Conjoint Professor Gregory Carter

Background: Methamphetamine dependence is a significant global health concern for which there are no approved medications. The cysteine prodrug, N-acetylcysteine (NAC), has been found to ameliorate glutamate dysregulation in addiction, and to reduce craving for methamphetamine and other drugs. We evaluated the efficacy and safety of NAC as a pharmacotherapy for methamphetamine dependence. Methods: A parallel double-blind randomised placebo-controlled trial of people dependent on methamphetamine recruited from Geelong, Melbourne and Wollongong, Australia, between July 2018 and December 2019. Participants were randomised to receive either 12 weeks of oral NAC (2400 mg/day) or matched placebo, delivered as a take-home medication. The primary outcome was methamphetamine use, measured in two ways: (a) change in days of use in the past 4 weeks from baseline to weeks 4, 8 and 12, assessed using the Timeline Followback; and (b) methamphetamine-positive oral fluid samples taken weekly. Analyses were intention-to-treat and based on imputed data. Secondary outcomes were craving, severity of dependence, withdrawal severity and psychiatric symptoms (depression, suicidality, hostility and psychotic symptoms). Significance levels were p < 0.025 for primary outcomes and p < 0.01 for secondary outcomes. Adverse events were compared between groups by system organ class. The study was prospectively registered, ACTRN12618000366257. Results: Participants (N = 153; 59% male, mean [SD] age 38 [8]) were randomised to placebo (n = 77) or NAC (n = 76). Both groups had a median (IQR) of 24 (15¿28) days of methamphetamine use in the 4 weeks prior to baseline. Both groups significantly reduced methamphetamine use (mean [SE] reduction of 7.3 [1.2]) days for placebo, 6.8 [1.2] for NAC) but NAC did not reduce days of methamphetamine use more than placebo (group difference of 0.5 days, 97.5% CI -3.4¿4.3). There was no significant effect of NAC on methamphetamine-positive oral fluid samples (placebo 79%, NAC 76%; mean difference -2.6, 97.5% CI -12.6¿7.4). NAC did not significantly reduce craving, severity of dependence, withdrawal, suicidality, depression, hostility or psychotic symptoms relative to placebo. Adverse events did not differ significantly between placebo and NAC groups. Interpretation: These findings suggest that take-home oral NAC has no significant effect on methamphetamine use or most clinically related outcomes amongst people who are dependent on the drug.

Background: Somatic disorders and somatic symptoms are common in primary care populations; however, little is known about the prevalence in surgical populations. Identification of inpatients with high somatic symptom burden and psychological co-morbidity could improve access to effective psychological therapies. Methods: Cross-sectional analysis (n = 465) from a prospective longitudinal cohort study of consecutive adult admissions with non-traumatic abdominal pain, at a tertiary hospital in New South Wales, Australia. We estimated somatic symptom prevalence with the Patient Health Questionnaire-15 at three cut-points: moderate (¿10), severe (¿15) and ¿bothered a lot¿ on ¿3 symptoms; and psychological co-morbidity with the Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 at standard (¿10) cut-points. We also examined gender differences for somatic symptoms and psychological co-morbidity. Results: Prevalence was moderate (52%), female predominance (odds ratio = 1.71; 95% confidence interval = [1.18, 2.48]), severe (20%), no gender difference (1.32; [0.83, 2.10]) and ¿bothered a lot¿ on ¿3 symptoms (53%), female predominance (2.07; [1.42, 3.03]). Co-morbidity of depressive, anxiety and somatic symptoms ranged from 8.2% to 15.9% with no gender differences. Conclusion: Somatic symptoms were common and psychological triple co-morbidity occurred in one-sixth of a clinical population admitted for abdominal pain. Co-ordinated surgical and psychological clinical intervention and changes in clinical service organisation may be warranted to provide optimal care.

Background: It is unknown how many distressed patients receive the additional supportive care recommended by Australian evidence-based distress management guidelines. The study identifies the (1) distress screening practices of Australian cancer services; (2) barriers to improving practices; and (3) implementation strategies which are acceptable to service representatives interested in improving screening practices. Method: Clinic leads from 220 cancer services were asked to nominate an individual involved in daily patient care to complete a cross-sectional survey on behalf of the service. Questions related to service characteristics; screening and management processes; and implementation barriers. Respondents indicated which implementation strategies were suitable for their health service. Results: A total of 122 representatives participated from 83 services (51%). The majority of respondents were specialist nurses or unit managers (60%). Approximately 38% of representatives¿ services never or rarely screen; 52% who screen do so for all patients; 55% use clinical interviewing only; and 34% follow referral protocols. The most common perceived barriers were resources to action screening results (74%); lack of time (67%); and lack of staff training (66%). Approximately 65% of representatives were interested in improving practices. Of the 8 implementation strategies, workshops (85%) and educational materials (69%) were commonly selected. Over half (59%) indicated a multicomponent implementation program was preferable. Conclusions: Although critical gaps across all guideline components were reported, there is a broad support for screening and willingness to improve. Potential improvements include additional services to manage problems identified by screening, more staff time for screening, additional staff training, and use of patient-report measures.

Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.Methods We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.Results 16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (-0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).Conclusions PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.

Background: Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods: AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged =18 years) with a clinical diagnosis of acute stroke in the previous 2¿15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings: Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76¿1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation: Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke. Funding: National Health and Medical Research Council of Australia.

Objective: The aims were to estimate the prevalence of CNCP in suicide decedents, and compare sociodemographic and clinical characteristics of people who die by suicide (i) with and without a history of CNCP and (ii) among decedents with CNCP who are younger (<65¿years) and older (65¿+¿years). Method: We examined all closed cases of intentional deaths in Australia in 2014, utilizing the National Coronial Information System. Results: We identified 2,590 closed cases of intentional deaths in Australia in 2014 in decedents over 18¿years of age. CNCP was identified in 14.6% of cases. Decedents with CNCP were more likely to be older, have more mental health and physical health problems, and fewer relationship problems, and were more likely to die by poisoning from drugs, compared with decedents without CNCP. Comparisons of older and younger decedents with CNCP found that compared to younger (<65¿years) decedents with CNCP, older decedents (65¿+¿years) were less likely to have mental health problems. Conclusions: This is the first national study to examine the characteristics of suicide deaths with a focus on people with CNCP. Primary care physicians should be aware of the increased risk for suicide in people living with CNCP, and it may be useful for clinicians to screen for CNCP among those presenting with suicidal behaviors.

Background: Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results. Objective: To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of =10. Methods: Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview. Results: Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22-0.24 lower compared to fully structured interviews and 0.06-0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of =10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82-0.92) and 0.86 (0.82-0.88). Conclusions: The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression.

Introduction and Aims: There has been a rapid increase in smoking crystalline methamphetamine in Australia. We compare the clinical and demographic characteristics of those who smoke versus inject the drug in a cohort of people who use methamphetamine. Design and Methods: Participants (N = 151) were dependent on methamphetamine, aged 18¿60 years, enrolled in a pharmacotherapy trial for methamphetamine dependence, and reported either injecting (n = 54) or smoking (n = 97) methamphetamine. Measures included the Timeline Followback, Severity of Dependence Scale, Amphetamine Withdrawal Questionnaire, Craving Experience Questionnaire and the Brief Psychiatric Rating Scale (symptoms of depression, hostility, psychosis and suicidality). Simultaneous regression was used to identify independent demographic correlates of smoking methamphetamine and to compare the clinical characteristics of participants who smoked versus injected. Results: Compared to participants who injected methamphetamine, those who smoked methamphetamine were younger and less likely to be unemployed, have a prison history or live alone. Participants who smoked methamphetamine used methamphetamine on more days in the past 4 weeks than participants who injected methamphetamine (26 vs. 19 days, P = 0.001); they did not differ significantly in their severity of methamphetamine dependence, withdrawal, craving or psychiatric symptoms (P > 0.05). After adjustment for demographic differences, participants who smoked had lower craving [b (SE) = -1.1 (0.5), P = 0.021] and were less likely to report psychotic symptoms [b (SE) = -1.8 (0.7), P = 0.013] or antidepressant use [b (SE) = -1.1 (0.5), P = 0.022]. Discussion and Conclusions: Smoking crystalline methamphetamine is associated with a younger less marginalised demographic profile than injecting methamphetamine, but a similarly severe clinical profile.

Background: A key challenge in behavioural medicine is developing interventions that can be delivered adequately (i.e., with fidelity) within real-world consultations. Accordingly, clinical trials should (but tend not to) report what is actually delivered (adherence), how well (competence) and the distinction between intervention and comparator conditions (differentiation). Purpose: To address this important clinical and research priority, we apply best practice guidelines to evaluate fidelity within a real-world, stepped-wedge evaluation of ¿EAT: Eating As Treatment¿, a new dietitian delivered health behaviour change intervention designed to reduce malnutrition in head and neck cancer (HNC) patients undergoing radiotherapy. Methods: Dietitians (n = 18) from five Australian hospitals delivered a period of routine care and following a randomly determined order each site received training and began delivering the EAT Intervention. A 20% random stratified sample of audio-recorded consultations (control n = 196; intervention n = 194) was coded by trained, independent, raters using a study specific checklist and the Behaviour Change Counselling Inventory. Intervention adherence and competence were examined relative to apriori benchmarks. Differentiation was examined by comparing control and intervention sessions (adherence, competence, non-specific factors, and dose), via multiple linear regression, logistic regression, or mixed-models. Results: Achievement of adherence benchmarks varied. The majority of sessions attained competence. Post-training consultations were clearly distinct from routine care regarding motivational and behavioural, but not generic, skills. Conclusions: Although what level of fidelity is ¿good enough¿ remains an important research question, findings support the real-world feasibility of integrating EAT into dietetic consultations with HNC patients and provide a foundation for interpreting treatment effects.

Technological advancements have brought multiple and diverse benefits to our human existence. In suicide prevention, new technologies have spurred great interest in and reports of the applicability to assessing, monitoring, and intervening in various community and clinical populations. We argue in this article that we need to better understand the complexities of implementation of technological advances; especially the accuracy, effectiveness, safety, ethical, and legal issues, even as implementation occurs at individual, clinical, and population levels, in order to achieve that measure of public health impact we all desire (i.e., greater benefit than harm).

The prevention of suicide and suicide-related behaviour are key policy priorities in Australia and internationally. The World Health Organization has recommended that member states develop self-harm surveillance systems as part of their suicide prevention efforts. This is also a priority under Australia¿s Fifth National Mental Health and Suicide Prevention Plan. The aim of this paper is to describe the development of a state-based self-harm monitoring system in Victoria, Australia. In this system, data on all self-harm presentations are collected from eight hospital emergency departments in Victoria. A natural language processing classifier that uses machine learning to identify episodes of self-harm is currently being developed. This uses the free-text triage case notes, together with certain structured data fields, contained within the metadata of the incoming records. Post-processing is undertaken to identify primary mechanism of injury, substances consumed (including alcohol, illicit drugs and pharmaceutical preparations) and presence of psychiatric disorders. This system will ultimately leverage routinely collected data in combination with advanced artificial intelligence methods to support robust community-wide monitoring of self-harm. Once fully operational, this system will provide accurate and timely information on all presentations to participating emergency departments for self-harm, thereby providing a useful indicator for Australia¿s suicide prevention efforts.

Background: The objective of this study was to develop and validate a short form of the Patient Health Questionnaire-9 (PHQ-9), a self-report questionnaire for assessing depressive symptomatology, using objective criteria. Methods: Responses on the PHQ-9 were obtained from 7,850 English-speaking participants enrolled in 20 primary diagnostic test accuracy studies. PHQ unidimensionality was verified using confirmatory factor analysis, and an item response theory model was fit. Optimal test assembly (OTA) methods identified a maximally precise short form for each possible length between one and eight items, including and excluding the ninth item. The final short form was selected based on prespecified validity, reliability, and diagnostic accuracy criteria. Results: A four-item short form of the PHQ (PHQ-Dep-4) was selected. The PHQ-Dep-4 had a Cronbach's alpha of 0.805. Sensitivity and specificity of the PHQ-Dep-4 were 0.788 and 0.837, respectively, and were statistically equivalent to the PHQ-9 (sensitivity¿=¿0.761, specificity¿=¿0.866). The correlation of total scores with the full PHQ-9 was high (r¿=¿0.919). Conclusion: The PHQ-Dep-4 is a valid short form with minimal loss of information of scores when compared to the full-length PHQ-9. Although OTA methods have been used to shorten patient-reported outcome measures based on objective, prespecified criteria, further studies are required to validate this general procedure for broader use in health research. Furthermore, due to unexamined heterogeneity, there is a need to replicate the results of this study in different patient populations.

Background: The Australian Institute of Health and Welfare has reported an increased rate of hospital-treated intentional self-harm in young females (2000¿2012) in Australia. These reported increases arise from institutional data that are acknowledged to underestimate the true rate, although the degree of underestimation is not known. Objective: To consider whether the reported increase in young females¿ hospital-treated intentional self-harm is real or artefactual and specify the degree of institutional underestimation. Methods: Averages for age- and gender-standardised event rates for hospital-treated intentional self-harm (national: Australian Institute of Health and Welfare; state: New South Wales Ministry of Health) were compared with sentinel hospital event rates for intentional self-poisoning (Hunter Area Toxicology Service, Calvary Mater Newcastle) in young people (15¿24 years) for the period 2000¿2012. A time series analysis of the event rates for the sentinel hospital was conducted. Results: The sentinel hospital event rates for young females of 444 per 100,000 were higher than the state (378 per 100,000) and national (331 per 100,000) rates. There was little difference in young male event rates ¿ sentinel unit: 166; state: 166 and national: 153 per 100,000. The sentinel hospital rates showed no change over time for either gender. Conclusion: There was no indication from the sentinel unit data of any increase in rates of intentional self-poisoning for young females. The sentinel and state rates were higher than the national rates, demonstrating the possible magnitude of underestimation of the national data. The reported increases in national rates of hospital-treated self-harm among young females might be due to artefactual factors, such as changes in clinical practice (greater proportion admitted), improved administrative coding of suicidal behaviours or possibly increased hospital presentations of community self-injury cases, but not intentional self-poisoning. A national system of sentinel units is needed for the accurate and timely monitoring of all hospital-treated self-harm.

The aim of this study was to determine the relationship between alcohol co-ingestion in an index deliberate self-poisoning (DSP) episode with repeated DSP and subsequent suicide. A retrospective cohort study was conducted involving 5,669 consecutive index presentations to a toxicology service following DSP between January 1, 1996, and October 31, 2010. Records were probabilistically matched to National Coronial Information System data to identify subsequent suicide. Index DSPs were categorized on co-ingestion of alcohol, and primary outcomes analyzed were repetition of any DSP, rates of repeated DSP, time to first repeat DSP, and subsequent suicide. Co-ingestion of alcohol occurred in 35.9% of index admissions. There was no difference between those who co-ingested alcohol (ALC+) and those who did not co-ingest alcohol (ALC-) in terms of proportion of repeat DSP, number of DSP events, or time to first repeat DSP event. Forty-one (1.0%) cases were probabilistically matched to a suicide death; there was no difference in the proportion of suicide between ALC+ and ALC- at 1 or 3¿years. There was no significant relationship between the co-ingestion of alcohol in an index DSP and subsequent repeated DSP or suicide. Clinically, this highlights the importance of mental health assessment of patients that present after DSP, irrespective of alcohol co-ingestion at the time of event.

Assessment of a patient after hospital-treated self-harm or psychiatric hospitalization often includes a risk assessment, resulting in a classification of high risk versus low risk for a future episode of self-harm. Through systematic review and a series of meta-analyses looking at unassisted clinician risk classification (eight studies; N¿=¿22,499), we found pooled estimates for sensitivity 0.31 (95% CI: 0.18¿0.50), specificity 0.85 (0.75¿0.92), positive predictive value 0.22 (0.21¿0.23), and negative predictive value 0.89 (0.86¿0.92). Clinician classification was too inaccurate to be clinically useful. After-care should therefore be allocated on the basis of a needs rather than risk assessment.

The repetition of hospital-treated self-harm by young people is common. However, little work has summarised the modifiable factors associated with this. A thorough understanding of those factors most strongly associated with repetition could guide the development of relevant clinical interventions. We systematically reviewed four databases (EMBASE, Medline, PubMed and PsycINFO) until 15 April 2016 to identify all observational studies of factors for the repetition of self-harm or suicide reattempts (together referred to as ¿self-harm behaviour¿) in young people. We quantified the magnitude of association with odds ratios (OR) and 95% confidence intervals (CIs) and calculated the population attributable risk (PAR) and population preventable fraction (PPF) for modifiable factors to provide an indication of the potential impact in reducing subsequent self-harm behaviour in this population. Seventeen studies were included comprising 10,726 participants. Borderline personality disorder (OR 3.47, 95% CI 1.84¿6.53; PAR 42.4%), any personality disorder (OR 2.54, 95% CI 1.71¿3.78; PAR 16.3%), and any mood disorder (OR 2.16, 95% CI 1.09¿4.29; PAR 42.2%) are important modifiable risk factors. Severity of hopelessness (OR 2.95, 95% CI 1.74¿5.01), suicidal ideation (OR 2.01, 95% CI 1.43¿2.81), and previous sexual abuse (OR 1.52, 95% CI 1.02¿2.28; PAR 12.8%) are also associated with repetition of self-harm. We recommend that clinical services should focus on identifying key modifiable risk factors at the individual patient level, whilst the reduction of exposure to child and adolescent sexual abuse would also be a useful goal for public health interventions.

Social influences on suicidal behaviors may be important but are less frequently studied than the influences of mental illness, physical illness, and demographic variables. Major international sporting events may have an impact on suicidal behaviors at the national and local level, an effect possibly mediated by gender and age. We examined the association of hospital-treated deliberate self-poisoning episodes (by gender and by age) in Tehran: before, during, and after the 2014 FIFA World Cup held in Brazil, in which the Iranian national team participated and was eliminated after the pool games. We used a time series analysis within an autoregressive integrated moving average model and found a significant increase in hospital-treated deliberate self-poisoning during the 4-week period of the 2014 FIFA World Cup in Brazil in females but a nonsignificant increase in males. A significant increase was also seen in the youngest age group (12¿20¿years), but not in the two older age groups. If the effects of nonsuccess at major international sporting events could be shown to have a potential harmful effect on aggregate local or national rates of suicidal behaviors, the possibility of preventative interventions and preemptive additional service provision could be planned in advance of these events.

This study reports the outcomes, during follow-up, of a low-cost postcard intervention in a Randomized Control Trial of hospital-treated self-poisoning (n¿=¿2300). The intervention was 9 postcards over 12 months (plus usual treatment) versus usual treatment. Three binary endpoints at 12¿24 months (n¿=¿2001) were: any suicidal ideation, suicide attempt, or self-cutting. There was a significant reduction in any suicidal ideation (RRR 0.20 CI 95% 0.13¿0.27), (NNT 8, 6¿13), and any suicide attempt (RRR 0.31, 0.06¿0.50), (NNT 35, 19¿195), in this non-western population. However, there was no effect on self-cutting (RRR -0.01, -1.05¿0.51). Sustained, brief contact by mail may reduce some forms of suicidal behavior in self-poisoning patients during the post intervention phase.

Background The aim of this review was to assess whether suicide prevention provided in the primary health care setting and delivered by GPs results in fewer suicide deaths, episodes of self-harm, attempts and lower frequency of thoughts about suicide. Methods We conducted a systematic review and meta-analysis using PRIMSA guidelines. Eligible studies: 1) evaluated an intervention provided by GPs; 2) assessed suicide, self-harm, attempted suicide or suicide ideation as outcomes, and; 3) used a quasi-experimental observational or trial design. Study specific effect sizes were combined using the random effects meta-analysis, with effects transformed into relative risk (RR). Results We extracted data from 14 studies for quantitative meta-analysis. The RR for suicide death in quasi-experimental observational studies comparing an intervention region against another region acting as a ¿control¿ was 1.26 (95% CI 0.58, 2.74). When suicide in the intervention region was compared before and after the GP program, the RR was 0.78 (95% CI 0.62, 0.97). There was no evidence of a treatment effect for GP training on rates of suicide death in one cRCT (RR 1.07, 95% CI 0.79, 1.45). There was no evidence of effect for the most other outcomes studied. Limitations All of the studies included in this review are likely to have a high level of bias. It is also possible that we excluded or missed relevant studies in our review process Conclusions Interventions have produced equivocal results, which varied by study design and outcome. Given these results, we cannot recommend the roll out of GP suicide prevention initiatives.

Methamphetamine dependence is a growing problem in Australia and globally. Currently, there are no approved pharmacotherapy options for the management of methamphetamine dependence. N-acetylcysteine is one potential pharmacotherapy option. It has received growing attention as a therapy for managing addictions because of its capacity to restore homeostasis to brain glutamate systems disrupted in addiction and thereby reduce craving and the risk of relapse. N-acetylcysteine also has antioxidant properties that protect against methamphetamine-induced toxicity and it may therefore assist in the management of the neuropsychiatric and neurocognitive effects of methamphetamine. This commentary overviews the actions of N-acetylcysteine and evidence for its efficacy in treating addiction with a particular focus on its potential utility for methamphetamine dependence. We conclude that the preliminary evidence indicates a need for full-scale trials to definitively establish whether N-acetylcysteine has a therapeutic benefit and the nature of this benefit, for managing methamphetamine dependence. [McKetin R, Dean O, Baker A. L, Carter G, Turner A, Kelly P. J, Berk M. A potential role for N-acetylcysteine in the management of methamphetamine dependence. Drug Alcohol Rev 2017;36:153¿159].

Background Prediction of suicidal behaviour is an aspirational goal for clinicians and policy makers; with patients classified as 'high risk' to be preferentially allocated treatment. Clinical usefulness requires an adequate positive predictive value (PPV). Aims To identify studies of predictive instruments and to calculate PPV estimates for suicidal behaviours. Method A systematic review identified studies of predictive instruments. A series of meta-analyses produced pooled estimates of PPV for suicidal behaviours. Results For all scales combined, the pooled PPVs were: suicide 5.5% (95% CI 3.9-7.9%), self-harm 26.3% (95% CI 21.8-31.3%) and self-harm plus suicide 35.9% (95% CI 25.8-47.4%). Subanalyses on self-harm found pooled PPVs of 16.1% (95% CI 11.3-22.3%) for high-quality studies, 32.5% (95% CI 26.1-39.6%) for hospital-treated self-harm and 26.8% (95% CI 19.5-35.6%) for psychiatric in-patients. Conclusions No 'high-risk' classification was clinically useful. Prevalence imposes a ceiling on PPV. Treatment should reduce exposure to modifiable risk factors and offer effective interventions for selected subpopulations and unselected clinical populations.

Objective: There is a need for a simple and brief tool that can be used in routine clinical practice for the quantitative measurement of mental state across all diagnostic groups. The main utilities of such a tool would be to provide a global metric for the mental state examination, and to monitor the progression over time using this metric. Method: We developed the mental state examination scale (MSES), and used it in an acute inpatient setting in routine clinical work to test its initial feasibility. Results: Using a clinical case, the utility of MSES is demonstrated in this paper. When managing the patient described, the MSES assisted the clinician to assess the initial mental state, track the progress of the recovery, and make timely treatment decisions by quantifying the components of the mental state examination. Conclusion: MSES may enhance the quality of clinical practice for clinicians, and potentially serve as an index of universal mental healthcare outcome that can be used in clinical practice, service evaluation, and healthcare economics.

Background: Several recent trials indicate low-dose ketamine produces rapid antidepressant effects. However, uncertainty remains in several areas: dose response, consistency across patient groups, effects on suicidality, and possible biases arising from crossover trials. Methods: A systematic search was conducted for relevant randomized trials in Medline, Embase, and PsycINFO databases up to August 2014. The primary endpoints were change in depression scale scores at days 1, 3 and 7, remission, response, suicidality, safety, and tolerability. Data were independently abstracted by 2 reviewers. Where possible, unpublished data were obtained on treatment effects in the first period of crossover trials. Results: Nine trials were identified, including 201 patients (52% female, mean age 46 years). Six trials assessed low-dose ketamine (0.5mg/kg i.v.) and 3 tested very low-dose ketamine (one trial assessed 50mg intra-nasal spray, another assessed 0.1-0.4mg/kg i.v., and another assessed 0.1-0.5mg/kg i.v., intramuscular, or s.c.). At day 3, the reduction in depression severity score was less marked in the very low-dose trials (P homogeneity <.05) and among bipolar patients. In analyses excluding the second period of crossover trials, response rates at day 7 were increased with ketamine (relative risk 3.4, 95% CI 1.6-7.1, P=.001), as were remission rates (relative risk 2.6, CI 1.2-5.7, P=.02). The absolute benefits were large, with day 7 remission rates of 24% vs 6% (P=.02). Seven trials provided unpublished data on suicidality item scores, which were reduced on days 1 and 3 (both P<.01) but not day 7. Conclusion: Low-dose ketamine appears more effective than very low dose. There is substantial heterogeneity in clinical response, with remission among one-fifth of patients at 1 week but most others having benefits that are less durable. Larger, longer term parallel group trials are needed to determine if efficacy can be extended and to further assess safety.

Background. Impaired health-related quality of life (HRQoL) post stroke is common, though prevalence estimates vary considerably. Few longitudinal studies explore post-stroke patterns of HRQoL and factors contributing to their change over time. Accurately identifying HRQoL after stroke is essential to understanding the extent of stroke effects. Objectives. This study aimed to assess change in levels of, and identify independent predictors of, HRQoL over the first 12-months post-stroke. Methods. Design. A prospective cohort study. Setting and participants. Community-dwelling stroke survivors in metropolitan Newcastle, New South Wales (NSW), Australia. Consecutively recruited stroke patients (n = 134) participated in face-to-face interviews at baseline, 3, 6, 9 and 12 months. Outcome measure. HRQoL (measured using the Assessment Quality-of-life).Independent measures. Physical and psycho-social functioning, including depression and anxiety (measured via Hospital Anxiety and Depression Scale), disability (Modified Rankin Scale), social support (Multi-dimensional Scale Perceived Social Support) and community participation (Adelaide Activities Profile).Analyses. A linear mixed model was used to establish the predictors of, change in HRQoL over time. Results. On multivariable analysis, HRQOL did not change significantly with time post-stroke. Higher HRQoL scores were independently associated with higher baseline HRQoL (P = 0.03), younger age (P = 0.006), lower disability (P = 0.003), greater community participation (P = 0.001) and no history of depression (P = 0.03). Conclusion. These results contribute to an understanding of HRQoL in the first year post-stroke. Community participation and stroke-related disability are potentially modifiable risk factors affecting post-stroke HRQoL. Interventions aimed at addressing participation and disability post-stroke should be developed and tested.

Purpose: The importance of distress identification and management in oncology has been established. We examined the relationship between distress and unmet bio-psychosocial needs, applying advanced statistical techniques, to identify which needs have the closest relationship to distress. Methods: Oncology outpatients (n¿=¿1066) undergoing QUICATOUCH screening in an Australian cancer centre completed the distress thermometer (DT) and problem list (PL). Principal component analysis (PCA), logistic regression and classification and regression tree (CART) analyses tested the relationship between DT score (at a cut-off point of 4) and PL items. Results: Sixteen items were reported by <5¿% of participants. PCA analysis identified four major components. Logistic regression analysis indicated three of these component scores, and four individual items (20 items in total) demonstrated a significant independent relationship with distress. The best CART model contained only two PL items: ¿worry¿ and ¿depression¿. Conclusions: The DT and PL function as intended, quantifying negative emotional experience (distress) and identifying bio-psychosocial sources of distress. We offer two suggestions to minimise PL response time whilst targeting PL items most related to distress, thereby increasing clinical utility. To identify patients who might require specialised psychological services, we suggest the DT followed by a short, case-finding instrument for patients over threshold on the DT. To identify other important sources of distress, we suggest using a modified PL of 14 key items, with the 15th item ¿any other problem¿ as a simple safety net question. Shorter times for patient completion and clinician response to endorsed PL items will maximise acceptance and clinical utility.

Background: Brief Contact Interventions (BCIs) have been of increasing interest to suicide prevention clinicians, researchers and policy makers. However, there has been no systematic assessment into the mechanisms underpinning BCIs. The aim of the current paper is to provide a systematic review of the proposed mechanisms underpinning BCIs across trial studies. Method: A systematic review was conducted of trials using BCIs (post-discharge telephone contacts; emergency or crisis cards; and postcard or letter contacts) for suicide or self-harm. Following PRISMA guidelines, we searched CENTRAL, MEDLINE, EMBASE, and the reference lists of all past reviews in the area. Secondary searches of reference lists were undertaken. Results: Sixteen papers provided a description of possible mechanisms which we grouped into three main areas: social support; suicide prevention literacy, and; learning alternative coping behaviours. After assessment of the studies and considering the plausibility of mechanisms, we suggest social support and improved suicide prevention literacy are the most likely mechanisms underpinning BCIs. Conclusion: Researchers need to better articulate and measure the mechanisms they believe underpin BCIs in trial studies. Understanding more about the mechanisms of BCIs' will inform the development of future interventions for self-harm and suicide.

Objective: To provide guidance for the organisation and delivery of clinical services and the clinical management of patients who deliberately self-harm, based on scientific evidence supplemented by expert clinical consensus and expressed as recommendations. Method: Articles and information were sourced from search engines including PubMed, EMBASE, MEDLINE and PsycINFO for several systematic reviews, which were supplemented by literature known to the deliberate self-harm working group, and from published systematic reviews and guidelines for deliberate self-harm. Information was reviewed by members of the deliberate self-harm working group, and findings were then formulated into consensus-based recommendations and clinical guidance. The guidelines were subjected to successive consultation and external review involving expert and clinical advisors, the public, key stakeholders, professional bodies and specialist groups with interest and expertise in deliberate self-harm. Results: The Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for deliberate self-harm provide up-to-date guidance and advice regarding the management of deliberate self-harm patients, which is informed by evidence and clinical experience. The clinical practice guidelines for deliberate self-harm is intended for clinical use and service development by psychiatrists, psychologists, physicians and others with an interest in mental health care. Conclusion: The clinical practice guidelines for deliberate self-harm address self-harm within specific population sub-groups and provide up-to-date recommendations and guidance within an evidence-based framework, supplemented by expert clinical consensus.

Background There is growing interest in brief contact interventions for self-harm and suicide attempt. Aims To synthesise the evidence regarding the effectiveness of brief contact interventions for reducing self-harm, suicide attempt and suicide. Method A systematic review and random-effects meta-analyses were conducted of randomised controlled trials using brief contact interventions (telephone contacts; emergency or crisis cards; and postcard or letter contacts). Several sensitivity analyses were conducted to examine study quality and subgroup effects. Results We found 14 eligible studies overall, of which 12 were amenable to meta-analyses. For any subsequent episode of self-harm or suicide attempt, there was a non-significant reduction in the overall pooled odds ratio (OR) of 0.87 (95% CI 0.74-1.04, P = 0119) for intervention compared with control. The number of repetitions per person was significantly reduced in intervention v. control (incidence rate ratio IRR = 066, 95% CI 0.54-0.80, P<0001). There was no significant reduction in the odds of suicide in intervention compared with control (OR = 0.58, 95% CI 0.24-1.38). Conclusions A non-significant positive effect on repeated self-harm, suicide attempt and suicide and a significant effect on the number of episodes of repeated self-harm or suicide attempts per person (based on only three studies) means that brief contact interventions cannot yet be recommended for widespread clinical implementation. We recommend further assessment of possible benefits in well-designed trials in clinical populations.

Objective Many patients who experience distress do not seek help, and little is known about the reasons for this. We explored the reasons for declining help among patients who had significant emotional distress. Methods Data were collected through QUICATOUCH screening at an Australian hospital. Oncology outpatients scoring 4 or more on the Distress Thermometer were asked if they would 'like help' with their distress. Those who declined help were asked their reasons. Demographic variables and a clinical measure of anxiety and depression (PSYCH-6) were used to identify factors associated with reasons for declining help. Results Of 311 patients with significant distress, 221 (71%) declined help. The most common reasons were 'I prefer to manage myself' (n = 99, 46%); 'already receiving help' (n = 52, 24%) and 'my distress is not severe enough' (n = 50, 23%). Younger patients and women were more likely to decline help and were more likely to already be receiving help. Distress score and PSYCH-6 scores were significantly lower among patients who rated their distress as not severe enough to require help. Nevertheless, there were patients who had maximal scores on distress and PSYCH in each group. Conclusions Two common patient barriers to help with distress are a preference for self-help and a belief that distress is not sufficiently severe to warrant intervention. These beliefs were held by a sizeable proportion of individuals who reported very high levels of distress. Qualitative research and subsequent interventions for overcoming these barriers are required to obtain the most benefit from distress screening programs.

Objective: Hospital-treated deliberate self-poisoning (DSP) is common and the existing national monitoring systems are often deficient. Clinical Practice Guidelines (UK and Australia) recommend universal psychosocial assessment within the general hospital as standard care. We compared presentation rates, patient characteristics, psychosocial assessment and aftercare in UK and Australia. Methods: We used a cross sectional design, for a ten year study of all DSP presentations identified through sentinel units in Oxford, UK (n. = 3042) and Newcastle, Australia (n. = 3492). Results: Oxford had higher presentation rates for females (standardised rate ratio 2.4: CI 99% 1.9, 3.2) and males (SRR 2.5: CI 99% 1.7, 3.5). Female to male ratio was 1.6:1, 70% presented after-hours, 95% were admitted to a general hospital and co-ingestion of alcohol occurred in a substantial minority (Oxford 24%, Newcastle 32%). Paracetamol, minor tranquilisers and antidepressants were the commonest drug groups ingested, although the overall pattern differed. Psychosocial assessment rates were high (Oxford 80%, Newcastle 93%). Discharge referral for psychiatric inpatient admission (Oxford 8%, Newcastle 28%), discharge to home (Oxford 80%, Newcastle 70%) and absconding (Oxford 11%, Newcastle 2%) differed between the two units. Conclusions: Oxford has higher age-standardised rates of DSP than Newcastle, although many other characteristics of patients are similar. Services can provide a high level of assessment as recommended in clinical guidelines. There is some variation in after-care. Sentinel service monitoring routine care of DSP patients can provide valuable comparisons between countries.

Hospital-treated deliberate self-poisoning (DSP) by central nervous system depressant drugs (CNS-D) has been associated with impairments in cognitive and psychomotor functions at the time of discharge. We aimed to replicate this finding and to compare recovery in the first month after discharge for CNS-D and CNS nondepressant drug ingestions. We also examined a series of multivariate explanatory models of recovery of neurocognitive outcomes over time. The CNS-D group was impaired at discharge compared with the CNS-nondepressant group in cognitive flexibility, cognitive efficiency, and working memory. There were no significant differences at discharge in visual attention, processing speed, visuomotor speed, or inhibition speed. Both groups improved in the latter measures over 1 month of follow-up. However, the CNS-D group's recovery was significantly slower for key neurocognitive domains underlying driving in complex traffic situations, namely, cognitive flexibility, cognitive efficiency, and working memory. Patients discharged after DSP with CNS-D drugs have impairments of some critical cognitive functions that may require up to 1 month to recover. Although more pre-than post-DSP variables were retained as explanatory models of neurocognitive performance overall, recovery over time could not be explained by any one of the measured covariates. Tests of cognitive flexibility could be used in clinical settings as a proxy measure for recovery of driving ability. Regulatory authorities should also consider the implications of these results for the period of nondriving advised after ingestion of CNS-D in overdose. Future research, with adequate sample size, should examine contributions of other variables to the pattern of recovery over time.

Background: Active Surveillance (AS) is recommended for the treatment of localised prostate cancer; however this option may be under-used, at least in part because of expectations of psychological adverse events in those offered or accepting AS. Objective: (1) Determine the impact on psychological wellbeing when treated with AS (non-comparative studies). (2) Compare AS with active treatments for the impact on psychological wellbeing (comparative studies). Method: We used the PRISMA guidelines and searched Medline, PsychInfo, EMBASE, CINHAL, Web of Science, Cochrane Library and Scopus for articles published January 2000-2014. Eligible studies reported original quantitative data on any measures of psychological wellbeing. Results: We identified 34 eligible articles (. n=. 12,497 individuals); 24 observational, eight RCTs, and two other interventional studies. Studies came from North America (16), Europe (14) Australia (3) and North America/Europe (1). A minority (5/34) were rated as high quality. Most (26/34) used validated instruments, whilst a substantial minority (14/34) used watchful waiting or no active treatment rather than Active Surveillance. There was modest evidence of no adverse impact on psychological wellbeing associated with Active Surveillance; and no differences in psychological wellbeing compared to active treatments. Conclusion: Patients can be informed that Active Surveillance involves no greater threat to their psychological wellbeing as part of the informed consent process, and clinicians need not limit access to Active Surveillance based on an expectation of adverse impacts on psychological wellbeing.

Background: The use of different depression self-report scales warrants co-calibration studies to establish relationships between scores from 2 or more scales. The goal of this study was to examine variations in measurement across 5 commonly used scales to measure depression among patients with cancer: Hospital Anxiety and Depression Scale-Depression subscale (HADS-D), Centre for Epidemiologic Studies Depression Scale (CES-D), Patient Health Questionnaire-9 (PHQ-9), Beck Depression Inventory-II (BDI-II), and Depression Anxiety and Stress Scale-Depression subscale (DASS-D). Methods: The depression scales were completed by 162 patients with cancer. Participants were also assessed by the major depressive episode module of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Rasch analysis and receiver operating characteristic curves were performed. Results: Rasch analysis of the 5 scales indicated that these all measured depression. The HADS and BDI-II had the widest measurement range, whereas the DASS-D had the narrowest range. Co-calibration revealed that the cutoff scores across the scales were not equivalent. The mild cutoff score on the PHQ-9 was easier to meet than the mild cutoff score on the CES-D, BDI-II, and DASS-D. The HADS-D possible cutoff score was equivalent to cutoff scores for major to severe depression on the other scales. Optimal cutoff scores for clinical assessment of depression were in the mild to moderate depression range for most scales. Conclusions: The labels of depression associated with the different scales are not equivalent. Most markedly, the HADS-D possible case cutoff score represents a much higher level of depression than equivalent scores on other scales. Therefore, use of different scales will lead to different estimates of prevalence of depression when used in the same sample.

Background: The confidence with which researchers can comment on intervention efficacy relies on evaluation and consideration of intervention fidelity. Accordingly, there have been calls to increase the transparency with which fidelity methodology is reported. Despite this, consideration and/or reporting of fidelity methods remains poor. We seek to address this gap by describing the methodology for promoting and facilitating the evaluation of intervention fidelity in The EAT (Eating As Treatment) project: a multi-site stepped wedge randomised controlled trial of a dietitian delivered behaviour change counselling intervention to improve nutrition (primary outcome) in head and neck cancer patients undergoing radiotherapy. Methods/Design: In accordance with recommendations from the National Institutes of Health Behaviour Change Consortium Treatment Fidelity Workgroup, we sought to maximise fidelity in this stepped wedge randomised controlled trial via strategies implemented from study design through to provider training, intervention delivery and receipt. As the EAT intervention is designed to be incorporated into standard dietetic consultations, we also address unique challenges for translational research. Discussion: We offer a strong model for improving the quality of translational findings via real world application of National Institutes of Health Behaviour Change Consortium recommendations. Greater transparency in the reporting of behaviour change research is an important step in improving the progress and quality of behaviour change research. Trial registration number:ACTRN12613000320752(Date of registration 21 March 2013)

Purpose: There is evidence that social isolation is a risk factor for suicide, and that social connections are protective. Only a limited number of studies have attempted to correlate the number of social connections a person has in their life and suicidal behaviour. Method: Two population-based case-control studies of young adults (18-34 years) were conducted in New South Wales, Australia. Cases included both suicides (n=84) and attempts (n=101). Living controls selected from the general population were matched to cases by age-group and sex. Social connections was the main exposure variable (representing the number of connections a person had in their life). Suicide and attempts as outcomes were modelled separately and in combination using conditional logistic regression modelling. The analysis was adjusted for marital status, socio-economic status, and diagnosis of an affective or anxiety disorder. Results: Following adjustment for other variables, those who had 3-4 social connections had 74% lower odds of suicide deaths or attempts (OR=0.26, 95% CI 0.08, 0.84, p=0.025), and those with 5-6 connections had 89% lower odds of suicide deaths or attempts (OR=0.11 95% CI 0.03, 0.35, p<0.001), compared to those with 0-2 social connections. With the number of social connection types specified as a continuous variable, the odds ratio was 0.39 per connection (95% CI 0.27, 0.56, p<0.001). Conclusions: A greater number of social connections was significantly associated with reduced odds of suicide or attempt. This suggests that suicide prevention initiatives that promote increased social connections at an individual, familial, and wider social levels might be effective.

Background: Given the stable number of potential organ donors after brain death, donors after circulatory death have been an increasing source of organs procured for transplant. Among the most important considerations for donation after circulatory death (DCD) is the prediction that death will occur within a reasonable period of time after the withdrawal of cardiorespiratory support (WCRS). Accurate prediction of time to death is necessary for the procurement process. We aimed to develop simple predictive rules for death in less than 60 min and test the accuracy of these rules in a pool of potential DCD donors. Methods: A multicenter prospective longitudinal cohort design of DCD eligible patients (n=318), with the primary binary outcome being death in less than 60 min after withdrawal of cardiorespiratory support conducted in 28 accredited intensive care units (ICUs) in Australia. We used a random split-half method to produce two samples, first to develop the predictive classification rules and then to estimate accuracy in an independent sample. Results: The best classification model used only three simple classification rules to produce an overall efficiency of 0.79 (0.72-0.85), sensitivity of 0.82 (0.73-0.90), and a positive predictive value of 0.80 (0.70-0.87) in the independent sample. Using only intensive care unit specialist prediction (a single classification rule) produced comparable efficiency 0.80 (0.73-0.86), sensitivity 0.87 (0.78-0.93), and positive predictive value 0.78 (0.68-0.86). Conclusion: This best predictive model missed only 18% of all potential donors. A positive prediction would be incorrect on only 20% of occasions, meaning there is an acceptable level of lost opportunity costs involved in the unnecessary assembly of transplantation teams and theatres.

Purpose: Few longitudinal studies explore post-stroke patterns of psychological morbidity and factors contributing to their change over time. We aimed to explore predictors of post-stroke depression (PSD) and post-stroke anxiety over a 12-month period. Methods: A prospective cohort study. Consecutively recruited stroke patients (n=134) participated in face-to-face interviews at baseline, 3, 6, 9, and 12 months. Primary outcome measures were depression and anxiety (measured via Hospital Anxiety and Depression Scale). Independent variables included disability (Modified Rankin Scale), Quality-of-life (Assessment Quality-of-life), social support (Multi-dimensional Scale Perceived Social Support) and community participation (Adelaide Activities Profile (AAP)). Secondary outcomes were predictors of resolution and development of PSD and anxiety. Results: Anxiety (47%) was more common than depression (22%) at baseline. Anxiety (but not depression) scores improved over time. Anxiety post-stroke was positively associated with baseline PSD (p<0.0001), baseline anxiety (p<0.0001) and less disability (p=0.042). PSD was associated with baseline anxiety (p<0.0001), baseline depression (p=0.0057), low social support (p=0.0161) and low community participation (p<0.0001). The only baseline factor predicting the resolution of PSD (if depressed at baseline) was increased social support (p=0.0421). Factors that predicted the onset of depression (if not depressed at baseline) were low community participation (p=0.0015) and higher disability (p=0.0057). Conclusion: While more common than depression immediately post-stroke, anxiety attenuates while the burden of depression persists over 12 months. Clinical programs should assess anxiety and depression, provide treatment pathways for those identified, and address modifiable risk factors, especially social support and social engagement.Implications for RehabilitationPsychological distress post stroke is persisting.Multi-disciplinary teams that establish goals with patients promoting social and community engagement could assist in managing psychological morbidity.A shift towards promoting longer-term monitoring and management of stroke survivors must be undertaken, and should consider the factors that support and hinder psychological morbidity.