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Objectives To evaluate how an approach to antidepressant deprescribing works, for whom, and in what contexts by (1) examining the experiences and perceptions of the approach for antidepressant users, (2) identifying the mechanisms of the approach and (3) describing what contexts are associated with antidepressant tapering.Design This mixed methods study was informed by the principles of realist evaluation and was conducted in the first 3 months of participation in the WiserAD randomised control trial.Setting General practice, Victoria, Australia.Participants 13 antidepressant users from general practice participating in the WiserAD trial for antidepressant deprescribing.Intervention A patient-facing, web-based structured support tool that consists of a personalised tapering schedule, an action plan for managing withdrawal symptoms, a daily mood, sleep and activity tracker and mental health nurse support.Primary/secondary outcome measures The outcomes of the study were revealed on data analysis as per a realist evaluation approach which tests and refines an initial programme theory.Results The contexts of learnt coping skills, knowledge and perceptions of antidepressants and feeling well were evident. Outcomes were intention to commence, initiation of deprescribing and successful completion of deprescribing. Key mechanisms for antidepressant deprescribing were (1) initiation of the deprescribing discussion; (2) patient self-efficacy; (3) provision of structured guidance; (4) coaching; (5) mood, sleep and activity tracking and (6) feelings of safety during the tapering period.Conclusions The WiserAD approach to antidepressant deprescribing supported participants to commence and/or complete tapering. The refined programme theory presents the WiserAD pragmatic framework for the application of antidepressant deprescribing in clinical practice.Trial registration number ClinicalTrials.gov NCT05355025; ACTRN12622000567729; ISRCTN11562922; Pre-results.

Abstract Background The evidence for the clinical utility of pharmacogenomic (PGx) testing is growing, and guidelines exist for the use of PGx testing to inform prescribing of 13 antidepressants. Although previous randomised controlled trials of PGx testing for antidepressant prescribing have shown an association with remission of depression in clinical psychiatric settings, few trials have focused on the primary care setting, where most antidepressant prescribing occurs. Methods The PRESIDE Trial is a stratified double-blinded randomised controlled superiority trial that aims to evaluate the impact of a PGx-informed antidepressant prescribing report (compared with standard prescribing using the Australian Therapeutic Guidelines) on depressive symptoms after 12 weeks, when delivered in primary care. Six hundred seventy-two patients aged 18–65 years of general practitioners (GPs) in Victoria with moderate to severe depressive symptoms, measured using the Patient Health Questionnaire-9 (PHQ-9), will be randomly allocated 1:1 to each arm using a computer-generated sequence. Participants and GPs will be blinded to the study arm. The primary outcome is a difference between arms in the change of depressive symptoms, measured using the PHQ-9 after 12 weeks. Secondary outcomes include a difference between the arms in change in PHQ-9 score at 4, 8 and 26 weeks, proportion in remission at 12 weeks, a change in side effect profile of antidepressant medications, adherence to antidepressant medications, change in quality of life and cost-effectiveness of the intervention. Discussion This trial will provide evidence as to whether PGx-informed antidepressant prescribing is clinically efficacious and cost-effective. It will inform national and international policy and guidelines about the use of PGx to select antidepressants for people with moderate to severe depressive symptoms presenting in primary care. Trial registration Australian and New Zealand Clinical Trial Registry ACTRN12621000181808. Registered on 22 February 2021.

Abstract Background This paper reports on the cost-effectiveness evaluation of Link-me – a digitally supported, systematic approach to triaging care for depression and anxiety in primary care that uses a patient-completed Decision Support Tool (DST). Methods The economic evaluation was conducted alongside a parallel, stratified individually randomised controlled trial (RCT) comparing prognosis-matched care to usual care at six- and 12-month follow-up. Twenty-three general practices in three Australian Primary Health Networks recruited 1,671 adults (aged 18 – 75 years), predicted by the DST to have minimal/mild or severe depressive or anxiety symptoms in three months. The minimal/mild prognostic group was referred to low intensity services. Participants screened in the severe prognostic group were offered high intensity care navigation, a model of care coordination. The outcome measures included in this evaluation were health sector costs (including development and delivery of the DST, care navigation and other healthcare services used) and societal costs (health sector costs plus lost productivity), psychological distress [Kessler Psychological Distress Scale (K10)] and quality adjusted life years (QALYs) derived from the EuroQol 5-dimension quality of life questionnaire with Australian general population preference weights applied. Costs were valued in 2018–19 Australian dollars (A$). Results Across all participants, the health sector incremental cost-effectiveness ratio (ICER) of Link-me per point decrease in K10 at six months was estimated at $1,082 (95% CI $391 to $6,204) increasing to $2,371 (95% CI $191 to Dominated) at 12 months. From a societal perspective, the ICER was estimated at $1,257/K10 point decrease (95% CI Dominant to Dominated) at six months, decreasing to $1,217 (95% CI Dominant to Dominated) at 12 months. No significant differences in QALYs were detected between trial arms and the intervention was dominated (less effective, more costly) based on the cost/QALY ICER. Conclusions The Link-me approach to stepped mental health care would not be considered cost-effective utilising a cost/QALY outcome metric commonly adopted by health technology assessment agencies. Rather, Link-me showed a trend toward cost-effectiveness by providing improvement in mental health symptoms, measured by the K10, at an additional cost. Trial registration Australian and New Zealand Clinical Trials Registry, ANZCTRN 12617001333303.

BackgroundResearch suggests that the rapid increase in worldwide antidepressant use is mainly due to a rise in long-term and potentially inappropriate use. It has been suggested that 1 in 3 antidepressant users among general practice patients are no longer experiencing clinical benefits from their medication and should commence deprescribing. However there are many barriers to antidepressant deprescribing for both patients and clinicians, which adds to the complex nature of reducing or ceasing the medication. As such, antidepressant deprescribing does not routinely occur in clinical practice. Evidence-based supports and interventions for safe and successful antidepressant deprescribing are needed to assist patients and their doctors. Interventions should also include an understanding of how an intervention works, why it works, and whom it is for. ObjectiveThis study aims to evaluate how the WiserAD approach to antidepressant deprescribing works, whom it is for, and the underlying circumstances by (1) examining the experiences and perceptions of WiserAD among antidepressant users, (2) identifying the underlying mechanisms of the WiserAD approach to antidepressant deprescribing, and (3) describing in what contexts and to what extent the underlying mechanisms of WiserAD are suited for antidepressant users. MethodsA mixed methods case study with realist evaluation will be conducted among participants in the WiserAD randomized controlled trial for antidepressant deprescribing. Quantitative data will be obtained from up to 12 participants from the intervention and control arms at baseline and 3-month follow-up. Baseline data will be used to characterize the sample using descriptive statistics. Paired samples t tests will also be performed to compare responses between baseline and 3-month follow-up for participant self-management, skills, confidence and knowledge, beliefs about medicines, current emotional health, and well-being symptoms. Qualitative data from the same participants will be collected via narrative interview at 3-month follow-up. Quantitative and qualitative data will be converged to form a “case,” and analysis will be conducted within each case with comparisons made across multiple cases. ResultsRecruitment of participants commenced in October 2022 and will be completed by March 2023. Analysis will be completed by June 2023. ConclusionsTo our knowledge, this will be the first realist evaluation of an antidepressant deprescribing intervention in general practice. Findings from this evaluation may assist in the implementation of the WiserAD approach to antidepressant deprescribing in routine clinical practice. International Registered Report Identifier (IRRID)PRR1-10.2196/42526

Abstract Background The use of general practice electronic health records (EHRs) for research purposes is in its infancy in Australia. Given these data were collected for clinical purposes, questions remain around data quality and whether these data are suitable for use in prediction model development. In this study we assess the quality of data recorded in 201,462 patient EHRs from 483 Australian general practices to determine its usefulness in the development of a clinical prediction model for total knee replacement (TKR) surgery in patients with osteoarthritis (OA). Methods Variables to be used in model development were assessed for completeness and plausibility. Accuracy for the outcome and competing risk were assessed through record level linkage with two gold standard national registries, Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) and National Death Index (NDI). The validity of the EHR data was tested using participant characteristics from the 2014–15 Australian National Health Survey (NHS). Results There were substantial missing data for body mass index and weight gain between early adulthood and middle age. TKR and death were recorded with good accuracy, however, year of TKR, year of death and side of TKR were poorly recorded. Patient characteristics recorded in the EHR were comparable to participant characteristics from the NHS, except for OA medication and metastatic solid tumour. Conclusions In this study, data relating to the outcome, competing risk and two predictors were unfit for prediction model development. This study highlights the need for more accurate and complete recording of patient data within EHRs if these data are to be used to develop clinical prediction models. Data linkage with other gold standard data sets/registries may in the meantime help overcome some of the current data quality challenges in general practice EHRs when developing prediction models.

Objective: The objective of this study was to develop and internally validate a clinical algorithm for use in general practice that predicts the probability of total knee replacement (TKR) surgery within the next five years for patients with osteoarthritis. The purpose of the model is to encourage early uptake of first-line treatment strategies in patients likely to undergo TKR and to provide a cohort for the development and testing of novel interventions that prevent or delay the progression to TKR. Method: Electronic health records (EHRs) from 201,462 patients with osteoarthritis aged 45 years and over from 483 general practices across Australia were linked with records from the Australian Orthopaedic Association National Joint Replacement Registry and the National Death Index. A Fine and Gray competing risk prediction model was developed using these data to predict the risk of TKR within the next five years. Results: During a follow-up time of 5 years, 15,979 (7.9%) patients underwent TKR and 13,873 (6.9%) died. Predictors included in the final algorithm were age, previous knee replacement, knee surgery (other than TKR), prescribing of osteoarthritis medication in the 12 months prior, comorbidity count and diagnosis of a mental health condition. Optimism corrected model discrimination was 0.67 (95% CI: 0.66 to 0.67) and model calibration acceptable. Conclusion: The model has the potential to reduce some of the economic burden associated with TKR in Australia. External validation and further optimisation of the algorithm will be carried out prior to implementation within Australian general practice EHR systems.

Abstract Background Hypertensive disorders of pregnancy (HDP) are the leading cause of maternal mortality in Indonesia. Focused HDP management pathways for Indonesian primary care practice have been developed from a consensus development process. However, the acceptability and feasibility of the pathways in practice have not been explored. This study reports on the implementation process of the pathways to determine their acceptability and feasibility in Indonesian practice. Methods The pathways were implemented in three public primary care clinics (Puskesmas) in Yogyakarta province for a month, guided by implementation science frameworks of Medical Research Council (MRC) and the Practical Robust Implementation and Sustainability Model (PRISM). The participating providers (general practitioners (GPs), midwives, and nurses) were asked to use recommendations in the pathways for a month. The pathway implementation evaluations were then conducted using clinical audits and a triangulation of observations, focus groups (FGs), and interviews with all of the participants. Clinical audit data were analysed descriptively, and qualitative data were analysed using a mix of the inductive-deductive approach of thematic analysis. Results A total of 50 primary care providers, four obstetricians, a maternal division officer in the local health office and 61 patients agreed to participate, and 48 of the recruited participants participated in evaluation FGs or interviews. All of the providers in the Puskesmas attempted to apply recommendations from the pathways to various degrees, mainly adopting preeclampsia risk factor screenings and HDP monitoring. The participants expressed that the recommendations empowered their practice when it came to HDP management. However, their practices were challenged by professional boundaries and hierarchical barriers among health care professionals, limited clinical resources, and regulations from the local health office. Suggestions for future scale-up studies were also mentioned, such as involving champion obstetricians and providing more patient education toolkits. Conclusion The HDP management pathways are acceptable and feasible in Indonesian primary care. A further scale-up study is desired and can be initiated with investigations to minimise the implementation challenges and enhance the pathways’ value in primary care practice.

Abstract Background Hypertensive disorders of pregnancy (HDP) are a significant contributor to the high maternal mortality rate in Indonesia. At the moment, limited guidelines are available to assist primary care providers in managing HDP cases. A previous review of 16 international HDP guidelines has identified opportunities for improving HDP management in Indonesian primary care, but it has not determined the suitability of the recommendations in practice. This study aims to achieve consensus among the experts regarding the recommendations suitability and to develop HDP pathways in Indonesian primary care. Methods Maternal health experts, including GPs, midwives, nurses, medical specialists and health policy researchers from Indonesia and overseas were recruited for the study. They participated in a consensus development process that applied a mix of quantitative and qualitative questions in three Delphi survey rounds. At the first and second-round survey, the participants were asked to rate their agreement on whether each of 125 statements about HDP and HDP management is appropriate for use in Indonesian primary care settings. The third-round survey presented the drafts of HDP pathways and sought participants’ agreement and further suggestions. The participants’ agreement scores were calculated with a statement needing a minimum of 70% agreement to be included in the HDP pathways. The participants’ responses and suggestions to the free text questions were analysed thematically. Results A total of 52 participants were included, with 48, 45 and 37 of them completing the first, second and third round of the survey respectively. Consensus was reached for 115 of the 125 statements on HDP definition, screening, management and long-term follow-up. Agreement scores for the statements ranged from 70.8–100.0%, and potential implementation barriers of the pathways were identified. Drafts of HDP management pathways were also agreed upon and received suggestions from the participants. Conclusions Most evidence-based management recommendations achieved consensus and were included in the developed HDP management pathways, which can potentially be implemented in Indonesian settings. Further investigations are needed to explore the acceptability and feasibility of the developed HDP pathways in primary care practice.

Abstract Background Indonesia has the highest maternal mortality rate in South East Asia, that a third of the mortality is caused by hypertensive disorders of pregnancy (HDP), including preeclampsia and eclampsia. Research suggests that maternal deaths from HDP are avoidable with appropriate initial management in primary care. However, little is known regarding the exact way HDP management is conducted in Indonesian primary care. This research aims to explore the way HDP management is provided, including its barriers and facilitators in Indonesian primary care settings. Methods This research applied a practical qualitative methodology using interviews with a topic guide. It is guided by the implementation science framework of the Medical Research Council (MRC) framework and Practical Robust Implementation and Sustainability Model (PRISM) to design and evaluate complex healthcare interventions. Primary care key stakeholders from Yogyakarta province were recruited from May–December 2018. The interviews were conducted in face-to-face, telephone, and teleconference interviews. Data from the interviews were analysed thematically using a mix of inductive and deductive approaches. Results A total of 24 participants were interviewed, consisting of four general practitioners, five midwives, three nurses, three obstetricians, a cardiologist, five policymakers and three women with a previous history of HDP. Referrals are the usual management performed for HDP women in primary care and the primary care providers’ practice is challenged by three identified themes: (i) providers’ limited confidence to perform HDP management, (ii) fragmented continuity of care, and (iii) community beliefs. Many participants also desired to have more focused guidance to improve HDP management in primary care practice. Conclusion Even though Indonesian antenatal care and referrals are generally accessible, there are many challenges and fragmentation of HDP management. The most prominent challenge is the primary care providers’ lack of confidence in performing the management and the ‘elephant’ of an urgent need of practice guidelines in primary care that has never been appropriately described in the literature. Further development of an evidence-based primary care-focused guidance will potentially improve primary care providers’ skills to perform optimal HDP management and provide appropriate education to their patients.

Background Financial incentives and audit/feedback are widely used in primary care to influence clinician behaviour and increase quality of care. While observational data suggest a decline in quality when these interventions are stopped, their removal has not been evaluated in a randomised controlled trial (RCT), to our knowledge. This trial aimed to determine whether chlamydia testing in general practice is sustained when financial incentives and/or audit/feedback are removed. Methods and findings We undertook a 2 × 2 factorial cluster RCT in 60 general practices in 4 Australian states targeting 49,525 patients aged 16–29 years for annual chlamydia testing. Clinics were recruited between July 2014 and September 2015 and were followed for up to 2 years or until 31 December 2016. Clinics were eligible if they were in the intervention group of a previous cluster RCT where general practitioners (GPs) received financial incentives (AU$5–AU$8) for each chlamydia test and quarterly audit/feedback reports of their chlamydia testing rates. Clinics were randomised into 1 of 4 groups: incentives removed but audit/feedback retained (group A), audit/feedback removed but incentives retained (group B), both removed (group C), or both retained (group D). The primary outcome was the annual chlamydia testing rate among 16- to 29-year-old patients, where the numerator was the number who had at least 1 chlamydia test within 12 months and the denominator was the number who had at least 1 consultation during the same 12 months. We undertook a factorial analysis in which we investigated the effects of removal versus retention of incentives (groups A + C versus groups B + D) and the effects of removal versus retention of audit/feedback (group B + C versus groups A + D) separately. Of 60 clinics, 59 were randomised and 55 (91.7%) provided data (group A: 15 clinics, 11,196 patients; group B: 14, 11,944; group C: 13, 11,566; group D: 13, 14,819). Annual testing decreased from 20.2% to 11.7% (difference −8.8%; 95% CI −10.5% to −7.0%) in clinics with incentives removed and decreased from 20.6% to 14.3% (difference −7.1%; 95% CI −9.6% to −4.7%) where incentives were retained. The adjusted absolute difference in treatment effect was −0.9% (95% CI −3.5% to 1.7%; p = 0.2267). Annual testing decreased from 21.0% to 11.6% (difference −9.5%; 95% CI −11.7% to −7.4%) in clinics where audit/feedback was removed and decreased from 19.9% to 14.5% (difference −6.4%; 95% CI −8.6% to −4.2%) where audit/feedback was retained. The adjusted absolute difference in treatment effect was −2.6% (95% CI −5.4% to −0.1%; p = 0.0336). Study limitations included an unexpected reduction in testing across all groups impacting statistical power, loss of 4 clinics after randomisation, and inclusion of rural clinics only. Conclusions Audit/feedback is more effective than financial incentives of AU$5–AU$8 per chlamydia test at sustaining GP chlamydia testing practices over time in Australian general practice. Trial registration Australian New Zealand Clinical Trials Registry ACTRN12614000595617 In a cluster randomized trial, Jane S Hocking and colleagues investigate the impact of removing financial incentives and/or audit and feedback on chlamydia testing in general practice in Australia. Author summary Why was this study done? Financial incentives and audit/feedback are widely used in primary care to influence clinician behaviour and increase quality of care. As healthcare costs continue to increase, governments and funding agencies are reassessing funding models for primary care, with widespread cuts to financial incentives. While observational data suggest a decline in quality when these interventions are stopped, their removal has not been evaluated in a randomised controlled trial (RCT). What did the researchers do and find? We conducted a 2 × 2 factorial cluster RCT in Australian general practices that aimed to determine the impact on chlamydia testing in general practice when incentive payments per activity and/or audit/feedback on activity performance were removed. Clinics were randomised into 1 of 4 groups: incentives removed but audit/feedback retained, audit/feedback removed but incentives retained, both removed, and both retained. The primary outcome was the annual chlamydia testing rate among 16- to 29-year-old patients. We found that removal of incentive payments had little impact on general practice chlamydia testing, but the removal of audit and feedback reduced testing. What do these results mean? Our payments were consistent with other incentives general practitioners (GPs) received at the time, suggesting that in the Australian general practice setting, incentive payments of this amount do not have a substantial impact on influencing GP preventive healthcare activities such as chlamydia testing. The removal of quarterly audit and feedback for GPs had a greater impact on testing rates, reflecting the importance of this strategy in influencing GP preventive healthcare activities. The provision of audit and feedback was costlier than the provision of financial incentives. However, using online video conferencing and fully automating the audit and feedback reports would reduce costs. Our results suggest that, in Australia at least, audit and feedback is more effective than incentive payments of AU$5 to AU$8 per activity at influencing GP behaviour.

Objective To identify and characterise activities for deprescribing used in general practice and to map the identified activities to pioneering principles of deprescribing.Setting Primary care.Data sources Medline, EMBASE (Ovid), CINAHL, Australian New Zealand Clinical Trials Registry (ANZCTR), Clinicaltrials.gov, ISRCTN registry, OpenGrey, Annals of Family Medicine, BMC Family Practice, Family Practice and British Journal of General Practice (BJGP) from inception to the end of June 2021.Study selection Included studies were original research (randomised controlled trial, quasi-experimental, cohort study, qualitative and case studies), protocol papers and protocol registrations.Data extraction Screening and data extraction was completed by one reviewer; 10% of the studies were independently reviewed by a second reviewer. Coding of full-text articles in NVivo was conducted and mapped to five deprescribing principles.Results Fifty studies were included. The most frequently used activities were identification of appropriate patients for deprescribing (76%), patient education (50%), general practitioners (GP) education (48%), and development and use of a tapering schedule (38%). Six activities did not align with the five deprescribing principles. As such, two principles (engage practice staff in education and appropriate identification of patients, and provide feedback to staff about deprescribing occurrences within the practice) were added.Conclusion Activities and guiding principles for deprescribing should be paired together to provide an accessible and comprehensive guide to deprescribing by GPs. The addition of two principles suggests that practice staff and practice management teams may play an instrumental role in sustaining deprescribing processes within clinical practice. Future research is required to determine the most of effective activities to use within each principle and by whom.

Abstract Background National and international guidelines for the management of hypertensive disorders of pregnancy (HDP) are available in developing countries. However, more detailed clinical pathways for primary care settings are limited. This study focuses on Indonesia, where 72% of women who died from HDP and its complications had received less appropriate treatment according to international guidelines. There is an urgent need to develop primary care focused pathways that enable general practitioners (GPs), midwives and other relevant providers to manage HDP better. Objectives This paper describes a study protocol for the development of HDP management pathways for Indonesian primary care settings. Methods This study design is informed by Implementation Science theories and consists of three phases. The exploratory phase will involve conducting semi-structured interviews with key Indonesian primary care stakeholders to explore their experiences and views on HDP management. The development phase will apply evidence from the literature review and results of the exploratory phase to develop HDP management pathways contextualised to Indonesian primary care settings. Consensus will be sought from approximately 50 experts, consist of general practitioners (GPs), midwives, obstetricians, nurses and policy makers using Delphi technique survey. The evaluation phase will involve a pilot study to evaluate the pathways’ acceptability and feasibility in a sample of Indonesian primary care practices using mixed methods. Discussion The implementation science frameworks inform and guide the phases in this study. Qualitative interviews in the exploratory phase are conducive to eliciting opinions from key stakeholders. Using Delphi technique at the development phase is suitable to seek participants’ consensus on HDP management in primary care. Observations, focus group discussions, interviews as well as analysis of patients’ medical records at the evaluation phase are expected to provide a comprehensive investigation of the implementation of the pathways in practice settings.

Objectives This was a 2-year follow-up study of a primary care-based counselling intervention (weave) for women experiencing intimate partner violence (IPV). We aimed to assess whether differences in depression found at 12 months (lower depression for intervention than control participants) would be sustained at 24 months and differences in quality in life, general mental and physical health and IPV would emerge.Design Cluster randomised controlled trial. Researchers blinded to allocation. Unit of randomisation: family doctors.Setting Fifty-two primary care clinics, Victoria, Australia.Participants Baseline: 272 English-speaking, female patients (intervention n=137, doctors=35; control n=135, doctors=37), who screened positive for fear of partner in past 12 months. Twenty-four-month response rates: intervention 59% (81/137), control 63% (85/135).Interventions Intervention doctors received training to deliver brief, woman-centred counselling. Intervention patients were invited to receive this counselling (uptake rate: 49%). Control doctors received standard IPV information; delivered usual care.Primary and secondary outcome measures Twenty-four months primary outcomes: WHO Quality of Life-Bref dimensions, Short-Form Health Survey (SF-12) mental health. Secondary outcomes: SF-12 physical health and caseness for depression and anxiety (Hospital Anxiety Depression Scale), post-traumatic stress disorder (Check List-Civilian), IPV (Composite Abuse Scale), physical symptoms (≥6 in last month). Data collected through postal survey. Mixed-effects regressions adjusted for location (rural/urban) and clustering.Results No differences detected between groups on quality of life (physical: 1.5, 95% CI −2.9 to 5.9; psychological: −0.2, 95% CI −4.8 to 4.4,; social: −1.4, 95% CI −8.2 to 5.4; environmental: −0.8, 95% CI −4.0 to 2.5), mental health status (−1.6, 95% CI −5.3 to 2.1) or secondary outcomes. Both groups improved on primary outcomes, IPV, anxiety.Conclusions Intervention was no more effective than usual care in improving 2-year quality of life, mental and physical health and IPV, despite differences in depression at 12 months. Future refinement and testing of type, duration and intensity of primary care IPV interventions is needed.Trial registration number ACTRN12608000032358.

S U M M A R Y: Background: Approximately 12–20% of those with osteoarthritis (OA) in Australia who undergo total knee replacement (TKR) surgery do not report any clinical improvement. There is a need to develop prediction tools for use in general practice that allow early identification of patients likely to undergo TKR and those unlikely to benefit from the surgery. First-line treatment strategies can then be implemented and optimised to delay or prevent the need for TKR. The identification of potential non-responders to TKR may provide the opportunity for new treatment strategies to be developed and help ensure surgery is reserved for those most likely to benefit. This statistical analysis plan (SAP) details the statistical methodology used to develop such prediction tools. Objective: To describe in detail the statistical methods used to develop and validate prediction models for TKR surgery in Australian patients with OA for use in general practice. Methods: This SAP contains a brief justification for the need for prediction models for TKR surgery in general practice. A description of the data sources that will be linked and used to develop the models, and estimated sample sizes is provided. The planned methodologies for candidate predictor selection, model development, measuring model performance and internal model validation are described in detail. Intended table layouts for presentation of model results are provided. Conclusion: Consistent with best practice guidelines, the statistical methodologies outlined in this SAP have been pre-specified prior to data pre-processing and model development.

Introduction Poor mental health is an important public health concern, but mental health problems are often under-recognised. Providing feedback to general practitioners (GPs) on their patients’ mental health status may improve the identification of cases in need of mental healthcare.Objectives To investigate the extent of initiation of mental healthcare after identification of poor mental health and to identify factors associated with non-initiation.Design Prospective cohort study with 1-year follow-up.Setting In a population-based health preventive programme, Check Your Health, we conducted a combined mental and physical health check in Randers Municipality, Denmark, in 2012–2015 in collaboration with local GPs.Participants Participants were 350 individuals aged 30–49 years old with screen-detected poor mental health who had not received mental healthcare within the past year. The cohort was derived from 14 167 randomly selected individuals of whom 52% (n=7348) participated. Mental health was assessed by the mental component summary score of the 12-item Short-Form Health Survey.Outcome The outcome was initiation of mental healthcare. Mental healthcare included psychometric testing by GP, talk therapy by GP, contact with a psychologist, contact with a psychiatrist and psychotropic medication.Results Within 1 year, 22% (95% CI 18 to 27) of individuals with screen-detected poor mental health initiated mental healthcare. Among individuals who initiated mental healthcare within follow-up, one in six had visited their GP once or less in the preceding year. Male sex (OR: 0.49 (95% CI 0.28 to 0.86)) and less impaired mental health (OR: 0.93 (95% CI 0.89 to 0.98)) were associated with non-initiation of mental healthcare. We found no overall association between socioeconomic factors and initiating mental healthcare.Conclusion Systematic provision of mental health test results to GPs may improve the identification of cases in need of mental healthcare, but does not translate into initiation of mental healthcare. Further research should focus on methods to improve initiation of mental healthcare, especially among men.Trial registration number NCT02028195.

Abstract Background Depression is a highly prevalent and costly disorder. Effective treatments are available but are not always delivered to the right person at the right time, with both under- and over-treatment a problem. Up to half the patients presenting to general practice report symptoms of depression, but general practitioners have no systematic way of efficiently identifying level of need and allocating treatment accordingly. Therefore, our team developed a new clinical prediction tool (CPT) to assist with this task. The CPT predicts depressive symptom severity in three months’ time and based on these scores classifies individuals into three groups (minimal/mild, moderate, severe), then provides a matched treatment recommendation. This study aims to test whether using the CPT reduces depressive symptoms at three months compared with usual care. Methods The Target-D study is an individually randomized controlled trial. Participants will be 1320 general practice patients with depressive symptoms who will be approached in the practice waiting room by a research assistant and invited to complete eligibility screening on an iPad. Eligible patients will provide informed consent and complete the CPT on a purpose-built website. A computer-generated allocation sequence stratified by practice and depressive symptom severity group, will randomly assign participants to intervention (treatment recommendation matched to predicted depressive symptom severity group) or comparison (usual care plus Target-D attention control) arms. Follow-up assessments will be completed online at three and 12 months. The primary outcome is depressive symptom severity at three months. Secondary outcomes include anxiety, mental health self-efficacy, quality of life, and cost-effectiveness. Intention-to-treat analyses will test for differences in outcome means between study arms overall and by depressive symptom severity group. Discussion To our knowledge, this is the first depressive symptom stratification tool designed for primary care which takes a prognosis-based approach to provide a tailored treatment recommendation. If shown to be effective, this tool could be used to assist general practitioners to implement stepped mental-healthcare models and contribute to a more efficient and effective mental health system. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR 12616000537459 ). Retrospectively registered on 27 April 2016. See Additional file 1 for trial registration data.

Abstract Background Engagement is essential in trials research but is rarely embedded across all stages of the research continuum. The development, use, effectiveness and value of engagement in trials research is poorly researched and understood, and models of engagement are rarely informed by theory. This article describes an innovative methodological approach for the development and application of a relational model of engagement in a stepped wedge designed cluster randomised controlled trial (RCT), the CORE study. The purpose of the model is to embed engagement across the continuum of the trial which will test if an experience-based co-design intervention improves psychosocial recovery for people affected by severe mental illness. Methods The model was developed in three stages and used a structured iterative approach. A context mapping assessment of trial sites was followed by a literature review on recruitment and retention of hard-to-reach groups in complex interventions and RCTs. Relevant theoretical and philosophical underpinnings were identified by an additional review of literature to inform model development and enactment of engagement activities. Results Policy, organisational and service user data combined with evidence from the literature on barriers to recruitment provided contextual information. Four perspectives support the theoretical framework of the relational model of engagement and this is organised around two facets: the relational and continuous. The relational facet is underpinned by relational ethical theories and participatory action research principles. The continuous facet is supported by systems thinking and translation theories. These combine to enact an ethics of engagement and evoke knowledge mobilisation to reach the higher order goals of the model. Conclusions Engagement models are invaluable for trials research, but there are opportunities to advance their theoretical development and application, particularly within stepped wedge designed studies where there may be a significant waiting period between enrolment in a study and receipt of an intervention.

Background: Process evaluations are essential to understand the contextual, relational, and organizational and system factors of complex interventions. The guidance for developing process evaluations for randomized controlled trials (RCTs) has until recently however, been fairly limited. Method/Design: A nested process evaluation (NPE) was designed and embedded across all stages of a stepped wedge cluster RCT called the CORE study. The aim of the CORE study is to test the effectiveness of an experience-based codesign methodology for improving psychosocial recovery outcomes for people living with severe mental illness (service users). Process evaluation data collection combines qualitative and quantitative methods with four aims: (1) to describe organizational characteristics, service models, policy contexts, and government reforms and examine the interaction of these with the intervention; (2) to understand how the codesign intervention works, the cluster variability in implementation, and if the intervention is or is not sustained in different settings; (3) to assist in the interpretation of the primary and secondary outcomes and determine if the causal assumptions underpinning the codesign interventions are accurate; and (4) to determine the impact of a purposefully designed engagement model on the broader study retention and knowledge transfer in the trial. Discussion: Process evaluations require prespecified study protocols but finding a balance between their iterative nature and the structure offered by protocol development is an important step forward. Taking this step will advance the role of qualitative research within trials research and enable more focused data collection to occur at strategic points within studies.

Cross-sectional studies have demonstrated that the brain-derived neurotrophic factor (BDNF) Val66Met single nucleotide polymorphism moderates the association between exposure to negative life events and depression outcomes. Yet, it is currently unclear whether this moderating effect is applicable to positive life events and if the moderating effect is stable over time. To address these gaps in the literature we examined clinical and BDNF genotypic data from a five-year prospective cohort of 310 primary care attendees. Primary care attendees were selected based on existence of depressive symptoms at screening. Depressive symptoms were assessed at baseline and annually for five years post-baseline using the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire-9 (PHQ-9). Linear mixed models assessed differences in depressive symptom severity over the five-year follow-up period by BDNF Val66Met and history of life events, both negative and positive. Analysis identified a novel three-way interaction between the BDNF Val66Met polymorphism, history of severe childhood abuse and time. Post hoc analysis stratified by time, showed a two-way interaction between Val66Met and severe childhood abuse at baseline that was not detectable at any other time point. An interaction between Val66Met and positive life events was not detected. Our longitudinal results suggest the BDNF Val66Met polymorphism moderates the depressive symptom severity experienced by those with a history of severe childhood abuse but does so in a time dependent manner. Our results further support the notion that gene-environment-depression interactions are dynamic and highlight the importance of longitudinal assessment of these interactions. Given these novel longitudinal findings; replication is required.

BackgroundCommunity level interventions to improve maternal and child health have been supported and well evaluated in resource poor settings, but less so in developed countries. PRISM--Program of Resources, Information and Support for Mothers--was a primary care and community-based cluster-randomised trial in sixteen municipalities in Victoria, Australia, which aimed to reduce depression in mothers and improve their physical health. The aim of this paper is to report the longer term outcomes of PRISM and to reflect on lessons learned from this universal community intervention to improve maternal health.MethodsMaternal health outcome data in PRISM were collected by postal questionnaire at six months and two years. At two years, the main outcome measures included the Edinburgh Postnatal Depression Scale (EPDS) and the SF-36. Secondary outcome measures included the Experience of Motherhood Scale (EOM) and the Parenting Stress Index (PSI). A primary intention to treat analysis was conducted, adjusting for the randomisation by cluster.Results7,169/18,424 (39%) women responded to the postal questionnaire at two years -3,894 (40%) in the intervention arm and 3,275 (38%) in the comparison arm. Respondents were mostly representative on available population data comparisons. There were no differences in depression prevalence (EPDS≥13) between the intervention and comparison arms (13.4% vs 13.1%; ORadj = 1.06, 95%CI 0.91-1.24). Nor did women's mental health (MCS: 48.6 vs 49.1) or physical health scores (PCS: 49.1 vs 49.0) on the SF-36 differ between the trial arms.ConclusionImprovement in maternal mental and physical health outcomes at the population level in the early years after childbirth remains a largely unmet challenge. Despite the lack of effectiveness of PRISM intervention strategies, important lessons about systems change, sustained investment and contextual understanding of the workability of intervention strategies can be drawn from the experience of PRISM. Trial Registration. Controlled-Trials.com ISRCTN03464021.

Multimorbidity is a major challenge for patients and healthcare providers. The limited evidence of the effectiveness of interventions for people with multimorbidity means that there is a need for much more research and trials of potential interventions. Here we present a consensus view from a group of international researchers working to improve care for people with multimorbidity to guide future studies of interventions. We suggest that there is a need for careful consideration of whom to include, how to target interventions that address specific problems and that do not add to treatment burden, and selecting outcomes that matter both to patients and the healthcare system. Innovative design of these interventions will be necessary as many will be introduced in service settings and it will be important to ensure methodological rigour, relevance to service delivery, and generalizability across healthcare systems.

BackgroundThis study aimed to estimate rates of chlamydia incidence and re-infection and to investigate the dynamics of chlamydia organism load in prevalent, incident and re-infections among young Australian women.Methods1,116 women aged 16 to 25 years were recruited from primary care clinics in Australia. Vaginal swabs were collected at 3 to 6 month intervals for chlamydia testing. Chlamydia organism load was measured by quantitative PCR.ResultsThere were 47 incident cases of chlamydia diagnosed and 1,056.34 person years of follow up with a rate of 4.4 per 100 person years (95% CI: 3.3, 5.9). Incident infection was associated with being aged 16 to 20 years [RR = 3.7 (95%CI: 1.9, 7.1)], being employed [RR = 2.4 (95%CI: 1.1, 4.9)] and having two or more new sex partners [RR = 5.5 (95%CI: 2.6, 11.7)]. Recent antibiotic use was associated with a reduced incidence [RR:0.1 (95%CI: 0.0, 0.5)]. There were 14 re-infections with a rate of 22.3 per 100 person years (95%CI: 13.2, 37.6). The median time to re-infection was 4.6 months. Organism load was higher for prevalent than incident infections (pConclusionsChlamydia is common among young women and a high proportion of women are re-infected within a short period of time, highlighting the need for effective partner treatment and repeat testing. The difference in organism load between prevalent and incident infections suggests prevalent infection may be more important for ongoing transmission of chlamydia.