Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Protopathic Stimulant Use Among Children With Symptoms of ADHD

The purpose of the current study was to examine protopathic stimulant use among children with the symptoms of ADHD but do not have a diagnosis of ADHD. Protopathic or prodromal stimulant use refers to the use of stimulants by children with the symptoms of ADHD prior to a diagnosis of ADHD. In the current study, we examined children with the symptoms of ADHD who received stimulant treatment across time and with respect to several background variables. Our results indicate that these children who receive stimulant treatment without a diagnosis of ADHD are significantly more like to be eventually diagnosed with ADHD than not. Results also indicate that these children who receive stimulant treatment but do not yet have a diagnosis of ADHD are significantly more likely to have insurance that does not pay for diagnostic procedures. These results are discussed in view of treatment

Staff Perspectives on Primary Care Teams as De Facto “Hubs” for Care Coordination in VA: a Qualitative Study

BackgroundImproving care coordination is a key priority for many healthcare systems. However, initiatives to improve care coordination are complex to implement and have produced mixed results. A better understanding of how to craft and support implementation of effective care coordination strategies is needed.ObjectiveTo identify and understand the challenges and factors encountered by Patient-Aligned Care Team (PACT) staff in performing care coordination tasks in outpatient clinics in the Veterans Health Administration (VA).DesignQualitative study using semi-structured formative evaluation interviews.ParticipantsFourteen interviews with 18 clinical frontline managers and staff from 12 clinic sites across five VA health systems.InterventionsThis paper reports on baseline data collected for the Coordination Toolkit and Coaching (CTAC) project. CTAC aims to improve patients' experience of care coordination within VA primary care and between PACT and other outpatient and community settings.ApproachWe conducted pre-implementation telephone interviews with frontline managers and staff, primarily nurse managers.Key resultsPACT staff described challenges in aligning care coordination priorities across different levels of the VA system, including staff, patients, and leadership. Additionally, PACT staff noted challenges coordinating care both within and outside the VA, and identified resource barriers impeding their care coordination efforts. To address these challenges, staff made several recommendations for improvement, including (1) contingency staffing to address staff burnout; (2) additional PACT training for new staff; (3) clarification of care coordination roles and responsibilities; and (4) and care coordination initiatives that align both with centrally initiated care coordination programs and frontline needs.ConclusionIn the VA and similarly complex healthcare systems, our findings suggest the need for care coordination strategies that are buttressed by a system-level vision for care coordination, backed up by clear roles and responsibilities for information exchange between primary care staff and other settings, and multidimensional accountability metrics that encompass patient-, staff-, and system-level goals

The Coordination Toolkit and Coaching Project: Cluster-Randomized Quality Improvement Initiative to Improve Patient Experience of Care Coordination

BackgroundGiven persistent gaps in coordination of care for medically complex primary care patients, efficient strategies are needed to promote better care coordination.ObjectiveThe Coordination Toolkit and Coaching project compared two toolkit-based strategies of differing intensity to improve care coordination at VA primary care clinics.DesignMulti-site, cluster-randomized QI initiative.ParticipantsTwelve VA primary care clinics matched in 6 pairs.InterventionsWe used a computer-generated allocation sequence to randomize clinics within each pair to two implementation strategies. Active control clinics received an online toolkit with evidence-based tools and QI coaching manual. Intervention clinics received the online toolkit plus weekly assistance from a distance coach for 12 months.Main measuresWe quantified patient experience of general care coordination using the Health Care System Hassles Scale (primary outcome) mailed at baseline and 12-month follow-up to serial cross-sectional patient samples. We measured the difference-in-difference (DiD) in clinic-level-predicted mean counts of hassles between coached and non-coached clinics, adjusting for clustering and patient characteristics using zero-inflated negative binomial regression and bootstrapping to obtain 95% confidence intervals. Other measures included care coordination QI projects attempted, tools adopted, and patient-reported exposure to projects.Key resultsN = 2,484 (49%) patients completed baseline surveys and 2,481 (48%) completed follow-ups. Six coached clinics versus five non-coached clinics attempted QI projects. All coached clinics versus two non-coached clinics attempted more than one project or projects that were multifaceted (i.e., involving multiple components addressing a common goal). Five coached versus three non-coached clinics used 1-2 toolkit tools. Both the coached and non-coached clinics experienced pre-post reductions in hassle counts over the study period (- 0.42 (- 0.76, - 0.08) non-coached; - 0.40 (- 0.75, - 0.06) coached). However, the DiD (0.02 (- 0.47, 0.50)) was not statistically significant; coaching did not improve patient experience of care coordination relative to the toolkit alone.ConclusionAlthough coached clinics attempted more or more complex QI projects and used more tools than non-coached clinics, coaching provided no additional benefit versus the online toolkit alone in patient-reported outcomes.Trial registrationClinicalTrials.gov identifier: NCT03063294

Effects of inhibition of PDE4 and TNF-α on local and remote injuries following ischaemia and reperfusion injury

1. The effects of phosphodiesterase (PDE)4 and TNF-α inhibition were assessed on the local and remote injuries following intestinal ischaemia and reperfusion (I/R) injury in rats. 2. The PDE4 inhibitor rolipram dose-dependently (1 – 10 mg kg(−1)) suppressed the local (intestine) and remote (lung) increases in vascular permeability and neutrophil recruitment following mild I/R injury. SB207499 (ariflo), a structurally-distinct PDE4 inhibitor, also suppressed the injuries following mild I/R injury. 3. In a severe model of I/R injury, treatment with rolipram (10 mg kg(−1)) partially reversed the local and remote increases in vascular permeability, neutrophil recruitment, intestinal haemorrhage and intestinal LTB(4) concentrations. The anti-TNF-α anti-serum was more effective than rolipram at inhibiting local and remote injuries and prevented the lethality associated with severe I/R. 4. Rolipram and anti-TNF-α prevented the increase in the concentrations of TNF-α in the lung and intestine, but rolipram only partially inhibited the elevation of this cytokine in serum. Rolipram had little effect on the increases of IL-1ß concentrations in lung and serum, whereas treatment with anti-TNF-α markedly increased the concentration of this cytokine. Concentrations of IL-10 rose significantly in the lung and serum and these increases were blocked by rolipram or anti-TNF-α. 5. The capacity of PDE4 inhibitors to block the recruitment of neutrophils into tissues, the production of LTB(4) and of the pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 appear to underlie their anti-inflammatory effects in our model of I/R injury. Overall, PDE4 inhibition was less effective than inhibition of TNF-α for protection against I/R injury

Trending Nutrition Controversies #3: Top Controversies in 2021

Each year, patients are bombarded with diverging and even contradictory reports concerning the impact of certain additives, foods, and nutrients on cardiovascular health and its risk factors. Accordingly, this third review of nutrition controversies examines the impact of artificial sweeteners, cacao, soy, plant-based meats, nitrates, and meats from grass compared to grain-fed animals on cardiovascular and other health outcomes with the goal of optimizing clinician-led diet counseling

Controversial Dietary Patterns: A High Yield Primer for Clinicians

In cardiology clinic visits, the discussion of optimal dietary patterns for prevention and management of cardiovascular disease is usually very limited. Herein, we explore the benefits and risks of various dietary patterns, including intermittent fasting, low carbohydrate, Paleolithic, whole food plant-based diet, and Mediterranean dietary patterns within the context of cardiovascular disease to empower clinicians with the evidence and information they need to maximally benefit their patients