The neuropeptide PDF is released by sixteen clock neurons in Drosophila and helps maintain circadian activity rhythms by coordinating a network of approximately 150 neuronal clocks. Whether PDF acts directly on elements of this neural network remains unknown. We address this question by adapting Epac1-camps, a genetically encoded cAMP FRET sensor, for use in the living brain. We find that a subset of the PDF-expressing neurons respond to PDF with long-lasting cAMP increases and confirm that such responses require the PDF receptor. In contrast, an unrelated Drosophila neuropeptide, DH31, stimulates large cAMP increases in all PDF-expressing clock neurons. Thus, the network of approximately 150 clock neurons displays widespread, though not uniform, PDF receptivity. This work introduces a sensitive means of measuring cAMP changes in a living brain with subcellular resolution. Specifically, it experimentally confirms the longstanding hypothesis that PDF is a direct modulator of most neurons in the Drosophila clock network.

ObjectivesTo assess the effectiveness of prone positioning to reduce the risk of death or respiratory failure in non-critically ill patients admitted to hospital with covid-19.DesignMulticentre pragmatic randomised clinical trial.Setting15 hospitals in Canada and the United States from May 2020 until May 2021.ParticipantsEligible patients had a laboratory confirmed or a clinically highly suspected diagnosis of covid-19, needed supplemental oxygen (up to 50% fraction of inspired oxygen), and were able to independently lie prone with verbal instruction. Of the 570 patients who were assessed for eligibility, 257 were randomised and 248 were included in the analysis.InterventionPatients were randomised 1:1 to prone positioning (that is, instructing a patient to lie on their stomach while they are in bed) or standard of care (that is, no instruction to adopt prone position).Main outcome measuresThe primary outcome was a composite of in-hospital death, mechanical ventilation, or worsening respiratory failure defined as needing at least 60% fraction of inspired oxygen for at least 24 hours. Secondary outcomes included the change in the ratio of oxygen saturation to fraction of inspired oxygen.ResultsThe trial was stopped early on the basis of futility for the pre-specified primary outcome. The median time from hospital admission until randomisation was 1 day, the median age of patients was 56 (interquartile range 45-65) years, 89 (36%) patients were female, and 222 (90%) were receiving oxygen via nasal prongs at the time of randomisation. The median time spent prone in the first 72 hours was 6 (1.5-12.8) hours in total for the prone arm compared with 0 (0-2) hours in the control arm. The risk of the primary outcome was similar between the prone group (18 (14%) events) and the standard care group (17 (14%) events) (odds ratio 0.92, 95% confidence interval 0.44 to 1.92). The change in the ratio of oxygen saturation to fraction of inspired oxygen after 72 hours was similar for patients randomised to prone positioning and standard of care.ConclusionAmong non-critically ill patients with hypoxaemia who were admitted to hospital with covid-19, a multifaceted intervention to increase prone positioning did not improve outcomes. However, wide confidence intervals preclude definitively ruling out benefit or harm. Adherence to prone positioning was poor, despite multiple efforts to increase it. Subsequent trials of prone positioning should aim to develop strategies to improve adherence to awake prone positioning.Study registrationClinicalTrials.gov NCT04383613.

Heart failure (HF) patients are at high risk of hospital readmission, which contributes to substantial health care costs. There is great interest in strategies to reduce rehospitalization for HF. However, many readmissions occur within 30 days of initial hospital discharge, presenting a challenge for interventions to be instituted in a short time frame. Potential strategies to reduce readmissions for HF can be classified into three different forms. First, patients who are at high risk of readmission can be identified even before their initial index hospital discharge. Second, ambulatory remote monitoring strategies may be instituted to identify early warning signs before acute decompensation of HF occurs. Finally, strategies may be employed in the emergency department to identify low-risk patients who may not need hospital readmission. If symptoms improve with initial therapy, low-risk patients could be referred to specialized, rapid outpatient follow-up care where investigations and therapy can occur in an outpatient setting.

ObjectivesTo assess the effectiveness of prone positioning to reduce the risk of death or respiratory failure in non-critically ill patients hospitalized with COVID-19DesignPragmatic randomized clinical trial of prone positioning of patients hospitalized with COVID-19 across 15 hospitals in Canada and the United States from May 2020 until May 2021.SettingsPatients were eligible is they had a laboratory-confirmed or a clinically highly suspected diagnosis of COVID-19, required supplemental oxygen (up to 50% fraction of inspired oxygen [FiO2]), and were able to independently prone with verbal instruction. (NCT04383613).Main Outcome MeasuresThe primary outcome was a composite of in-hospital death, mechanical ventilation, or worsening respiratory failure defined as requiring at least 60% FiO2 for at least 24 hours. Secondary outcomes included the change in the ratio of oxygen saturation to FiO2 (S/F ratio).ResultsA total of 248 patients were included. The trial was stopped early on the basis of futility for the pre-specified primary outcome. The median time from hospital admission until randomization was 1 day, the median age of patients was 56 years (interquartile range [IQR] 45,65), 36% were female, and 90% of patients were receiving oxygen via nasal prongs at the time of randomization. The median time spent prone in the first 72 hours was 6 hours total (IQR 1.5,12.8) for the prone arm compared to 0 hours (0,2) in the control arm. The risk of the primary outcome was similar between the prone group (18 [14.3%] events) and the standard care group (17 [13.9%] events), odds ratio 0.92 (95% CI 0.44 to 1.92). The change in the S/F ratio after 72 hours was similar for patients randomized to prone compared to standard of care.ConclusionAmong hypoxic but not critically patients with COVID-19 in hospital, a multifaceted intervention to increase prone positioning did not improve outcomes. Adherence to prone positioning was poor, despite multiple efforts. Subsequent trials of prone positioning should aim to develop strategies to improve adherence to awake prone positioning.What is already known on this topicProne positioning is considered standard of care for mechanically ventilated patients who have severe acute respiratory distress syndrome. Recent data suggest prone positioning is beneficial for patients with COVID-19 who are requiring high flow oxygen. It is unknown of prone positioning is beneficial for patients not on high flow oxygen.What this study addsProne positioning is generally not well tolerated and innovative approaches are needed to improve adherence. Clinical and physiologic outcomes were not improved with prone positioning among hypoxic but not critically ill patients hospitalized with COVID-19.

N octurnists (overnight hospitalists) have been widely implemented in teaching hospitals in the United States in an effort to meet Accreditation Council for Graduate Medical Education workload standards, 1 improve overnight supervision and enhance the quality of patient care. [2][3][4][5][6][7][8] Recent data indicate that about 50% of US teaching hospitals have nocturnists. 9 Several single-centre surveys from the US suggest that nocturnist programs improve perceived quality of care, increase resident satisfaction with overnight supervision and may enhance efficiency. 3,7 However, studies have not shown reductions in hospital length of stay or rates of mortality or hospital readmission. 2 Canadian teaching hospitals have been slow to implement nocturnists. 10 Nocturnal coverage is typically provided by firstyear residents from multiple disciplines, with staff available by telephone. Nocturnists are rare, and typically all admissions are performed by residents, without caps on volumes of existing patients or new admissions. Moreover, many Canadian teaching hospitals rely on teams of residents to cover all admitted medical patients, with no caps on the number of patients per resident. In contrast, in US hospitals, first-year internal medicine residents can manage a maximum of 10 patients. 1 Limits on Canadian resident work hours are determined at the provincial level rather than nationally, as in the US. Only Quebec has stipulated a maximum shift length (16 h), with most provinces still allowing 24-hour shifts. In Europe, resident work hours are restricted to 48-hour work weeks, and 13-hour shift limits are common. 11

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BackgroundEfforts to increase physician engagement in quality and safety are most often approached from an organisational or administrative perspective. Given hospital-based physicians’ strong professional identification, physician-led strategies may offer a novel strategic approach to enhancing physician engagement. It remains unclear what role medical leadership can play in leading programmes to enhance physician engagement. In this study, we explore physicians’ experience of participating in a Medical Safety Huddle initiative and how participation influences engagement with organisational quality and safety efforts.MethodsWe conducted a qualitative study of the Medical Safety Huddle initiative implemented across six sites. The initiative consisted of short, physician focused and led, weekly meetings aimed at reviewing, anticipating and addressing patient safety issues. We conducted 29 semistructured interviews with leaders and participants. We applied an interpretive thematic analysis to the data using self-determination theory as an analytic lens.ResultsThe results of the thematic analysis are organised in two themes, (1) relatedness and meaningfulness, and (2) progress and autonomy, representing two forms of intrinsic motivation for engagement that we found were leveraged through participation in the initiative. First, participation enabled a sense of community and a ‘safe space’ in which professionally relevant safety issues are discussed. Second, participation in the initiative created a growing sense of ability to have input in one’s work environment. However, limited collaboration with other professional groups around patient safety and the ability to consistently address reported concerns highlights the need for leadership and organisational support for physician engagement.ConclusionThe Medical Safety Huddle initiative supports physician engagement in quality and safety through intrinsic motivation. However, the huddles’ implementation must align with the organisation’s multipronged patient safety agenda to support multidisciplinary collaborative quality and safety efforts and leaders must ensure mechanisms to consistently address reported safety concerns for sustained physician engagement.