Participant recruitment and attrition in surgical randomised trials with placebo controls versus non-operative controls: a meta-epidemiological study and meta-analysis.

OBJECTIVE: To compare differences in recruitment and attrition between placebo control randomised trials of surgery, and trials of the same surgical interventions and conditions that used non-operative (non-placebo) controls. DESIGN: Meta-epidemiological study. DATA SOURCES: Randomised controlled trials were identified from an electronic search of MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from their inception date to 21 November 2018. STUDY SELECTION: Placebo control trials evaluating efficacy of any surgical intervention and non-operative control trials of the same surgical intervention were included in this study. 25 730 records were retrieved from our systemic search, identifying 61 placebo control and 38 non-operative control trials for inclusion in analysis. OUTCOME MEASURES: Primary outcome measures were recruitment and attrition. These were assessed in terms of recruitment rate (number of participants enrolled, as a proportion of those eligible) and overall attrition rate (composite of dropout, loss to follow-up and cross-overs, expressed as proportion of total sample size). Secondary outcome measures included participant cross-over rate, dropout and loss to follow-up. RESULTS: Unadjusted pooled recruitment and attrition rates were similar between placebo and non-operative control trials. Study characteristics were not significantly different apart from time to primary timepoint which was shorter in studies with placebo controls (365 vs 274 days, p=0.006). After adjusting for covariates (follow-up duration and number of timepoints), the attrition rate of placebo control trials was almost twice as high compared with non-operative controlled-trials (incident rate ratio (IRR) (95% CI) 1.8 (1.1 to 3.0), p=0.032). The incorporation of one additional follow-up timepoint (regardless of follow-up duration) was associated with reduced attrition in placebo control surgical trials (IRR (95% CI) 0.64 (0.52 to 0.79), p<0.001). CONCLUSIONS: Placebo control trials of surgery have similar recruitment issues but higher attrition compared with non-operative (non-placebo) control trials. Study design should incorporate strategies such as increased timepoints for given follow-up duration to mitigate losses to follow-up and dropout. PROSPERO REGISTRATION NUMBER: CRD42019117364.

Models for delivery and co-ordination of primary or secondary health care (or both) to older adults living in aged care facilities.

BACKGROUND: The number of older people is increasing worldwide and public expenditure on residential aged care facilities (ACFs) is expected to at least double, and possibly triple, by 2050. Co-ordinated and timely care in residential ACFs that reduces unnecessary hospital transfers may improve residents' health outcomes and increase satisfaction with care among ACF residents, their families and staff. These benefits may outweigh the resources needed to sustain the changes in care delivery and potentially lead to cost savings. Our systematic review comprehensively and systematically presents the available evidence of the effectiveness, safety and cost-effectiveness of alternative models of providing health care to ACF residents. OBJECTIVES: Main objective To assess the effectiveness and safety of alternative models of delivering primary or secondary health care (or both) to older adults living in ACFs. Secondary objective To assess the cost-effectiveness of the alternative models. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, five other databases and two trials registers (WHO ICTRP, ClinicalTrials.gov) on 26 October 2022, together with reference checking, citation searching and contact with study authors to identify additional studies. SELECTION CRITERIA: We included individual and cluster-randomised trials, and cost/cost-effectiveness data collected alongside eligible effectiveness studies. Eligible study participants included older people who reside in an ACF as their place of permanent abode and healthcare professionals delivering or co-ordinating the delivery of healthcare at ACFs. Eligible interventions focused on either ways of delivering primary or secondary health care (or both) or ways of co-ordinating the delivery of this care. Eligible comparators included usual care or another model of care. Primary outcomes were emergency department visits, unplanned hospital admissions and adverse effects (defined as infections, falls and pressure ulcers). Secondary outcomes included adherence to clinical guideline-recommended care, health-related quality of life of residents, mortality, resource use, access to primary or specialist healthcare services, any hospital admissions, length of hospital stay, satisfaction with the health care by residents and their families, work-related satisfaction and work-related stress of ACF staff. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, extracted data, and assessed risk of bias and certainty of evidence using GRADE. The primary comparison was any alternative model of care versus usual care. MAIN RESULTS: We included 40 randomised trials (21,787 participants; three studies only reported number of beds) in this review. Included trials evaluated alternative models of care aimed at either all residents of the ACF (i.e. no specific health condition; 11 studies), ACF residents with mental health conditions or behavioural problems (12 studies), ACF residents with a specific condition (e.g. residents with pressure ulcers, 13 studies) or residents requiring a specific type of care (e.g. residents after hospital discharge, four studies). Most alternative models of care focused on 'co-ordination of care' (n = 31). Three alternative models of care focused on 'who provides care' and two focused on 'where care is provided' (i.e. care provided within ACF versus outside of ACF). Four models focused on the use of information and communication technology. Usual care, the comparator in all studies, was highly heterogeneous across studies and, in most cases, was poorly reported. Most of the included trials were susceptible to some form of bias; in particular, performance (89%), reporting (66%) and detection (42%) bias. Compared to usual care, alternative models of care may make little or no difference to the proportion of residents with at least one emergency department visit (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.84 to 1.20; 7 trials, 1276 participants; low-certainty evidence), but may reduce the proportion of residents with at least one unplanned hospital admission (RR 0.74, 95% CI 0.56 to 0.99, I2 = 53%; 8 trials, 1263 participants; low-certainty evidence). We are uncertain of the effect of alternative models of care on adverse events (proportion of residents with a fall: RR 1.15, 95% CI 0.83 to 1.60, I² = 74%; 3 trials, 1061 participants; very low-certainty evidence) and adherence to guideline-recommended care (proportion of residents receiving adequate antidepressant medication: RR 5.29, 95% CI 1.08 to 26.00; 1 study, 65 participants) as the certainty of the evidence is very low. Compared to usual care, alternative models of care may have little or no effect on the health-related quality of life of ACF residents (MD -0.016, 95% CI -0.036 to 0.004; I² = 23%; 12 studies, 4016 participants; low-certainty evidence) and probably make little or no difference to the number of deaths in residents of ACFs (RR 1.03, 95% CI 0.92 to 1.16, 24 trials, 3881 participants, moderate-certainty evidence). We did not pool the cost-effectiveness or cost data as the specific costs associated with the various alternative models of care were incomparable, both across models of care as well as across settings. Based on the findings of five economic evaluations (all interventions focused on co-ordination of care), we are uncertain of the cost-effectiveness of alternative models of care compared to usual care as the certainty of the evidence is very low. AUTHORS' CONCLUSIONS: Compared to usual care, alternative models of care may make little or no difference to the number of emergency department visits but may reduce unplanned hospital admissions. We are uncertain of the effect of alternative care models on adverse events (i.e. falls, pressure ulcers, infections) and adherence to guidelines compared to usual care, as the certainty of the evidence is very low. Alternative models of care may have little or no effect on health-related quality of life and probably have no effect on mortality of ACF residents compared to usual care. Importantly, we are uncertain of the cost-effectiveness of alternative models of care due to the limited, disparate data available.

Referral Patterns for People With Musculoskeletal Complaints in General Practice: An Analysis From an Australian Primary Care Database.

OBJECTIVE: Our objective was to examine referral patterns for people with musculoskeletal complaints presenting to Australian general practitioners (GPs). METHODS: This longitudinal analysis from the Population Level Analysis Reporting (POLAR) database includes 133,279 patients with low back (≥18 years old) or neck, shoulder, and/or knee (≥45 years old) complaints seen by 4,538 GPs across 269 practices from 2014 through 2018. Referrals to allied health and medical and/or surgical specialists were included. We determined the number of patients with referrals and GPs who made referrals and examined their timing, associations, and trends over time. RESULTS: A total of 43,666 patients (33%) received and 3,053 GPs (67%) made at least one referral. Most referrals were to allied health (n = 25,830, 19%), followed by surgeons (n = 18,805, 14%). Surgical referrals were higher for knee complaints (n = 6,140, 24%) compared with low back, neck, and shoulder complaints (range 8%-15%). The referral category varied predominantly by body region followed by gender, socioeconomic status, and primary health network. Time to allied health referral ranged between median (interquartile range [IQR]) 14 days (0-125 days) for neck complaints and 56 days (5-177 days) for knee complaints. Surgical referrals occurred sooner for those with knee complaints (15 days, IQR 0-128 days). There was a 2.2% (95% confidence interval [CI] 1.9%-2.4%) annual increase in the proportion of allied health referrals and a 1.9% (95% CI 1.6%-2.1%) decrease in surgical referrals across all sites. CONCLUSION: One-third of patients receive, and two-thirds of GPs make, referrals for musculoskeletal complaints. Understanding the reasons for referral and differences between GPs who refer more and less frequently may identify factors that explain variations in practice.

Baricitinib and ß-Cell Function in Patients with New-Onset Type 1 Diabetes.

BACKGROUND: Janus kinase (JAK) inhibitors, including baricitinib, block cytokine signaling and are effective disease-modifying treatments for several autoimmune diseases. Whether baricitinib preserves ß-cell function in type 1 diabetes is unclear. METHODS: In this phase 2, double-blind, randomized, placebo-controlled trial, we assigned patients with type 1 diabetes diagnosed during the previous 100 days to receive baricitinib (4 mg once per day) or matched placebo orally for 48 weeks. The primary outcome was the mean C-peptide level, determined from the area under the concentration-time curve, during a 2-hour mixed-meal tolerance test at week 48. Secondary outcomes included the change from baseline in the glycated hemoglobin level, the daily insulin dose, and measures of glycemic control assessed with the use of continuous glucose monitoring. RESULTS: A total of 91 patients received baricitinib (60 patients) or placebo (31 patients). The median of the mixed-meal-stimulated mean C-peptide level at week 48 was 0.65 nmol per liter per minute (interquartile range, 0.31 to 0.82) in the baricitinib group and 0.43 nmol per liter per minute (interquartile range, 0.13 to 0.63) in the placebo group (P = 0.001). The mean daily insulin dose at 48 weeks was 0.41 U per kilogram of body weight per day (95% confidence interval [CI], 0.35 to 0.48) in the baricitinib group and 0.52 U per kilogram per day (95% CI, 0.44 to 0.60) in the placebo group. The levels of glycated hemoglobin were similar in the two trial groups. However, the mean coefficient of variation of the glucose level at 48 weeks, as measured by continuous glucose monitoring, was 29.6% (95% CI, 27.8 to 31.3) in the baricitinib group and 33.8% (95% CI, 31.5 to 36.2) in the placebo group. The frequency and severity of adverse events were similar in the two trial groups, and no serious adverse events were attributed to baricitinib or placebo. CONCLUSIONS: In patients with type 1 diabetes of recent onset, daily treatment with baricitinib over 48 weeks appeared to preserve ß-cell function as estimated by the mixed-meal-stimulated mean C-peptide level. (Funded by JDRF International and others; BANDIT Australian New Zealand Clinical Trials Registry number, ACTRN12620000239965.).

Health facility availability and readiness for family planning and maternity and neonatal care services in Nepal: Analysis of cross-sectional survey data.

OBJECTIVES: To determine the availability and readiness of health facilities to provide family planning, antenatal care and basic emergency obstetric and newborn care in Nepal in 2021. Secondary objectives were to identify progress since 2015 and factors associated with readiness. METHOD: This is a secondary analysis of cross-sectional Nepal Health Facility Survey (NHFS) data collected in 2015 and 2021. The main outcome measures were availability and readiness of family planning, antenatal care, and basic emergency obstetric and newborn care services. Readiness indices were calculated using WHO-recommended service availability and readiness assessment (SARA) methods (score range 0 to 100%, with 100% indicating facilities are fully prepared to provide a specific service). We used independent t-tests to compare readiness indices in 2015 and 2021. Factors potentially associated with readiness (rurality setting, ecological region, managing authority, management meeting, quality assurance activities, and external supervision) were explored using multivariable linear regression. RESULTS: There were 940 and 1565 eligible health facilities in the 2015 and 2021 surveys, respectively. Nearly all health facilities provided family planning (2015: n = 919 (97.8%); 2021: n = 1530 (97.8%)) and antenatal care services (2015: n = 920 (97.8%); 2021: n = 1538 (98.3%)) in both years, but only half provided delivery services (2015: n = 457 (48.6%); 2021: n = 804 (51.4%)). There were suboptimal improvements in readiness indices over time: (2015-21: family planning 68.0% to 70.9%, p<0.001, antenatal care 49.5% to 54.1%, p<0.001 and basic emergency obstetric and newborn care 56.7% to 58.0%, p = 0.115). The regression model comprising combined datasets of both NHFSs indicates facilities with regular management meetings and/or quality assurance activities had significantly greater readiness for all three indices. Similarly, public facilities had greater readiness for family planning and basic emergency obstetric and newborn care while they had lower readiness for antenatal care. CONCLUSIONS: Readiness to deliver family planning, antenatal care and basic emergency obstetric and newborn care services in Nepal remains inadequate, with little improvement observed over six years.

Patterns of Imaging Requests By General Practitioners for People With Musculoskeletal Complaints: An Analysis From a Primary Care Database.

OBJECTIVE: The aim of this study was to examine imaging requested by general practitioners (GPs) for patients with low back, neck, shoulder, and knee complaints over 5 years (2014-2018). METHODS: This analysis from the Australian Population Level Analysis and Reporting database included patients presenting with a diagnosis of low back, neck, shoulder, and/or knee complaints. Eligible imaging requests included low back and neck x-ray, computed tomography (CT), and magnetic resonance imaging (MRI); knee x-ray, CT, MRI, and ultrasound; and shoulder x-ray, MRI, and ultrasound. We determined number of imaging requests and examined their timing, associated factors, and trends over time. Primary analysis included imaging requests from 2 weeks before diagnosis to 1 year after diagnosis. RESULTS: There were 133,279 patients (57% low back, 25% knee, 20% shoulder, and 11% neck complaints). Imaging was most common among those with a shoulder (49%) complaint, followed by knee (43%), neck (34%), and low back complaints (26%). Most requests occurred simultaneously with the diagnosis. Imaging modality varied by body region and, to a lesser extent, by gender, socioeconomic status, and primary health network. For low back, there was a 1.3% (95% confidence interval [95% CI] 1.0-1.6) annual increase in proportion of MRI and a concomitant 1.3% (95% CI 0.8-1.8) decrease in CT requests. For neck, there was a 3.0% (95% CI 2.1-3.9) annual increase in proportion of MRI and a concomitant 3.1% (95% CI 2.2-4.0) decrease in x-ray requests. CONCLUSION: GPs commonly request early diagnostic imaging for musculoskeletal complaints at odds with recommended practice. We observed a trend towards more complex imaging for neck and back complaints.

Evaluating an audit and feedback intervention for reducing overuse of pathology test requesting by Australian general practitioners: protocol for a factorial cluster randomised controlled trial.

INTRODUCTION: Consistent evidence shows pathology services are overused worldwide and that about one-third of testing is unnecessary. Audit and feedback (AF) is effective for improving care but few trials evaluating AF to reduce pathology test requesting in primary care have been conducted. The aim of this trial is to estimate the effectiveness of AF for reducing requests for commonly overused pathology test combinations by high-requesting Australian general practitioners (GPs) compared with no intervention control. A secondary aim is to evaluate which forms of AF are most effective. METHODS AND ANALYSIS: This is a factorial cluster randomised trial conducted in Australian general practice. It uses routinely collected Medicare Benefits Schedule data to identify the study population, apply eligibility criteria, generate the interventions and analyse outcomes. On 12 May 2022, all eligible GPs were simultaneously randomised to either no intervention control or to one of eight intervention groups. GPs allocated to an intervention group received individualised AF on their rate of requesting of pathology test combinations compared with their GP peers. Three separate elements of the AF intervention will be evaluated when outcome data become available on 11 August 2023: (1) invitation to participate in continuing professional development-accredited education on appropriate pathology requesting, (2) provision of cost information on pathology test combinations and (3) format of feedback. The primary outcome is the overall rate of requesting of any of the displayed combinations of pathology tests of GPs over 6 months following intervention delivery. With 3371 clusters, assuming no interaction and similar effects for each intervention, we anticipate over 95% power to detect a difference of 4.4 requests in the mean rate of pathology test combination requests between the control and intervention groups. ETHICS AND DISSEMINATION: Ethics approval was received from the Bond University Human Research Ethics Committee (#JH03507; approved 30 November 2021). The results of this study will be published in a peer-reviewed journal and presented at conferences. Reporting will adhere to Consolidated Standards of Reporting Trials. TRIAL REGISTRATION NUMBER: ACTRN12622000566730.

The Edmonton Classification System for Cancer Pain in Patients with Bone Metastasis: a descriptive cohort study.

PURPOSE: We describe the prevalence of the Edmonton Classification System for Cancer Pain (ECS-CP) features in patients with bone metastasis and cancer-induced bone pain (CIBP) and the relationship between ECS-CP features, pain intensity, and opioid consumption. METHODS: We assessed ECS-CP features and recoded pain mechanisms and opioid use in adult patients with bone metastasis. Validated measures were used to assess pain intensity, incident pain, psychological distress, addictive behavior, and cognition. RESULTS: Among 147 eligible patients, 95.2% completed the assessment. Mean participant age was 73.2 years, the majority female (52.1%) with breast cancer occurring most commonly (25.7%). One or more ECS-CP features were present in 96.4% and CIBP in 75.7% of patients. The median average and worst pain scores were 3 and 6, respectively. Neuropathic pain was the most prevalent pain mechanism (45.0%) and was associated with breakthrough pain frequency (p=0.014). Three-quarters had incident pain, which was strongly associated with a higher average and worst pain scores (3.5 and 7, p<0.001 for both), background oral morphine equivalent daily dose (26.7mg, p=0.005), and frequency of daily breakthrough analgesia (1.7 doses/day, p=0.007). Psychological distress (n=90, 64.3%) was associated with a significantly higher average pain score (4, p=0.009) and a slightly higher worst pain score (7, p=0.054). Addictive behaviour and cognitive dysfunction were relatively uncommon (18.6% and 12.9%, respectively). CONCLUSION: There is a need to promote standardized assessment and classification of pain syndromes such as CIBP. The ECS-CP may allow us to consider CIBP in a systematic manner and develop personalized pain interventions appropriate to the pain profile. TRIAL REGISTRATION: Retrospectively registered in ANZCTR ACTRN12622000853741 (16/06/2022).

A randomized controlled trial of moderated online social therapy for family carers of first-episode psychosis patients in a specialist treatment setting.

BACKGROUND: Family members, who provide the majority of informal care during the recovery period from first-episode psychosis (FEP), experience high levels of psychological distress. However, there is a lack of effective and accessible interventions for FEP carers. OBJECTIVE: To determine the effectiveness of an online intervention ("Altitudes") in relation to the primary outcome of FEP-carer stress at 6 months follow-up. METHODS: We conducted a cluster randomized controlled trial in which FEP carers were randomized to Altitudes combined with specialized treatment as usual (STAU) or STAU alone. In addition to questionnaires, we included multiple waves of intensive ecological momentary assessment (EMA) to measure carer stress and family outcomes in 164 carers of young (15-27 years) FEP patients. RESULTS: Both groups improved over time on stress and a range of secondary outcomes, including mental health symptoms, self-efficacy, and expressed emotion with no group by time interactions. At 12 months there were significantly fewer visits to emergency departments by FEP patients in the Altitudes group (p = 0.022). Modelling of multiple EMA waves revealed that more time spent by carers with FEP patients predicted greater worry, expressed emotion, and adaptive coping. CONCLUSIONS: Engagement and usability findings for Altitudes were positive. Further refinements to our online carer interventions may be needed to engage carers in purposeful skill development for improved management of stress and communication with the young person compared with existing specialist family interventions. TRIAL REGISTRATION: ACTRN12616000968471.

Methadone rotation versus other opioid rotation for refractory cancer induced bone pain: protocol of an exploratory randomised controlled open-label study.

BACKGROUND: A third of patients with advanced cancer and bone metastasis suffer from cancer induced bone pain (CIBP), impeding quality of life, psychological distress, depression and anxiety. This study will evaluate the impact of an opioid rotation, comparing methadone rotation with other opioid rotation in patients with refractory CIBP. METHODS: This open-label randomised controlled trial will recruit cancer patients with CIBP and inadequate pain control despite established baseline opioid and/or intolerable opioid side effects from cancer and palliative care services. Participants will be at least 18 years old, with a predicted prognosis of greater than 8 weeks, meet the core diagnostic criteria for CIBP, have a worst pain score of ≥ 4 of 10 from CIBP and/ or have opioid toxicity (graded ≥ 2 on Common Terminology Criteria for Adverse Events). Participants will have sufficiently proficient English to complete questionnaires and provide informed consent. Participants will be randomised 1:1 to be rotated to methadone to another opioid. The primary objective is to examine the impact of opioid rotation in improving CIBP by comparing analgesic efficacy, safety and tolerability in the two arms. Secondary objectives will assess changes in the intensity, duration and frequency of breakthrough pain, requirement of breakthrough analgesia, overall opioid escalation index, and time taken to observe improvement in pain reduction, pain interference and quality of life. DISCUSSION: Laboratory studies suggest the involvement of neuropathic involvement in the mechanism of CIBP, though there remains no clear evidence of the routine use of neuropathic agents. Methadone as an analgesic agent may have a role to play in this cohort of patients, thus warranting further exploratory studies. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry No: ACTRN12621000141842. Registered 11 February 2021.

Prevalence and characteristics of musculoskeletal complaints in primary care: an analysis from the population level and analysis reporting (POLAR) database.

BACKGROUND: Electronic health record datasets have been used to determine the prevalence of musculoskeletal complaints in general practice but not to examine the associated characteristics and healthcare utilisation at the primary care level. AIM: To describe the prevalence and characteristics of patients presenting to general practitioners with musculoskeletal complaints. DESIGN AND SETTING: A five-year analysis within three Primary Health Networks (PHNs) in Victoria, Australia. METHOD: We included patients with at least one face-to-face consultation 2014 to 2018 inclusive and a low back (≥ 18 years), and/or neck, shoulder or knee (≥ 45 years) complaint determined by SNOMED codes derived from diagnostic text within the medical record. We determined prevalence, socio-demographic characteristics and diagnostic codes for patients with an eligible diagnosis; and number of consultations within one year of diagnosis. RESULTS: 324,793/1,294,021 (25%) presented with at least one musculoskeletal diagnosis, of whom 41% (n = 133,279) fulfilled our inclusion criteria. There were slightly more females (n = 73,428, 55%), two-thirds (n = 88,043) were of working age (18-64 years) and 83,816 (63%) had at least one comorbidity. Over half had a low back diagnosis (n = 76,504, 57%) followed by knee (n = 33,438, 25%), shoulder (n = 26,335, 20%) and neck (n = 14,492, 11%). Most codes included 'pain' and/or 'ache' (low back: 58%, neck: 41%, shoulder: 32%, knee 26%). Median (IQR) all-cause consultations per patient within one year of diagnosis was 7 (4-12). CONCLUSION: The burden of MSK complaints at the primary care level is high as evidenced by the prevalence of people with musculoskeletal complaints presenting to a general practitioner, the preponderance of comorbidities and the numerous consultations per year. Identification and evaluation of strategies to reduce this burden are needed.

Fontan Hepatopathy-Managing Unknowns.

BACKGROUND AND AIMS: How to best monitor Fontan-associated liver disease (FALD) remains unclear. We describe results from a prospective liver care pathway in adults (n=84) with a Fontan circulation. METHODS: Routine assessment of the liver, by acoustic radiation force frequency and ultrasound was undertaken. Results, including liver biochemistry, systemic ventricular function (echocardiography), functional class, medication use and clinical endpoints (varices, hepatocellular carcinoma, heart transplantation and death) were collated. RESULTS: Most individuals returned a cirrhotic range acoustic radiation force impulse imaging (ARFI) result. ARFI values were greater in the proportion of individuals with hepatic nodularity (p=0.024). Univariate analysis demonstrated moderate correlation with platelet number (Spearmans rho= -0.376, p=0.049). Patients with clinical endpoints had lower platelets (p=0.012) but only a trend to hepatic nodularity (p=0.057). Clinical endpoints were more common in those with ventricular dysfunction (p=0.011). Multivariate analysis revealed that age at Fontan and being on angiotensin converting enzyme inhibitors (ACEI) predicted ARFI score (ß=0.06 [95% CI 0.01-0.09], p=0.007 and ß=0.53 [95% CI 0.17-0.89], p=0.005, respectively). However, these associations were not significant once adjusted for Fontan type, age at ARFI, systemic ventricle morphology, ventricle function, or Model for End-stage Liver Disease (MELD-XI) excluding international normalised ratio (INR) (p>0.05 for all). CONCLUSIONS: Ideal FALD monitoring remains unclear. ARFI has utility as a binary non-invasive indicator of cirrhosis, highlighting individuals who may need more frequent ongoing monitoring for hepatocellular carcinoma. However, no definite advantage to serial ARFI, once cirrhotic range ARFI results are present, has been identified.

Concordance in salivary cortisol and subjective anxiety to the trier social stress test in social anxiety disorder.

BACKGROUND: Social anxiety disorder (SAD) is characterised by an excessive fear of negative social evaluation. There is a limited understanding of how individuals with SAD react physiologically and subjectively to social stress. METHOD: The Trier Social Stress Test (TSST), an acute social stress task, was completed by 40 SAD individuals (50% female) and 41 healthy controls (matched on age, sex, and education) to examine salivary cortisol and self-reported stress reactivity. Salivary cortisol concentrations and self-reported affect (anxiety, sadness, tiredness, withdrawal, and happiness) were assessed at baseline and across nine-time points during the TSST. RESULTS: Bayesian salivary cortisol analyses revealed no group differences in salivary cortisol levels at baseline or during the TSST, with results comparative after the removal of 17 cortisol non-responders (21%). Contrastingly, the groups significantly differed on self-reported affect. At baseline, the SAD group (vs. controls) reported heightened negative affect and diminished happiness. In response to the TSST, the SAD group (vs. controls) displayed greater negative affect reactivity and diminished happiness reactivity, and significantly higher rates of change in their anxiety and sadness over time. After accounting for differences in the temporal resolution of self-reported versus cortisol responses, a moderate positive association was found between salivary cortisol and anxiety reactivity to social stress that was comparable between the groups. CONCLUSIONS: Despite elevated subjective anxiety, our findings suggest concordance in psychobiological stress reactivity in SAD and healthy controls. We discuss the possibility of heightened subjective sensitivity to social evaluative stress as a core treatment target for SAD.

Effect of an Individualized Audit and Feedback Intervention on Rates of Musculoskeletal Diagnostic Imaging Requests by Australian General Practitioners: A Randomized Clinical Trial.

Importance: Audit and feedback can improve professional practice, but few trials have evaluated its effectiveness in reducing potential overuse of musculoskeletal diagnostic imaging in general practice. Objective: To evaluate the effectiveness of audit and feedback for reducing musculoskeletal imaging by high-requesting Australian general practitioners (GPs). Design, Setting, and Participants: This factorial cluster-randomized clinical trial included 2271 general practices with at least 1 GP who was in the top 20% of referrers for 11 imaging tests (of the lumbosacral or cervical spine, shoulder, hip, knee, and ankle/hind foot) and for at least 4 individual tests between January and December 2018. Only high-requesting GPs within participating practices were included. The trial was conducted between November 2019 and May 2021, with final follow-up on May 8, 2021. Interventions: Eligible practices were randomized in a 1:1:1:1:1 ratio to 1 of 4 different individualized written audit and feedback interventions (n = 3055 GPs) that varied factorially by (1) frequency of feedback (once vs twice) and (2) visual display (standard vs enhanced display highlighting highly requested tests) or to a control condition of no intervention (n = 764 GPs). Participants were not masked. Main Outcomes and Measures: The primary outcome was the overall rate of requests for the 11 targeted imaging tests per 1000 patient consultations over 12 months, assessed using routinely collected administrative data. Primary analyses included all randomized GPs who had at least 1 patient consultation during the study period and were performed by statisticians masked to group allocation. Results: A total of 3819 high-requesting GPs from 2271 practices were randomized, and 3660 GPs (95.8%; n = 727 control, n = 2933 intervention) were included in the primary analysis. Audit and feedback led to a statistically significant reduction in the overall rate of imaging requests per 1000 consultations compared with control over 12 months (adjusted mean, 27.7 [95% CI, 27.5-28.0] vs 30.4 [95% CI, 29.8-30.9], respectively; adjusted mean difference, -2.66 [95% CI, -3.24 to -2.07]; P < .001). Conclusions and Relevance: Among Australian general practitioners known to frequently request musculoskeletal diagnostic imaging, an individualized audit and feedback intervention, compared with no intervention, significantly decreased the rate of targeted musculoskeletal imaging tests ordered over 12 months. Trial Registration: ANZCTR Identifier: ACTRN12619001503112.

Editorial Commentary: Arthroscopic Treatment Should No Longer Be Offered to People With Subacromial Impingement.

Arthroscopic treatment should no longer be offered to people with subacromial impingement. In many people, subacromial impingement (or subacromial pain syndrome) is self-limiting and may not require any specific treatment. This is evident by the fact that almost 50% of people with new-onset shoulder pain consult their primary care doctor only once. The best-available evidence from randomized controlled trials indicates that glucocorticoid injection provides rapid, modest, short-term pain relief. Exercise therapy has also been found to provide no added benefit over glucocorticoid injection. Subacromial decompression (bursectomy and acromioplasty) for subacromial pain syndrome provides no important benefit on pain, function, or health-related quality of life. Acromioplasty does not improve the outcomes of rotator cuff repair.

Clinical impact of whole-genome sequencing in patients with early-onset dementia.

BACKGROUND: In the clinical setting, identification of the genetic cause in patients with early-onset dementia (EOD) is challenging due to multiple types of genetic tests required to arrive at a diagnosis. Whole-genome sequencing (WGS) has the potential to serve as a single diagnostic platform, due to its superior ability to detect common, rare and structural genetic variation. METHODS: WGS analysis was performed in 50 patients with EOD. Point mutations, small insertions/deletions, as well as structural variants (SVs) and short tandem repeats (STRs), were analysed. An Alzheimer's disease (AD)-related polygenic risk score (PRS) was calculated in patients with AD. RESULTS: Clinical genetic diagnosis was achieved in 7 of 50 (14%) of the patients, with a further 8 patients (16%) found to have established risk factors which may have contributed to their EOD. Two pathogenic variants were identified through SV analysis. No expanded STRs were found in this study cohort, but a blinded analysis with a positive control identified a C9orf72 expansion accurately. Approximately 37% (7 of 19) of patients with AD had a PRS equivalent to >90th percentile risk. DISCUSSION: WGS acts as a single genetic test to identify different types of clinically relevant genetic variations in patients with EOD. WGS, if used as a first-line clinical diagnostic test, has the potential to increase the diagnostic yield and reduce time to diagnosis for EOD.

The delivery of intergenerational programmes in the nursing home setting and impact on adolescents and older adults: A mixed studies systematic review.

BACKGROUND: Interventions to support a more "age friendly" world are a key objective set out by the World Health Organization with health and wellbeing benefits being increasingly identified for both young and old. Whilst multiple studies have explored intergenerational engagement between kindergarten aged children and older adults, there is limited collective knowledge of programme design and the potential impact that these programmes have on adolescents engaging with older adults in the nursing home setting. OBJECTIVES: The aims of this systematic review were to: a) examine intergenerational programme development and delivery in the nursing home setting and b) report on the impact of intergenerational engagement on adolescents and older adults. DESIGN: A systematic mixed studies review of intergenerational programmes targeting adolescents and older adults. DATA SOURCE: MEDLINE, CINAHL, Embase, PsycINFO, Scopus and ERIC (1995 and 2021) and reference lists were hand-searched. REVIEW METHODS: The first author conducted a review of the titles and abstracts based on inclusion and exclusion criteria. All authors then reviewed and discussed each paper to determine inclusion. Qualitative appraisal using the Mixed-Methods Appraisal Tool was conducted, and all evidence from the quantitative, qualitative, and mixed-methods studies was identified and thematically analysed using a convergent qualitative synthesis design. RESULTS: Ten papers were identified for review (six qualitative studies, two quantitative studies and two mixed methods studies). Inconsistencies in the inclusion criteria for older adults limited opportunities to explore the benefits for people with or without dementia. Few studies described the process of programme design, and there were wide variations in programme delivery. Programmes ranged from six weeks to eight months with a variety of activities and interactions implemented. Engaging in intergenerational programmes resulted in improved wellbeing and perceptions of social inclusion and reduced ageism. No correlations between programme design and impact were identified. CONCLUSIONS: Intergenerational programmes have important socio-emotional benefits for both adolescents and older adults. There is limited understanding of what meaningful intergenerational engagement entails as there is a lack of transparency surrounding the mechanics behind the programmes that are associated to positive change in the literature. In addition, there is currently no evidence of the longitudinal impacts or the broader social implications of these types of interventions. Future research is needed to explore programme design, the longitudinal effects, and the wider impacts of intergenerational programmes at a community and societal level. TWEETABLE ABSTRACT: Design and impact of intergenerational engagement between adolescents and older adults in the nursing home setting: a systematic review.

Worldwide prevalence of Lynch syndrome in patients with colorectal cancer: Systematic review and meta-analysis.

PURPOSE: Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, with an estimated prevalence of 2% to 3% of CRC. A prevalence study is needed to provide accurate estimates of the true prevalence of LS. METHODS: MEDLINE (Ovid), Embase, and Web of Science were searched. Prevalence was calculated by random effects meta-analysis models. I2 score was used to assess heterogeneity across studies. Meta-regression was performed for between-study variance. RESULTS: A total of 51 studies were included in this review. The overall pooled yield of LS screening was 2.2% based on all methods of detection. Studies performing germline tests on all participants with CRC reported higher prevalence (5.1%) as opposed to studies only performing germline tests on participants with tumors with mismatch repair deficiency (1.6%) or microsatellite instability (1.1%). Selected cohorts of CRC had a higher prevalence of germline LS diagnoses. CONCLUSION: LS prevalence across multiple ethnic, geographic, and clinical populations is remarkably similar. Universal germline testing of patients presenting with cancer identifies that most CRCs are attributed to LS. Young patients presenting with CRC and those who fulfill criteria for a familial risk provide the highest returns for LS identification. Our study supports the universal germline CRC screening for LS.

Symptom burden in malignant and non-malignant disease on admission to a palliative care unit.

BACKGROUND: There is increasing recognition that patients with non-malignant diseases have comparable physical and psychosocial symptom burden to patients with cancer. There is currently limited data directly comparing symptom burden between these patient groups. OBJECTIVE: To investigate differences in symptom burden between patients with malignant and non-malignant conditions admitted to a palliative care unit (PCU). METHOD: A cross-sectional study involving 186 patients admitted to a PCU was undertaken. Patients were dichotomised into malignant or non-malignant disease categories. Symptom burden at admission was assessed using the Symptom Assessment Scale and Palliative Care Problem Severity Score. Group differences in symptoms were analysed using univariate and multivariate approaches. RESULTS: One hundred patients (53.8%) had cancer, with upper gastrointestinal the most common type (18.0%). Among the 86 patients with non-malignant disease, neurological conditions were most prevalent (40.7%). Patients admitted with non-malignant diseases were older, more functionally impaired and more likely to be deteriorating or terminal. A malignant diagnosis was associated with a higher likelihood of clinician-assessed pain, patient-assessed pain, fatigue, psychological/spiritual symptoms and other symptoms. However, when adjusted for confounders, disease category ceased to be a significant predictor of symptom burden. Younger patients experienced worse pain and patients in terminal phase experienced less symptom burden. CONCLUSION: Symptom burden was similar between patients with malignant and non-malignant disease after adjustment for confounders. Further research is needed to understand the palliative care needs of patients with non-malignant disease.

Strategies for the Management of Solitary Pulmonary Nodules: A Survey of Patient Preferences.

BACKGROUND: Guideline-based strategies for evaluation of solitary pulmonary nodules are tailored to the likelihood of malignancy. Surveillance, biopsy, and resection are all reasonable approaches in fit individuals when the likelihood of malignancy is intermediate. Given the paucity of data demonstrating superior outcomes and important trade-offs among strategies, guidelines emphasize the importance of eliciting patient preferences and engaging in shared decision making; however, there is little literature on what patient preferences actually are. METHODS: This study conducted a cross-sectional, interview-administered questionnaire survey in 100 adults recruited from a metropolitan teaching hospital (The Royal Melbourne Hospital, Parkville, Victoria, Australia). The questionnaire used a hypothetical scenario designed to elicit patient preferences for different management strategies of solitary pulmonary nodules with a probability of malignancy between 10% and 70%. RESULTS: The mean age of participants was 62 years (range, 45 to 80 years), 56% were male, and 94% were current smokers or ex-smokers. Ninety-four percent completed all questions. At 10% probability of malignancy, 36.3% preferred surveillance, 42.4% preferred needle biopsy, and 21.2% preferred surgical resection. Preference for surgical resection increased to 53.5% and 86.2% when the probability of malignancy was 30% and 70%, respectively. Changes in the diagnostic yield of computed tomography biopsy significantly altered preferences when the probability of malignancy was 10% or 30%. CONCLUSIONS: The majority of participants surveyed expressed a preference for some type of biopsy over observation at all levels of solitary pulmonary nodule probability of malignancy evaluated. In an era of increasing solitary pulmonary nodule detection and patient-centered care, if confirmed in broader studies, these findings have considerable implications for processes of care and resource allocation.