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.).

Methadone versus other opioids for refractory malignant bone pain: a pilot randomised controlled study.

PURPOSE: Refractory cancer-induced bone pain (CIBP) affects a patient's functional capacity and quality of life, but there is limited evidence to guide opioid choice. We assessed the feasibility, tolerability and possible efficacy of methadone rotation (MR) compared to other opioid rotations (OOR) in this cohort. METHODS: Adults with CIBP and worst pain intensity ≥ 4/10 and/or opioid toxicity graded ≥ 2 on the Common Terminology Criteria for Adverse Events were randomised 1:1 to methadone or another opioid rotation. Standardised assessment tools were used at pre-defined study time points up to 14 days. RESULTS: Of 51 eligible participants, 38 (74.5%) consented, and 29 (76.3%, MR: 14, OOR: 15) completed the fourteen days follow-up post-opioid rotation. Both groups displayed significant reduction in average (MR: d = - 1.2, p = 0.003, OOR: d = - 0.8, p = 0.015) and worst pain (MR: d = - 0.9, p = 0.042, OOR: d = - 0.6, p = 0.048) and total pain interference score (MR: d = - 1.1, p = 0.042, OOR: d = - 0.7, p = 0.007). Oral morphine equivalent daily dose was reduced significantly in MR compared to the OOR group (d = - 0.8, p = 0.05). The incidence of opioid-related adverse events following MR was unchanged but lower in the OOR group (d = 0.9, 95% CI 0.1,1.7, p = 0.022). There were no within-group or between-group differences in satisfaction with analgesia at the end of the study. CONCLUSION: This pilot study demonstrated that MR and OOR in patients with refractory CIBP are feasible, safe and acceptable to patients. Appropriately powered multi-centre randomised controlled studies are needed to confirm the efficacy of MR and OOR in this cohort. TRIAL REGISTRATION: ACTRN12621000141842 registered 11 February 2021.

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.

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).

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.

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.

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.

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.

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.

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.

Risk of Fractures and Other Injuries in Children Treated with Antiseizure Medications for Epilepsy.

This study aimed to investigate the prevalence of fractures and non-fracture injuries, including associated risk factors, in children with epilepsy prescribed antiseizure medications (ASM). A controlled, cross-sectional study was conducted in a hospital outpatient setting, comparing children with epilepsy prescribed ASMs with their non-epileptic siblings. Information was collected by questionnaire included history of fractures, non-fracture injuries and epilepsy, comorbidities and ASM use. 261 participants completed the questionnaire, 133 children with epilepsy (aged 10.7 ± 3.5 years, mean ± SD) and 128 siblings (10.1 ± 3.7 years). There were 49 non-seizure-related fractures in 34 ASM patients while prescribed ASMs, compared with 21 lifetime fractures in 15 controls, giving a 2.7 (95% CI 1.3-5.3, p = 0.007) times greater fracture prevalence in children treated with ASMs compared to healthy siblings. The rates of non-fracture injuries were similar across groups, except that concussion was more common in children taking ASMs (9.0% vs 1.6%, p = 0.026). Duration of ASM use and generalized tonic-clonic seizures (GTCS) were independent predictors of fractures (OR 1.55; 95% CI 1.03-2.31, p = 0.03; OR 2.50; 95% CI 1.05-5.94, p = 0.04, respectively). Fewer than 20% of participants and/or their families were aware that ASM use was related to bone health. Children with epilepsy treated with ASMs had a higher fracture prevalence than their sibling controls. Duration of ASM treatment and GTCS were associated with fracture risk. Longitudinal prospective studies are required to further explore risk and the direct impact of epilepsy on bone health.

Relationship between procedural volume and complication rates for catheter ablation of atrial fibrillation: a systematic review and meta-analysis.

AIMS: There are conflicting data as to the impact of procedural volume on outcomes with specific reference to the incidence of major complications after catheter ablation for atrial fibrillation. Questions regarding minimum volume requirements and whether these should be per centre or per operator remain unclear. Studies have reported divergent results. We performed a systematic review and meta-analysis of studies reporting the relationship between either operator or hospital atrial fibrillation (AF) ablation volumes and incidence of complications. METHODS AND RESULTS: Databases were searched for studies describing the relationship between operator or hospital AF ablation volumes and incidence of complications which were published prior to 12 June 2020. Of 1593 articles identified, 14 (315 120 patients) were included in the meta-analysis. Almost two-thirds of the procedures were performed in low-volume centres. Both hospital volume of ≥50 and ≥100 procedures/year were associated with a significantly lower incidence of complications compared to <50/year (4.2% vs. 5.5%, OR = 0.58, 95% CI 0.50-0.66, P < 0.001) or <100/year (5.5% vs. 6.2%, OR = 0.62, 95% CI 0.53-0.73, P < 0.001), respectively. Hospitals performing ≥50 procedures/year demonstrated significantly lower mortality compared with those performing <50 procedures/year (0.16% vs. 0.55%, OR = 0.33, 95% CI 0.26-0.43, P < 0.001). A similar relationship existed between proceduralist volume of <50/year and incidence of complications [3.75% vs. 12.73%, P < 0.001; OR = 0.27 (0.23-0.32)]. CONCLUSION: There is an inverse relationship between both hospital and proceduralist AF ablation volume and the incidence of complications. Implementation of minimum hospital and operator AF ablation volume standards should be considered in the context of a broader strategy to identify AF ablation Centers of Excellence.

Environmental enrichment for stroke and other non-progressive brain injury.

BACKGROUND: Rehabilitation is effective for recovery after stroke and other non-progressive brain injuries but it is unclear if the rehabilitation environment itself, outside of limited therapy hours, is maximally conducive to recovery. Environmental enrichment is a relatively new concept within rehabilitation for humans. In this review, this is defined as an intervention designed to facilitate physical (motor and sensory), cognitive and social activity by the provision of equipment and organisation of a structured, stimulating environment. The environment should be designed to encourage (but not force) activities without additional specialised rehabilitation input. OBJECTIVES: To assess the effects of environmental enrichment on well-being, functional recovery, activity levels and quality of life in people who have stroke or non-progressive brain injury. SEARCH METHODS: We conducted the search on 26 October 2020. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (from 1950); Embase (from 1980); the Cumulative Index to Nursing and Allied Health Literature (CINAHL; from 1982); the Allied and Complementary Medicine Database (AMED; from 1985); PsycINFO (from 1806); the Physiotherapy Evidence Database (PEDro; from 1999); and 10 additional bibliographic databases and ongoing trial registers. SELECTION CRITERIA: We planned to include randomised controlled trials (RCTs) that compared environmental enrichment with standard services. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligible studies, extracted data, and assessed study quality. Any disagreements were resolved through discussion with a third review author. We determined the risk of bias for the included study and performed a 'best evidence' synthesis using the GRADE approach. MAIN RESULTS: We identified one RCT, involving 53 participants with stroke, comparing environmental enrichment (which included physical, cognitive and social activities such as reading material, board and card games, gaming technology, music, artwork, and computer with Internet) with standard services in an inpatient rehabilitation setting. We excluded five studies, found two studies awaiting classification and one ongoing study which described environmental enrichment in their interventions. Of the excluded studies, three were non-RCTs and two described co-interventions with a significant component of rehabilitation. Based on the single small included RCT at high risk of bias, data are insufficient to provide any reliable indication of benefit or risk to guide clinical practice in terms of the provision of environmental enrichment. AUTHORS' CONCLUSIONS: The gap in current research should not, however, be interpreted as proof that environmental enrichment is ineffective. Further research is needed with robust study designs, such as cluster RCTs, and consistent outcome measurement evaluating the effectiveness of environmental enrichment in different settings (inpatient versus outpatient), the relative effectiveness of various components of environmental enrichment, cost-effectiveness, and safety of the intervention in people following stroke or other non-progressive brain injuries. It should be noted, however, that it is challenging to randomise or double-blind trials of environmental enrichment given the nature of the intervention.

Mainstreaming genomics: training experience of hospital medical officers at the Royal Melbourne Hospital.

The rapid evolution and wide applicability of genomic testing means that medical practitioners outside the field are not appropriately skilled to understand the utility of genomics for their patients. Rotating junior doctors through genomic medicine provides them with the hands-on experience necessary to understand the complexities in this field. In this study, we analysed the training experience of 12 hospital medical officers who rotated through genomic medicine at the Royal Melbourne Hospital. Here, we demonstrate that immersion in clinical genomics aids in mainstreaming genomics knowledge.

Clinicopathological features and outcomes of progression of CLL on the BCL2 inhibitor venetoclax.

The BCL2 inhibitor venetoclax achieves responses in ∼79% of patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (RR-CLL/SLL), irrespective of risk factors associated with poor response to chemoimmunotherapy. A limitation of this targeted therapy is progressive disease (PD) in some patients. To define the risk factors for progression, the clinicopathological features of PD, and the outcomes for patients after venetoclax failure, we analyzed 67 heavily pretreated patients on 3 early phase clinical trials. Investigations at progression included positron emission tomography scan and biopsy. Twenty-five (37%) patients manifested PD on therapy: 17 with Richter transformation (RT) and 8 with progressive CLL/SLL. RT occurred significantly earlier (median 7.9 months) than progressive CLL (median 23.4 months) (P = .003). Among patients who received the recommended phase 2 dose of venetoclax or higher (≥400 mg/d), fludarabine refractoriness and complex karyotype were associated with progression (hazard ratio 7.01 [95% confidence interval 1.7-28.5]; P = .002 and 6.6 [1.5-29.8]; P = .005, respectively), whereas del(17p) and/or TP53 mutation were not (P = .75). Median postprogression survival was 13 (<1-49.9) months. Bruton tyrosine kinase inhibitors were active in progressive CLL, but outcomes were mixed. Patients with disease that is fludarabine refractory or who have complex cytogenetics should have occult RT excluded before initiating venetoclax therapy.

Practice Patterns in Parathyroid Surgery: A Survey of Asia-Pacific Parathyroid Surgeons.

BACKGROUND: Practice variations exist amongst parathyroid surgeons depending on their expertise and resources. Our study aims to elucidate the choice of surgical techniques and adjuncts used in parathyroid surgery by surgeons in the Asia-Pacific region. METHODS: A 25-question online survey was sent to members of five endocrine surgery associations. Questions covered training background, practice environment and preferred techniques in parathyroid surgery. Respondents were divided into three regions: Australia/New Zealand, South/South East Asia and East Asia, and responses were analysed according to region, specialty, case volume and years in practice. RESULTS: One hundred ninety-six surgeons returned the questionnaire. Most surgeons (98%) routinely perform preoperative imaging, with 75% preferring dual imaging with 99mTcsestamibi and ultrasound. Ten per cent of surgeons use parathyroid 4DCT as first-line imaging, more commonly in East Asia (p = 0.038). Minimally invasive parathyroidectomy is the favoured technique of choice (97%). Most surgeons reporting robotic or endoscopic approaches are from East Asia. Rapid intraoperative parathyroid hormone is accessible to just under half of the surgeons but less available in Australian/New Zealand (p < 0.001). The use of intraoperative neuromonitoring is not commonly used, even less so amongst Asian surgeons (p = 0.048) and surgeons with low case load (p = 0.013). CONCLUSION: Dual localisation techniques are the preferred choice of investigations in preparation for parathyroid surgery, with minimally invasive surgery without neuromonitoring the preferred approach. Use of adjuncts is sporadic and limited to certain centres.

The projected burden of primary total knee and hip replacement for osteoarthritis in Australia to the year 2030.

BACKGROUND: Comprehensive national joint replacement registries with well-validated data offer unique opportunities for examining the potential future burden of hip and knee osteoarthritis (OA) at a population level. This study aimed to forecast the burden of primary total knee (TKR) and hip replacements (THR) performed for OA in Australia to the year 2030, and to model the impact of contrasting obesity scenarios on TKR burden. METHODS: De-identified TKR and THR data for 2003-2013 were obtained from the Australian Orthopaedic Association National Joint Replacement Registry. Population projections and obesity trends were obtained from the Australian Bureau of Statistics, with public and private hospital costs sourced from the National Hospital Cost Data Collection. Procedure rates were projected according to two scenarios: (1) constant rate of surgery from 2013 onwards; and (2) continued growth in surgery rates based on 2003-2013 growth. Sensitivity analyses were used to estimate future TKR burden if: (1) obesity rates continued to increase linearly; or (2) 1-5% of the overweight or obese population attained a normal body mass index. RESULTS: Based on recent growth, the incidence of TKR and THR for OA is estimated to rise by 276% and 208%, respectively, by 2030. The total cost to the healthcare system would be $AUD5.32 billion, of which $AUD3.54 billion relates to the private sector. Projected growth in obesity rates would result in 24,707 additional TKRs totalling $AUD521 million. A population-level reduction in obesity could result in up to 8062 fewer procedures and cost savings of up to $AUD170 million. CONCLUSIONS: If surgery trends for OA continue, Australia faces an unsustainable joint replacement burden by 2030, with significant healthcare budget and health workforce implications. Strategies to reduce national obesity could produce important TKR savings.

Quantifying Use of a Health Virtual Community of Practice for General Practitioners' Continuing Professional Development: A Novel Methodology and Pilot Evaluation.

BACKGROUND: Health care practitioners (HPs), in particular general practitioners (GPs), are increasingly adopting Web-based social media platforms for continuing professional development (CPD). As GPs are restricted by time, distance, and demanding workloads, a health virtual community of practice (HVCoP) is an ideal solution to replace face-to-face CPD with Web-based CPD. However, barriers such as time and work schedules may limit participation in an HVCoP. Furthermore, it is difficult to gauge whether GPs engage actively or passively in HVCoP knowledge-acquisition for Web-based CPD, as GPs' competencies are usually measured with pre- and posttests. OBJECTIVE: This study investigated a method for measuring the engagement features needed for an HVCoP (the Community Fracture Capture [CFC] Learning Hub) for learning and knowledge sharing among GPs for their CPD activity. METHODS: A prototype CFC Learning Hub was developed using an Igloo Web-based social media software platform and involved a convenience sample of GPs interested in bone health topics. This Hub, a secure Web-based community site, included 2 key components: an online discussion forum and a knowledge repository (the Knowledge Hub). The discussion forum contained anonymized case studies (contributed by GP participants) and topical discussions (topics that were not case studies). Using 2 complementary tools (Google Analytics and Igloo Statistical Tool), we characterized individual participating GPs' engagement with the Hub. We measured the GP participants' behavior by quantifying the number of online sessions of the participants, activities undertaken within these online sessions, written posts made per learning topic, and their time spent per topic. We calculated time spent in both active and passive engagement for each topic. RESULTS: Seven GPs participated in the CFC Learning Hub HVCoP from September to November 2017. The complementary tools successfully captured the GP participants' engagement in the Hub. GPs were more active in topics in the discussion forum that had direct clinical application as opposed to didactic, evidence-based discussion topics (ie, topical discussions). From our knowledge hub, About Osteoporosis and Prevention were the most engaging topics, whereas shared decision making was the least active topic. CONCLUSIONS: We showcased a novel complementary analysis method that allowed us to quantify the CFC Learning Hub's usage data into (1) sessions, (2) activities, (3) active or passive time spent, and (4) posts made to evaluate the potential engagement features needed for an HVCoP focused on GP participants' CPD process. Our design and evaluation methods for ongoing use and engagement in this Hub may be useful to evaluate future learning and knowledge-sharing projects for GPs and may allow for extension to other HPs' environments. However, owing to the limited number of GP participants in this study, we suggest that further research with a larger cohort should be performed to validate and extend these findings.

Compliance with screening for and recommended management of maternal group B streptococcus carriage in pregnancy.

BACKGROUND: Universal screening of pregnant women at 35-37 weeks gestation is recommended for detection of anogenital group B streptococcus carriage. Intrapartum chemoprophylaxis is prescribed to carriers to prevent transmission to babies, reducing early-onset neonatal group B streptococcal sepsis. AIMS: To review compliance with, and the effects of education on group B streptococcus screening and intrapartum chemoprophylaxis practices at The Royal Women's Hospital, Melbourne, Australia. MATERIALS AND METHODS: A retrospective audit of women delivering in February 2016 and February-March 2017 was conducted. In February 2017, updated early-onset group B streptococcal disease prevention guidelines were released and promoted with targeted education of clinical staff. Compliance was considered appropriate if practices followed up-to-date local protocols. RESULTS: Screening rate for group B streptococcus was 84.4% (599/710) and carriage rate 19.5% (109/558), while intrapartum antibiotic prophylaxis was optimal in 83% of those labouring greater than four hours (39/47). There was no significant difference in compliance between 2016 and 2017. Of 113 women with unknown group B streptococcal status at delivery, only five of 33 (15%) with clinical risk factors for early-onset neonatal disease received intrapartum prophylaxis. CONCLUSIONS: Compliance remained stable, with no change during or after implementation of new protocols. Compliance with protocols was low for cases with unknown group B streptococcal status at delivery but with the presence of one or more clinical risk factors for early-onset group B streptococcal sepsis.

Skin-Liver Distance and Interquartile Range-Median Ratio as Determinants of Interoperator Concordance in Acoustic Radiation Force Impulse Imaging.

CONTEXT AND AIMS: The accuracy of acoustic radiation force impulse (ARFI) ultrasound compared to liver biopsy is higher when there is concordance between F-scores of two or more operators. We hypothesized that when the first operator interquartile range/median-velocity ratio (IMR) is <0.3 and skin-liver distance (SLD) is <2.5 cm, there is greater interoperator concordance and a second operator is not necessary. SUBJECTS AND METHODS: Two-operator ARFI ultrasound measurements (F-score, SLD, and IMR) were recorded for 927 consecutive patients. Chi-squared testing compared interoperator concordance for SLD <2.5 cm versus SLD ≥2.5 cm and IMR <0.3 versus IMR ≥0.3 when SLD <2.5 cm, in each of the F-score groups of 0/1, 2, 3, and 4. RESULTS: Statistically significant differences were demonstrated between SLD <2.5 cm and SLD ≥2.5 cm groups for F-scores 0/1 or 4 (P = 0.005) and F-scores 2 or 3 (P < 0.001). Concordance, when SLD measured <2.5 cm, was more than 85% for all F-score groups. In the SLD <2.5 cm group, concordance fell below 85% when IMR ≥0.3, for all F-scores except F2. Specifically, P values comparing IMR <0.3 and IMR ≥0.3 in the various first operator F-score groups were P = 0.040 for F0/F1, P = 0.580 for F2, P = 0.342 for F3, and P < 0.001 for F4. CONCLUSIONS: ARFI measurements from one operator can be considered acceptable when SLD <2.5 cm and IMR <0.3. Otherwise, adding a second operator can improve confidence in the result.