The relationship between physician burnout and depression, anxiety, suicidality and substance abuse: A mixed methods systematic review

IntroductionThe World Health Organization defines burnout as a problem associated with employment, a category distinct from psychological disorders such as depression, anxiety, suicidality and disorders of substance abuse. Evaluating the association between burnout as an occupational exposure and psychological morbidity may indicate that burnout can act as an occupational risk factor for mental ill-health. The systematic review explores this relationship in physicians due to the increased risk in this population and the implications for healthcare delivery.MethodsA mixed methods systematic review of the literature was conducted across Medline, Cinahl Plus, PsycInfo, Web of Science and The Cochrane Library. Databases were systematically searched using keywords relating to physician burnout and depression, anxiety, suicidality and substance abuse. Identified articles were screened for eligibility by two independent researchers. Data extraction was performed and studies assessed for risk of bias. Quantitative and qualitative results were integrated using a convergent segregated approach and results portrayed as a narrative synthesis.ResultsSixty-one articles were included in the review. There was notable heterogeneity in the measurement and criteria used to define burnout limiting the assimilation of results. Despite this, all studies that measured the association between depression and burnout reported a significant association. Studies that reported association between burnout and anxiety were similarly uniformly consistent. Most studies that reported the association between burnout and suicidality indicated that a significant association exists however difficulty in measurement of suicidality may have influenced variability of results. The reported association between substance abuse and burnout was more variable, suggesting that any association is likely to be weak or influenced by other variables. Qualitative studies described the manifestations of chronic workplace stress as well as perceived links with psychological morbidity. These included lack of time for work-life balance, the contribution of professional relationships and a culture of invulnerability that exists among physicians.ConclusionThe systematic review cannot conclude causality but suggests that physician burnout is associated with depression, anxiety and suicidality. Qualitative data provides insight into the nature of this association. The review indicates the need for longitudinal research and provides considerations for intervention strategies to prevent the development and progression of burnout.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020172938, identifier: CRD42020172938

Comparison of rapid laboratory tests for failure of passive transfer in the bovine

peer-reviewedBackground Failure of passive transfer of maternal immunity via colostrum can occur in the bovine, and a number of blood tests have been developed to test calves for this failure. It is not clear which test is most suitable for this purpose. The objective was to examine the most commonly used tests for failure of passive transfer and to decide which is most suitable for routine laboratory use. 126 serum samples were taken from calves of dairy cows after birth but prior to colostrum feeding, and at 48 h of age. Five different tests were compared against radial immunodiffusion which is considered the appropriate reference method. These tests were serum gamma-glutamyltransferase levels, serum protein levels, serum globulin levels, an enzyme linked immunosorbent assay and the zinc sulphate turbidity test. Results The tests examined displayed high sensitivity but widely varying specificity. Examination of the use of different cut-off points allowed some improvement in specificity at the expense of sensitivity, but the tests which had performed best at the original cut-off points still displayed the best performance. Gamma-glutamyltransferase levels as a measure of colostrum absorption returned, in this study, the best balance between sensitivity and specificity. The ELISA used in this study and serum globulin levels displayed performance similar to the gamma-glutamyltransferase levels. Serum total protein was less successful than others examined at providing both sensitivity and specificity but may, when performed via refractometer, be useful for on-farm testing. As currently performed the poor sensitivity for which the zinc sulphate turbidity test is most often criticized is evident. Modification of the cut-off point to increase specificity is less successful at balancing these parameters than the ELISA, gamma-glutamyltransferase levels, and globulin levels. Conclusions Gamma-glutamyltransferase levels, ELISA testing and circulating globulin levels performed best in detecting failure of passive transfer in serum samples, although all three had some practical considerations

Estimation of respiration rate and sleeping position using a wearable accelerometer

The 42nd Annual International Conferences of the IEEE Engineering in Medicine and Biology Society, EMBS Virtual Academy, 20-24 July 2020Wearable inertial sensors offer the possibility to monitor sleeping position and respiration rate during sleep, enabling a comfortable and low-cost method to remotely monitor patients. Novel methods to estimate respiration rate and position during sleep using accelerometer data are presented, with algorithm performance examined for two sensor locations, and accelerometer-derived respiration rate compared across sleeping positions. Eleven participants (9 male; aged: 47.82±14.14 years; BMI 30.9±5.27 kg/m 2 ; AHI 5.77±4.18) undergoing a scheduled clinical polysomnography (PSG) wore a tri-axial accelerometer on their chest and upper abdomen. PSG cannula flow and position data were used as benchmark data for respiration rate (breaths per minute, bpm) and position. Sleeping position was classified using logistic regression, with features derived from filtered acceleration and orientation. Accelerometer-derived respiration rate was estimated for 30 s epochs using an adaptive peak detection algorithm which combined filtered acceleration and orientation data to identify individual breaths. Sensor-derived and PSG respiration rates were then compared. Mean absolute error (MAE) in respiration rate did not vary between sensor locations (abdomen: 1.67±0.37 bpm; chest: 1.89±0.53 bpm; p=0.52), while reduced MAE was observed when participants lay on their side (1.58±0.54 bpm) compared to supine (2.43±0.95 bpm), p<; 0.01. MAE was less than 2 bpm for 83.6% of all 30 s windows across all subjects. The position classifier distinguished supine and left/right with a ROC AUC of 0.87, and between left and right with a ROC AUC of 0.94. The proposed methods may enable a low-cost solution for in-home, long term sleeping posture and respiration monitoring.European Research CouncilScience Foundation IrelandInsight Research Centre2020-10-06 JG: PDF replaced with correct versio

Airway inflammatory markers in individuals with cystic fibrosis and non-cystic fibrosis bronchiectasis.

Bronchiectasis is an airway disease characterized by thickening of the bronchial wall, chronic inflammation , and destruction of affected bronchi. Underlying etiologies include severe pulmonary infection and cystic fibrosis (CF); however, in a substantial number of patients with non-CF-related bronchiectasis (NCFB), no cause is found. The increasing armamentarium of therapies now available to combat disease in CF is in stark contrast to the limited tools employed in NCFB. Our study aimed to evaluate similarities and differences in airway inflammatory markers in patients with NCFB and CF, and to suggest potential common treatment options. The results of this study show that NCFB bronchoalveolar lavage fluid samples possessed significantly increased NE activity and elevated levels of matrix metalloproteinases 2 (MMP-2) and MMP-9 compared to healthy controls (P \u3c 0.01); however, the levels detected were lower than in CF (P \u3c 0.01). Interleukin-8 (IL-8) concentrations were significantly elevated in NCFB and CF compared to controls (P \u3c 0.05), but in contrast, negligible levels of IL-18 were detected in both NCFB and CF. Analogous concentrations of IL-10 and IL-4 measured in NCFB and CF were statistically elevated above the healthy control values (P \u3c 0.05 and P \u3c 0.01, respectively). These results indicate high levels of important proinflammatory markers in both NCFB and CF and support the use of appropriate anti-inflammatory therapies already employed in the treatment of CF bronchiectasis in NCFB

Preoperative Exercise to Improve Fitness in Patients Undergoing Complex Surgery for Cancer of the Lung or Oesophagus (PRE-HIIT): Protocol for a Randomized Controlled Trial

Patients with cancer of the lung or oesophagus, undergoing curative treatment, usually require a thoracotomy and a complex oncological resection. These surgeries carry a risk of major morbidity and mortality, and risk assessment, preoperative optimisation, and enhanced recovery after surgery (ERAS) pathways are modern approaches to optimise outcomes. Pre-operative fitness is an established predictor of postoperative outcome, accordingly, targeting pre-operative fitness through exercise prehabilitation has logical appeal. Exercise prehabilitation is challenging to implement however due to the short opportunity for intervention between diagnosis and surgery. Therefore, individually prescribed, intensive exercise training protocols which convey clinically meaningful improvements in cardiopulmonary fitness over a short period need to be investigated. This project will examine the influence of exercise prehabilitation on physiological outcomes and postoperative recovery and, through evaluation of health economics, the impact of the programme on hospital costs

Feeding the world\u27s largest fish: highly variable whale shark residency patterns at a provisioning site in the Philippines

Provisioning wildlife for tourism is a controversial yet widespread practice. We analysed the residency patterns of juvenile whale sharks (Rhincodon typus) in Oslob, Philippines, where provisioning has facilitated a large shark-watching operation since 2011. We identified 208 individual sharks over three years, with an average of 18.6 (s.d.&thinsp;=&thinsp;7.8, range&thinsp;=&thinsp;6&ndash;43) individuals sighted per week. Weekly shark abundance varied seasonally and peak-season abundance (approx. May&ndash;November) increased across years. Whale sharks displayed diverse individual site visitation patterns ranging from a single visit to sporadic visits, seasonal residency and year-round residency. Nine individuals became year-round residents, which represents a clear response to provisioning. The timing of the seasonal peak at Oslob did not align with known non-provisioned seasonal aggregations elsewhere in the Philippines, which could suggest that seasonal residents at Oslob exploit this food source when prey availability at alternative sites is low. Since prolonged residency equates to less time foraging naturally, provisioning could influence foraging success, alter distributions and lead to dependency in later life stages. Such impacts must be carefully weighed against the benefits of provisioning (i.e. tourism revenue in a remote community) to facilitate informed management decisions

Intense exercise for survival among men with metastatic castrate-resistant prostate cancer (INTERVAL-GAP4): A multicentre, randomized, controlled phase III study protocol

Introduction: Preliminary evidence supports the beneficial role of physical activity on prostate cancer outcomes. This phase III randomised controlled trial (RCT) is designed to determine if supervised high-intensity aerobic and resistance exercise increases overall survival (OS) in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods and analysis: Participants (n=866) must have histologically documented metastatic prostate cancer with evidence of progressive disease on androgen deprivation therapy (defined as mCRPC). Patients can be treatmentnaive for mCRPC or on first-line androgen receptor-targeted therapy for mCRPC (ie, abiraterone or enzalutamide) without evidence of progression at enrolment, and with no prior chemotherapy for mCRPC. Patients will receive psychosocial support and will be randomly assigned (1:1) to either supervised exercise (high-intensity aerobic and resistance training) or self-directed exercise (provision of guidelines), stratified by treatment status and site. Exercise prescriptions will be tailored to each participant’s fitness and morbidities. The primary endpoint is OS. Secondary endpoints include time to disease progression, occurrence of a skeletal-related event or progression of pain, and degree of pain, opiate use, physical and emotional quality of life, and changes in metabolic biomarkers. An assessment of whether immune function, inflammation, dysregulation of insulin and energy metabolism, and androgen biomarkers are associated with OS will be performed, and whether they mediate the primary association between exercise and OS will also be investigated. This study will also establish a biobank for future biomarker discovery or validation. Ethics and dissemination: Validation of exercise as medicine and its mechanisms of action will create evidence to change clinical practice. Accordingly, outcomes of this RCT will be published in international, peer-reviewed journals, and presented at national and international conferences. Ethics approval was first obtained at Edith Cowan University (ID: 13236 NEWTON), with a further 10 investigator sites since receiving ethics approval, prior to activation. Trial registration number: NCT02730338

Distinct effects on mRNA export factor GANP underlie neurological disease phenotypes and alter gene expression depending on intron content

Defects in the mRNA export scaffold protein GANP, encoded by the MCM3AP gene, cause autosomal recessive early-onset peripheral neuropathy with or without intellectual disability. We extend here the phenotypic range associated with MCM3AP variants, by describing a severely hypotonic child and a sibling pair with a progressive encephalopathic syndrome. In addition, our analysis of skin fibroblasts from affected individuals from seven unrelated families indicates that disease variants result in depletion of GANP except when they alter critical residues in the Sac3 mRNA binding domain. GANP depletion was associated with more severe phenotypes compared with the Sac3 variants. Patient fibroblasts showed transcriptome alterations that suggested intron content-dependent regulation of gene expression. For example, all differentially expressed intronless genes were downregulated, including ATXN7L3B, which couples mRNA export to transcription activation by association with the TREX-2 and SAGA complexes. Our results provide insight into the molecular basis behind genotype-phenotype correlations in MCM3AP-associated disease and suggest mechanisms by which GANP defects might alter RNA metabolism.Peer reviewe

Biogeography in the deep : hierarchical population genomic structure of two beaked whale species

Funding for this research was provided by the Office of Naval Research, Award numbers N000141613017 and N000142112712. ABO was supported by a partial studentship from the University of St Andrews, School of Biology; OEG by the Marine Alliance for Science and Technology for Scotland (Scottish Funding Council grant HR09011); ELC by a Rutherford Discovery Fellowship from the Royal Society of New Zealand Te Aparangi; NAS by a Ramon y Cajal Fellowship from the Spanish Ministry of Innovation; MLM by the European Union’s Horizon 2020 Research and Innovation Programme (Marie Skłodowska-Curie grant 801199); CR by the Marine Institute (Cetaceans on the Frontier) and the Irish Research Council; and MTO by the Hartmann Foundation.The deep sea is the largest ecosystem on Earth, yet little is known about the processes driving patterns of genetic diversity in its inhabitants. Here, we investigated the macro- and microevolutionary processes shaping genomic population structure and diversity in two poorly understood, globally distributed, deep-sea predators: Cuvier’s beaked whale (Ziphius cavirostris) and Blainville’s beaked whale (Mesoplodon densirostris). We used double-digest restriction associated DNA (ddRAD) and whole mitochondrial genome (mitogenome) sequencing to characterise genetic patterns using phylogenetic trees, cluster analysis, isolation-by-distance, genetic diversity and differentiation statistics. Single nucleotide polymorphisms (SNPs; Blainville’s n = 43 samples, SNPs=13988; Cuvier’s n = 123, SNPs= 30479) and mitogenomes (Blainville’s n = 27; Cuvier’s n = 35) revealed substantial hierarchical structure at a global scale. Both species display significant genetic structure between the Atlantic, Indo-Pacific and in Cuvier’s, the Mediterranean Sea. Within major ocean basins, clear differentiation is found between genetic clusters on the east and west sides of the North Atlantic, and some distinct patterns of structure in the Indo-Pacific and Southern Hemisphere. We infer that macroevolutionary processes shaping patterns of genetic diversity include biogeographical barriers, highlighting the importance of such barriers even to highly mobile, deep-diving taxa. The barriers likely differ between the species due to their thermal tolerances and evolutionary histories. On a microevolutionary scale, it seems likely that the balance between resident populations displaying site fidelity, and transient individuals facilitating gene flow, shapes patterns of connectivity and genetic drift in beaked whales. Based on these results, we propose management units to facilitate improved conservation measures for these elusive species.Publisher PDFPeer reviewe