St Vincent's Health

CONTEXT: Many observational studies have shown that physical activity reduces the risk of cognitive decline; however, evidence from randomized trials is lacking. OBJECTIVE: To determine whether physical activity reduces the rate of cognitive decline among older adults at risk. DESIGN AND SETTING: Randomized controlled trial of a 24-week physical activity intervention conducted between 2004 and 2007 in metropolitan Perth, Western Australia. Assessors of cognitive function were blinded to group membership. PARTICIPANTS: We recruited volunteers who reported memory problems but did not meet criteria for dementia. Three hundred eleven individuals aged 50 years or older were screened for eligibility, 89 were not eligible, and 52 refused to participate. A total of 170 participants were randomized and 138 participants completed the 18-month assessment. INTERVENTION: Participants were randomly allocated to an education and usual care group or to a 24-week home-based program of physical activity. MAIN OUTCOME MEASURE: Change in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores (possible range, 0-70) over 18 months. RESULTS: In an intent-to-treat analysis, participants in the intervention group improved 0.26 points (95% confidence interval, -0.89 to 0.54) and those in the usual care group deteriorated 1.04 points (95% confidence interval, 0.32 to 1.82) on the ADAS-Cog at the end of the intervention. The absolute difference of the outcome measure between the intervention and control groups was -1.3 points (95% confidence interval,-2.38 to -0.22) at the end of the intervention. At 18 months, participants in the intervention group improved 0.73 points (95% confidence interval, -1.27 to 0.03) on the ADAS-Cog, and those in the usual care group improved 0.04 points (95% confidence interval, -0.46 to 0.88). Word list delayed recall and Clinical Dementia Rating sum of boxes improved modestly as well, whereas word list total immediate recall, digit symbol coding, verbal fluency, Beck depression score, and Medical Outcomes 36-Item Short-Form physical and mental component summaries did not change significantly. CONCLUSIONS: In this study of adults with subjective memory impairment, a 6-month program of physical activity provided a modest improvement in cognition over an 18-month follow-up period. TRIAL REGISTRATION: anzctr.org.au Identifier: ACTRN12605000136606.

Psychiatric comorbidities are common among patients with schizophrenia. Substance abuse comorbidity predominates. Anxiety and depressive symptoms are also very common throughout the course of illness, with an estimated prevalence of 15% for panic disorder, 29% for posttraumatic stress disorder, and 23% for obsessive-compulsive disorder. It is estimated that comorbid depression occurs in 50% of patients, and perhaps (conservatively) 47% of patients also have a lifetime diagnosis of comorbid substance abuse. This article chronicles these associations, examining whether these comorbidities are "more than chance" and might represent (distinct) phenotypes of schizophrenia. Among the anxiety disorders, the evidence at present is most abundant for an association with obsessive-compulsive disorder. Additional studies in newly diagnosed antipsychotic-naive patients and their first-degree relatives and searches for genetic and environmental risk factors are needed to replicate preliminary findings and further investigate these associations.

BACKGROUND: HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults. OBJECTIVE: The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease. METHODS: The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches. RESULTS: The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.

OBJECTIVES: This guideline provides recommendations for the clinical management of schizophrenia and related disorders for health professionals working in Australia and New Zealand. It aims to encourage all clinicians to adopt best practice principles. The recommendations represent the consensus of a group of Australian and New Zealand experts in the management of schizophrenia and related disorders. This guideline includes the management of ultra-high risk syndromes, first-episode psychoses and prolonged psychoses, including psychoses associated with substance use. It takes a holistic approach, addressing all aspects of the care of people with schizophrenia and related disorders, not only correct diagnosis and symptom relief but also optimal recovery of social function. METHODS: The writing group planned the scope and individual members drafted sections according to their area of interest and expertise, with reference to existing systematic reviews and informal literature reviews undertaken for this guideline. In addition, experts in specific areas contributed to the relevant sections. All members of the writing group reviewed the entire document. The writing group also considered relevant international clinical practice guidelines. Evidence-based recommendations were formulated when the writing group judged that there was sufficient evidence on a topic. Where evidence was weak or lacking, consensus-based recommendations were formulated. Consensus-based recommendations are based on the consensus of a group of experts in the field and are informed by their agreement as a group, according to their collective clinical and research knowledge and experience. Key considerations were selected and reviewed by the writing group. To encourage wide community participation, the Royal Australian and New Zealand College of Psychiatrists invited review by its committees and members, an expert advisory committee and key stakeholders including professional bodies and special interest groups. RESULTS: The clinical practice guideline for the management of schizophrenia and related disorders reflects an increasing emphasis on early intervention, physical health, psychosocial treatments, cultural considerations and improving vocational outcomes. The guideline uses a clinical staging model as a framework for recommendations regarding assessment, treatment and ongoing care. This guideline also refers its readers to selected published guidelines or statements directly relevant to Australian and New Zealand practice. CONCLUSIONS: This clinical practice guideline for the management of schizophrenia and related disorders aims to improve care for people with these disorders living in Australia and New Zealand. It advocates a respectful, collaborative approach; optimal evidence-based treatment; and consideration of the specific needs of those in adverse circumstances or facing additional challenges.

This paper represents an expert-based consensus statement on pain assessment among older adults. It is intended to provide recommendations that will be useful for both researchers and clinicians. Contributors were identified based on literature prominence and with the aim of achieving a broad representation of disciplines. Recommendations are provided regarding the physical examination and the assessment of pain using self-report and observational methods (suitable for seniors with dementia). In addition, recommendations are provided regarding the assessment of the physical and emotional functioning of older adults experiencing pain. The literature underlying the consensus recommendations is reviewed. Multiple revisions led to final reviews of 2 complete drafts before consensus was reached.

BACKGROUND: As the world is battling the COVID-19 pandemic, frontline health care workers (HCWs) are among the most vulnerable groups at risk of mental health problems. The many risks to the wellbeing of HCWs are not well understood. Of the literature, there is a paucity of information around how to best prevent psychological distress, and what steps are needed to mitigate harm to HCWs' wellbeing. METHODS: A systematic review using PRISMA methodology was used to investigate the psychological impact on HCWs facing epidemics or pandemics, using three electronic databases (PubMed, MEDLINE and CINAHL), dating back to 2002 until the 21st of August 2020. The search strategy included terms for HCWs (e.g., nurse and doctor), mental health (e.g., wellbeing and psychological), and viral outbreaks (e.g., epidemic and pandemic). Only studies with greater than 100 frontline HCWs (i.e. doctors or nurses in close proximity to infected patients) were included. RESULTS: A total of 55 studies were included, with 53 using quantitative methodology and 2 were qualitative. 50 of the quantitative studies used validated measurement tools while 5 used novel questionnaires. The studies were conducted across various countries and included people with SARS (13 studies), Ebola (1), MERS (3) and COVID-19 (38). Findings suggest that the psychological implications to HCWs are variable with several studies demonstrating an increased risk of acquiring trauma or stress-related disorders, depression and anxiety. Fear of the unknown or becoming infected were at the forefront of the mental challenges faced. Being a nurse and being female appeared to confer greater risk. The perceived stigma from family members and society heightened negative implications; predominantly stress and isolation. Coping strategies varied amongst the contrasting sociocultural settings and appeared to differ amongst doctors, nurses and other HCWs. Implemented changes, and suggestions for prevention in the future consistently highlighted the need for greater psychosocial support and clearer dissemination of disease-related information. CONCLUSION: This review can inform current and future research priorities in the maintenance of wellbeing amongst frontline HCWs. Change needs to start at the level of policy-makers to offer an enhanced variety of supports to HCWs who play a critical role during largescale disease outbreaks. Psychological implications are largely negative and require greater attention to be mitigated, potentially through the involvement of psychologists, raised awareness and better education. The current knowledge of therapeutic interventions suggests they could be beneficial but more long-term follow-up is needed.

Human adult mesenchymal stem cells (MSCs) support the engineering of functional tissue constructs by secreting angiogenic and cytoprotective factors, which act in a paracrine fashion to influence cell survival and vascularization. MSCs have been isolated from many different tissue sources, but little is known about how paracrine factor secretion varies between different MSC populations. We evaluated paracrine factor expression patterns in MSCs isolated from adipose tissue (ASCs), bone marrow (BMSCs), and dermal tissues [dermal sheath cells (DSCs) and dermal papilla cells (DPCs)]. Specifically, mRNA expression analysis identified insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor-D (VEGF-D), and interleukin-8 (IL-8) to be expressed at higher levels in ASCs compared with other MSC populations whereas VEGF-A, angiogenin, basic fibroblast growth factor (bFGF), and nerve growth factor (NGF) were expressed at comparable levels among the MSC populations examined. Analysis of conditioned media (CM) protein confirmed the comparable level of angiogenin and VEGF-A secretion in all MSC populations and showed that DSCs and DPCs produced significantly higher concentrations of leptin. Functional assays examining in vitro angiogenic paracrine activity showed that incubation of endothelial cells in ASC(CM) resulted in increased tubulogenic efficiency compared with that observed in DPC(CM). Using neutralizing antibodies we concluded that VEGF-A and VEGF-D were 2 of the major growth factors secreted by ASCs that supported endothelial tubulogenesis. The variation in paracrine factors of different MSC populations contributes to different levels of angiogenic activity and ASCs maybe preferred over other MSC populations for augmenting therapeutic approaches dependent upon angiogenesis.

BACKGROUND: Sarcopenia can predispose individuals to falls, fractures, hospitalization, and mortality. The prevalence of sarcopenia depends on the population studied and the definition used for the diagnosis. OBJECTIVE: This systematic review and meta-analysis aimed to investigate the association between sarcopenia and mortality and if it is dependent on the population and sarcopenia definition. METHODS: A systematic search was conducted in MEDLINE, EMBASE, and Cochrane from 1 January 2010 to 6 April 2020 for articles relating to sarcopenia and mortality. Articles were included if they met the following criteria - cohorts with a mean or median age ≥18 years and either of the following sarcopenia definitions: Asian Working Group for Sarcopenia (AWGS and AWGS2019), European Working Group on Sarcopenia in Older People (EWGSOP and EWGSOP2), Foundation for the National Institutes of Health (FNIH), International Working Group for Sarcopenia (IWGS), or Sarcopenia Definition and Outcomes Consortium (SDOC). Hazard ratios (HR) and odds ratios (OR) were pooled separately in meta-analyses using a random-effects model, stratified by population (community-dwelling adults, outpatients, inpatients, and nursing home residents). Subgroup analyses were performed for sarcopenia definition and follow-up period. RESULTS: Out of 3,025 articles, 57 articles were included in the systematic review and 56 in the meta-analysis (42,108 participants, mean age of 49.4 ± 11.7 to 86.6 ± 1.0 years, 40.3% females). Overall, sarcopenia was associated with a significantly higher risk of mortality (HR: 2.00 [95% CI: 1.71, 2.34]; OR: 2.35 [95% CI: 1.64, 3.37]), which was independent of population, sarcopenia definition, and follow-up period in subgroup analyses. CONCLUSIONS: Sarcopenia is associated with a significantly higher risk of mortality, independent of population and sarcopenia definition, which highlights the need for screening and early diagnosis in all populations.

BACKGROUND: Postoperative cognitive dysfunction (POCD) has been documented after cardiac and noncardiac surgery. The type of surgery and anesthetic has been assumed to be associated with the incidence but there are few prospective data comparing the incidence after different procedures. In this study, we sought to determine the association of the type of surgical procedure and anesthesia on the incidence of POCD after procedures involving light sedation, general anesthesia for noncardiac surgery, and general anesthesia for cardiac surgery involving cardiopulmonary bypass. METHODS: Eight neuropsychological tests were administered at baseline and at 7 days and 3 months postoperatively to subjects from 3 procedure groups and a nonoperative control group. Reliable change index was used to calculate POCD. The study sample consisted of subjects involved in 3 separate trials investigating coronary angiography (CA) (percutaneous diagnostic procedure) under sedation, major noncardiac surgery (total hip joint replacement [THJR] surgery) under general anesthesia, and coronary artery bypass graft (CABG) surgery under general anesthesia. RESULTS: Data were collected from 644 patients in the patient groups and 34 subjects in the control group. Neuropsychological results were available for POCD at day 7 for THJR surgery (n=162) and CABG surgery (n=281). The incidence of POCD at day 7 was 17% for THJR surgery and 43% for CABG surgery (adjusted odds ratio=0.2, 95% confidence interval [CI]: 0.1, 0.4; P<0.01). At 3 months, the incidence of POCD for all groups combined (n=636) was 17% (21% for CA under sedation, 16% for THJR surgery, and 16% for CABG surgery). The mean (95% CI) for the difference in proportions of POCD among groups was 0.00 (-0.07, 0.07) (P=0.91) for CABG versus THJR; -0.05 (-0.12, 0.03) (P=0.21) for CABG versus CA; and -0.05 (-0.13, 0.03) (P=0.24) for THJR versus CA. There were no significant differences among groups (adjusted odds ratio=1.21, 95% CI: 0.94, 1.55; P=0.13). CONCLUSIONS: The incidence of POCD in old and elderly patients at day 7 was higher after CABG surgery than THJR surgery, but POCD at 3 months was independent of the nature or the type of procedure or anesthetic when comparing CA, THJR, and CABG surgery groups. Cardiovascular risk factors were not predictive of POCD after any procedure.

OBJECTIVE: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. METHODS: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. RESULTS: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. CONCLUSIONS: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors.

The first officially documented management of the mentally ill in China was in the Tang Dynasty (618–907 AD), when homeless widows, orphans and the mentally ill were cared for in the Bei Tian Fang, a type of charity facility administrated by monks 1. The first western style psychiatric hospital for the homeless mentally ill was established and funded in 1898 by an American missionary, John Kerr, in what is currently the Guangzhou Brain Hospital. In the next 50 years, psychiatric hospitals were built very slowly in a limited number of large cities. The number of psychiatrists gradually increased to 100, and the number of beds gradually amounted to 1,000. After the founding of the People's Republic of China in 1949, psychiatric hospitals were gradually built in every province. The role of these early provincial hospitals was to maintain social security and stability. Following the first National Mental Health Meeting in 1958, community mental health work started in Beijing, Shanghai, Hunan, Sichuan and Jiangsu. Facilities were established in these areas to train professionals and to develop work plans for the prevention and treatment of psychoses, including early detection and treatment and relapse prevention 2. Though community mental health programs almost ceased during the Cultural Revolution (1966–1976), work-rehabilitation centers for patients with psychoses and caring networks were organized by neighborhood committees (the lowest level of governmental facilities) in Shanghai 3, and a treatment model for 256 patients with schizophrenia and their families was developed in a suburb of Beijing 4. In the 1980s, the health, civil affairs and public security sectors set up a three-tier network (at city, district/county and street/town levels) for the prevention and treatment of psychoses. Successful experiences with treatment models, such as work-rehabilitation centers in urban communities in Shanghai and Shenyang, and family-based therapy in rural areas in Haidian District in Beijing and Yantai Shangdong, were extended to other places 2. With the economic reform, hospitals were encouraged, as part of the market economy, to make a profit. Financially dependent mental health rehabilitation facilities closed or were transformed into small-scale psychiatric hospitals. In Shanghai, before 1990, there was at least one community-level rehabilitation facility in each district or town. By June 2004, the numbers of these facilities had decreased by 62% 5. By the late 1990s, some psychiatrists started to doubt the rationale for large hospital-based and profit-making models for mental health service delivery, and the Ministry of Health began to reconsider principles and approaches for mental health care. Through advocacy by the Ministry, senior ranked officials facilitated the establishment of a mental health plan. In November 1999, a high-level mental health seminar was convened by ten Chinese Ministries and the World Health Organization (WHO) in Beijing. The meeting resulted in a declaration that all levels of government would improve their leadership for and support of mental health care, strengthen inter-sectoral collaboration and cooperation, establish a mental health strategy and action plan, facilitate the enactment of a national mental health law, and protect patients’ rights 6. The first National Mental Health Plan (2002–2010) was signed by the Ministries of Health, Public Security and Civil Affairs, and China Disabled Persons’ Federation (CDPF) in April 2002. It identified a series of detailed targets and indices to achieve the main goals of: a) establishing an effective system of mental health care led by the government with the participation and cooperation of other sectors; b) accelerating the process of mental health legislation development and implementation; c) improving the knowledge and raising the awareness of mental health among all citizens; d) strengthening mental health services to decrease burden and disability; and e) developing human resources for mental health services and enhancing the capacity of current psychiatric hospitals 7. In August 2004, the Proposal on Further Strengthening Mental Health Work was approved by the Ministries of Health, Education, Public Security, Civil Affairs, Justice and Finance, and the CDPF. This proposal provides explicit instructions on interventions for psychological and behavioral problems for key population subgroups (including children and adolescents, women, the elderly and victims of disasters), treatment and rehabilitation of mental disorders, research on mental health and surveillance of mental disorders, and the protection of the rights of the mentally ill. The Proposal serves as the de facto Chinese national mental health policy. The mental health service model proposed in the above two documents is led by psychiatric hospitals, supported by departments of psychiatry in general hospitals, community-based health facilities and rehabilitation centres. In a large epidemiological study carried out in four provinces (Shandong, Zhejiang, Qinghai and Gansu) from 2001 to 2005, the adjusted 1-month prevalence of any mental disorder in people aged 18 years or older was 17.5% (95% CI 16.6–18.5), and that of psychotic disorders was 1.0% (95% CI 0.8–1.1) 8. In health economic terms, the estimated total disability adjusted life years (DALYs) of ten psychiatric conditions, including unipolar depressive disorder, bipolar disorder, schizophrenia, alcohol use disorders, Alzheimer's and other dementias, drug use disorders, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, and insomnia (primary), was 253,851,896 years in China in 2004 9. This translates into a loss of gross domestic product (GDP) amounting to a country-wide total of CNY 2,681 billion, with schizophrenia and bipolar disorder accounting for CNY 532 billion. The huge burden of mental disorders highlights the pressing need for improved mental health services. However, similar to most countries, the rate of treatment gap of those with mental disorders is unacceptably high in China, with 91.8% of all individuals with any diagnosis of mental disorders never seeking help. For psychotic disorders, 27.6% never sought help and 12.0% saw non-mental health professionals only 8. The vast majority of mental health professionals in China are psychiatrists or psychiatric nurses, with few clinical psychologists and social workers, and no occupational therapists. Psychiatrists and licensed psychiatric nurses are accredited by the Ministry of Health, psychological counselors by the Ministry of Human Resources and Social Security, and psychotherapists by both Ministries. In 2004, there were 16,103 licensed psychiatrists and psychiatric registrars (1.24/100,000 population) and 24,793 licensed psychiatric nurses (1.91/100,000 population) 9. Relative to the global average mental health workforce (i.e., 4.15 psychiatrists and 12.97 psychiatric nurses per 100,000 population respectively) 10, mental health human resources in China are quite limited. The shortage of skilled mental health professionals represents one of the most critical issues facing the Chinese mental health system currently. In 2004, there were 557 psychiatric hospitals. Among them, 359 (64.5%) had 100 or more beds, and 44 (7.9%) had 500 or more beds. The total number of psychiatric beds was 129,314, i.e. 1.00/10,000 population 11, which is significantly lower than the global average of 4.36/10,000 psychiatric beds 10. China does not organize its services in catchment areas. Specialist mental health services remain the predominant component of the system. China's community-based mental health system was largely eliminated with the introduction of the market economy. Therefore, mental health service provision has become primarily hospital-based. Patients can access tertiary psychiatric hospitals directly, bypassing the primary and secondary health care levels. This partly reflects the disproportionate concentration of health resources in large cities. The funding model for the mental health system is complex, with hospital inpatient services provided by three ministries, Health, Civil Affairs and Public Security, while other facilities are administered under other ministries. According to the WHO, only 2.35% of the total health budget is spent on mental health and less than 15% of the population has health insurance that includes coverage of psychiatric disorders 10. China is undergoing a rapid change, with an economic growth rate of 7.5–13.0% per annum in the last ten years 12. However, the growth in wealth has not been equitably distributed, resulting in an increasing gap between the rich and the poor. It is evident that those with the greatest socio-economic disadvantage are often those with the highest mental health care needs 13. In October 2003, supported by the Ministry of Health, an application process was initiated for specialized public health projects that would have investment from the Ministry of Finance. All relevant public health sectors were active in developing appropriate models with critical indicators and drafting proposals for funding. Although several approaches and different models were considered, the mental health sector was yet to identify a suitable and practical model for China. A delegation led by Guihua Xu (Vice Director of China Centre for Disease Control) and three psychiatrists, Xin Yu, Hong Ma and Jin Liu from Peking University Institute of Mental Health, visited Melbourne, in order to build knowledge and understanding of the Victorian community mental health service system. The delegates and their Australian hosts also began to analyze the concept of community in China, and to investigate possible ways to integrate mental health care into secondary and tertiary facilities in the country. Complemented by other international exchanges with the USA, Norway, Thailand, Japan, UK and Germany, and guided by international benchmarks on mental health services by WHO and previous experiences in community mental health in China, a mental health sector model for reform emerged. The model has at its core a patient-centered approach that is community-based, seamless, function-oriented and multi-disciplinary. Due to China's vast, multi-ethnic and diverse population, social harmony and stability is a well recognized concern for the Chinese government. The focus on psychoses, especially those associated with violent or socially disruptive behaviours, was considered as a critical step to engage government in mental health issues. Although community-based mental health services were the long-term goal, current lack of resources and capacity in community mental health and primary mental health, combined with the difficulty in attracting mental health professionals to work in the community, meant that a different, less ambitious and more targeted model needed to be followed initially. An integrated hospital and community treatment model for psychoses was suggested, and a pilot project that included monitoring, intervention, prevention and rehabilitation management of psychoses was proposed. In September 2004, after competing with over fifty proposals and supported by a group of leading sociologists, economists and psychiatrists in China, the program for mental health service reform was the only non-communicable disease program included in China's national public health program. This event became a major historical milestone for China: mental health became officially included into public health. The mental health reform program formally received support from Ministry of Finance in December 2004, and was named the 686 Program after its initial funding of CNY 6.86 million. The National Centre for Mental Health of China located at Peking University Institute of Mental Health was authorized to be the implementing facility for this program by the Ministry of Health. The project was overseen by a national working group as well as an international advisory group with experts mainly from the University of Melbourne. By early 2005, 60 demonstration sites were established, with one urban and one rural area in each of the 30 provinces of China, covering a population of 43 million. The priority in the first year was to build a capable mental health workforce through an extensive training program. A two-level training mode was adopted, first at the national level utilizing a train-the-trainer approach, and then with trained trainers delivering the programs at the provincial level. The contents of the training included guidance on project management, standardized treatment protocols, case management, information management, family education, and the training of police and neighborhood committees. In 2006, the 686 Program incorporated an intervention component into the training program, which was then called the National Continuing Management and Intervention Program for Psychoses. The aim was to consolidate the reform through the key provisions of continuity of care, treatment accessibility, and equitable mental health care. Four types of psychoses were included: schizophrenia, bipolar disorder, delusional disorder, and schizoaffective disorder. Patients screened for possible psychosis were referred from psychiatric hospitals or departments, the CDPF, community and village health centres, and neighborhood or village committees. These patients were subsequently examined by psychiatrists, and those who met diagnostic criteria for psychotic disorders were evaluated for their risk of violence based on a 0 to 5 score scale established by the national working group. The patients at risk of violence received monthly follow-up and, if they were socio-economically disadvantaged, were provided with free medication, laboratory tests, and a subsidy for hospitalization. About 5% of patients who received free medications were treatment refractory and were therefore provided with second generation antipsychotics, mainly risperidone. In the event of any psychiatric emergencies or severe cases of medication side effects, the program provided free crisis management. Moreover, as some patients were physically restrained or chained at home, the program provided support for the unlocking and freeing of these patients, and hospitalization when necessary. After hospitalization, if patients lacked finances to pay for treatment, they were included in the free services mentioned above. A key challenge for successful implementation of the 686 Program was the limited capacity of the workforce to deliver the program at the local level. To meet this enormous challenge, a tripartite training program was collaboratively developed in 2007 by the Peking University Institute of Mental Health, the University of Melbourne and the Chinese University of Hong Kong. The primary aim of the program was to train up multi-skilled case workers by: a) developing understanding of the key principles of community-based mental health care in general and case b) practical in developing service plans to and continuity of c) appropriate ways to build with the families and d) to work in and e) to and for principles from health social occupational a set of knowledge and for case management was A key for the training program was to a rehabilitation focus in a community to a of community mental health facilities hospitals, training centres, mental health support and by the community mental health provided for such clinical The program needed to build that included different sectors and facilities into the mental health service including local health, civil public the and In a total of facilities in this program, including 44 provincial hospitals, hospitals, hospitals, urban community health urban community health village urban neighborhood committees and village committees. A mental health was also By the of a total of for the program. Among who were mainly for the patients and leading community for case for who mainly crisis intervention for for psychiatrists for psychiatric nurses for and at different levels for from the police in demonstration sites that the number of violent from in to in of and that of major violent from to of By the of general population in were by this program. A total of patients were patients received follow-up (the average follow-up in demonstration sites was patients received free medication, free crisis management interventions were and patients were a subsidy for restrained patients were In the first year of the 686 a total of training were and people were including psychiatrists, psychiatric nurses, community case community workers, public security and family To 500 mental health professionals from in China have in tripartite program training of ten mental health professionals from China have had practical training in Hong and more than 100 hospital and of mental health departments have study in Melbourne. of the most of the program has been in the area of This has the greatest on long-term with the 686 national on mental health have been the on of National Mental Health Work to improve and reform mental health work the Work the first in Chinese mental were in the of the the of Health hospitals were to be improved as part of public health service capacity the on of Public Health which the management of psychoses was included as one of national public health service and the on Management of which of different sectors in the management of psychoses, and the relevant were A government is an for in a of in China. However, the and the of the mental health problems as well as the are the of mental health All of mental health services in China and of this be the mental health service system development and service in China of the main problems are the is huge in China. Although national are quite and a among provinces and in of and levels. In some rich and or the mental health service system is provinces or cities. However, in some western the reform process is by and lack of resources and In those the national mental health become Resources are not between the community and psychiatric hospitals. Though community mental health is as part of the of public health and national funding has been to each to and up of the patients at community general lack knowledge and for these In the next two or three years, CNY to the of psychiatric hospitals that are often located in less and the funding primarily based on psychiatric hospital beds than care received from and treatment This hospitals to be in community services. In social insurance only the of hospitalization, leading more patients to use inpatient services. are psychoses. It is from the social stability of psychosis treatment and management is the priority of the government. However, to the lack of relevant and is under the of mentally Social and resources the treatment rate of patients with psychoses. However, of psychosis is or patients’ levels are are yet to be is less The focus on psychosis management psychiatry less are to be trained as psychiatrists, and psychiatric hospitals professionals with levels of education, training and The is to psychiatric facilities into health in which are as This from training in with other sectors is Although the of each relevant or sector has been in cooperation and collaboration is not or established, with the health and mental health sectors working in in areas. In a with government such as China, mental health development needs and support from government at all levels. this the mental health sector to the management of psychoses by In China needs to develop awareness of the of and their role in social resources and services for mentally ill patients in the community to their in urban areas and village in rural areas training in order to and develop care plans for four types of psychotic patients to the 686 at the primary care and to up patients at least four per the large number of patients with mental disorders in China, community and care for most patients needs to be and be supported to care in the community for their mentally ill The limited of funding only support the and of in the national program, the mental health facilities that these professionals have to make a in order to pay their Mental health service for psychoses be provided by the government as of the service or insurance for the support and investment in clinical and health research are to establish treatment and that are relevant in a Chinese Moreover, economic from the of and long-term and for patients with mental disorders are needed to and provided by the Social Security This reform program in China is with in years by the WHO and supported by other international In the WHO that develop community-based services for people with mental disorders This has been by a for action to scale up services for people with mental disorders the development of the Mental Health the of the and the in World The work on the 686 Program and other in China are in and in mental health service However, mental health services in China, as in and have a to to meet the of mental health care in the research provides relevant information to in the of effective and health services However, of this work to national and international is by the of from in psychiatric work by has a level of by China well as and of these countries, and no in the and is by a psychiatric in the main international supported action to improve of and research the of from this and similar The World and the the of the of have the to this Although China's mental health service reform has only on psychoses the scale of the reform, and the numbers of psychiatric patients a and ambitious program, which has had to huge The reform began than the reform of general health care in China, and is with the Chinese public health strategy and the for to the WHO With of needs and development of appropriate public health of effective strengthening of human of and China be in a to build and strengthen a national community mental health system and service for the of the mental health of its Jin Liu and Hong Ma to this and Xin is the The and for their and support to mental health reform in China, and for to the and as to also all those who have or in the establishment implementation of the 686

BACKGROUND: Pressure ulcers (i.e. bedsores, pressure sores, pressure injuries, decubitus ulcers) are areas of localised damage to the skin and underlying tissue. They are common in the elderly and immobile, and costly in financial and human terms. Pressure-relieving support surfaces (i.e. beds, mattresses, seat cushions etc) are used to help prevent ulcer development. OBJECTIVES: This systematic review seeks to establish:(1) the extent to which pressure-relieving support surfaces reduce the incidence of pressure ulcers compared with standard support surfaces, and,(2) their comparative effectiveness in ulcer prevention. SEARCH METHODS: In April 2015, for this fourth update we searched The Cochrane Wounds Group Specialised Register (searched 15 April 2015) which includes the results of regular searches of MEDLINE, EMBASE and CINAHL and The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015, Issue 3). SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-randomised trials, published or unpublished, that assessed the effects of any support surface for prevention of pressure ulcers, in any patient group or setting which measured pressure ulcer incidence. Trials reporting only proxy outcomes (e.g. interface pressure) were excluded. Two review authors independently selected trials. DATA COLLECTION AND ANALYSIS: Data were extracted by one review author and checked by another. Where appropriate, estimates from similar trials were pooled for meta-analysis. MAIN RESULTS: For this fourth update six new trials were included, bringing the total of included trials to 59.Foam alternatives to standard hospital foam mattresses reduce the incidence of pressure ulcers in people at risk (RR 0.40 95% CI 0.21 to 0.74). The relative merits of alternating- and constant low-pressure devices are unclear. One high-quality trial suggested that alternating-pressure mattresses may be more cost effective than alternating-pressure overlays in a UK context.Pressure-relieving overlays on the operating table reduce postoperative pressure ulcer incidence, although two trials indicated that foam overlays caused adverse skin changes. Meta-analysis of three trials suggest that Australian standard medical sheepskins prevent pressure ulcers (RR 0.56 95% CI 0.32 to 0.97). AUTHORS' CONCLUSIONS: People at high risk of developing pressure ulcers should use higher-specification foam mattresses rather than standard hospital foam mattresses. The relative merits of higher-specification constant low-pressure and alternating-pressure support surfaces for preventing pressure ulcers are unclear, but alternating-pressure mattresses may be more cost effective than alternating-pressure overlays in a UK context. Medical grade sheepskins are associated with a decrease in pressure ulcer development. Organisations might consider the use of some forms of pressure relief for high risk patients in the operating theatre.

BACKGROUND AND OBJECTIVE: The beneficial effects of self-care include improved well-being and lower morbidity, mortality, and healthcare costs. In this article we address the current state of self-care research and propose an agenda for future research based on the inaugural conference of the International Center for Self-Care Research held in Rome, Italy in June 2019. The vision of this Center is a world where self-care is prioritized by individuals, families, and communities and is the first line of approach in every health care encounter. The mission of the Center is to lead the self-care research endeavor, improving conceptual clarity and promoting interdisciplinary work informed by a shared vision addressing knowledge gaps. A focused research agenda can deepen our theoretical understanding of self-care and the mechanisms underlying self-care, which can contribute to the development of effective interventions that improve outcomes. METHODS: During conference discussions, we identified seven major reasons why self-care is challenging, which can be grouped into the general categories of behavior change and illness related factors. We identified six specific knowledge gaps that, if addressed, may help to address these challenges: the influence of habit formation on behavior change, resilience in the face of stressful life events that interfere with self-care, the influence of culture on self-care behavioral choices, the difficulty performing self-care with multiple chronic conditions, self-care in persons with severe mental illness, and the influence of others (care partners, family, peer supporters, and healthcare professionals) on self-care. PLANS TO ACHIEVE RESULTS: To achieve the vision and mission of the Center, we will lead a collaborative program of research that addresses self-care knowledge gaps and improves outcomes, create a supportive international network for knowledge transfer and support of innovations in self-care research, and support and train others in self-care research. Beyond these specific short-term goals, important policy implications of this work are discussed.

CD39 is the cell surface-located prototypic member of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) family. Biological actions of CD39 are a consequence (at least in part) of the regulated phosphohydrolytic activity on extracellular nucleotides. This ecto-enzymatic cascade in tandem with CD73 (ecto-5'-nucleotidase) also generates adenosine and has major effects on both P2 and adenosine receptor signalling. Despite the early recognition of CD39 as a B lymphocyte activation marker, little is known of the role of CD39 in humoral or cellular immune responses. There is preliminary evidence to suggest that CD39 may impact upon antibody affinity maturation. Pericellular nucleotide/nucleoside fluxes caused by dendritic cell expressed CD39 are also involved in the recruitment, activation and polarization of naïve T cells. We have recently explored the patterns of CD39 expression and the functional role of this ecto-nucleotidase within quiescent and activated T cell subsets. Our data indicate that CD39, together with CD73, efficiently distinguishes T regulatory cells (Treg) from other resting or activated T cells in mice (and humans). Furthermore, CD39 serves as an integral component of the suppressive machinery of Treg, acting, at least in part, through the modulation of pericellular levels of adenosine. We have also shown that the coordinated regulation of CD39/CD73 expression and of the adenosine receptor A2A activates an immunoinhibitory loop that differentially regulates Th1 and Th2 responses. The in vivo relevance of this network is manifest in the phenotype of Cd39-null mice that spontaneously develop features of autoimmune diseases associated with Th1 immune deviation. These data indicate the potential of CD39 and modulated purinergic signalling in the co-ordination of immunoregulatory functions of dendritic and Treg cells. Our findings also suggest novel therapeutic strategies for immune-mediated diseases.

Although poly(ADP-ribose) polymerase (PARP) inhibitors are active in homologous recombination (HR)-deficient cancers, their utility is limited by acquired resistance after restoration of HR. Here, we report that dinaciclib, an inhibitor of cyclin-dependent kinases (CDKs) 1, 2, 5, and 9, additionally has potent activity against CDK12, a transcriptional regulator of HR. In BRCA-mutated triple-negative breast cancer (TNBC) cells and patient-derived xenografts (PDXs), dinaciclib ablates restored HR and reverses PARP inhibitor resistance. Additionally, we show that de novo resistance to PARP inhibition in BRCA1-mutated cell lines and a PDX derived from a PARP-inhibitor-naive BRCA1 carrier is mediated by residual HR and is reversed by CDK12 inhibition. Finally, dinaciclib augments the degree of response in a PARP-inhibitor-sensitive model, converting tumor growth inhibition to durable regression. These results highlight the significance of HR disruption as a therapeutic strategy and support the broad use of combined CDK12 and PARP inhibition in TNBC.

AIMS: Cognitive impairment occurs often in patients with chronic heart failure (CHF) and may contribute to sub-optimal self-care. This study aimed to test the impact of cognitive impairment on self-care. METHODS AND RESULTS: In 93 consecutive patients hospitalized with CHF, self-care (Self-Care of Heart Failure Index) was assessed. Multiple regression analysis was used to test a model of variables hypothesized to predict self-care maintenance, management, and confidence. Variables in the model were mild cognitive impairment (MCI; Mini-Mental State Exam and Montreal Cognitive Assessment), depressive symptoms (Cardiac Depression Scale), age, gender, social isolation, education level, new diagnosis, and co-morbid illnesses. Sixty-eight patients (75%) were coded as having MCI and had significantly lower self-care management (eta(2)= 0.07, P < 0.01) and self-confidence scores (eta(2)= 0.05, P < 0.05). In multivariate analysis, MCI, co-morbidity index, and NYHA class III or IV explained 20% of the variance in self-care management (P < 0.01); MCI made the largest contribution explaining 9% of the variance. Increasing age and symptoms of depression explained 13% of the variance in self-care confidence scores (P < 0.01). CONCLUSION: Cognitive impairment, a hidden co-morbidity, may impede patients' ability to make appropriate self-care decisions. Screening for MCI may alert health professionals to those at greater risk of failed self-care.

BACKGROUND: A multidisciplinary collaboration investigated the world's largest, most catastrophic epidemic thunderstorm asthma event that took place in Melbourne, Australia, on Nov 21, 2016, to inform mechanisms and preventive strategies. METHODS: Meteorological and airborne pollen data, satellite-derived vegetation index, ambulance callouts, emergency department presentations, and data on hospital admissions for Nov 21, 2016, as well as leading up to and following the event were collected between Nov 21, 2016, and March 31, 2017, and analysed. We contacted patients who presented during the epidemic thunderstorm asthma event at eight metropolitan health services (each including up to three hospitals) via telephone questionnaire to determine patient characteristics, and investigated outcomes of intensive care unit (ICU) admissions. FINDINGS: ). At 1800 AEDT, a gust front crossed Melbourne, plunging temperatures 10°C, raising humidity above 70%, and concentrating particulate matter. Within 30 h, there were 3365 (672%) excess respiratory-related presentations to emergency departments, and 476 (992%) excess asthma-related admissions to hospital, especially individuals of Indian or Sri Lankan birth (10% vs 1%, p<0·0001) and south-east Asian birth (8% vs 1%, p<0·0001) compared with previous 3 years. Questionnaire data from 1435 (64%) of 2248 emergency department presentations showed a mean age of 32·0 years (SD 18·6), 56% of whom were male. Only 28% had current doctor-diagnosed asthma. 39% of the presentations were of Asian or Indian ethnicity (25% of the Melbourne population were of this ethnicity according to the 2016 census, relative risk [RR] 1·93, 95% CI 1·74-2·15, p <0·0001). Of ten individuals who died, six were Asian or Indian (RR 4·54, 95% CI 1·28-16·09; p=0·01). 35 individuals were admitted to an intensive care unit, all had asthma, 12 took inhaled preventers, and five died. INTERPRETATION: Convergent environmental factors triggered a thunderstorm asthma epidemic of unprecedented magnitude, tempo, and geographical range and severity on Nov 21, 2016, creating a new benchmark for emergency and health service escalation. Asian or Indian ethnicity and current doctor-diagnosed asthma portended life-threatening exacerbations such as those requiring admission to an ICU. Overall, the findings provide important public health lessons applicable to future event forecasting, health care response coordination, protection of at-risk populations, and medical management of epidemic thunderstorm asthma. FUNDING: None.

Results from recent clinical trials of antibodies that target amyloid-β (Aβ) for Alzheimer's disease have created excitement and have been heralded as corroboration of the amyloid cascade hypothesis. However, while Aβ may contribute to disease, genetic, clinical, imaging and biochemical data suggest a more complex aetiology. Here we review the history and weaknesses of the amyloid cascade hypothesis in view of the new evidence obtained from clinical trials of anti-amyloid antibodies. These trials indicate that the treatments have either no or uncertain clinical effect on cognition. Despite the importance of amyloid in the definition of Alzheimer's disease, we argue that the data point to Aβ playing a minor aetiological role. We also discuss data suggesting that the concerted activity of many pathogenic factors contribute to Alzheimer's disease and propose that evolving multi-factor disease models will better underpin the search for more effective strategies to treat the disease.

The AMP-activated protein kinase (AMPK) and cAMP signaling systems are both key regulators of cellular metabolism. In this study, we show that AMPK activity is attenuated in response to cAMP-elevating agents through modulation of at least two of its subunit phosphorylation sites, viz. -Thr 172 and 1-Ser 485 / 2-Ser 491 , in the clonal -cell line INS-1 as well as in mouse embryonic fibroblasts and COS cells. Forskolin, isobutylmethylxanthine, and the glucose-dependent insulinotropic peptide inhibited AMPK activity and reduced phosphorylation of the activation loop -Thr 172 via inhibition of calcium/calmodulindependent protein kinase kinase- and -, but not LKB1. These agents also enhanced phosphorylation of -Ser 485/491 by the cAMP-dependent protein kinase. AMPK -Ser 485/491 phosphorylation was necessary but not sufficient for inhibition of AMPK activity in response to forskolin/isobutylmethylxanthine. We show that AMPK -Ser 485/491 can be a site for autophosphorylation, which may play a role in limiting AMPK activation in response to energy depletion or other regulators. Thus, our findings not only demonstrate cross-talk between the cAMP/cAMP-dependent protein kinase and AMPK signaling modules, but also describe a novel mechanism by which multisite phosphorylation of AMPK contributes to regulation of its enzyme activity.

Glaucoma is increasingly recognized as a neurodegenerative disorder, characterized by the accelerated loss of retinal ganglion cells (RGCs) and their axons. Open angle glaucoma prevalence and incidence increase exponentially with increasing age, yet the pathophysiology underlying increasing age as a risk factor for glaucoma is not well understood. Accumulating evidence points to age-related mitochondrial dysfunction playing a key role in the etiology of other neurodegenerative disorders including amyotrophic lateral sclerosis, Alzheimer and Parkinson disease. The 2 major functions of mitochondria are the generation of ATP through oxidative phosphorylation and the regulation of cell death by apoptosis. This review details evidence to support our hypothesis that age-associated mitochondrial dysfunction renders RGCs susceptible to glaucomatous injury by reducing the energy available for repair processes and predisposing RGCs to apoptosis. Eliciting the role of mitochondria in glaucoma pathogenesis may uncover novel therapeutic targets for protecting the optic nerve and preventing vision loss in glaucoma.