More than sleep problems? Testing five key health behaviors as reasons for quality of life issues among shift workers.

BACKGROUND: The shift work schedule is a common work arrangement that can disrupt typical sleep-wake rhythms and lead to negative health consequences. The present study aims to examine the effect of shift work on health-related quality of life (QoL) and explore potential behaviorial mediators (i.e., sleep, eating, exercise, smoking, drinking). METHODS: A cross-sectional survey was conducted among 4,449 petroleum workers in southwest China. Data on shift work status, health behaviors, and physical and mental health QoL were collected. We tested our model using path analysis and the Monte Carlo approach among 2,129 included participants. RESULTS: After adjusting for covariates, shift work did not exhibit a significant direct association with QoL. However, shift work indirectly related to poorer physical health quality of life via less frequent healthy food consumption; shift work also indirectly related to poorer mental health QoL via both less frequent healthy food consumption and physical exercise. No significant indirect effects were found via sleeping, smoking, or drinking. CONCLUSIONS: Results suggest that shift work presents a challenge for QoL among Chinese petroleum workers due to their lesser engagement in two specific health behaviors: healthy eating and physical exercise. Healthy eating and exercise may present an even more prominent threat to shift workers' QoL than sleep and substance use. Strategies targeting shift work schedule as well as eating and exercise behaviors may help protect against poor QoL and adverse physical and mental health outcomes in this vulnerable group.

Meta-analysis assessing the sensitivity and specificity of 18F-FDG PET/CT for the diagnosis of prosthetic valve endocarditis (PVE) using individual patient data (IPD).

IMPORTANCE: The use of 18F-FDG PET/CT in diagnostic algorithms for PVE has increased since publication of studies and guidelines advocating its use. The assessment of test accuracy has been limited by small study sizes. We undertook a systematic review using individual patient data (IPD) meta-analysis techniques. OBJECTIVE: To estimate the summary sensitivity and specificity of 18F-FDG PET/CT in diagnosing PVE. We also assessed the effect of patient factors on test accuracy as defined by changes in the odds ratios associated with each factor. The effect of the PET/CT study on the final diagnosis was also assessed when compared to the preliminary Duke classification to determine in which patient group 18F-FDG PET/CT had the greatest utility. STUDY SELECTION: Studies were included if PET/CT was performed for suspicion of PVE and IPD of both the PET/CT result and final diagnosis defined by a gold-standard assessment was available. There were 3 possible final diagnoses ("definite PVE," "possible PVE," and "rejected PVE"). RESULTS: Seventeen studies were included with IPD available for 537 patients (from 538 scans). The summary sensitivity and specificity were 85% (95% CI 74.2%-91.8%) and 86.5% (95% CI 75.8%-92.9%) respectively when patients with final diagnosis of "possible PVE" were classified as positive for PVE. When this group was classified as negative for PVE, sensitivity was 87.4% (95% CI 80.4%-92.1%) and specificity was 84.9% (95% CI 71.5%-92.6%). Patients with a known pathogen (especially coagulase negative staphylococcal species), elevated CRP, a biological or aortic valve infection appeared more likely to have an accurate PET/CT diagnosis. Those with a mechanical valve, prior antibiotic treatment or a transcatheter aortic valve replacement valve were less likely to have an accurate test. Time since valve implantation and the presence of surgical adhesive did not appear to affect test accuracy. Of the patients with a preliminary Duke classification of "possible PVE," 84% received a more conclusive final diagnosis of "definite" or "rejected" PVE after the PET/CT study. CONCLUSIONS AND RELEVANCE: 18F-FDG PET/CT has high sensitivity and specificity in diagnosing PVE and the diagnostic utility is greatest in patients with a preliminary Duke classification of "possible PVE." Some patient factors appear to affect test accuracy, though these results should be interpreted with caution given low patient numbers for subgroup analyses.

Exploring Barriers and Facilitators to Reducing the Environmental Impact of the Operating Room.

INTRODUCTION: The operating room (OR) is a major contributor to greenhouse gas emissions both nationally and globally. Successful implementation of quality improvement initiatives requires understanding of key stakeholders' perspectives of the issues at hand. Our aim was to explore surgical, anesthesia, and OR staff member perspectives on barriers and facilitators to reducing OR waste. MATERIALS AND METHODS: Identified stakeholders from a single academic medical center were interviewed to identify important barriers and facilitators to reducing surgical waste. Two team members with qualitative research experience used deductive logic guided by the Theoretical Domains Framework of behavior change to identify themes within transcripts. RESULTS: Nineteen participants including surgeons (n = 3, 15.8%), surgical residents (n = 5, 26.3%), an anesthesiologist (n = 1, 5.3%), anesthesia residents (n = 2, 10.5%), nurse anesthetists (n = 2, 10.5%), nurses (n = 5, 26.3%), and a surgical technologist (n = 1, 5.3%) were interviewed. Twelve of the 14 themes within the Theoretical Domains Framework were discovered in transcripts. Barriers within these themes included lack of resources to pursue environmental sustainability in the OR and the necessity of maintaining sterility for patient safety. Facilitators included emphasizing surgeon leadership within the OR to reduce unused supplies and spreading awareness of the environmental and economic impact of surgical waste. CONCLUSIONS: Interviewed stakeholders were able to identify areas where improvements around surgical waste reduction and management could be made at the institution by describing barriers and facilitators to sustainability-driven interventions. Future surgical waste reduction initiatives at this institution will be guided by these important perspectives.

An open-label randomised controlled trial evaluating the efficacy of a meningococcal serogroup B (4CMenB) vaccine on Neisseria gonorrhoeae infection in gay and bisexual men: the MenGO study protocol.

BACKGROUND: Gonorrhoea is an ongoing public health concern due to its rising incidence and the emergence of antibiotic resistance. There are an estimated 82 million new Neisseria gonorrhoeae infections each year, with several populations at higher risk for gonococcal infection, including gay and bisexual men (GBM). If left untreated, infection can lead to serious morbidity including infertility, sepsis and increased risk of HIV acquisition. Development of a gonorrhoea vaccine has been challenging, however there is observational evidence that serogroup B meningococcal vaccines, used to protect against the closely related bacteria Neisseria meningitidis, could provide cross-protection against N. gonorrhoeae. METHODS: The MenGO (Meningococcal vaccine efficacy against Gonorrhoea) study is a phase III open-label randomised control trial in GBM to evaluate the efficacy of the four-component meningococcal serogroup B vaccine, 4CMenB, against gonorrhoea. A total of 130 GBM will be recruited at the Gold Coast Sexual Health Clinic, Australia, and randomised to either receive 2 doses of 4CMenB or no intervention. Participants will be followed up for 24 months with testing for N. gonorrhoeae and other sexually transmissible infections every three months. Demographics, sexual behaviour risk, antibiotic use, and blood samples for analysis of N. gonorrhoeae-specific immune responses, will be collected during the study. The primary outcome is the number of N. gonorrhoeae infections in participants over 2 years measured by nucleic acid amplification test (NAAT). Secondary outcomes are vaccine-induced N. gonorrhoeae-specific immune responses, and adverse events in trial participants. DISCUSSION: This trial will determine if the 4CMenB vaccine is able to reduce N. gonorrhoeae infection. If shown to be effective, 4CMenB could be used in gonococcal prevention. Analysis of 4CMenB-induced immune responses will increase understanding of the type of immune response needed to prevent N. gonorrhoeae, which may enable identification of a potential correlate of protection to aid future gonorrhoea vaccine development. TRIAL REGISTRATION: The trial has been registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12619001478101) on 25 October 2019.

Discovery of the oldest bilaterian from the Ediacaran of South Australia.

Analysis of modern animals and Ediacaran trace fossils predicts that the oldest bilaterians were simple and small. Such organisms would be difficult to recognize in the fossil record, but should have been part of the Ediacara Biota, the earliest preserved macroscopic, complex animal communities. Here, we describe Ikaria wariootia gen. et sp. nov. from the Ediacara Member, South Australia, a small, simple organism with anterior/posterior differentiation. We find that the size and morphology of Ikaria match predictions for the progenitor of the trace fossil Helminthoidichnites-indicative of mobility and sediment displacement. In the Ediacara Member, Helminthoidichnites occurs stratigraphically below classic Ediacara body fossils. Together, these suggest that Ikaria represents one of the oldest total group bilaterians identified from South Australia, with little deviation from the characters predicted for their last common ancestor. Further, these trace fossils persist into the Phanerozoic, providing a critical link between Ediacaran and Cambrian animals.

Effect of a Senior Cardiology Nursing Role on Streamlining Assessment of Emergency Cardiology Presentations During COVID-19: An Observational Study.

INTRODUCTION: The Emergency Cardiology Coordinator (ECC) was a senior nursing role implemented from 14 April 2020 to 15 September 2020 at the Gold Coast Hospital and Health Service in South-East Queensland, Australia to streamline and expedite assessment of patients presenting to the Emergency Department (ED) with suspected cardiac problems. ECC implementation occurred in the context of the emergence of COVID-19. Evaluation of the impact of the ECC role focussed primarily on the time interval from triage to cardiology consult (TTCC). METHODS: ED and Cardiology Department data were extracted from electronic medical records for the period 2 September 2019 to 1 March 2021. The TTCC for each presenting problem (chest pain, palpitations, shortness of breath, altered level of consciousness) was compared between patients seen by the ECC and those not seen on the days the ECC worked. The effect of COVID-19 on TTCC was assessed by an interrupted time series analysis. Data recorded by the ECC included patients seen and interventions provided. RESULTS: The ECC saw 378 patients. Most presented with chest pain (269/378, 71.2%). The ECC determined that 68.8% (260/378) required a cardiac assessment. Following COVID-19 the median weekly TTCC increased by 0.029 hours (1.74 min) each week on average relative to that beforehand (p=0.008). For patients seen by the ECC the median TTCC was 2.07 hours (interquartile range [IQR]: 1.44, 3.16) compared to 2.58 hours (IQR: 1.73, 3.80; p=0.007) for patients not seen by the ECC. Chest pain (ECC: 1.94 hours; no ECC: 2.41 hours; p=0.06) and non-obvious cardiac presenting problems (ECC: 1.77 hours; no ECC 3.05 hours; p=0.004) displayed the largest reductions in TTCC when the ECC was involved. Presentations with palpitations, respiratory distress and altered level of consciousness had similar TTCCs. CONCLUSION: The ECC role resulted in an overall decrease in TTCC despite the role coinciding with the emergence of COVID-19. In order to clarify the optimal strategy for the ECC role, further analyses involving patient risk factors and presenting problems along with a health economic evaluation of this model of care and the effect on patient outcomes will be required.

Thoracic Surgery and the Elderly; Is Lobectomy Safe in Octogenarians?

PURPOSE: Non-small cell lung cancer is the most common malignancy of the elderly, with 5-year survival estimates of 16.8%. The prognostic benefit of surgical resection for early lung cancer is irrefutable and maintained irrespective of age, even in patients over 75 years. Concerningly, despite the prognostic benefit of surgery there are deviations from standard treatment protocols with increasing age due to concerns of increased morbidity and mortality with surgery, without evidence to support this. METHOD: A state-wide retrospective registry study of Queensland's Cardiac Outcomes Registry's (QCOR) Thoracic Database examining the influence of age on the safety of Lung Resection (1 January 2016-20 April 2022). RESULTS: This included 1,232 patients, mean age at surgery was 66 years (range 14-91 years), with 918 thoracotomies performed. Three deaths occurred within 30-days (0.24%). Octogenarians (n=60) had lower rates of smoking (26% vs 6%), respiratory, cardiovascular, and cerebrovascular disease suggesting this subset of patients is carefully selected. Octogenarian status was not associated with an increased all-cause morbidity (p=0.09) or 30-day mortality (p=0.06). Further to this it was not associated with re-operation (4.4% vs 8.3%, p=0.1), increased postoperative stay (6.66 vs 6.65 days, p=0.99) or myocardial infarction. An independent predictor of morbidity was male sex (OR 1.58, CI 1.2-2.1 p=0.001). CONCLUSION: Age ≥80 years did not increase surgical morbidity or mortality in the appropriately selected patient and should not be a barrier to referral for consideration of surgical resection.

Clinical prediction scores and the utility of time to blood culture positivity in stratifying the risk of infective endocarditis in Staphylococcus aureus bacteraemia.

BACKGROUND: Infective endocarditis (IE) complicates up to a quarter of Staphylococcus aureus bacteraemia (SAB) cases. Risk scores predict IE complicating SAB but have undergone limited external validation, especially in community-acquired infections and those who use IV drugs. Addition of the time to positive culture (TTP) may provide incremental risk prognostication. OBJECTIVES: To externally validate risk scores for predicting IE in SAB and assess the incremental value of TTP. METHODS: The modified Duke score was calculated for adults hospitalized with SAB at a major tertiary institution. All patients underwent echocardiography. Sensitivity and specificity of the risk scores for predicting IE were calculated, and the incremental value of TTP was assessed. RESULTS: One hundred and six cases were analysed and 18 (17%) met definite IE criteria. The optimal TTP to predict IE was 11.5 h (sensitivity 88.9%; specificity 71.6%). The sensitivity of VIRSTA and PREDICT (Predicting risk of endocarditis using a clinical tool) were similar (94.4% for both) and higher than POSITIVE (Prediction Of Staphylococcus aureus Infective endocarditis Time to positivity, IV drug use, Vascular phenomena, pre-Existing heart condition; 77.8%). The receiver-operator characteristic AUCs were VIRSTA 0.83, PREDICT 0.75, POSITIVE 0.89 and TTP 0.85. Adding TTP to VIRSTA (i.e. VIRSTA+) resulted in the highest AUC (0.90), sensitivity (100%) and negative predictive value (100%), albeit with a low specificity (33%). CONCLUSIONS: The VIRSTA and POSITIVE scores were the strongest predictors for IE complicating SAB. The addition of TTP to VIRSTA (VIRSTA+) significantly improved discriminatory value and may be safely used to rationalize echocardiography strategies.

Streptococcus anginosus group infections in hospitalised children and young people.

AIM: The Streptococcus anginosus group (SAG) comprises three bacterial species colonising the mouth and gastrointestinal and genitourinary tracts and capable of serious pyogenic infections. Although well-described in adults, studies in children are limited. Here, we characterise paediatric SAG infections from a single Australian centre. METHODS: Hospitalised patients aged ≤18 years with positive SAG cultures from January 2009 to December 2019 were identified from Pathology Queensland's Gold Coast Laboratory database and their medical records were reviewed. RESULTS: Two-hundred children (62% male), median age 12 years (interquartile range 6-16), with positive SAG cultures were identified. Overall, 90% received intravenous antibiotics, 89% underwent surgical drainage, 23% were readmitted and 15% required additional surgery. The most common sites were the abdomen (39%), soft tissues (36%) and head and neck regions (21%). Since 2011, Pathology Queensland reported SAG at the species level (n = 133). Of these, S. anginosus was the most prevalent (39%), then S. constellatus (34%) and S. intermedius (27%). Compared with the other two species, S. intermedius was most commonly associated with head and neck infections (relative risk (RR) = 2.2, 95% confidence interval (CI) 1.4-3.5), while S. constellatus (RR = 1.7, 95% CI 1.2-2.4) and S. anginosus (RR = 1.5, 95% CI 1.0-2.0) were each associated with a higher risk of intra-abdominal infection than S. intermedius. Since February 2015, the number of children admitted with SAG-associated intra-abdominal infection per 1000 hospitalisations increased by 29% annually compared with an annual decline of 8% in previous years. CONCLUSIONS: SAG infections occur at various anatomical sites. Despite antibiotics and surgical management, almost one-quarter are re-hospitalised for further treatment.

Long term tailored implementation of structured "TREAT" journal clubs in allied health: a hybrid effectiveness-implementation study.

BACKGROUND: Allied Health Professionals (AHPs) commonly use journal clubs (JCs) to support Evidence-Based Practice (EBP). There is however little research regarding implementing and sustaining JCs in the long term, and their impact on EBP use and skills in AHPs. This study investigated the impact of implementing a structured JC format, called "TREAT" (previously only investigated across 6 sessions), over a longer period of 16 sessions for AHPs in a public health service. The study also investigated AHP's attendance, adherence, satisfaction and barriers and enablers to implementing the format. METHODS: A mixed methods hybrid-effectiveness implementation design was employed, guided by the Knowledge-to-Action cycle. EBP skills, confidence, use, and attitudes were assessed (Adapted Fresno Test, EBPQ, tailored journal club culture questionnaire) at baseline, and after 10 and 16-monthly sessions. Satisfaction and impact on clinical practice were explored using questionnaires at 10 and 16-months, with free-form responses identifying enablers and barriers to EBP culture and implementation. Data on attendance and adherence to the TREAT format were also collected. RESULTS: Six JCs comprising a total of 132 unique participants from seven Allied Health professions were assessed across three time points. EBP skills improved on the Adapted Fresno Test after 10-monthly (6.6 points: 95% CI, 0.43 to 12.7) and 16-monthly sessions (7.8 points, 95% CI, 0.85 to 14.7), and on self-reported total EBPQ ratings of confidence at 10-months (4.9 points: 95% CI, 2.2 to 7.5) and 16-months (5.7 points: 95% CI 2.7 to 8.7). Of 132 AHPs, 88 reported adopting new treatments/resources and 64 reported updating clinical procedures. Mean attendance was 5.7 sessions (SD = 3.8). Adherence to TREAT components in each session was 86% (95% CI, 83% to 89%). Most participants recommended the format and reported a desire to continue. Enablers to the JC included using clinically relevant topics and active participation while reported barriers included limited time to prepare. CONCLUSIONS: Despite variable attendance, TREAT JCs can continue to be implemented within a service for 16 monthly-sessions, and may contribute to improved EBP skills and confidence and changes in clinical practice over time. Tailoring of implementation strategies was shown to be important to address local enablers and barriers.

Decade-scale stability and change in a marine bivalve microbiome.

Predicting how populations and communities of organisms will respond to anthropogenic change is of paramount concern in ecology today. For communities of microorganisms, however, these predictions remain challenging, primarily due to data limitations. Information about long-term dynamics of host-associated microbial communities, in particular, is lacking. In this study, we use well-preserved and freshly collected samples of soft tissue from a marine bivalve host, Donax gouldii, at a single site to quantify the diversity and composition of its microbiome over a decadal timescale. Site-level measurements of temperature, salinity and chlorophyll a allowed us to test how the microbiome of this species responded to two natural experiments: a seasonal increase in temperature and a phytoplankton bloom. Our results show that ethanol-preserved tissue can provide high-resolution information about temporal trends in compositions of host-associated microbial communities. Specifically, we found that the richness of amplicon sequence variants (ASVs) associated with D.gouldii did not change significantly over time despite increases in water temperature (+1.6°C due to seasonal change) and chlorophyll a concentration (more than ninefold). The phylogenetic composition of the communities, on the other hand, varied significantly between all collection years, with only six ASVs persisting over our sampling period. Overall, these results suggest that the diversity of microbial taxa associated with D.gouldii has remained stable over time and in response to seasonal environmental change over the course of more than a decade, but such stability is underlain by substantial turnover in the composition of the microbiome.

Efficacy of the Zero Suicide framework in reducing recurrent suicide attempts: cross-sectional and time-to-recurrent-event analyses.

BACKGROUND: The Zero Suicide framework is a system-wide approach to prevent suicides in health services. It has been implemented worldwide but has a poor evidence-base of effectiveness. AIMS: To evaluate the effectiveness of the Zero Suicide framework, implemented in a clinical suicide prevention pathway (SPP) by a large public mental health service in Australia, in reducing repeated suicide attempts after an index attempt. METHOD: A total of 604 persons with 737 suicide attempt presentations were identified between 1 July and 31 December 2017. Relative risk for a subsequent suicide attempt within various time periods was calculated using cross-sectional analysis. Subsequently, a 10-year suicide attempt history (2009-2018) for the cohort was used in time-to-recurrent-event analyses. RESULTS: Placement on the SPP reduced risk for a repeated suicide attempt within 7 days (RR = 0.29; 95% CI 0.11-0.75), 14 days (RR = 0.38; 95% CI 0.18-0.78), 30 days (RR = 0.55; 95% CI 0.33-0.94) and 90 days (RR = 0.62; 95% CI 0.41-0.95). Time-to-recurrent event analysis showed that SPP placement extended time to re-presentation (HR = 0.65; 95% CI 0.57-0.67). A diagnosis of personality disorder (HR = 2.70; 95% CI 2.03-3.58), previous suicide attempt (HR = 1.78; 95% CI 1.46-2.17) and Indigenous status (HR = 1.46; 95% CI 0.98-2.25) increased the hazard for re-presentation, whereas older age decreased it (HR = 0.92; 95% CI 0.86-0.98). The effect of the SPP was similar across all groups, reducing the risk of re-presentation to about 65% of that seen in those not placed on the SPP. CONCLUSIONS: This paper demonstrates a reduction in repeated suicide attempts after an index attempt and a longer time to a subsequent attempt for those receiving multilevel care based on the Zero Suicide framework.

Mortality in spontaneous coronary artery dissection: A systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review and meta-analysis was to provide a comprehensive estimate for spontaneous coronary artery dissection (SCAD) related mortality, and explore factors associated with an increased risk of death. BACKGROUND: SCAD is an infrequent but increasingly recognized cause of acute coronary syndrome. Despite a growing body of evidence, there have been few detailed examinations of SCAD associated mortality. METHODS: We searched MEDLINE, EMBASE, Cochrane, Web of Science and Google Scholar databases through May 7, 2020. We included studies reporting mortality data, confirmed SCAD with coronary angiography and included ≥10 participants. We excluded non-English studies, conference abstracts, review articles and duplicate datasets. Random-effects meta-analysis and meta-regression were used to evaluate estimates and predictors of mortality. RESULTS: From an initial 1,131 articles, 34 studies with 2,817 patients were eligible for inclusion. The weighted mean age was 50 years, and 84% of participants were female. The pooled estimate for SCAD mortality was 1% (Proportion 0.01; 95% CI, 0.00-0.02). The mean duration of follow-up was 33 months. Meta-regression showed male sex was associated with 3.5-fold increased odds of mortality (OR, 3.50; 95% CI, 1.22-10.03). In addition, smoking (current or previous) was associated with a 15-fold increased risk of mortality (OR 15.32; 95% CI, 2.88-81.41). CONCLUSIONS: This meta-analysis has shown that SCAD is associated with favorable survival outcomes with an estimated mortality of 1% over a mean follow-up period of 33 months. We also found male sex and smoking were associated with an increased risk of mortality.

Correlation between translabial ultrasound parameters and outcomes in retropubic mid-urethral slings: can we predict success?

PURPOSE: The aim of this study was to assess the association between four-dimensional translabial ultrasound (4D-TLUS) features of the retropubic mid-urethral sling (MUS) and post-operative pelvic floor symptoms. METHODS: A prospective cohort study was performed involving 100 women who had a solitary retropubic MUS (TVT Exact™) between Jan 2013 and Dec 2017 for urodynamic stress incontinence (SI) at a tertiary urogynaecological centre. All patients completed a standardised interview and had free flowmetry, prolapse evaluation and assessment for mesh exposure and tenderness. 4D-TLUS parameters measured included pelvic organ descent, levator ani status, sling-symphysis pubis (SP) gap at rest and Valsalva, angle formed by cranial and caudal ends of the sling, cranio-caudal and dorso-ventral sling-symphysis pubis distance at Valsalva. The primary outcome was treatment success as defined by patient report of cure or improvement and no objective demonstrable SI. RESULTS: Eighty-nine (89%) patients reported treatment success. Two patients (2%) had mesh exposure; one was symptomatic with pain, requiring complete sling removal. There was a significant association between treatment success and a SP gap at Valsalva of 10-12 mm (p = 0.001); and independently with a SP angle at Valsalva of 45°-80° (p = 0.007). A narrower SP gap at Valsalva closer to 10 mm was associated with voiding symptoms (p = 0.036). CONCLUSION: Sling-pubis gap and sling-pubis angle at Valsalva appear to be significantly associated with treatment success in retropubic MUS. There is a significant association between a narrower sling-pubis gap at Valsalva and voiding symptoms.

Vasodilators for primary Raynaud's phenomenon.

BACKGROUND: Numerous agents have been suggested for the symptomatic treatment of primary Raynaud's phenomenon. Apart from calcium channel blockers, which are considered to be the drugs of choice, evidence of the effects of alternative pharmacological treatments is limited. This is an update of a review first published in 2008. OBJECTIVES: To assess the effects of drugs with vasodilator effects on primary Raynaud's phenomenon as determined by frequency, severity, and duration of vasospastic attacks; quality of life; adverse events; and Raynauds Condition Score. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases, and the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trial register to November 16, 2020. SELECTION CRITERIA: We included randomized controlled trials evaluating effects of oral, intravenous, and topical formulations of any drug with vasodilator effects on subjective symptoms, severity scores, and radiological outcomes in primary Raynaud's phenomenon. Treatment with calcium channel blockers was not assessed in this review, nor were these agents compared. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, assessed studies using the Cochrane "Risk of bias" tool, and extracted study data. Outcomes of interest included frequency, severity, and duration of attacks; quality of life (QoL); adverse events (AEs); and the Raynaud Condition Score (RCS). We assessed the certainty of the evidence using GRADE. MAIN RESULTS: We identified seven new studies for this update. In total, we included 15 studies involving 635 participants. These studies compared different vasodilators to placebo. Individual studies used different methods and measures to report different outcomes. Angiotensin-converting enzyme (ACE) inhibitors Combining data from three studies revealed a possible small increase in the frequency of attacks per week after treatment (captopril or enalapril) compared to placebo (mean difference [MD] 0.79, 95% confidence interval [CI] 0.43 to 1.17; low-certainty evidence). There was no evidence of a difference between groups in severity of attacks (MD -0.17, 95% CI -4.66 to 4.31; 34 participants, 2 studies; low-certainty evidence); duration of attacks (MD 0.54, 95% CI -2.42 to 1.34; 14 participants, 1 study; low-certainty evidence); or AEs (risk ratio [RR] 1.35, 95% CI 0.67 to 2.73; 46 participants, 3 studies; low-certainty evidence). QoL and RCS were not reported. Alpha blockers Two studies used alpha blockers (buflomedil or moxisylyte). We were unable to combine data due to the way results were presented. Buflomedil probably reduced the frequency of attacks compared to placebo (MD -8.82, 95% CI -11.04 to -6.60; 31 participants, 1 study; moderate-certainty evidence) and may improve severity scores (MD -0.41, 95% CI -0.62 to -0.30; moderate-certainty evidence). With moxisylyte, investigators reported fewer attacks (P < 0.02), less severe symptoms (P < 0.01), and shorter duration of attacks, but the clinical relevance of these results is unclear. No evidence of a difference in AEs between buflomedil and placebo groups was noted (RR 1.41, 95% CI 0.27 to 7.28; 31 participants, 1 study; moderate-certainty evidence). More AEs were observed in participants in the moxisylyte group than in the placebo group. Prostaglandin/prostacyclin analogues One study compared beraprost versus placebo. There was no evidence of benefit for frequency (MD 2.00, 95% CI -0.35 to 4.35; 118 participants, low-certainty evidence) or severity (MD -0.06, 95% CI -0.34 to 0.22; 118 participants, low-certainty evidence) of attacks. Overall, more AEs were noted in the beraprost group (RR 1.59, 95% CI 1.05 to 2.42; 125 participants; low-certainty evidence). This study did not report on duration of attacks, QoL, or RCS. Thromboxane synthase inhibitors One study compared a thromboxane synthase inhibitor (dazoxiben) versus placebo. There was no evidence of benefit for frequency of attacks (MD 0.8, 95% CI -1.81 to 3.41; 6 participants; very low-certainty evidence). Adverse events were not reported in subgroup analyses of participants with primary Raynaud's phenomenon, and the study did not report on duration of attacks, severity of symptoms, QoL, or RCS. Selective serotonin reuptake inhibitors One study compared ketanserin with placebo. There may be a slight reduction in the number of attacks per week with ketanserin compared to placebo (MD -14.0, 95% CI -27.72 to -0.28; 41 participants; very low-certainty evidence) and reduced severity score (MD -133.00, 95% CI -162.40 to -103.60; 41 participants; very low-certainty evidence). There was no evidence that ketanserin reduced the duration of attacks (MD -4.00, 95% CI -14.82 to 6.82; 41 participants; very low-certainty evidence), or that AEs were increased in either group (RR 1.54, 95% CI 0.89 to 2.65; 41 participants; very low-certainty evidence). This study did not report on QoL or RCS. Nitrate/nitrate derivatives Four studies compared topical treatments of nitroglycerin or glyceryl trinitrate versus placebo, each reporting on limited outcomes. Meta-analysis demonstrated no evidence of effect on frequency of attacks per week (MD -1.57, 95% CI -4.31 to 1.17; 86 participants, 2 studies; very low-certainty evidence). We were unable to pool any data for the remaining outcomes. Phosphodiesterase inhibitors Three studies compared phosphodiesterase inhibitors (vardenafil, cilostazol or PF-00489791) to an equivalent placebo. Results showed no evidence of a difference in frequency of attacks (standardized MD [SMD] -0.05, 95% CI -6.71 to 6.61; 111 participants, 2 studies; low-certainty evidence), severity of attacks (MD -0.03, 95% CI -1.04 to 0.97; 111 participants, 2 studies; very low-certainty evidence), duration of attacks (MD -1.60, 95% CI -7.51 to 4.31; 73 participants, 1 study; low-certainty evidence), or RCS (SMD -0.8, 95% CI -1.74 to 0.13; 79 participants, 2 studies; low-certainty evidence). Study authors reported that 35% of participants on cilostazol complained of headaches, which were not reported in the placebo group. PF-00489791 caused 34 of 54 participants to experience AEs versus 43 of 102 participants receiving placebo (RR 1.49). Headache was most common, affecting 14 participants (PF-00489791) versus nine participants (placebo). AUTHORS' CONCLUSIONS: The included studies investigated several different vasodilators (topical and oral) for treatment of primary Raynaud's phenomenon. Small sample sizes, limited data, and variability in outcome reporting yielded evidence of very low to moderate certainty. Evidence is insufficient to support the use of vasodilators and suggests that vasodilator use may even worsen disease.

Content analysis of euthanasia polls in Australia and New Zealand: words do matter.

BACKGROUND: There has been widespread public and political interest in Euthanasia and Physician-Assisted Suicide (EPAS) in recent years. Polling in Australia and New Zealand has generally shown a majority of people support some form of legal EPAS; however, the level of support varies between polls. AIM: To explore whether public support for and opposition to EPAS as measured in historic Australian and New Zealand polls has been influenced by the wording of survey questions. METHODS: Australian and New Zealand random-sample post-1995 EPAS poll questions asked of the general public were identified and subjected to content analysis. Individual phrases and words were considered in terms of their favourability towards or unfavourability against EPAS and each poll question was assigned a net favourability score. Variation of support for EPAS based on year, location and favourability of language was analysed by various statistical methods. RESULTS: Mean public support for EPAS in Australia and New Zealand between 1995 and the present was 70.2% with support ranging between 47 and 85%. Support did not vary by location and has remained unchanged over time. However, support was positively associated with increasing levels of favourable wording, accounting for over 20% variation in mean support. Allusions to hopelessness had an especially strong effect on increasing support for EPAS. CONCLUSION: Use of emotive phrases and language is associated with influencing attitudes to EPAS in Australia and New Zealand. Therefore, caution should be exercised when interpreting public support for EPAS based on individual polls.

Safety and efficacy of telephone clinics during the COVID-19 pandemic in the provision of care for patients with cancer.

BACKGROUND: Due to the COVID-19 pandemic, telephone clinics have been utilised to reduce the risk of transmission. Evidence supporting its quality and safety is required. AIMS: Assess the efficacy and safety of telephone clinics in delivering care to established oncology patients and assess patient and health professionals' preference (telephone vs face-to-face clinics). METHODS: Retrospective chart audit in the month preceding and month following the introduction of telephone clinics at the Gold Coast University Hospital and a patient and health professional questionnaire. RESULTS: In total, 1212 clinical encounters occurred in the month post the introduction of telephone clinics (vs 1208 encounters prior). There were no statistically significant differences in 24-h (18 vs 22, P = 0.531) or 7-day admissions (50 vs 46, P = 0.665) comparing encounters in the month prior to the introduction of telephone clinics versus the month post, but there was a statistically significant difference in 30-day mortality post systemic therapy in favour of the post-telephone clinic period (7 vs 0 patients, P = 0.008). Of the 222 patients who undertook the questionnaire, 42.3% preferred telephone clinics (95% confidence interval (CI) 35.97-48.97), 25.2% preferred face-to-face clinics (95% CI 19.92-31.39) and 32.4% did not prefer one method over another. Of the 24 health professionals who undertook the questionnaire, 70.8% felt patients preferred phone clinics. CONCLUSIONS: Generally, patients and clinicians viewed telephone clinics favourably. Nevertheless, a large portion of patients still prefer face-to-face clinics. Services should be tailored to individual preferences. Although there were no 'red flags' in terms of mortality or admission rates, further longitudinal research is required.

Effects of cannabinoids in Amyotrophic Lateral Sclerosis (ALS) murine models: a systematic review and meta-analysis.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder that results from motor neuron damage. Cannabinoids have been proposed as treatments for ALS because of their anti-excitotoxicity, anti-oxidant and anti-inflammatory effects. Preclinical studies in mice models of ALS have been published using a range of cannabinoid formulations and doses. To date, there has been no rigorous evaluation of these trials to assess a potential cannabinoid treatment effect. This review and meta-analysis was undertaken to provide evidence for or against a treatment effect of cannabinoids in murine ALS models. Evidence of a treatment effect in mice may provide motivation for trials in human ALS. We identified a total of 10 studies; nine studies using cannabinoid treatment in transgenic SOD1-G93A ALS-model mice and one study in TDP-43 transgenic mice. Eight of the nine studies that used SOD1-G93A mice expressed similarly high copy numbers of the transgene while one study used a low-copy number line. Outcomes evaluated were survival time and disease progression. The latter was measured by motor function and bodyweight decline. Meta-analysis of the mean difference in survival time across the seven studies showed an increase in survival of 3.84 days (95% CI: 0.35-7.32 days; p = 0.031) for cannabinoid treated compared to control SOD1-G93A mice. It was not possible to conduct meta-analyses for motor function decline or weight loss. However, eight of nine studies reported significant improvements in measures of motor function decline and one reported non-significant improvements. Weight loss was significantly attenuated in four of five studies reporting this measure while the other study reported a non-significant attenuation. This review provides some evidence for the efficacy of cannabinoids in prolonging survival time in an ALS mouse model. A delay in disease progression is also suggested following cannabinoid treatment though it was not possible to consolidate the results from reviewed studies. However, studies have moderate to high risk of bias and are highly heterogeneous. Although this review provides some evidence to support the conduct of a cannabinoid trial in human ALS, more standardized studies on specific cannabinoids are necessary before supporting therapeutic potential of cannabinoids in treating patients with ALS. OPEN SCIENCE BADGES: This article has received a badge for *Preregistration* because the study was pre-registered at https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=89274. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. Read the Editorial Highlight for this article on page 168.

An improved clinical model to predict stimulated C-peptide in children with recent-onset type 1 diabetes.

BACKGROUND: Stimulated C-peptide measurement after a mixed meal tolerance test (MMTT) is the accepted gold standard for assessing residual beta-cell function in type 1 diabetes (T1D); however, this approach is impractical outside of clinical trials. OBJECTIVE: To develop an improved estimate of residual beta-cell function in children with T1D using commonly measured clinical variables. SUBJECTS/METHODS: A clinical model to predict 90-minute MMTT stimulated C-peptide in children with recent-onset T1D was developed from the combined AbATE, START, and TIDAL placebo subjects (n = 46) 6 months post-recruitment using multiple linear regression. This model was then validated in a clinical cohort (Hvidoere study group, n = 262). RESULTS: A model of estimated C-peptide at 6 months post-diagnosis, which included age, gender, body mass index (BMI), hemoglobin A1c (HbA1c), and insulin dose predicted 90-minute stimulated C-peptide measurements (adjusted R2 = 0.63, P < 0.0001). The predictive value of insulin dose and HbA1c alone (IDAA1c) for 90-minute stimulated C-peptide was significantly lower (R2 = 0.37, P < 0.0001). The slopes of linear regression lines of the estimated and stimulated 90-minute C-peptide levels obtained at 6 and 12 months post diagnosis in the Hvidoere clinical cohort were R2 = 0.36, P < 0.0001 at 6 months and R2 = 0.37, P < 0.0001 at 12 months. CONCLUSIONS: A clinical model including age, gender, BMI, HbA1c, and insulin dose predicts stimulated C-peptide levels in children with recent-onset T1D. Estimated C-peptide is an improved surrogate to monitor residual beta-cell function outside clinical trial settings.

Trends in contact lens microbial keratitis 1999 to 2015: a retrospective clinical review.

IMPORTANCE: Contact lens microbial keratitis (CLMK) is the most common cause of microbial keratitis in our community. BACKGROUND: Define the trend in rate of CLMK and define patient demographics/culture results that may have a predictive value in patients with CLMK. DESIGN: Retrospective review of clinical records of patients with MK. PARTICIPANTS: All patients with positive corneal scraping between 1999 and 2015 at the Princess Alexandra Hospital, Brisbane, Queensland identified through local microbiology database. METHODS: Trend in CLMK tested with chi-squared test of peak 3 years vs other years and Poisson regression of interrupted time series. Patient characteristics predictive of CLMK were defined by creating a polynomial regression model by stepwise variable selection. MAIN OUTCOME MEASURES: Yearly rate of CLMK. RESULTS: Records of 895 episodes of MK were included. The most common: risk factor was contact lens wear (324, 36.2%), isolated organism was Pseudomonas aeruginosa (P. aeruginosa 181, 55.9%) and treatment was monotherapy with a fluoroquinolone 172, 53%). CLMK was most common between 2009 and 2011 (49.5% vs other years 32%, P < 0.001). Poisson regression of the interrupted time series showed there was a significant decrease in the rate over time after 2010 (P < 0.001). Independent factors predictive of CLMK in multivariate regression were young age (15-49 years) and corneal culture positive for P. aeruginosa CONCLUSIONS AND RELEVANCE: The rate of CLMK in our community ranged between 32% and 50% and the rate of disease appears to have peaked during 2009 to 2011 and subsequently declined.