a new taxonomy to inform the development and implementation of an HPD classifier tool to categorize HPDs into errors associated with cognitive, technical, and team dynamic functions. The HPD classifier tool was then used to concurrently analyze surgical adverse events in 3 adult hospital affiliates—a level I municipal trauma center, a quaternary care university hospital, and a US Veterans Administration hospital—from January 2, 2018, to June 30, 2018. Surgical trainees presented data describing all adverse events associated with surgical services at weekly hospital-based morbidity and mortality conferences.

A total of 188 adverse events were recorded, including 182 adverse events (96.8%) among 5365 patients who underwent surgical operations and 6 adverse events (3.2%) among patients undergoing nonoperative treatment. Among these 188 adverse events, 106 (56.4%) were associated with HPDs. Among these 106 HPD adverse events over half were attributed to human performance deficiencies in execution, planning or problem solving, communication, teamwork, and rules violation. Among the adverse events listed in Table 1 of the article were surgical site infection and wound dehiscence (12.2%); unexpected bleeding or transfusion (8%); deep venous thrombosis and pulmonary embolism (6.4%); unplanned intubation, pneumonia, and the patient needing a ventilator more than 48 hours after the operation has ended (5.9%), sepsis or septic shock (4.3%).

The authors conclude that human performance deficiencies were identified in more than half of adverse events, most commonly associated with cognitive error in the execution of care. It is unclear how many of these adverse events relate to human performance deficiencies including cognitive error.

New Drugs: Where Did We Go Wrong and What Can We Do Better?

Wieseler B, McGauran N, Kaiser T. BMJ. 2019 Jul 10;366:l4340. [CrossRef] [PubMed]

The authors reviewed the efficacy of new medications approved in Germany. Medicine regulators around the world are pursuing a strategy aimed at accelerating the development and approval of drugs. These approaches are based on the assumption that faster access to new drugs benefits patients. The rhetoric of novelty and innovation creates an assumption that new products are better than existing ones.

But although gaps in the therapeutic armamentarium undoubtedly exist, research covering drug approvals since the 1970s suggests only a limited number of new drugs provide real advances over existing drugs. Most studies put the proportion of true innovation at under 15%, with no clear improvement over time.

In one large study, investigators found that only 54 (25%) of the 216 new drugs entering the German market between 2011 and 2017 were judged to have a considerable, or major, added benefit. For 16% of these new agents, this additional benefit was either minor or could not be quantified. In addition, for 58% of these medications there was no proof of added benefit vs.  standard of care in the approved patient population.

"Rather than waiting for drug companies to decide what to develop, they could define the health system's needs and implement measures to ensure the development of the treatments required," they write, adding that this could include needs-oriented public-private partnerships and not-for-profit drug development.

In response to the article, the Association of Research-Based Pharmaceutical Companies in Germany issued a statement pointing out that the assessment of additional benefit "is not an easy matter — there is not always a 'right' or 'wrong.'"