Publishing protocols for partnered research.

Published scientific protocols are advocated as a means of controlling bias in research reporting. Indeed, many journals require a study protocol with manuscript submission. However, publishing protocols of partnered research (PPR) can be challenging in light of the research model's dynamic nature, especially as no current reporting standards exist. Nevertheless, as these protocols become more prevalent, a priori documentation of methods in partnered research studies becomes increasingly important. Using as illustration a suite of studies aimed at improving coordination and communication in the primary care setting, we sought to identify challenges in publishing PPR relative to traditional designs, present alternative solutions to PPR publication, and propose an initial checklist of content to be included in protocols of partnered research. Challenges to publishing PPR include reporting details of research components intended to be co-created with operational partners, changes to sampling and entry strategy, and alignment of scientific and operational goals. Proposed solutions include emulating reporting standards of qualitative research, participatory action research, and adaptive trial designs, as well as embracing technological tools that facilitate publishing adaptive protocols, with version histories that are able to be updated as major protocol changes occur. Finally, we present a proposed checklist of reporting elements for partnered research protocols.

Impact of Inhaled Epoprostenol in Patients on COVID-19 Acute Respiratory Distress Syndrome (ARDS).

Background: Coronavirus disease 2019 (COVID-19), a novel respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can progress to critical illness and the development of acute respiratory distress syndrome (ARDS). Variability in clinical presentation has led to 2 distinct theoretical classifications of COVID-19 ARDS based on different phenotypical presentations. The first of which follows closely to traditional ARDS presenting as severe hypoxemia with markedly reduced lung compliance, whereas the second presents as severe hypoxemia with preserved to high lung compliance. With uncertainty surrounding the specific pathological and mechanistic nature of COVID-19, we designed this study to elucidate the potential benefits of inhaled epoprostenol in COVID-19 ARDS. Methods: This was a retrospective, observational, cohort study conducted at a 425-bed teaching hospital. Chart reviews of patients' electronic medical records were conducted and the following data were documented on a password-protected spreadsheet: patient demographics, administration of intravenous fluids and/or corticosteroids, rate and duration of inhaled epoprostenol (0.01-0.05 mcg/kg/min over 7 mL/hr per dose), and ventilator settings while on inhaled epoprostenol, mortality, and intensive care unit (ICU) length of stay (LOS). The primary objective was to evaluate the effect of inhaled epoprostenol on the number of ventilator-free days in COVID-19 patients. Secondary objectives included assessing the effects on ventilator settings, mortality, and ICU LOS. Results: Over the span of 8 months, the charts of 848 patients diagnosed with COVID-19 were reviewed for inclusion in the study. Of those patients, 40 patients (intervention arm) who received at least 1 dose of inhaled epoprostenol (0.01-0.05 mcg/kg/min over 7 mL/hr per dose) were randomly selected for entry into the study. In the control arm, 40 patients with a diagnosis of COVID-19 who did not receive epoprostenol were randomly selected. There were no statistically significant differences in outcomes between the epoprostenol and control arms, in regard to ventilator-free days, ICU LOS, hospital LOS, and in-hospital mortality. Based on maximum ventilator settings during the first 3 days of inhaled epoprostenol use, there were no statistically significant differences between the 2 groups except for an unexpectedly lower oxygen saturation in the epoprostenol group. Conclusion: The use of inhaled epoprostenol did not have a statistically significant effect on ventilator-free days, ventilator settings, hospital and ICU LOS, and overall in-hospital mortality.

Frequency and correlates of treatment intensification for elevated cholesterol levels in patients with cardiovascular disease.

BACKGROUND: Although current performance measures define low-density-lipoprotein cholesterol (LDL-C) levels <100 mg/dL in patients with cardiovascular disease (CVD) as good quality, they provide a snapshot and do not address whether treatment intensification was performed to manage elevated LDL-C levels. METHODS: We determined the proportion of patients with CVD (n = 22,888) with LDL-C <100 mg/dL and the proportion with uncontrolled LDL-C levels (≥100 mg/dL) who received treatment intensification within the 45-day follow-up in a Veterans Affairs Network. We evaluated facility, provider, and patient correlates of treatment intensification. RESULTS: Low-density-lipoprotein cholesterol levels were at goal in 16,350 (71.4%) patients. An additional 2,093 (one third of those eligible for treatment intensification) received treatment intensification. Controlling for clustering between facilities and patient's illness severity: history of diabetes (odds ratio [OR] 1.15, 95% CI 1.01-1.32), hypertension (OR 1.19, 95% CI 1.01-1.42), good medication adherence (OR 2.20, 95% CI 1.91-2.54), and a higher number of lipid panels (OR 1.20, 95% CI 1.14-1.27) were associated with treatment intensification. Patients older than 75 years (OR 0.65, 95% CI 0.56-0.75) and women (OR 0.66, 95% CI 0.43-1.00) were less likely to receive treatment intensification. Teaching status of the facility, physician or specialist primary care provider, and patient's race were not associated with treatment intensification. CONCLUSIONS: Only one third of the CVD patients with elevated LDL-C received treatment intensification. Diabetic and hypertensive patients were more likely to receive treatment intensification, whereas, older patients, female patients, and patients with poor medication adherence were less likely to receive treatment intensification. Our findings highlight areas for quality improvement initiatives.

Correlates of repeat lipid testing in patients with coronary heart disease.

IMPORTANCE: Understanding the frequency and correlates of redundant lipid testing could identify areas for quality improvement initiatives aimed at improving the efficiency of cholesterol care in patients with coronary heart disease (CHD). OBJECTIVE: To determine the frequency and correlates of repeat lipid testing in patients with CHD who attained low-density lipoprotein cholesterol (LDL-C) goals and received no treatment intensification. DESIGN, SETTING, AND PARTICIPANTS: We assessed the proportion of patients with LDL-C levels of less than 100 mg/dL and no intensification of lipid-lowering therapy who underwent repeat lipid testing during an 11-month follow-up period. We performed logistic regression analyses to evaluate facility, provider, and patient characteristics associated with repeat testing. In total, we analyzed 35,191 patients with CHD in a Veterans Affairs network of 7 medical centers with associated community-based outpatient clinics. MAIN OUTCOMES AND MEASURES: Frequency and correlates of repeat lipid testing in patients having CHD with LDL-C levels of less than 100 mg/dL and no further treatment intensification with lipid-lowering therapies. RESULTS: Of 27,947 patients with LDL-C levels of less than 100 mg/dL, 9200 (32.9%) had additional lipid assessments without treatment intensification during the following 11 months (12 ,686 total additional panels; mean, 1.38 additional panel per patient). Adjusting for facility-level clustering, patients with a history of diabetes mellitus (odds ratio [OR], 1.16; 95% CI, 1.10-1.22), a history of hypertension (OR, 1.21; 95% CI, 1.13-1.30), higher illness burden (OR, 1.39; 95% CI, 1.23-1.57), and more frequent primary care visits (OR, 1.32; 95% CI, 1.25-1.39) were more likely to undergo repeat testing, whereas patients receiving care at a teaching facility (OR, 0.74; 95% CI, 0.69-0.80) or from a physician provider (OR, 0.93; 95% CI, 0.88-0.98) and those with a medication possession ratio of 0.8 or higher (OR, 0.75; 95% CI, 0.71-0.80) were less likely to undergo repeat testing. Among 13,114 patients who met the optional LDL-C target level of less than 70 mg/dL, repeat lipid testing was performed in 8177 (62.4% of those with LDL-C levels of <70 mg/dL) during 11 follow-up months. CONCLUSIONS AND RELEVANCE: One-third of patients having CHD with LDL-C levels at goal underwent repeat lipid panels. Our results highlight areas for quality improvement initiatives to reduce redundant lipid testing. These efforts would be more important if the forthcoming cholesterol guidelines adopt a medication dose-based approach in place of the current treat-to-target approach.