The University of Notre Dame Australia

PURPOSE: To update the World Society of the Abdominal Compartment Syndrome (WSACS) consensus definitions and management statements relating to intra-abdominal hypertension (IAH) and the abdominal compartment syndrome (ACS). METHODS: We conducted systematic or structured reviews to identify relevant studies relating to IAH or ACS. Updated consensus definitions and management statements were then derived using a modified Delphi method and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) guidelines, respectively. Quality of evidence was graded from high (A) to very low (D) and management statements from strong RECOMMENDATIONS (desirable effects clearly outweigh potential undesirable ones) to weaker SUGGESTIONS (potential risks and benefits of the intervention are less clear). RESULTS: In addition to reviewing the consensus definitions proposed in 2006, the WSACS defined the open abdomen, lateralization of the abdominal musculature, polycompartment syndrome, and abdominal compliance, and proposed an open abdomen classification system. RECOMMENDATIONS included intra-abdominal pressure (IAP) measurement, avoidance of sustained IAH, protocolized IAP monitoring and management, decompressive laparotomy for overt ACS, and negative pressure wound therapy and efforts to achieve same-hospital-stay fascial closure among patients with an open abdomen. SUGGESTIONS included use of medical therapies and percutaneous catheter drainage for treatment of IAH/ACS, considering the association between body position and IAP, attempts to avoid a positive fluid balance after initial patient resuscitation, use of enhanced ratios of plasma to red blood cells and prophylactic open abdominal strategies, and avoidance of routine early biologic mesh use among patients with open abdominal wounds. NO RECOMMENDATIONS were possible regarding monitoring of abdominal perfusion pressure or the use of diuretics, renal replacement therapies, albumin, or acute component-parts separation. CONCLUSION: Although IAH and ACS are common and frequently associated with poor outcomes, the overall quality of evidence available to guide development of RECOMMENDATIONS was generally low. Appropriately designed intervention trials are urgently needed for patients with IAH and ACS.

AIM: The aim of this study was to describe systematically the best available intervention evidence for children with cerebral palsy (CP). METHOD: This study was a systematic review of systematic reviews. The following databases were searched: CINAHL, Cochrane Library, DARE, EMBASE, Google Scholar MEDLINE, OTSeeker, PEDro, PsycBITE, PsycINFO, and speechBITE. Two independent reviewers determined whether studies met the inclusion criteria. These were that (1) the study was a systematic review or the next best available; (2) it was a medical/allied health intervention; and (3) that more than 25% of participants were children with CP. Interventions were coded using the Oxford Levels of Evidence; GRADE; Evidence Alert Traffic Light; and the International Classification of Function, Disability and Health. RESULTS: Overall, 166 articles met the inclusion criteria (74% systematic reviews) across 64 discrete interventions seeking 131 outcomes. Of the outcomes assessed, 16% (21 out of 131) were graded 'do it' (green go); 58% (76 out of 131) 'probably do it' (yellow measure); 20% (26 out of 131) 'probably do not do it' (yellow measure); and 6% (8 out of 131) 'do not do it' (red stop). Green interventions included anticonvulsants, bimanual training, botulinum toxin, bisphosphonates, casting, constraint-induced movement therapy, context-focused therapy, diazepam, fitness training, goal-directed training, hip surveillance, home programmes, occupational therapy after botulinum toxin, pressure care, and selective dorsal rhizotomy. Most (70%) evidence for intervention was lower level (yellow) while 6% was ineffective (red). INTERPRETATION: Evidence supports 15 green light interventions. All yellow light interventions should be accompanied by a sensitive outcome measure to monitor progress and red light interventions should be discontinued since alternatives exist.

The purpose of this study is to empirically test an integrative model linking tourists’ emotional experiences, perceived overall image, satisfaction, and intention to recommend. The model was tested using data collected from domestic tourists visiting Sardinia, Italy. Results show that tourists’ emotional experiences act as antecedents of perceived overall image and satisfaction evaluations. In addition, overall image has a positive influence on tourist satisfaction and intention to recommend. The study expands current theorizations by examining the merits of emotions in tourist behavior models. From a practical perspective, the study offers important implications for destination marketers.

OBJECTIVES: To provide guidance for the management of mood disorders, based on scientific evidence supplemented by expert clinical consensus and formulate recommendations to maximise clinical salience and utility. METHODS: Articles and information sourced from search engines including PubMed and EMBASE, MEDLINE, PsycINFO and Google Scholar were supplemented by literature known to the mood disorders committee (MDC) (e.g., books, book chapters and government reports) and from published depression and bipolar disorder guidelines. Information was reviewed and discussed by members of the MDC and findings were then formulated into consensus-based recommendations and clinical guidance. The guidelines were subjected to rigorous successive consultation and external review involving: expert and clinical advisors, the public, key stakeholders, professional bodies and specialist groups with interest in mood disorders. RESULTS: The Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (Mood Disorders CPG) provide up-to-date guidance and advice regarding the management of mood disorders that is informed by evidence and clinical experience. The Mood Disorders CPG is intended for clinical use by psychiatrists, psychologists, physicians and others with an interest in mental health care. CONCLUSIONS: The Mood Disorder CPG is the first Clinical Practice Guideline to address both depressive and bipolar disorders. It provides up-to-date recommendations and guidance within an evidence-based framework, supplemented by expert clinical consensus. MOOD DISORDERS COMMITTEE: Professor Gin Malhi (Chair), Professor Darryl Bassett, Professor Philip Boyce, Professor Richard Bryant, Professor Paul Fitzgerald, Dr Kristina Fritz, Professor Malcolm Hopwood, Dr Bill Lyndon, Professor Roger Mulder, Professor Greg Murray, Professor Richard Porter and Associate Professor Ajeet Singh. INTERNATIONAL EXPERT ADVISORS: Professor Carlo Altamura, Dr Francesco Colom, Professor Mark George, Professor Guy Goodwin, Professor Roger McIntyre, Dr Roger Ng, Professor John O'Brien, Professor Harold Sackeim, Professor Jan Scott, Dr Nobuhiro Sugiyama, Professor Eduard Vieta, Professor Lakshmi Yatham. AUSTRALIAN AND NEW ZEALAND EXPERT ADVISORS: Professor Marie-Paule Austin, Professor Michael Berk, Dr Yulisha Byrow, Professor Helen Christensen, Dr Nick De Felice, A/Professor Seetal Dodd, A/Professor Megan Galbally, Dr Josh Geffen, Professor Philip Hazell, A/Professor David Horgan, A/Professor Felice Jacka, Professor Gordon Johnson, Professor Anthony Jorm, Dr Jon-Paul Khoo, Professor Jayashri Kulkarni, Dr Cameron Lacey, Dr Noeline Latt, Professor Florence Levy, A/Professor Andrew Lewis, Professor Colleen Loo, Dr Thomas Mayze, Dr Linton Meagher, Professor Philip Mitchell, Professor Daniel O'Connor, Dr Nick O'Connor, Dr Tim Outhred, Dr Mark Rowe, Dr Narelle Shadbolt, Dr Martien Snellen, Professor John Tiller, Dr Bill Watkins, Dr Raymond Wu.

BACKGROUND: The TARGIT-A trial compared risk-adapted radiotherapy using single-dose targeted intraoperative radiotherapy (TARGIT) versus fractionated external beam radiotherapy (EBRT) for breast cancer. We report 5-year results for local recurrence and the first analysis of overall survival. METHODS: TARGIT-A was a randomised, non-inferiority trial. Women aged 45 years and older with invasive ductal carcinoma were enrolled and randomly assigned in a 1:1 ratio to receive TARGIT or whole-breast EBRT, with blocks stratified by centre and by timing of delivery of targeted intraoperative radiotherapy: randomisation occurred either before lumpectomy (prepathology stratum, TARGIT concurrent with lumpectomy) or after lumpectomy (postpathology stratum, TARGIT given subsequently by reopening the wound). Patients in the TARGIT group received supplemental EBRT (excluding a boost) if unforeseen adverse features were detected on final pathology, thus radiotherapy was risk-adapted. The primary outcome was absolute difference in local recurrence in the conserved breast, with a prespecified non-inferiority margin of 2·5% at 5 years; prespecified analyses included outcomes as per timing of randomisation in relation to lumpectomy. Secondary outcomes included complications and mortality. This study is registered with ClinicalTrials.gov, number NCT00983684. FINDINGS: Patients were enrolled at 33 centres in 11 countries, between March 24, 2000, and June 25, 2012. 1721 patients were randomised to TARGIT and 1730 to EBRT. Supplemental EBRT after TARGIT was necessary in 15·2% [239 of 1571] of patients who received TARGIT (21·6% prepathology, 3·6% postpathology). 3451 patients had a median follow-up of 2 years and 5 months (IQR 12-52 months), 2020 of 4 years, and 1222 of 5 years. The 5-year risk for local recurrence in the conserved breast was 3·3% (95% CI 2·1-5·1) for TARGIT versus 1·3% (0·7-2·5) for EBRT (p=0·042). TARGIT concurrently with lumpectomy (prepathology, n=2298) had much the same results as EBRT: 2·1% (1·1-4·2) versus 1·1% (0·5-2·5; p=0·31). With delayed TARGIT (postpathology, n=1153) the between-group difference was larger than 2·5% (TARGIT 5·4% [3·0-9·7] vs EBRT 1·7% [0·6-4·9]; p=0·069). Overall, breast cancer mortality was much the same between groups (2·6% [1·5-4·3] for TARGIT vs 1·9% [1·1-3·2] for EBRT; p=0·56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1·4% [0·8-2·5] vs 3·5% [2·3-5·2]; p=0·0086), attributable to fewer deaths from cardiovascular causes and other cancers. Overall mortality was 3·9% (2·7-5·8) for TARGIT versus 5·3% (3·9-7·3) for EBRT (p=0·099). Wound-related complications were much the same between groups but grade 3 or 4 skin complications were significantly reduced with TARGIT (four of 1720 vs 13 of 1731, p=0·029). INTERPRETATION: TARGIT concurrent with lumpectomy within a risk-adapted approach should be considered as an option for eligible patients with breast cancer carefully selected as per the TARGIT-A trial protocol, as an alternative to postoperative EBRT. FUNDING: University College London Hospitals (UCLH)/UCL Comprehensive Biomedical Research Centre, UCLH Charities, National Institute for Health Research Health Technology Assessment programme, Ninewells Cancer Campaign, National Health and Medical Research Council, and German Federal Ministry of Education and Research.

This document outlines recommendations for physiotherapy management for COVID-19 in the acute hospital setting. It includes: recommendations for physiotherapy workforce planning and preparation; a screening tool for determining requirement for physiotherapy; and recommendations for the selection of physiotherapy treatments and personal protective equipment. It is intended for use by physiotherapists and other relevant stakeholders in the acute care setting caring for adult patients with confirmed or suspected COVID-19.

ABSTRACT We study merger and acquisition (M&A) payment choices of European bidders for publicly and privately held targets in the 1997–2000 period. Europe is an ideal venue for studying the importance of corporate governance in making M&A payment choices, given the large number of closely held firms and the wide range of capital markets, institutional settings, laws, and regulations. The tradeoff between corporate governance concerns and debt financing constraints is found to have a large bearing on the bidder's payment choice. Consistent with earlier evidence, we find that several deal and target characteristics significantly affect the method of payment choice.

INTRODUCTION: The aim of this study was to develop consensus recommendations on safety parameters for mobilizing adult, mechanically ventilated, intensive care unit (ICU) patients. METHODS: A systematic literature review was followed by a meeting of 23 multidisciplinary ICU experts to seek consensus regarding the safe mobilization of mechanically ventilated patients. RESULTS: Safety considerations were summarized in four categories: respiratory, cardiovascular, neurological and other. Consensus was achieved on all criteria for safe mobilization, with the exception being levels of vasoactive agents. Intubation via an endotracheal tube was not a contraindication to early mobilization and a fraction of inspired oxygen less than 0.6 with a percutaneous oxygen saturation more than 90% and a respiratory rate less than 30 breaths/minute were considered safe criteria for in- and out-of-bed mobilization if there were no other contraindications. At an international meeting, 94 multidisciplinary ICU clinicians concurred with the proposed recommendations. CONCLUSION: Consensus recommendations regarding safety criteria for mobilization of adult, mechanically ventilated patients in the ICU have the potential to guide ICU rehabilitation whilst minimizing the risk of adverse events.

IMPORTANCE: Checkpoint inhibitors have replaced docetaxel as the new standard second-line therapy in advanced non-small cell lung carcinoma (NSCLC), but little is known about the potential predictive value of clinical and molecular characteristics. OBJECTIVE: To estimate the relative efficacy of checkpoint inhibitor vs docetaxel overall and in subgroups defined by clinicopathological characteristics. DATA SOURCES: This systematic review and meta-analysis searched MEDLINE, Embase, PubMed, and the Cochrane Central Register of Controlled Trials for randomized clinical trials published in the English language between January 1, 1996, and January 30, 2017. STUDY SELECTION: Randomized clinical trials that compared a checkpoint inhibitor (nivolumab, pembrolizumab, or atezolizumab) with docetaxel. For each trial included in this study, the trial name, year of publication or conference presentation, patients' clinicopathological characteristics, type of chemotherapy, and type of checkpoint inhibitor were extracted. Data collection for this study took place from February 1 to March 31, 2017. DATA EXTRACTION AND SYNTHESIS: Two reviewers performed study selection, data abstraction, and risk of bias assessment. Hazard ratios (HR) and 95% CIs for the overall population and subgroups were extracted. Pooled treatment estimates were calculated using the inverse-variance-weighted method. RESULTS: In total, 5 trials involving 3025 patients with advanced NSCLC were included in this meta-analysis. These patients were randomized to receive a checkpoint inhibitor (nivolumab, 427 [14.1%]; pembrolizumab, 691 [22.8%]; or atezolizumab, 569 [18.8%]) or docetaxel (1338 [44.2%]). Checkpoint inhibitors were associated with prolonged overall survival, compared with docetaxel (HR, 0.69; 95% CI, 0.63-0.75; P < .001). They prolonged overall survival in the EGFR wild-type subgroup (HR, 0.67; 95% CI, 0.60-0.75; P < .001), but not in the EGFR mutant subgroup (HR, 1.11; 95% CI, 0.80-1.53; P = .54; interaction, P = .005), and they prolonged overall survival in the KRAS mutant subgroup (HR, 0.65; 95% CI, 0.44-0.97; P = .03) but not in the KRAS wild-type subgroup (HR, 0.86; 95% CI, 0.67-1.11; P = .24; interaction, P = .24). The relative treatment benefits were similar according to smoking status (never smokers [HR, 0.79] vs ever smokers [HR, 0.69]; interaction, P = .40), performance status (0 [HR, 0.69] vs 1 [HR, 0.68]; interaction, P = .85), age (<65 years [HR, 0.71] vs ≥65 years [HR, 0.69]; interaction, P = .74), histology (squamous [HR, 0.67] vs nonsquamous [HR, 0.70]; interaction, P = .71), or sex (male [HR, 0.69] vs female [HR, 0.70]; interaction, P = .82). CONCLUSION AND RELEVANCE: Checkpoint inhibitors, compared with docetaxel, are associated with significantly prolong overall survival in second-line therapy in NSCLC. The finding of no overall survival benefit for patients with EGFR mutant tumors suggests that checkpoint inhibitors should be considered only after other effective therapies have been exhausted. The findings of this meta-analysis could also assist in the design and interpretation of future trials and in economic analyses.

OBJECTIVE: To summarize evidence on the rates of co-occurring impairments, diseases, and functional limitations with cerebral palsy into succinct clinical messages. METHODS: A search was conducted of the databases PubMed, Medline, CINAHL, and PsycINFO, and the results were supplemented with hand searches. Two independent reviewers determined whether retrieved abstracts met the following inclusion criteria: human subjects; >90% were children or adults with cerebral palsy; published after 1999; and population-based data. Articles were appraised, analyzing design, participants, level of evidence, rates of impairments, and functional implications. Methodologic quality was rated by using a standardized checklist. RESULTS: A total of 1366 papers were identified in the search; 82 were appraised and 30 were included in the meta-analyses. High-level evidence existed, as rated on the Oxford 2011 LEVELS OF EVIDENCE: 97% of prevalence studies were level 1. The data were of a moderate to high quality grade (with the exception of sleep disorders), allowing plain English clinical messages to be developed. CONCLUSIONS: Among children with cerebral palsy, 3 in 4 were in pain; 1 in 2 had an intellectual disability; 1 in 3 could not walk; 1 in 3 had a hip displacement; 1 in 4 could not talk; 1 in 4 had epilepsy; 1 in 4 had a behavior disorder; 1 in 4 had bladder control problems; 1 in 5 had a sleep disorder; 1 in 5 dribbled; 1 in 10 were blind; 1 in 15 were tube-fed; and 1 in 25 were deaf.

The role of the generalist teacher is now affirmed as being an important component in the success or otherwise of inclusive education practice. Issues about the effectiveness of teacher preparation for working in inclusive classes have arisen. An evaluation of pre-service teachers' perceptions regarding their preparedness for inclusion had some interesting findings. The study found that increasing knowledge about legislation and policy related to inclusion, and improving levels of confidence in becoming inclusive teachers, did not likewise address their concerns, or perceived stress, about having students with disabilities in their classes. As universities re-evaluate their teacher preparation courses, a range of pertinent issues are identified that require consideration.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a lifetime risk of one in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. The combination of all ALS-associated signals reveals a role for perturbations in vesicle-mediated transport and autophagy and provides evidence for cell-autonomous disease initiation in glutamatergic neurons.

OBJECTIVE: Systematic reviews of randomized, controlled trials (RCTs) indicate lower mortality and necrotizing enterocolitis (NEC) and shorter time to full feeds after probiotic supplementation in preterm (<34 weeks' gestation) very low birth weight (VLBW; birth weight <1500 g) neonates. The objective of this study was to update our 2007 systematic review of RCTs of probiotic supplementation for preventing NEC in preterm VLBW neonates. METHODS: We searched in March 2009 the Cochrane Central register; Medline, Embase, and Cinahl databases; and proceedings of the Pediatric Academic Society meetings and gastroenterology conferences. Cochrane Neonatal Review Group search strategy was followed. Selection criteria were RCTs of any enteral probiotic supplementation that started within first 10 days and continued for > or =7 days in preterm VLBW neonates and reported on stage 2 NEC or higher (Modified Bell Staging). RESULTS: A total of 11 (N = 2176), including 4 new (n = 783), trials were eligible for inclusion in the meta-analysis by using a fixed-effects model. The risk for NEC and death was significantly lower. Risk for sepsis did not differ significantly. No significant adverse effects were reported. Trial sequential analysis) showed 30% reduction in the incidence of NEC (alpha = .05 and .01; power: 80%). CONCLUSIONS: The results confirm the significant benefits of probiotic supplements in reducing death and disease in preterm neonates. The dramatic effect sizes, tight confidence intervals, extremely low P values, and overall evidence indicate that additional placebo-controlled trials are unnecessary if a suitable probiotic product is available.

This research examined factors associated with Internet addiction in adolescence using a population-based cross-sectional survey with self-reported questionnaires. Participants were recruited from high school students, ages 13 to 18 years, registered on the secondary school registry in Guangzhou city using a stratified random sampling technique. Internet addiction was assessed using the Internet Addiction Test (IAT). Information was also collected on demographics, health behaviors, and perception of personal condition. Depression was assessed by the Zung Self-Rating Depression Scale. The majority of respondents were classified as normal users of the Internet (n = 1,392, 89.2%), with 158 (10.2%) moderately and 10 (0.6%) severely addicted to the Internet. Results from the multivariate logistic regression analyses suggested a 50% increased odds for males to be addicted to the Internet (OR = 1.5, 95% CI = 1.1-2.2) when compared to females. Other potential risk factors included drinking behavior (OR = 1.7, 95% CI = 1.1-2.8), family dissatisfaction (OR = 2.4, 95% CI = 1.3-4.3), and experience of recent stressful events (OR = 10.0, 95% CI = 6.5-12.2). Stress-related variables were associated with Internet addiction among adolescents as they are also related to other addictions. Clinicians need to be aware of potential comorbidities of other problems such as stress and family dissatisfaction among adolescent Internet addiction patients.

BACKGROUND: This is an updated version of the original Cochrane review published in 2010, Issue 9. Non-invasive brain stimulation techniques aim to induce an electrical stimulation of the brain in an attempt to reduce chronic pain by directly altering brain activity. They include repetitive transcranial magnetic stimulation (rTMS), cranial electrotherapy stimulation (CES), transcranial direct current stimulation (tDCS) and reduced impedance non-invasive cortical electrostimulation (RINCE). OBJECTIVES: To evaluate the efficacy of non-invasive brain stimulation techniques in chronic pain. SEARCH METHODS: We searched CENTRAL (2013, Issue 6), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS and clinical trials registers. The original search for the review was run in November 2009 and searched all databases from their inception. To identify studies for inclusion in this update we searched from 2009 to July 2013. SELECTION CRITERIA: Randomised and quasi-randomised studies of rTMS, CES, tDCS or RINCE if they employed a sham stimulation control group, recruited patients over the age of 18 with pain of three months duration or more and measured pain as a primary outcome. DATA COLLECTION AND ANALYSIS: Two authors independently extracted and verified data. Where possible we entered data into meta-analyses. We excluded studies judged as being at high risk of bias from the analysis. We used the GRADE system to summarise the quality of evidence for core comparisons. MAIN RESULTS: We included an additional 23 trials (involving 773 participants randomised) in this update, making a total of 56 trials in the review (involving 1710 participants randomised). This update included a total of 30 rTMS studies, 11 CES, 14 tDCS and one study of RINCE(the original review included 19 rTMS, eight CES and six tDCS studies). We judged only three studies as being at low risk of bias across all criteria.Meta-analysis of studies of rTMS (involving 528 participants) demonstrated significant heterogeneity. Pre-specified subgroup analyses suggest that low-frequency stimulation is ineffective (low-quality evidence) and that rTMS applied to the dorsolateral prefrontal cortex is ineffective (very low-quality evidence). We found a short-term effect on pain of active high-frequency stimulation of the motor cortex in single-dose studies (low-quality evidence, standardised mean difference (SMD) 0.39 (95% confidence interval (CI) -0.27 to -0.51 P < 0.01)). This equates to a 12% (95% CI 8% to 15%) reduction in pain, which does not exceed the pre-established criteria for a minimal clinically important difference (≥ 15%). Evidence for multiple-dose studies was heterogenous but did not demonstrate a significant effect (very low-quality evidence).For CES (six studies, 270 participants) no statistically significant difference was found between active stimulation and sham (low-quality evidence).Analysis of tDCS studies (11 studies, 193 people) demonstrated significant heterogeneity and did not find a significant difference between active and sham stimulation (very low-quality evidence). Pre-specified subgroup analysis of tDCS applied to the motor cortex (n = 183) did not demonstrate a statistically significant effect and this lack of effect was consistent for subgroups of single or multiple-dose studies.One small study (n = 91) at unclear risk of bias suggested a positive effect of RINCE over sham stimulation on pain (very low-quality evidence).Non-invasive brain stimulation appears to be frequently associated with minor and transient side effects, though there were two reported incidences of seizure related to active rTMS in the included studies. AUTHORS' CONCLUSIONS: Single doses of high-frequency rTMS of the motor cortex may have small short-term effects on chronic pain. It is likely that multiple sources of bias may exaggerate this observed effect. The effects do not meet the predetermined threshold of minimal clinical significance and multiple-dose studies do not consistently demonstrate effectiveness. The available evidence suggests that low-frequency rTMS, rTMS applied to the pre-frontal cortex, CES and tDCS are not effective in the treatment of chronic pain. While the broad conclusions for rTMS and CES have not changed substantially, the addition of this new evidence and the application of the GRADE system has modified some of our interpretation and the conclusion regarding the effectiveness of tDCS has changed. We recommend that previous readers should re-read this update. There is a need for larger, rigorously designed studies, particularly of longer courses of stimulation. It is likely that future evidence may substantially impact upon the presented results.

Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20-105) years and follow up of 2.2 million person-years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI ≥ 30 kg/m(2) ) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non-obese women. Compared to a BMI of 25 kg/m(2) , the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m(2) was 0.87 (95% confidence interval [CI], 0.85-0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09-1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored.

This review summarises current understanding of how bone is sculpted through adaptive processes, designed to meet the mechanical challenges it faces in everyday life and athletic pursuits, serving as an update for clinicians, researchers and physical therapists. Bone's ability to resist fracture under the large muscle and locomotory forces it experiences during movement and in falls or collisions is dependent on its established mechanical properties, determined by bone's complex and multidimensional material and structural organisation. At all levels, bone is highly adaptive to habitual loading, regulating its structure according to components of its loading regime and mechanical environment, inclusive of strain magnitude, rate, frequency, distribution and deformation mode. Indeed, the greatest forces habitually applied to bone arise from muscular contractions, and the past two decades have seen substantial advances in our understanding of how these forces shape bone throughout life. Herein, we also highlight the limitations of in vivo methods to assess and understand bone collagen, and bone mineral at the material or tissue level. The inability to easily measure or closely regulate applied strain in humans is identified, limiting the translation of animal studies to human populations, and our exploration of how components of mechanical loading regimes influence mechanoadaptation.

Importance: Standard treatment for endometrial cancer involves removal of the uterus, tubes, ovaries, and lymph nodes. Few randomized trials have compared disease-free survival outcomes for surgical approaches. Objective: To investigate whether total laparoscopic hysterectomy (TLH) is equivalent to total abdominal hysterectomy (TAH) in women with treatment-naive endometrial cancer. Design, Setting, and Participants: The Laparoscopic Approach to Cancer of the Endometrium (LACE) trial was a multinational, randomized equivalence trial conducted between October 7, 2005, and June 30, 2010, in which 27 surgeons from 20 tertiary gynecological cancer centers in Australia, New Zealand, and Hong Kong randomized 760 women with stage I endometrioid endometrial cancer to either TLH or TAH. Follow-up ended on March 3, 2016. Interventions: Patients were randomly assigned to undergo TAH (n = 353) or TLH (n = 407). Main Outcomes and Measures: The primary outcome was disease-free survival, which was measured as the interval between surgery and the date of first recurrence, including disease progression or the development of a new primary cancer or death assessed at 4.5 years after randomization. The prespecified equivalence margin was 7% or less. Secondary outcomes included recurrence of endometrial cancer and overall survival. Results: Patients were followed up for a median of 4.5 years. Of 760 patients who were randomized (mean age, 63 years), 679 (89%) completed the trial. At 4.5 years of follow-up, disease-free survival was 81.3% in the TAH group and 81.6% in the TLH group. The disease-free survival rate difference was 0.3% (favoring TLH; 95% CI, -5.5% to 6.1%; P = .007), meeting criteria for equivalence. There was no statistically significant between-group difference in recurrence of endometrial cancer (28/353 in TAH group [7.9%] vs 33/407 in TLH group [8.1%]; risk difference, 0.2% [95% CI, -3.7% to 4.0%]; P = .93) or in overall survival (24/353 in TAH group [6.8%] vs 30/407 in TLH group [7.4%]; risk difference, 0.6% [95% CI, -3.0% to 4.2%]; P = .76). Conclusions and Relevance: Among women with stage I endometrial cancer, the use of total abdominal hysterectomy compared with total laparoscopic hysterectomy resulted in equivalent disease-free survival at 4.5 years and no difference in overall survival. These findings support the use of laparoscopic hysterectomy for women with stage I endometrial cancer. Trial Registration: clinicaltrials.gov Identifier: NCT00096408; Australian New Zealand Clinical Trials Registry: CTRN12606000261516.

BACKGROUND AND OBJECTIVES: Studies reporting an association between hearing loss and depression in older adults are conflicting and warrant a systematic review and meta-analysis of the evidence. RESEARCH DESIGN AND METHODS: A search of academic databases (e.g., MEDLINE) and gray literature (e.g., OpenGrey) identified relevant articles published up to July 17, 2018. Cross-sectional or cohort designs were included. Outcome effects were computed as odds ratios (ORs) and pooled using random-effects meta-analysis (PROSPERO: CRD42018084494). RESULTS: A total of 147,148 participants from 35 studies met inclusion criteria. Twenty-four studies were cross-sectional and 11 were cohort designs. Overall, hearing loss was associated with statistically significantly greater odds of depression in older adults (OR = 1.47, 95% confidence interval [CI] = 1.31-1.65). When studies were stratified by design, hearing loss was associated with greater odds of depression in cross-sectional studies (OR = 1.54, 95% CI = 1.31-1.80) and cohort studies (OR = 1.39, 95% CI = 1.16 - 1.67), and there was no difference between cross-sectional or cohort effect estimates (Q = 0.64, p = .42). There was no effect of moderator variables (i.e., hearing aid use) on the association between hearing loss and depression, but these findings must be interpreted with caution. There was no presence of publication bias but certainty in the estimation of the overall effect was classified as "low." DISCUSSION AND IMPLICATIONS: Older adults may experience increased odds of depression associated with hearing loss, and this association may not be influenced by study or participant characteristics.

This is the first meta-analysis of the pooled prevalence of insomnia in the general population of China. A systematic literature search was conducted via the following databases: PubMed, PsycINFO, EMBASE and Chinese databases (China National Knowledge Interne (CNKI), WanFang Data and SinoMed). Statistical analyses were performed using the Comprehensive Meta-Analysis program. A total of 17 studies with 115,988 participants met the inclusion criteria for the analysis. The pooled prevalence of insomnia in China was 15.0% (95% Confidence interval [CI]: 12.1%-18.5%). No significant difference was found in the prevalence between genders or across time period. The pooled prevalence of insomnia in population with a mean age of 43.7 years and older (11.6%; 95% CI: 7.5%-17.6%) was significantly lower than in those with a mean age younger than 43.7 years (20.4%; 95% CI: 14.2%-28.2%). The prevalence of insomnia was significantly affected by the type of assessment tools (Q = 14.1, P = 0.001). The general population prevalence of insomnia in China is lower than those reported in Western countries but similar to those in Asian countries. Younger Chinese adults appear to suffer from more insomnia than older adults. TRIAL REGISTRATION: CRD 42016043620.