South Eastern Sydney Local Health District

IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

OBJECTIVE: To determine the prevalence of impaired vision, peripheral sensation, lower limb muscle strength, reaction time, and balance in a large community-dwelling population of women aged 65 years and over, and to determine whether impaired performances in these tests are associated with falls. DESIGN: One-year prospective study. SETTING: Conducted as part of the Randwick Falls and Fractures Study, in Sydney, Australia. PARTICIPANTS: Four hundred fourteen women aged 65 to 99 years (mean age 73.7 years, SD = 6.3) were randomly selected from the community; 341 of these women were included in the 1-year prospective study. MAIN RESULTS: The prevalence of impairment in all tests increased with age. In the year following assessment, 207 subjects (60.7%) experienced no falls, 63 subjects (18.5%) fell one time only, and 71 subjects (20.8%) fell on two or more occasions. After controlling for age, multiple falling was associated with low contrast visual acuity and contrast sensitivity, poor vibration sense and proprioception, reduced lower limb strength, slow reaction time, and impaired balance, as indicated by four sway tests and two clinical stability measures. Discriminant function analysis identified visual contrast sensitivity, proprioception in the lower limbs, quadriceps strength, reaction time, and sway on a compliant (foam rubber) surface with the eyes open as the variables that significantly discriminated between subjects who experienced multiple falls and subjects who experienced no falls or one fall only (Wilks' lambda = 0.73 (P < 0.001), canonical correlation = 0.52). This procedure correctly classified 75% of subjects into multiple faller or nonmultiple faller groups. CONCLUSIONS: These findings support previous results conducted in retirement village and institutional setting and indicate that the test procedure aids in the identification of older community-dwelling women at risk of falls.

PURPOSE: Oral Morphine Equivalent (OME) doses are increasingly being used as a metric to represent opioid use. Driven by a growing need from pharmacoepidemiological studies, the objective of this study was to develop a comprehensive OME conversion table that can be used by researchers to calculate OMEs in a consistent and systematic way. METHODS: Clinical guidelines and literature sources were collated and synthesised to develop recommended OME conversion factors that can be used for research studies on opioids (including different formulations and routes of administration) currently available internationally including Australia, the United Kingdom, Europe, the United States and Canada. RESULTS: No single resource includes all opioids that are currently available. Although there was some variation in conversion factors reported in different sources, overall, suggested conversion factors were mostly consistent across national and international sources. CONCLUSIONS: The use of the OME metric appears optimal for opioid utilisation studies as it facilities both interpretation and comparison between opioids and geographical locations. We have presented a synthesis of published OME conversion factors that can be applied to pharmacoepidemiological studies of opioids, in addition to a discussion of the considerations and caveats in using OME as a metric for opioid use. Copyright © 2015 John Wiley & Sons, Ltd.

OBJECTIVE: To determine whether a 12-month program of regular exercise can improve balance, reaction time, neuromuscular control, and muscle strength and reduce the rate of falling in older women. DESIGN: A randomized, controlled trial of 12 months duration. SETTING: Conducted as part of the Randwick Falls and Fractures Study in Sydney, Australia. PARTICIPANTS: One hundred ninety-seven women aged 60 to 85 years (mean age 71.6, SD = 5.4) who were randomly recruited from the community. OUTCOME MEASURES: Accidental falls, postural sway, reaction time, neuromuscular control, and lower limb muscle strength. MAIN RESULTS: Exercise and control subjects were tested before, midway through, and at the end of the trial. At initial testing, exercisers and controls performed similarly in all tests and were well matched in relevant health and lifestyle factors. The mean number of classes attended for the 75 exercise subjects who completed the program was 60.0 (range 26-82). At the end of the trial, the exercise subjects showed improved performance in all five strength measures, in reaction time, neuromuscular control, body sway on a firm surface with the eyes open, and body sway on a compliant surface with the eyes open and closed. In contrast, there were no significant improvements in any of the test measures in the controls. In one test measure, hip flexion strength, the exercisers showed continued improvement throughout the study year. There was no significant difference in the proportion of fallers between the exercise and control subjects. Interesting trends were evident, however, between falls frequency and adherence to the exercise program. CONCLUSIONS: These findings show that exercise can produce long-term benefits with regard to improving sensorimotor function in older persons. The findings also suggest that high compliance to an exercise program may reduce falls frequency, although further studies are required to conclusively demonstrate that exercise offers an effective means of preventing falls.

OBJECTIVE: This study aimed to report on the trends in incidence and prevalence rates of diabetes mellitus in Saudi Arabia over the last 25 years (1990-2015). DESIGN: A descriptive review. METHODS: A systematic search was conducted for English-language, peer reviewed publications of any research design via Medline, EBSCO, PubMed and Scopus from 1990 to 2015. Of 106 articles retrieved, after removal of duplicates and quality appraisal, 8 studies were included in the review and synthesised based on study characteristics, design and findings. FINDINGS: Studies originated from Saudi Arabia and applied a variety of research designs and tools to diagnosis diabetes. Of the 8 included studies; three reported type 1 diabetes and five on type 2 diabetes. Overall, findings indicated that the incidence and prevalence rate of diabetes is rising particularly among females, older children/adolescent and in urban areas. CONCLUSION: Further development are required to assess the health intervention, polices, guidelines, self-management programs in Saudi Arabia.

This paper presents the results of a qualitative study conducted by midwife researchers into women's experience of new motherhood. Data were collected using focus groups involving 55 first-time mothers and analysed using grounded theory method. The analysis produced six categories: 'realizing', 'unready', 'drained', 'aloneness', 'loss' and 'working it out'. The core category, 'becoming a mother', integrates all other categories and encapsulates the process of change experienced by women. Also explained are factors mediating the often distressing experience of becoming a mother. The analysis provides a conceptualization of early motherhood enabling the development of strategies for midwives, nurses and other helping women negotiate this challenge.

The PI3K/Akt/mTOR pathway has a central role in cancer metastasis and radiotherapy. To develop effective therapeutics to improve radiosensitivity, understanding the possible pathways of radioresistance involved and the effects of a combination of the PI3K/Akt/mTOR inhibitors with radiotherapy on prostate cancer (CaP) radioresistant cells is needed. We found that compared with parent CaP cells, CaP-radioresistant cells demonstrated G0/G1 and S phase arrest, activation of cell cycle check point, autophagy and DNA repair pathway proteins, and inactivation of apoptotic proteins. We also demonstrated that compared with combination of single PI3K or mTOR inhibitors (BKM120 or Rapamycin) and radiation, low-dose of dual PI3K/mTOR inhibitors (BEZ235 or PI103) combined with radiation greatly improved treatment efficacy by repressing colony formation, inducing more apoptosis, leading to the arrest of the G2/M phase, increased double-strand break levels and less inactivation of cell cycle check point, autophagy and non-homologous end joining (NHEJ)/homologous recombination (HR) repair pathway proteins in CaP-radioresistant cells. This study describes the possible pathways associated with CaP radioresistance and demonstrates the putative mechanisms of the radiosensitization effect in CaP-resistant cells in the combination treatment. The findings from this study suggest that the combination of dual PI3K/Akt/mTOR inhibitors (BEZ235 or PI103) with radiotherapy is a promising modality for the treatment of CaP to overcome radioresistance.

OBJECTIVES: Gonorrhoea and MDR Neisseria gonorrhoeae remain public health concerns globally. Enhanced, quality-assured, gonococcal antimicrobial resistance (AMR) surveillance is essential worldwide. The WHO global Gonococcal Antimicrobial Surveillance Programme (GASP) was relaunched in 2009. We describe the phenotypic, genetic and reference genome characteristics of the 2016 WHO gonococcal reference strains intended for quality assurance in the WHO global GASP, other GASPs, diagnostics and research worldwide. METHODS: The 2016 WHO reference strains (n = 14) constitute the eight 2008 WHO reference strains and six novel strains. The novel strains represent low-level to high-level cephalosporin resistance, high-level azithromycin resistance and a porA mutant. All strains were comprehensively characterized for antibiogram (n = 23), serovar, prolyliminopeptidase, plasmid types, molecular AMR determinants, N. gonorrhoeae multiantigen sequence typing STs and MLST STs. Complete reference genomes were produced using single-molecule PacBio sequencing. RESULTS: The reference strains represented all available phenotypes, susceptible and resistant, to antimicrobials previously and currently used or considered for future use in gonorrhoea treatment. All corresponding resistance genotypes and molecular epidemiological types were described. Fully characterized, annotated and finished references genomes (n = 14) were presented. CONCLUSIONS: The 2016 WHO gonococcal reference strains are intended for internal and external quality assurance and quality control in laboratory investigations, particularly in the WHO global GASP and other GASPs, but also in phenotypic (e.g. culture, species determination) and molecular diagnostics, molecular AMR detection, molecular epidemiology and as fully characterized, annotated and finished reference genomes in WGS analysis, transcriptomics, proteomics and other molecular technologies and data analysis.

BACKGROUND: Severe mental illness (SMI) is thought to be associated with lower diet quality and adverse eating behaviours contributing towards physical health disparities. A rigorous review of the studies looking at dietary intake in psychotic disorders and bipolar disorder is lacking.AimsTo conduct a systematic, comprehensive evaluation of the published research on dietary intake in psychotic disorders and bipolar disorder. METHOD: Six electronic databases were searched for studies reporting on dietary intakes in psychotic disorders and bipolar disorder. Dietary-assessment methods, and dietary intakes, were systematically reviewed. Where possible, data was pooled for meta-analysis and compared with healthy controls. RESULTS: In total, 58 eligible studies were identified. People with SMI were found to have significantly higher dietary energy (mean difference 1332 kJ, 95% CI 487-2178 kJ/day, P = 0.002, g = 0.463) and sodium (mean difference 322 mg, 95% CI 174-490 mg, P &lt; 0.001, g = 0.414) intake compared with controls. Qualitative synthesis suggested that higher energy and sodium intakes were associated with poorer diet quality and eating patterns. CONCLUSIONS: These dietary components should be key targets for preventative interventions to improve weight and other physical health outcomes in people with SMI.Declaration of interestS.B.T. and E.T. have clinical dietitian appointments within the South Eastern Sydney Local Health District and do not receive any further funding.

This paper describes the methodological and theoretical context and underpinnings of a study that examined community psychiatric nurses' work with family caregivers of older people with depression. The study used grounded theory research methods, with its theoretical foundations drawn from symbolic interactionism. The aims of the study were to describe and conceptualize the processes involved when community nurses work and interact with family caregivers and to develop an explanatory theory of these processes. This paper begins with an explanation of the rationale for using grounded theory as the method of choice, followed by a discussion of the theoretical underpinnings of the study, including a brief summary of the nature and origins of symbolic interactionism. Key premises of symbolic interactionism regarded as central to the study are outlined and an analytical overview of the grounded theory method is provided. The paper concludes with a commentary on some of the issues and debates in the use of grounded theory in nursing research. The main purpose of this paper is to provide a methodical and critical review of symbolic interactionism and grounded theory that can help readers, particularly those who are intending to use grounded theory, better understand the processes involved in applying this method to their research.

Norovirus (NoV) is the leading cause of viral gastroenteritis globally. Since 1996, NoV variants of a single genetic lineage, GII.4, have been associated with at least six pandemics of acute gastroenteritis and caused between 62 and 80% of all NoV outbreaks. The emergence of these novel GII.4 variants has been attributed to rapid evolution and antigenic variation in response to herd immunity; however, the contribution of recombination as a mechanism facilitating emergence is increasingly evident. In this study, we sought to examine the role that intragenotype recombination has played in the emergence of GII.4 variants. Using a genome-wide approach including 25 complete genome sequences generated as part of this study, 11 breakpoints were identified within the NoV GII.4 lineage. The breakpoints were located at three recombination hot spots: near the open reading frame 1/2 (ORF1/2) and ORF2/3 overlaps, as well as within ORF2, which encodes the viral capsid, at the junction of the shell and protruding domains. Importantly, we show that recombination contributed to the emergence of the recent pandemic GII.4 variant, New Orleans 2009, and a newly identified GII.4 variant, termed Sydney 2012. Reconstructing the evolutionary history of the GII.4 lineage reveals the widespread impact of both inter- and intragenotype recombination on the emergence of many GII.4 variants. Lastly, this study highlights the many challenges in the identification of true recombination events and proposes that guidelines be applied for identifying NoV recombinants.

The impact of COVID-19 across health services, including treatment services for people who use drugs, is emerging but likely to have a high impact. Treatment services for people who use drugs provide essential treatment services including opiate agonist treatment and needle syringe programmes alongside other important treatment programmes across all substance types including withdrawal and counselling services. Drug and alcohol hospital consultation-liaison clinicians support emergency departments and other services provided in hospital settings in efficiently managing patients who use drugs and present with other health problems.COVID-19 will impact on staff availability for work due to illness. Patients may require home isolation and quarantine periods. Ensuring ongoing supply of opiate treatment during these periods will require significant changes to how treatment is provided. The use of monthly depot buprenorphine as well as moving from a framework of supervised dosing will be required for patients on sublingual buprenorphine and methadone. Ensuring ready access to take-home naloxone for patients is crucial to reduce overdose risks. Delivery of methadone and buprenorphine to the homes of people with confirmed COVID-19 infections is likely to need to occur to support home isolation.People who use drugs are likely to be more vulnerable during the COVID-19 epidemic, due to poorer health literacy and stigma and discrimination towards this group. People who use drugs may prioritise drug use above other health concerns. Adequate supply of clean injecting equipment is important to prevent outbreaks of blood-borne viruses. Opiate users may misinterpret SARS-CoV2 symptoms as opiate withdrawal and manage this by using opioids. Ensuring people who use drugs have access to drug treatment as well as access to screening and testing for SARS-CoV2 where this is indicated is important.

For most men, first-time fatherhood involves significant changes in self-identity and their relationship with their female partner. This paper presents some findings from a longitudinal, qualitative study into the first 6 months of new fatherhood for a group of 15 Australian men. The discussion draws on a series of semistructured interviews undertaken on a minimum of four occasions from a few days before the child was born until 5-6 months after birth. We found that first-time fathering in contemporary western society requires men to be simultaneously provider, guide, household help and nurturer. The demands of these roles, and the tensions they sometimes produce, challenge men's relationships with their female partners, the meaning and place of work in their lives and their sense of self as competent adults. Almost all the men we interviewed found the early weeks and months of fatherhood more uncomfortable than rewarding, despite looking forward to fatherhood very positively. Their experience appeared more closely aligned to their difficulties with meeting social expectations and roles rather than individual deficits.

IMPORTANCE: There are no medications approved for treating cannabis dependence or withdrawal. The cannabis extract nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal. OBJECTIVE: To evaluate the safety and efficacy of nabiximols in treating cannabis withdrawal. DESIGN, SETTING, AND PARTICIPANTS: A 2-site, double-blind randomized clinical inpatient trial with a 28-day follow-up was conducted in New South Wales, Australia. Participants included 51 DSM-IV-TR cannabis-dependent treatment seekers. INTERVENTIONS: A 6-day regimen of nabiximols (maximum daily dose, 86.4 mg of Δ9-tetrahydrocannabinol and 80 mg of cannabidiol) or placebo with standardized psychosocial interventions during a 9-day admission. MAIN OUTCOMES AND MEASURES: Severity of cannabis withdrawal and cravings (Cannabis Withdrawal Scale), retention in withdrawal treatment, and adverse events. Secondary outcomes include postwithdrawal cannabis use, health outcomes, and psychosocial outcomes. RESULTS: Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal relative to placebo (F8,377.97 = 2.39; P = .01), including effects on withdrawal-related irritability, depression, and cannabis cravings. Nabiximols had a more limited, but still positive, therapeutic benefit on sleep disturbance, anxiety, appetite loss, physical symptoms, and restlessness. Nabiximols patients remained in treatment longer during medication use (unadjusted hazard ratio, 3.66 [95% CI, 1.18-11.37]; P = .02), with 2.84 the number needed to treat to achieve successful retention in treatment. Participants could not reliably differentiate between nabiximols and placebo treatment (χ21 = 0.79; P = .67), and those receiving nabiximols did not report greater intoxication (F1,6 = 0.22; P = .97). The number (F1,50 = 0.3; P = .59) and severity (F1,50 = 2.69; P = .10) of adverse events did not differ significantly between groups. Both groups showed reduced cannabis use at follow-up, with no advantage of nabiximols over placebo for self-reported cannabis use (F1,48 = 0.29; P = .75), cannabis-related problems (F1,49 = 2.33; P = .14), or cannabis dependence (F1,50 < 0.01; P = .89). CONCLUSIONS AND RELEVANCE: In a treatment-seeking cohort, nabiximols attenuated cannabis withdrawal symptoms and improved patient retention in treatment. However, placebo was as effective as nabiximols in promoting long-term reductions in cannabis use following medication cessation. The data support further evaluation of nabiximols for management of cannabis dependence and withdrawal in treatment-seeking populations. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12611000398909.

OBJECTIVES: To compare treatment of acute illness at home and in hospital, assessing safety, effect on geriatric complications, and patient/carer satisfaction. DESIGN: Randomised controlled trial. SETTING: A tertiary referral hospital affiliated with the University of New South Wales. PARTICIPANTS: 100 patients (69% older than 65 years) with a variety of acute conditions, who were assessed in the emergency department as requiring admission to hospital. INTERVENTIONS: Patients were allocated at random to be treated by a hospital-in-the-home (HIH) service in their usual residence or to be admitted to hospital. MAIN OUTCOME MEASURES: Geriatric complications (confusion, falls, urinary incontinence or retention, faecal incontinence or constipation, phlebitis and pressure areas), patient/carer satisfaction, adverse events, and death. RESULTS: There was a lower incidence of confusion (0 v. 20.4% [95% CI, 9.1%-31.7%]; P = 0.0005), urinary complications (incontinence or retention) (2.0% [95% CI, -1.8%, 5.8%] v. 16.3% [95% CI, 6.0%, 26.6%]; P = 0.01), and bowel complications (incontinence or constipation) (0 v. 22.5% [95% CI, 10.7%, 34.1%]; P = 0.0003) among HIH-treated patients. No significant difference in number of adverse events and deaths (to 28 days after discharge) in the two groups was found (although numbers were small). Patient and carer satisfaction was significantly higher in the HIH group. CONCLUSIONS: Home treatment appears to provide a safe alternative to hospitalisation for selected patients, and may be preferable for some older patients. We found high levels of both patient and carer satisfaction with home treatment.

BACKGROUND: There are increasing concerns regarding pharmaceutical opioid harms including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin. OBJECTIVES: To assess the effects of maintenance agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence. SEARCH METHODS: The search included the Cochrane Drugs and Alcohol Group's Specialised Register of Trials; the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 5); PubMed (January 1966 to May 2015); EMBASE (Ovid) (January 1974 to May 2015); CINAHL (EBSCOhost) (1982 to May 2015); ISI Web of Science (to May 2014); and PsycINFO (Ovid) (1806 to May 2014). SELECTION CRITERIA: We included randomised controlled trials examining maintenance opioid agonist treatments that made the following two comparisons:1. full opioid agonists (methadone, morphine, oxycodone, levo-alpha-acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment and2. full or partial opioid agonist maintenance versus placebo, detoxification only, or psychological treatment (without opioid agonist treatment). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: We identified six randomised controlled trials that met inclusion criteria (607 participants).We found moderate quality evidence from two studies of no difference between methadone and buprenorphine in self reported opioid use (risk ratio (RR) 0.37, 95% confidence interval (CI) 0.08 to 1.63) or opioid positive urine drug tests (RR 0.81, 95% CI 0.56 to 1.18). There was low quality evidence from three studies of no difference in retention between buprenorphine and methadone maintenance treatment (RR 0.69, 95% CI 0.39 to 1.22). There was moderate quality evidence from two studies of no difference between methadone and buprenorphine on adverse events (RR 1.10, 95% CI 0.64 to 1.91).We found low quality evidence from three studies favouring maintenance buprenorphine treatment over detoxification or psychological treatment in terms of fewer opioid positive urine drug tests (RR 0.63, 95% CI 0.43 to 0.91) and self reported opioid use in the past 30 days (RR 0.54, 95% CI 0.31 to 0.93). There was no difference on days of unsanctioned opioid use (standardised mean difference (SMD) -0.31, 95% CI -0.66 to 0.04). There was moderate quality evidence favouring buprenorphine maintenance over detoxification or psychological treatment on retention in treatment (RR 0.33, 95% CI 0.23 to 0.47). There was moderate quality evidence favouring buprenorphine maintenance over detoxification or psychological treatment on adverse events (RR 0.19, 95% CI 0.06 to 0.57).The main weaknesses in the quality of the data was the use of open-label study designs. AUTHORS' CONCLUSIONS: There was low to moderate quality evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine appeared equally effective. Maintenance treatment with buprenorphine appeared more effective than detoxification or psychological treatments.Due to the overall low to moderate quality of the evidence and small sample sizes, there is the possibility that the further research may change these findings.

A multidrug-resistant Escherichia coli isolate recovered in Australia produced a carbapenem-hydrolyzing β-lactamase. Molecular investigations revealed the first identification of the bla(NDM-1) metallo-β-lactamase gene in that country. In addition, this E. coli isolate expressed the extended-spectrum β-lactamase CTX-M-15, together with two 16S rRNA methylases, namely, ArmA and RmtB, conferring a high level of resistance to aminoglycosides.

BACKGROUND: Virtual-reality based rehabilitation (VR) shows potential as an engaging and effective way to improve upper-limb function and cognitive abilities following a stroke. However, an updated synthesis of the literature is needed to capture growth in recent research and address gaps in our understanding of factors that may optimize training parameters and treatment effects. METHODS: Published randomized controlled trials comparing VR to conventional therapy were retrieved from seven electronic databases. Treatment effects (Hedge's g) were estimated using a random effects model, with motor and functional outcomes between different protocols compared at the Body Structure/Function, Activity, and Participation levels of the International Classification of Functioning. RESULTS: Thirty-three studies were identified, including 971 participants (492 VR participants). VR produced small to medium overall effects (g = 0.46; 95% CI: 0.33-0.59, p < 0.01), above and beyond conventional therapies. Small to medium effects were observed on Body Structure/Function (g = 0.41; 95% CI: 0.28-0.55; p < 0.01) and Activity outcomes (g = 0.47; 95% CI: 0.34-0.60, p < 0.01), while Participation outcomes failed to reach significance (g = 0.38; 95% CI: -0.29-1.04, p = 0.27). Superior benefits for Body Structure/Function (g = 0.56) and Activity outcomes (g = 0.62) were observed when examining outcomes only from purpose-designed VR systems. Preliminary results (k = 4) suggested small to medium effects for cognitive outcomes (g = 0.41; 95% CI: 0.28-0.55; p < 0.01). Moderator analysis found no advantage for higher doses of VR, massed practice training schedules, or greater time since injury. CONCLUSION: VR can effect significant gains on Body Structure/Function and Activity level outcomes, including improvements in cognitive function, for individuals who have sustained a stroke. The evidence supports the use of VR as an adjunct for stroke rehabilitation, with effectiveness evident for a variety of platforms, training parameters, and stages of recovery.

Congenital CMV infection is a leading cause of childhood disability. Many children born with congenital CMV infection are asymptomatic or have nonspecific symptoms and therefore are typically not diagnosed. A strategy of newborn CMV screening could allow for early detection and intervention to improve clinical outcomes. Interventions might include antiviral drugs or nonpharmaceutical therapies such as speech-language therapy or cochlear implants. Using published data from developed countries, we analyzed existing evidence of potential benefit that could result from newborn CMV screening. We first estimated the numbers of children with the most important CMV-related disabilities (i.e. hearing loss, cognitive deficit, and vision impairment), including the age at which the disabilities occur. Then, for each of the disabilities, we examined the existing evidence for the effectiveness of various interventions. We concluded that there is good evidence of potential benefit from nonpharmaceutical interventions for children with delayed hearing loss that occurs by 9 months of age. Similarly, we concluded that there is fair evidence of potential benefit from antiviral therapy for children with hearing loss at birth and from nonpharmaceutical interventions for children with delayed hearing loss occurring between 9 and 24 months of age and for children with CMV-related cognitive deficits. We found poor evidence of potential benefit for children with delayed hearing loss occurring after 24 months of age and for children with vision impairment. Overall, we estimated that in the United States, several thousand children with congenital CMV could benefit each year from newborn CMV screening, early detection, and interventions.

BACKGROUND: Interest in the use of cannabis and cannabinoids to treat chronic non-cancer pain is increasing, because of their potential to reduce opioid dose requirements. We aimed to investigate cannabis use in people living with chronic non-cancer pain who had been prescribed opioids, including their reasons for use and perceived effectiveness of cannabis; associations between amount of cannabis use and pain, mental health, and opioid use; the effect of cannabis use on pain severity and interference over time; and potential opioid-sparing effects of cannabis. METHODS: The Pain and Opioids IN Treatment study is a prospective, national, observational cohort of people with chronic non-cancer pain prescribed opioids. Participants were recruited through community pharmacies across Australia, completed baseline interviews, and were followed up with phone interviews or self-complete questionnaires yearly for 4 years. Recruitment took place from August 13, 2012, to April 8, 2014. Participants were asked about lifetime and past year chronic pain conditions, duration of chronic non-cancer pain, pain self-efficacy, whether pain was neuropathic, lifetime and past 12-month cannabis use, number of days cannabis was used in the past month, and current depression and generalised anxiety disorder. We also estimated daily oral morphine equivalent doses of opioids. We used logistic regression to investigate cross-sectional associations with frequency of cannabis use, and lagged mixed-effects models to examine temporal associations between cannabis use and outcomes. FINDINGS: 1514 participants completed the baseline interview and were included in the study from Aug 20, 2012, to April 14, 2014. Cannabis use was common, and by 4-year follow-up, 295 (24%) participants had used cannabis for pain. Interest in using cannabis for pain increased from 364 (33%) participants (at baseline) to 723 (60%) participants (at 4 years). At 4-year follow-up, compared with people with no cannabis use, we found that participants who used cannabis had a greater pain severity score (risk ratio 1·14, 95% CI 1·01-1·29, for less frequent cannabis use; and 1·17, 1·03-1·32, for daily or near-daily cannabis use), greater pain interference score (1·21, 1·09-1·35; and 1·14, 1·03-1·26), lower pain self-efficacy scores (0·97, 0·96-1·00; and 0·98, 0·96-1·00), and greater generalised anxiety disorder severity scores (1·07, 1·03-1·12; and 1·10, 1·06-1·15). We found no evidence of a temporal relationship between cannabis use and pain severity or pain interference, and no evidence that cannabis use reduced prescribed opioid use or increased rates of opioid discontinuation. INTERPRETATION: Cannabis use was common in people with chronic non-cancer pain who had been prescribed opioids, but we found no evidence that cannabis use improved patient outcomes. People who used cannabis had greater pain and lower self-efficacy in managing pain, and there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect. As cannabis use for medicinal purposes increases globally, it is important that large well designed clinical trials, which include people with complex comorbidities, are conducted to determine the efficacy of cannabis for chronic non-cancer pain. FUNDING: National Health and Medical Research Council and the Australian Government.