Identifying the top research priorities in medically not yet explained symptoms (MNYES): a James Lind Alliance priority setting partnership.

OBJECTIVES: This study establishes research priorities for medically not yet explained symptoms (MNYES), also known as persistent physical symptoms or medically unexplained symptoms, from the perspective of patients, caregivers and clinicians, in a priority setting partnership (PSP) following the James Lind Alliance (JLA) approach. Research into such symptoms in general has been poorly funded over the years and so far has been primarily researcher-led with minimal input from patients, caregivers and clinicians; and sometimes has been controversial. DESIGN: JLA PSP method. The PSP termed these symptoms MNYES. METHODS: The study was conducted according to the JLA's detailed methodology for conducting priority setting exercises. It involved five key stages: defining the appropriate term for the conditions under study by the PSP Steering Group; gathering questions on MNYES from patients, caregivers and clinicians in a publicly accessible survey; checking these research questions against existing evidence; interim prioritisation in a second survey; and a final multi-stakeholder consensus meeting to determine the top 10 unanswered research questions using the modified nominal group methodology. RESULTS: Over 700 responses from UK patients, caregivers and clinicians were identified in the two surveys and charities contributed from a broad range of medical specialties and primary care. The final top 10 unanswered research questions cover, among others: treatment strategies, personalisation of treatment, collaborative care pathways, training for clinicians and outcomes that matter to patients. INTERPRETATION: The top 10 unanswered research questions are expected to generate much needed, relevant and impactful research into MNYES.

Effect of a brief motivational interview and text message intervention targeting tobacco smoking, alcohol use and medication adherence to improve tuberculosis treatment outcomes in adult patients with tuberculosis: a multicentre, randomised controlled trial of the ProLife programme in South Africa.

OBJECTIVE: To investigate the effectiveness of a complex behavioural intervention, ProLife, on tuberculosis (TB) treatment success, medication adherence, alcohol use and tobacco smoking. DESIGN: Multicentre, individual, randomised controlled trial where participants were assigned (1:1) to the ProLife intervention or usual care. SETTING: 27 primary care clinics in South Africa. PARTICIPANTS: 574 adults starting treatment for drug-sensitive pulmonary TB who smoked tobacco or reported harmful/hazardous alcohol use. INTERVENTIONS: The intervention, delivered by lay health workers (LHWs), consisted of three brief motivational interviewing (MI) sessions, augmented with short message service (SMS) messages, targeting medication adherence, alcohol use and tobacco smoking. OUTCOME MEASURES: The primary outcome was successful versus unsuccessful TB treatment at 6-9 months, from TB records. Secondary outcomes were biochemically confirmed sustained smoking cessation, reduction in the Alcohol Use Disorder Identification Test (AUDIT) score, improved TB and antiretroviral therapy (ART) adherence and ART initiation, each measured at 3 and 6 months by questionnaires; and cure rates in patients who had bacteriology-confirmed TB at baseline, from TB records. RESULTS: Between 15 November 2018 and 31 August 2019, 574 participants were randomised to receive either the intervention (n=283) or usual care (n=291). TB treatment success rates did not differ significantly between intervention (67.8%) and control (70.1%; OR 0.9, 95% CI 0.64% to 1.27%). There was no evidence of an effect at 3 and 6 months, respectively, on continuous smoking abstinence (OR 0.65, 95% CI 0.37 to 1.14; OR 0.76, 95% CI 0.35 to 1.63), TB medication adherence (OR 1.22, 95% CI 0.52 to 2.87; OR 0.89, 95% CI 0.26 to 3.07), taking ART (OR 0.79, 95% CI 0.38 to 1.65; OR 2.05, 95% CI 0.80 to 5.27) or AUDIT scores (mean score difference 0.55, 95% CI -1.01 to 2.11; -0.04, 95% CI -2.0 to 1.91) and adjusting for baseline values. Cure rates were not significantly higher (OR 1.16, 95% CI 0.83 to 1.63). CONCLUSIONS: Simultaneous targeting of multiple health risk behaviours with MI and SMS using LHWs may not be an effective approach to improve TB outcomes. TRIAL REGISTRATION NUMBER: ISRCTN62728852.

ImPROving TB outcomes by modifying LIFE-style behaviours through a brief motivational intervention followed by short text messages (ProLife): study protocol for a randomised controlled trial.

BACKGROUND: South Africa is among the seven highest tuberculosis (TB) burden countries. Harmful lifestyle behaviours, such as smoking and alcohol, and poor adherence to medication can affect clinical outcomes. Modification of these behaviours is likely to improve TB treatment outcomes and has proven possible using motivational interviewing (MI) techniques or use of short message service (SMS) text messaging. There have been no studies assessing the effect of combined MI and SMS interventions on multiple lifestyle factors and TB treatment outcomes. METHODS: This is a prospective, multicentre, two-arm individual randomised controlled trial looking at the effectiveness and cost-effectiveness of a complex behavioural intervention (the ProLife programme) on improving TB and lifestyle-related outcomes in three provinces of South Africa. The ProLife programme consists of an MI counselling strategy, delivered by lay health workers, augmented with subsequent SMS. We aim to recruit 696 adult participants (aged 18 years and over) with drug-sensitive pulmonary TB who are current smokers and/or report harmful or hazardous alcohol use. Patients will be consecutively enrolled at 27 clinics in three different health districts in South Africa. Participants randomised individually to the intervention arm will receive three MI counselling sessions one month apart. Each MI session will be followed by twice-weekly SMS messages targeting treatment adherence, alcohol use and tobacco smoking, as appropriate. We will assess the effect on TB treatment success, using standard World Health Organization (WHO) treatment outcome definitions (primary outcome), as well as on a range of secondary outcomes including smoking cessation, reduction in alcohol use, and TB medication and anti-retroviral therapy adherence. Secondary outcomes will be measured at the three-month and six-month follow-ups. DISCUSSION: This trial aligns with the WHO agenda of integrating TB care with the care for chronic diseases of lifestyle, such as provision of smoking cessation treatments, and with the use of digital technologies. If the ProLife programme is found to be effective and cost-effective, the programme could have significant implications for TB treatment globally and could be successfully implemented in a wide range of TB treatment settings. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN62728852. Registered on 13 April 2018.

Screening and case finding for major depressive disorder using the Patient Health Questionnaire (PHQ-9): a meta-analysis.

OBJECTIVE: The Patient Health Questionnaire (PHQ-9) is a widely used screening tool for major depressive disorder (MDD), although there is debate surrounding its diagnostic properties. For the PHQ-9, we aimed to: 1. Establish the diagnostic performance at the standard cutoff point (10). 2. Compare the diagnostic performance at the standard cutoff point in different clinical settings. 3. Assess whether there is selective reporting of cutoff points other than 10. METHODS: We searched three databases - Embase, MEDLINE and PSYCHInfo - and performed a reverse citation search in Web of Science. We selected for inclusion studies of any design that assessed the PHQ-9 in adult populations against recognized gold-standard instruments for the diagnosis of either Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases criteria for major depression. Included studies had to report sufficient information to calculate 2*2 contingency tables. Data extraction and synthesis were performed independently by two researchers. For the included studies, we calculated pooled sensitivity, pooled specificity, positive likelihood, negative likelihood ratio and diagnostic odds ratio for cutoff points 7 to 15. RESULTS: Thirty-six studies (21,292 patients) met inclusion criteria. Pooled sensitivity for cutoff point 10 was 0.78 [95% confidence interval (CI), 0.70-0.84], and pooled specificity was 0.87 (95% CI, 0.84-0.90). At this cutoff, the PHQ-9 is a better screener in primary care than secondary care settings. No conclusions could be drawn at cutoff points other than 10 due to selective reporting of data. CONCLUSIONS: For MDD, the PHQ-9 has acceptable diagnostic properties at cutoff point 10 in different settings. We recommend that future studies report the full range of cutoff points to allow exploration of optimal cutoff points in different settings.