Self-reported reasons for reducing or stopping antidepressant medications in primary care: thematic analysis of the diamond longitudinal study.

BACKGROUND: Current treatment guidelines advise that the deprescribing of antidepressants should occur around 6 months post-remission of symptoms. However, this is not routinely occurring in clinical practice, with between 30% and 50% of antidepressant users potentially continuing treatment with no clinical benefit. To support patients to deprescribe antidepressant treatment when clinically appropriate, it is important to understand what is important to patients when making the decision to reduce or cease antidepressants in a naturalistic setting. AIM: The current study aimed to describe the self-reported reasons primary care patients have for reducing or stopping their antidepressant medication. METHODS: Three hundred and seven participants in the diamond longitudinal study reported taking an SSRI/SNRI over the life of the study. Of the 307, 179 reported stopping or tapering their antidepressant during computer-assisted telephone interviews and provided a reason for doing so. A collective case study approach was used to collate the reasons for stopping or tapering. FINDINGS: Reflexive thematic analysis of patient-reported factors revealed five overarching themes; 1. Depression; 2. Medication; 3. Healthcare system; 4. Psychosocial, and; 5. Financial. These findings are used to inform suggestions for the development and implementation of antidepressant deprescribing discussions in clinical practice.

Economic evaluation of a Decision Support Tool to guide intensity of mental health care in general practice: the Link-me pragmatic randomised controlled trial.

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.

Economic evaluation of the Target-D platform to match depression management to severity prognosis in primary care: A within-trial cost-utility analysis.

BACKGROUND: Target-D, a new person-centred e-health platform matching depression care to symptom severity prognosis (minimal/mild, moderate or severe) has demonstrated greater improvement in depressive symptoms than usual care plus attention control. The aim of this study was to evaluate the cost-effectiveness of Target-D compared to usual care from a health sector and partial societal perspective across 3-month and 12-month follow-up. METHODS AND FINDINGS: A cost-utility analysis was conducted alongside the Target-D randomised controlled trial; which involved 1,868 participants attending 14 general practices in metropolitan Melbourne, Australia. Data on costs were collected using a resource use questionnaire administered concurrently with all other outcome measures at baseline, 3-month and 12-month follow-up. Intervention costs were assessed using financial records compiled during the trial. All costs were expressed in Australian dollars (A$) for the 2018-19 financial year. QALY outcomes were derived using the Assessment of Quality of Life-8D (AQoL-8D) questionnaire. On a per person basis, the Target-D intervention cost between $14 (minimal/mild prognostic group) and $676 (severe group). Health sector and societal costs were not significantly different between trial arms at both 3 and 12 months. Relative to a A$50,000 per QALY willingness-to-pay threshold, the probability of Target-D being cost-effective under a health sector perspective was 81% at 3 months and 96% at 12 months. From a societal perspective, the probability of cost-effectiveness was 30% at 3 months and 80% at 12 months. CONCLUSIONS: Target-D is likely to represent good value for money for health care decision makers. Further evaluation of QALY outcomes should accompany any routine roll-out to assess comparability of results to those observed in the trial. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616000537459).

Patient reported self-help strategies and the perceived benefits for managing sub-threshold depressive symptoms: A nested qualitative study of Australian primary care attendees.

BACKGROUND: Subthreshold depression is common in primary care, but there is little information about the self-help strategies that patients use and the perceived benefits of these. AIM: This study sought to elicit the self-help strategies that primary care attendees identified as beneficial for the self-management of subthreshold depressive symptoms and the implications for general practitioners. METHOD: Semi-structured telephone interviews were conducted with 14 people (April-May 2017) from the Target-D randomised controlled trial (RCT). Target-D investigated whether using a patient-centred clinical prediction tool and an e-health platform to match mental health management options to prognosis was beneficial for improving depressive symptoms at 3 months compared to usual care. Interviews were thematically analysed to identify self-help strategies and their perceived benefits. RESULTS: Four overarching domains for the self-management strategies were identified: social, cognitive, behavioural and restorative. Interviewees reported using strategies across multiple domains, which included undertaking enjoyable, immersive activities, that provided relief from automatic negative thoughts and had a perceived cognitive benefit. Differences in the perceived sense of agency were noted around the self-regulation of mood, which indicated more explicit direction to patient-identified self-help management strategies by general practitioners for some may be of benefit in routine care. CONCLUSION: Some of the reported self-management strategies aligned with evidence-based approaches such as physical activity and mindfulness for mental health symptom management. These findings can inform low-intensity interventions within stepped care models for mental health in primary care, social prescribing models and, help to guide the management of patients by GPs for subthreshold depression.

Deprescribing intervention activities mapped to guiding principles for use in general practice: a scoping review.

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.

Moving from "let's fix them" to "actually listen": the development of a primary care intervention for mental-physical multimorbidity.

BACKGROUND: Effective person-centred interventions are needed to support people living with mental-physical multimorbidity to achieve better health and wellbeing outcomes. Depression is identified as the most common mental health condition co-occurring with a physical health condition and is the focus of this intervention development study. The aim of this study is to identify the key components needed for an effective intervention based on a clear theoretical foundation, consideration of how motivational interviewing can inform the intervention, clinical guidelines to date, and the insights of primary care nurses. METHODS: A multimethod approach to intervention development involving review and integration of the theoretical principles of Theory of Planned Behavior and the patient-centred clinical skills of motivational interviewing, review of the expert consensus clinical guidelines for multimorbidity, and incorporation of a thematic analysis of group interviews with Australian nurses about their perspectives of what is needed in intervention to support people living with mental-physical multimorbidity. RESULTS: Three mechanisms emerged from the review of theory, guidelines and practitioner perspective; the intervention needs to actively 'engage' patients through the development of a collaborative and empathic relationship, 'focus' on the patient's priorities, and 'empower' people to make behaviour change. CONCLUSION: The outcome of the present study is a fully described primary care intervention for people living with mental-physical multimorbidity, with a particular focus on people living with depression and a physical health condition. It builds on theory, expert consensus guidelines and clinician perspective, and is to be tested in a clinical trial.

Clinical efficacy of a Decision Support Tool (Link-me) to guide intensity of mental health care in primary practice: a pragmatic stratified randomised controlled trial.

BACKGROUND: The volume and heterogeneity of mental health problems that primary care patients present with is a substantial challenge for health systems, and both undertreatment and overtreatment are common. We developed Link-me, a patient-completed Decision Support Tool, to predict severity of depression or anxiety, identify priorities, and recommend interventions. In this study, we aimed to examine if Link-me reduces psychological distress among individuals predicted to have minimal/mild or severe symptoms of anxiety or depression. METHODS: In this pragmatic stratified randomised controlled trial, adults aged 18-75 years reporting depressive or anxiety symptoms or use of mental health medication were recruited from 23 general practices in Australia. Participants completed the Decision Support Tool and were classified into three prognostic groups (minimal/mild, moderate, severe), and those in the minimal/mild and severe groups were eligible for inclusion. Participants were individually and randomly assigned (1:1) by a computer-generated allocation sequence to receive either prognosis-matched care (intervention group) or usual care plus attention control (control group). Participants were not blinded but intervention providers were only notified of those allocated to the intervention group. Outcome assessment was blinded. The primary outcome was the difference in the change in scores between the intervention and control group, and within prognostic groups, on the 10-item Kessler Psychological Distress Scale at 6 months post randomisation. The trial was registered on the Australian and New Zealand Clinical Trials Registry, ACTRN12617001333303. OUTCOMES: Between Nov 21, 2017, and Oct 31, 2018, 24 616 patients were invited to complete the eligibility screening survey. 1671 of these patients were included and randomly assigned to either the intervention group (n=834) or the control group (n=837). Prognosis-matched care was associated with greater reductions in psychological distress than usual care plus attention control at 6 months (p=0·03), with a standardised mean difference (SMD) of -0·09 (95% CI -0·17 to -0·01). This reduction was also seen in the severe prognostic group (p=0·003), with a SMD of -0·26 (-0·43 to -0·09), but not in the minimal/mild group (p=0·73), with a SMD of 0·04 (-0·17 to 0·24). In the complier average causal effect analysis in the severe prognostic group, differences were larger among those who received some or all aspects of the intervention (SMD range -0·58 to -1·15). No serious adverse effects were recorded. INTERPRETATION: Prognosis-based matching of interventions reduces psychological distress in patients with anxiety or depressive symptoms, particularly in those with severe symptoms, and is associated with better outcomes when patients access the recommended treatment. Optimisation of the Link-me approach and implementation into routine practice could help reduce the burden of disease associated with common mental health conditions such as anxiety and depression. FUNDING: Australian Government Department of Health.

Matching depression management to severity prognosis in primary care: results of the Target-D randomised controlled trial.

BACKGROUND: Mental health treatment rates are increasing, but the burden of disease has not reduced. Tools to support efficient resource distribution are required. AIM: To investigate whether a person-centred e-health (Target-D) platform matching depression care to symptom severity prognosis can improve depressive symptoms relative to usual care. DESIGN AND SETTING: Stratified individually randomised controlled trial in 14 general practices in Melbourne, Australia, from April 2016 to February 2019. In total, 1868 participants aged 18-65 years who had current depressive symptoms; internet access; no recent change to antidepressant; no current antipsychotic medication; and no current psychological therapy were randomised (1:1) via computer-generated allocation to intervention or usual care. METHOD: The intervention was an e-health platform accessed in the GP waiting room, comprising symptom feedback, priority-setting, and prognosis-matched management options (online self-help, online guided psychological therapy, or nurse-led collaborative care). Management options were flexible, neither participants nor staff were blinded, and there were no substantive protocol deviations. The primary outcome was depressive symptom severity (9-item Patient Health Questionnaire [PHQ-9]) at 3 months. RESULTS: In intention to treat analysis, estimated between- arm difference in mean PHQ-9 scores at 3 months was -0.88 (95% confidence interval [CI] = -1.45 to -0.31) favouring the intervention, and -0.59 at 12 months (95% CI = -1.18 to 0.01); standardised effect sizes of -0.16 (95% CI = -0.26 to -0.05) and -0.10 (95% CI = -0.21 to 0.002), respectively. No serious adverse events were reported. CONCLUSION: Matching management to prognosis using a person-centred e-health platform improves depressive symptoms at 3 months compared to usual care and could feasibly be implemented at scale. Scope exists to enhance the uptake of management options.

A Web-Based Mental Health Intervention to Improve Social and Occupational Functioning in Adults With Type 2 Diabetes (The Springboard Trial): 12-Month Outcomes of a Randomized Controlled Trial.

BACKGROUND: People with type 2 diabetes mellitus (T2DM) often experience mental health symptoms that exacerbate illness and increase mortality risk. Access to psychological support is low in people with T2DM. Detection of depression is variable in primary care and can be further hampered by mental health stigma. Electronic mental health (eMH) programs may provide an accessible, private, nonstigmatizing mental health solution for this group. OBJECTIVE: This study aims to evaluate the efficacy over 12 months of follow-up of an eMH program (myCompass) for improving social and occupational functioning in a community sample of people with T2DM and self-reported mild-to-moderate depressive symptoms. myCompass is a fully automated and self-guided web-based public health program for people with depression or anxiety. The effects of myCompass on depressive symptoms, diabetes-related distress, anxiety symptoms, and self-care behavior were also examined. METHODS: Adults with T2DM and mild-to-moderate depressive symptoms (N=780) were recruited via online advertisements, community organizations, and general practices. Screening, consent, and self-report questionnaires were administered online. Eligible participants were randomized to receive either myCompass (n=391) or an attention control generic health literacy program (Healthy Lifestyles; n=379) for 8 weeks. At baseline and at 3, 6, and 12 months postintervention, participants completed the Work and Social Adjustment Scale, the Patient Health Questionnaire-9 item, the Diabetes Distress Scale, the Generalized Anxiety Disorder Questionnaire-7 item, and items from the Self-Management Profile for Type 2 Diabetes. Glycosylated hemoglobin measurements were obtained at baseline and 6 and 12 months postintervention. RESULTS: A total of 38.9% (304/780) of the trial participants completed all postintervention assessments. myCompass users logged in on an average of 6 times and completed an average of 0.29 modules. Healthy Lifestyles users logged in on an average of 4 times and completed an average of 1.37 modules. At baseline, the mean scores on several outcome measures, including the primary outcome of work and social functioning, were close to the normal range, despite a varied and extensive recruitment process. Intention-to-treat analyses revealed slightly greater improvement at 12 months in work and social functioning for the Healthy Lifestyles group relative to the myCompass group. All participants reported equivalent improvements in depression anxiety, diabetes distress, diabetes self-management, and glycemic control across the trial. CONCLUSIONS: The Healthy Lifestyles group reported higher ratings of social and occupational functioning than the myCompass group, but no differences were observed for any secondary outcome. Although these findings should be interpreted in light of the near-floor symptom scores at baseline, the trial yields important insights into how people with T2DM might be engaged in eMH programs and the challenges of focusing specifically on mental health. Several avenues emerge for continued investigation into how best to deal with the growing mental health burden in adults with T2DM. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number (ACTRN) 12615000931572; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368109&isReview=true.

Morpholino Oligomer-Induced Dystrophin Isoforms to Map the Functional Domains in the Dystrophin Protein.

Dystrophin plays a crucial role in maintaining sarcolemma stability during muscle contractions, and mutations that prevent the expression of a functional protein cause Duchenne muscular dystrophy (DMD). Antisense oligonucleotide-mediated manipulation of pre-messenger RNA splicing to bypass Duchenne-causing mutations and restore functional dystrophin expression has entered the clinic for the most common DMD mutations. The rationale of "exon skipping" is based upon genotype-phenotype correlations observed in Becker muscular dystrophy, a milder allelic disorder generally characterized by in-frame deletions and internally truncated but semi-functional dystrophin isoforms. However, there is a lack of genotype-phenotype correlations downstream of DMD exon 55, as deletions in this region are rare and most single exon deletions would disrupt the reading frame. Consequently, the amenability of mutations in this region of the DMD gene to exon skipping strategies remains unknown. Here, we induced "Becker muscular dystrophy-like" in-frame dystrophin isoforms in vivo by intraperitoneal injection of peptide-conjugated phosphorodiamidate morpholino oligomers targeting selected exons. The dystrophin isoform encoded by the transcript lacking exons 56+57 appears to be more functional than that encoded by the 58+59-deleted transcript, as determined by higher dystrophin expression, stabilized ß-dystroglycan, and less severe dystrophic pathology, indicating some potential for the strategy to address Duchenne-causing mutations affecting these exons.

Quality Improvement in Atrial Fibrillation detection after ischaemic stroke (QUIT-AF).

BACKGROUND: Paroxysmal atrial fibrillation (PAF) is a frequent cause of recurrent stroke but can be difficult to detect because of its episodic and often asymptomatic nature. We sought to improve rate of PAF detection through a quality improvement project (QIP) to deliver early prolonged inpatient cardiac monitoring on the stroke unit (SU). METHODS: A structured protocol for cardiac monitoring using 5-day event recorders was established. 'In-house' cardiac monitoring was implemented. Performance data on this change in service was analysed prospectively and summary statistics obtained. RESULTS: One-hundred and two ischaemic stroke (IS) patients undertook 5-day event recorder monitoring. Provision of monitors as an inpatient (IP) increased from 20% (pre-QIP pilot 2018) to 65.7% (during QIP). New AF was detected in 15 patients (14.7% vs 8.6% pre-QIP pilot 2018) with majority of new AF (13 patients; 19%) detected when monitors applied early (IP) after IS. CONCLUSION: Although this study had a number of limitations, it did demonstrate that early and prolonged non-invasive IP cardiac monitoring could be delivered 'in-house' on the SU and improve AF detection rates.

Single Exon Skipping Can Address a Multi-Exon Duplication in the Dystrophin Gene.

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease typically caused by protein-truncating mutations that preclude synthesis of a functional dystrophin. Exonic deletions are the most common type of DMD lesion, however, whole exon duplications account for between 10-15% of all reported mutations. Here, we describe in vitro evaluation of antisense oligonucleotide-induced splice switching strategies to re-frame the transcript disrupted by a multi-exon duplication within the DMD gene. Phosphorodiamidate morpholino oligomers and phosphorodiamidate morpholino oligomers coupled to a cell penetrating peptide were evaluated in a Duchenne muscular dystrophy patient cell strain carrying an exon 14-17 duplication. Two strategies were employed; the conventional approach was to remove both copies of exon 17 in addition to exon 18, and the second strategy was to remove only the first copy of exon 17. Both approaches result in a larger than normal but in-frame DMD transcript, but surprisingly, the removal of only the first exon 17 appeared to be more efficient in restoring dystrophin, as determined using western blotting. The emergence of a normal sized DMD mRNA transcript that was not apparent in untreated samples may have arisen from back splicing and could also account for some of the dystrophin protein being produced.

The role of the general practitioner in managing age-related hearing loss: perspectives of general practitioners, patients and practice staff.

BACKGROUND: For people with hearing loss, the General Practitioner (GP) can play an instrumental role in early detection of hearing loss as well as guiding appropriate and timely choices for addressing hearing concerns. The aim of this study was to generate a conceptual framework for understanding the role of the GP in managing age-related hearing loss. METHODS: Concept mapping techniques were used to gather the perspectives of GPs (n = 8), adults with hearing loss (n = 22), and professionals working with GPs (n = 5), in Australia. Participants generated statements describing the role of the GP in managing age-related hearing loss, and then grouped the statements to identify key themes, via an online portal. RESULTS: Ninety-eight items describing the role of the GP in managing age-related hearing loss were identified across six concepts: 1) Determine - Diagnose - Discuss, 2) Ask - Assess - Act, 3) Know - Refer - Coordinate, 4) Inform - Advise - Partner, 5) Educate - Strategise - Encourage, 6) Reassure - Support - Empower. CONCLUSIONS: The role of the GP in managing age-related hearing loss is multifaceted and requires partnership that motivates and empowers patients' to overcome their hearing concerns. Enlisting the help of Practice Nurses, Practice Managers and local audiologists could help GPs improve their hearing loss detection and intervention rates.

The Role of the General Practitioner in Managing Age-Related Hearing Loss: A Scoping Review.

Purpose The purpose of this review was to examine the research activity relating to the role of the general practitioner (GP) in managing age-related hearing loss in older adults. Method A literature search of peer-reviewed journal articles published in English was conducted in online bibliographic databases using multiple variations of the keywords "general practitioner" and "hearing." Results The search strategy identified 3,255 articles. The abstracts of all articles were screened with 124 full-text records subsequently assessed for eligibility. Forty-nine articles met the inclusion criteria and were included in this review. Conclusions For people with hearing loss, the GP can play an instrumental role in guiding appropriate and timely choices for addressing hearing concerns. There are a range of quick, easy, and sensitive methods available to GPs to assist the objective evaluation of hearing. The evidence suggests that implementing hearing screening programs targeting older adults will increase rates of hearing loss detection and subsequently increase the number of patients receiving hearing loss intervention. Education and training appear key to improving GPs' screening, management, and referral of patients with hearing loss in the primary health care setting.

A Mobile Phone App to Improve the Mental Health of Taxi Drivers: Single-Arm Feasibility Trial.

BACKGROUND: Psychological distress among taxi drivers is 5 times higher than that in the general population, and more than half of all drivers have experienced 3 or more potentially traumatic events in their lifetime. Nevertheless, help-seeking for mental health problems in this male-dominated, predominately immigrant workforce is low. Mobile technologies have the potential to increase mental health awareness, teach self-help skills, and encourage help-seeking in this hard-to-reach population. OBJECTIVE: This study aimed to assess the feasibility, acceptability, and potential efficacy of Driving to Health, a mobile phone-friendly mental health website app designed for people working as taxi drivers. METHODS: Drivers (n=46) were recruited from the Melbourne Airport Taxi Holding Yard to participate in a single-arm trial. Self-reported, paper-based assessments were completed at baseline and at 1 month. Feasibility was measured by completion rates, representativeness of study participants, and levels of use. Acceptability was assessed by measuring users' perception of the quality of the app and anticipated levels of future use. The efficacy of Driving to Health to increase awareness, self-help behaviors, and intentions to seek help was assessed using the user version of the Mobile App Rating Scale (uMARS) and the General Help-Seeking Questionnaire (GHSQ). Psychological symptoms were measured using the short form of the Depression, Anxiety, and Stress Scale (DASS-21). Data were analyzed using complete case analysis. RESULTS: In total, 42 participants comprising drivers from 10 different countries of origin, and 14 different languages, completed pre- and poststudy measures (42/46, 91% completion rate). Just under half (45%) of all users used the app more than once with an average visit of 4 min 8 seconds. Responding to the uMARS, 62% (26/42) of the participants said that they would recommend the app to many people. Nearly all (40/42, 95%) participants said that Driving to Health increased awareness of their own mental health; 86% (36/42) said that it increased their mental health knowledge; and 76% (32/42) said that it increased their self-help behaviors. Increases in help-seeking intentions on the GHSQ were not significant, and increases on all 3 scales of DASS-21 were not reliable or meaningful. CONCLUSIONS: This study suggests that Driving to Health is an acceptable and feasible electronic health intervention for a hard-to-reach population. Our findings also suggest that Driving to Health results in increases in mental health awareness, behaviors, and willingness to seek help.

Antidepressant treatment for primary care patients with depressive symptoms: Data from the diamond longitudinal cohort study.

BACKGROUND: In light of emerging evidence questioning the safety of antidepressants, it is timely to investigate the appropriateness of antidepressant prescribing. This study estimated the prevalence of possible over- and under-treatment with antidepressants among primary care attendees and investigated the factors associated with potentially inappropriate antidepressant use. METHODS: In all, 789 adult primary care patients with depressive symptoms were recruited from 30 general practices in Victoria, Australia, in 2005 and followed up every 3 months in 2006 and annually from 2007 to 2011. For this study, we first assessed appropriateness of antidepressant use in 2007 at the 2-year follow-up to enable history of depression to be taken into account, providing 574 (73%) patients with five yearly assessments, resulting in a total of 2870 assessments. We estimated the prevalence of use of antidepressants according to the adapted National Institute for Health and Care Excellence guidelines and used regression analysis to identify factors associated with possible over- and under-treatment. RESULTS: In 41% (243/586) of assessments where antidepressants were indicated according to adapted National Institute for Health and Care Excellence guidelines, patients reported not taking them. Conversely in a third (557/1711) of assessments where guideline criteria were unlikely to be met, participants reported antidepressant use. Being female and chronic physical illness were associated with antidepressant use where guideline criteria were not met, but no factors were associated with not taking antidepressants where guideline criteria were met. CONCLUSIONS: Much antidepressant treatment in general practice is for people with minimal or mild symptoms, while people with moderate or severe depressive symptoms may miss out. There is considerable scope for improving depression care through better allocation of antidepressant treatment.

The influence of personality on trajectories of distress, health and functioning in mild-to-moderately depressed adults with type 2 diabetes.

Identification of mental health risk is important for optimising diabetes care in type 2 diabetes mellitus (T2DM). Personality is linked to diabetes health and may assist detection of individuals with T2DM most at risk of chronic mental health difficulties. This study examined the moderator effect of personality factors on changes in psychological distress and functioning in adults with T2DM and mild-to-moderate depressive symptoms across a 12-month period. Data were obtained from participants in a randomised controlled trial of adults with T2DM.  Participants completed measures of depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder-7), general functioning (Work and Social Adjustment Scale), diabetes distress (Diabetes Distress Scale), and diabetes self-management (Self-Management Profile for Type 2 Diabetes) at baseline, 3-, 6- and 12-months. Glycaemic control (HbA1c) was measured at baseline, 6- and 12-months. Two hundred trial completers agreed to complete a personality inventory (Big Five Inventory). Low neuroticism was linked with reduced depression, anxiety, functional impairment and diabetes distress over the year. High extraversion was associated with decreased anxiety and functional impairment. High conscientiousness was linked to increased healthy eating. No personality trait moderated HbA1c levels. Personality screening may help identify mental health risk and guide medical carer approach in T2DM patients.

Recruiting to a Randomized Controlled Trial of a Web-Based Program for People With Type 2 Diabetes and Depression: Lessons Learned at the Intersection of e-Mental Health and Primary Care.

BACKGROUND: E-mental health (eMH) interventions are now widely available and they have the potential to revolutionize the way that health care is delivered. As most health care is currently delivered by primary care, there is enormous potential for eMH interventions to support, or in some cases substitute, services currently delivered face to face in the community setting. However, randomized trials of eMH interventions have tended to recruit participants using online recruitment methods. Consequently, it is difficult to know whether participants who are recruited online differ from those who attend primary care. OBJECTIVE: This paper aimed to document the experience of recruiting to an eMH trial through primary care and compare the characteristics of participants recruited through this and other recruitment methods. METHODS: Recruitment to the SpringboarD randomized controlled trial was initially focused on general practices in 2 states of Australia. Over 15 months, we employed a comprehensive approach to engaging practice staff and supporting them to recruit patients, including face-to-face site visits, regular contact via telephone and trial newsletters, and development of a Web-based patient registration portal. Nevertheless, it became apparent that these efforts would not yield the required sample size, and we therefore supplemented recruitment through national online advertising and promoted the study through existing networks. Baseline characteristics of participants recruited to the trial through general practice, online, or other sources were compared using the analysis of variance and chi square tests. RESULTS: Between November 2015 and October 2017, 780 people enrolled in SpringboarD, of whom 740 provided information on the recruitment source. Of these, only 24 were recruited through general practice, whereas 520 were recruited online and 196 through existing networks. Key barriers to general practice recruitment included perceived mismatch between trial design and diabetes population, prioritization of acute health issues, and disruptions posed by events at the practice and community level. Participants recruited through the 3 different approaches differed in age, gender, employment status, depressive symptoms, and diabetes distress, with online participants being distinguished from those recruited through general practice or other sources. However, most differences reached only a small effect size and are unlikely to be of clinical importance. CONCLUSIONS: Time, labor, and cost-intensive efforts did not translate into successful recruitment through general practice in this instance, with barriers identified at several different levels. Online recruitment yielded more participants, who were broadly similar to those recruited via general practice.

A Web-Based Cognitive Behavior Therapy Intervention to Improve Social and Occupational Functioning in Adults With Type 2 Diabetes (The SpringboarD Trial): Randomized Controlled Trial.

BACKGROUND: Depressive symptoms are common in people with type 2 diabetes mellitus (T2DM). Effective depression treatments exist; however, access to psychological support is characteristically low. Web-based cognitive behavioral therapy (CBT) is accessible, nonstigmatizing, and may help address substantial personal and public health impact of comorbid T2DM and depression. OBJECTIVE: The aim of this study was to evaluate the Web-based CBT program, myCompass, for improving social and occupational functioning in adults with T2DM and mild-to-moderate depressive symptoms. myCompass is a fully automated, self-guided public health treatment program for common mental health problems. The impact of treatment on depressive symptoms, diabetes-related distress, anxiety symptoms, and self-care behavior was also examined. METHODS: Participants with T2DM and mild-to-moderate depressive symptoms (N=780) were recruited online via Google and Facebook advertisements targeting adults with T2DM and via community and general practice settings. Screening, consent, and self-report scales were all self-administered online. Participants were randomized using double-blind computerized block randomization to either myCompass (n=391) for 8 weeks plus a 4-week tailing-off period or an active placebo intervention (n=379). At baseline and postintervention (3 months), participants completed the Work and Social Adjustment Scale, the primary outcome measure. Secondary outcome measures included the Patient Health Questionnaire-9 item, Diabetes Distress Scale, Generalized Anxiety Disorder Questionnaire-7 item, and items from the Self-Management Profile for Type 2 Diabetes. RESULTS: myCompass users logged in an average of 6 times and completed an average of .29 modules. Healthy Lifestyles users logged in an average of 4 times and completed an average of 1.37 modules. At baseline, mean scores on several outcome measures, including the primary outcome of work and social functioning, were near to the normal range, despite an extensive recruitment process. Approximately 61.6% (473/780) of participants completed the postintervention assessment. Intention-to-treat analyses revealed improvement in functioning, depression, anxiety, diabetes distress, and healthy eating over time in both groups. Except for blood glucose monitoring and medication adherence, there were no specific between-group effects. Follow-up analyses suggested the outcomes did not depend on age, morbidity, or treatment engagement. CONCLUSIONS: Improvement in social and occupational functioning and the secondary outcomes was generally no greater for myCompass users than for users of the control program at 3 months postintervention. These findings should be interpreted in light of near-normal mean baseline scores on several variables, the self-selected study sample, and sample attrition. Further attention to factors influencing uptake and engagement with mental health treatments by people with T2DM, and the impact of illness comorbidity on patient conceptualization and experience of mental health symptoms, is essential to reduce the burden of T2DM. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615000931572; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368109&isReview=true (Archived by WebCite at http://www.webcitation.org/7850eg8pi).

Antisense Oligonucleotides Targeting Angiogenic Factors as Potential Cancer Therapeutics.

Cancer is one of the leading causes of death worldwide, and conventional cancer therapies such as surgery, chemotherapy, and radiotherapy do not address the underlying molecular pathologies, leading to inadequate treatment and tumor recurrence. Angiogenic factors, such as EGF, PDGF, bFGF, TGF-ß, TGF-α, VEGF, endoglin, and angiopoietins, play important roles in regulating tumor development and metastasis, and they serve as potential targets for developing cancer therapeutics. Nucleic acid-based therapeutic strategies have received significant attention in the last two decades, and antisense oligonucleotide-mediated intervention is a prominent therapeutic approach for targeted manipulation of gene expression. Clinical benefits of antisense oligonucleotides have been recognized by the U.S. Food and Drug Administration, with full or conditional approval of Vitravene, Kynamro, Exondys51, and Spinraza. Herein we review the scope of antisense oligonucleotides that target angiogenic factors toward tackling solid cancers.