Using primary care databases for addiction research:An introduction and overview of strengths and weaknesses

Primary care databases extract and combine routine data from the electronic patient records of various participating practices on a regular basis. These databases can be used for innovative and relevant addiction research, but such use requires a thorough understanding of how data were originally collected and how they need to be processed and statistically analysed to produce sound scientific evidence. The aims of this paper are therefore to (1) make a case for why primary care databases should be considered more frequently for addiction research; (2) provide an overview of how primary care databases are constructed; (3) highlight important methodological and statistical strengths and weaknesses of using primary care databases for research; and (4) give practical advice about how a researcher can get access to databases. Three major primary care databases from the UK serve as examples: Clinical Practice Research Datalink (CPRD), The Health Improvement Network (THIN), and QResearch

Association of socio-economic position and suicide/attempted suicide in low and middle income countries in South and South-East Asia - a systematic review

BACKGROUND: Forty percent of the world’s suicide deaths occur in low and middle income countries (LAMIC) in Asia. There is a recognition that social factors, such as socioeconomic position (SEP), play an important role in determining suicidal risk in high income countries, but less is known about the association in LAMIC. METHODS: The objective of this systematic review was to synthesise existing evidence of the association between SEP and attempted suicide/suicide risk in LAMIC countries in South and South East Asia. Web of Science, MEDLINE, MEDLINE in Process, EMBASE, PsycINFO, and article reference lists/forward citations were searched for eligible studies. Epidemiological studies reporting on the association of individual SEP with suicide and attempted suicide were included. Study quality was assessed using an adapted rating tool and a narrative synthesis was conducted. RESULTS: Thirty-one studies from nine countries were identified; 31 different measures of SEP were reported, with education being the most frequently recorded. Most studies suggest that lower levels of SEP are associated with an increased risk of suicide/attempted suicide, though findings are not always consistent between and within countries. Over half of the studies included in this review were of moderate/low quality. The SEP risk factors with the most consistent association across studies were asset based measures (e.g. composite measures); education; measures of financial difficulty and subjective measures of financial circumstance. Several studies show a greater than threefold increased risk in lower SEP groups with the largest and most consistent association with subjective measures of financial circumstance. CONCLUSION: The current evidence suggests that lower SEP increases the likelihood of suicide/attempted suicide in LAMIC in South and South East Asia. However, the findings are severely limited by study quality; larger better quality studies are therefore needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2014:CRD42014006521 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-2301-5) contains supplementary material, which is available to authorized users

Risk of neuropsychiatric adverse events associated with varenicline:systematic review and meta-analysis

Objective To determine the risk of neuropsychiatric adverse events associated with use of varenicline compared with placebo in randomised controlled trials. Design Systematic review and meta-analysis comparing study effects using two summary estimates in fixed effects models, risk differences, and Peto odds ratios. Data sources Medline, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov. Eligibility criteria for selecting studies Randomised controlled trials with a placebo comparison group that reported on neuropsychiatric adverse events (depression, suicidal ideation, suicide attempt, suicide, insomnia, sleep disorders, abnormal dreams, somnolence, fatigue, anxiety) and death. Studies that did not involve human participants, did not use the maximum recommended dose of varenicline (1 mg twice daily), and were cross over trials were excluded. Results In the 39 randomised controlled trials (10 761 participants), there was no evidence of an increased risk of suicide or attempted suicide (odds ratio 1.67, 95% confidence interval 0.33 to 8.57), suicidal ideation (0.58, 0.28 to 1.20), depression (0.96, 0.75 to 1.22), irritability (0.98, 0.81 to 1.17), aggression (0.91, 0.52 to 1.59), or death (1.05, 0.47 to 2.38) in the varenicline users compared with placebo users. Varenicline was associated with an increased risk of sleep disorders (1.63, 1.29 to 2.07), insomnia (1.56, 1.36 to 1.78), abnormal dreams (2.38, 2.05 to 2.77), and fatigue (1.28, 1.06 to 1.55) but a reduced risk of anxiety (0.75, 0.61 to 0.93). Similar findings were observed when risk differences were reported. There was no evidence for a variation in depression and suicidal ideation by age group, sex, ethnicity, smoking status, presence or absence of psychiatric illness, and type of study sponsor (that is, pharmaceutical industry or other). Conclusions This meta-analysis found no evidence of an increased risk of suicide or attempted suicide, suicidal ideation, depression, or death with varenicline. These findings provide some reassurance for users and prescribers regarding the neuropsychiatric safety of varenicline. There was evidence that varenicline was associated with a higher risk of sleep problems such as insomnia and abnormal dreams. These side effects, however,are already well recognised. Systematic review registration PROSPERO 2014:CRD42014009224

Physicians' prescribing preferences were a potential instrument for patients' actual prescriptions of antidepressants

OBJECTIVES: To investigate whether physicians' prescribing preferences were valid instrumental variables for the antidepressant prescriptions they issued to their patients. STUDY DESIGN AND SETTING: We investigated whether physicians' previous prescriptions of (1) tricyclic antidepressants (TCAs) vs. selective serotonin reuptake inhibitors (SSRIs) and (2) paroxetine vs. other SSRIs were valid instruments. We investigated whether the instrumental variable assumptions are likely to hold and whether TCAs (vs. SSRIs) were associated with hospital admission for self-harm or death by suicide using both conventional and instrumental variable regressions. The setting for the study was general practices in the United Kingdom. RESULTS: Prior prescriptions were strongly associated with actual prescriptions: physicians who previously prescribed TCAs were 14.9 percentage points (95% confidence interval [CI], 14.4, 15.4) more likely to prescribe TCAs, and those who previously prescribed paroxetine were 27.7 percentage points (95% CI, 26.7, 28.8) more likely to prescribe paroxetine, to their next patient. Physicians' previous prescriptions were less strongly associated with patients' baseline characteristics than actual prescriptions. We found no evidence that the estimated association of TCAs with self-harm/suicide using instrumental variable regression differed from conventional regression estimates (P-value = 0.45). CONCLUSION: The main instrumental variable assumptions held, suggesting that physicians' prescribing preferences are valid instruments for evaluating the short-term effects of antidepressants

Who is accessing community lateral flow device testing and why:Characteristics and motivations of individuals participating in COVID-19 community testing in two English local authority areas

BACKGROUND: Antigen testing using lateral flow devices (LFDs) plays an important role in the management of the novel coronavirus pandemic of 2019 (COVID-19) by rapidly identifying individuals who are asymptomatically carrying high levels of the virus. By January 2021, LFD community testing sites were set up across English local authority areas to support the management and containment of regional COVID-19 cases, initially targeting essential workers unable to work from home during the national lockdown. This study aimed to examine the characteristics and motivations of individuals accessing community LFD testing across two local authority areas (LAAs) in the South West of England. METHODS: Data were collected as part of a service evaluation from December 22(nd) 2020 until March 15(th) 2021 for two LAAs. Demographic and postcode data were collected from an online test appointment booking platform and the National Health Service testing service online system, with data accessed from Public Health England. An online survey was sent to individuals who made a testing appointment at an LAA1 site using the online booking platform, consisting of 12 questions to collect data on individual’s motivations for and experiences of testing. RESULTS: Data were available for individuals who completed 12,516 tests in LAA1 and 12,327 tests in LAA2. Most individuals who engaged with testing were female, working age, white, and worked as early years or education staff, health and social care staff, and supermarket or food production staff. 1249 individuals completed the survey with 60% of respondents reported getting tested for work-related reasons. Individuals first heard about LFD testing through various channels including work, media, and word of mouth, and decided to get tested based on the ease and convenience of testing, workplace communications, and to identify asymptomatic cases to help stop the spread. Most tests were completed by individuals living in less deprived areas based on national deciles of deprivation. CONCLUSIONS: While national and local COVID-19 testing strategies have evolved, community and personal LFD testing remains a crucial pillar of the testing strategy. Future studies should collect quantitative and qualitative data from residents to most effectively shape testing offers based on the needs and preferences of their population. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-12986-4

Varenicline Versus Nicotine Replacement Therapy for Long-Term Smoking Cessation:An Observational Study Using the Clinical Practice Research Datalink

Background Smoking is the leading avoidable cause of illness and premature mortality. The first-line treatments for smoking cessation are nicotine replacement therapy and varenicline. Meta-analyses of experimental studies have shown that participants allocated to the varenicline group were 1.57 times (95% confidence interval 1.29 to 1.91 times) as likely to be abstinent 6 months after treatment as those allocated to the nicotine replacement therapy group. However, there is limited evidence about the effectiveness of varenicline when prescribed in primary care. We investigated the effectiveness and rate of adverse events of these medicines in the general population. Objective To estimate the effect of prescribing varenicline on smoking cessation rates and health outcomes. Data sources Clinical Practice Research Datalink. Methods We conducted an observational cohort study using electronic medical records from the Clinical Practice Research Datalink. We extracted data on all patients who were prescribed varenicline or nicotine replacement therapy after 1 September 2006 who were aged ≥ 18 years. We investigated the effects of varenicline on smoking cessation, all-cause mortality and cause-specific mortality and hospitalisation for: (1) chronic lung disease, (2) lung cancer, (3) coronary heart disease, (4) pneumonia, (5) cerebrovascular disease, (6) diabetes, and (7) external causes; primary care diagnosis of myocardial infarction, chronic obstructive pulmonary disease, depression, or prescription for anxiety; weight in kg; general practitioner and hospital attendance. Our primary outcome was smoking cessation 2 years after the first prescription. We investigated the baseline differences between patients prescribed varenicline and patients prescribed nicotine replacement therapy. We report results using multivariable-adjusted, propensity score and instrumental variable regression. Finally, we developed methods to assess the relative bias of the different statistical methods we used. Results People prescribed varenicline were healthier at baseline than those prescribed nicotine replacement therapy in almost all characteristics, which highlighted the potential for residual confounding. Our instrumental variable analysis results found little evidence that patients prescribed varenicline had lower mortality 2 years after their first prescription (risk difference 0.67, 95% confidence interval –0.11 to 1.46) than those prescribed nicotine replacement therapy. They had similar rates of all-cause hospitalisation, incident primary care diagnoses of myocardial infarction and chronic obstructive pulmonary disease. People prescribed varenicline subsequently attended primary care less frequently. Patients prescribed varenicline were more likely (odds ratio 1.46, 95% confidence interval 1.42 to 1.50) to be abstinent 6 months after treatment than those prescribed nicotine replacement therapy when estimated using multivariable-adjusted for baseline covariates. Patients from more deprived areas were less likely to be prescribed varenicline. However, varenicline had similar effectiveness for these groups. Conclusion Patients prescribed varenicline in primary care were more likely to quit smoking than those prescribed nicotine replacement therapy, but there was little evidence that they had lower rates of mortality or morbidity in the 4 years following the first prescription. There was little evidence of heterogeneity in effectiveness across the population

What are the effects of varenicline compared with nicotine replacement therapy on long-term smoking cessation and clinically important outcomes? Protocol for a prospective cohort study

INTRODUCTION: Smoking is a major avoidable cause of ill-health and premature death. Treatments that help patients successfully quit smoking have an important effect on health and life expectancy. Varenicline is a medication that can help smokers successfully quit smoking. However, there are concerns that it may cause adverse effects, such as increase in the occurrence of depression, self-harm and suicide and cardiovascular disease. In this study we aim to examine the effects of varenicline versus other smoking cessation pharmacotherapies on smoking cessation, health service use, all-cause and cause-specific mortality and physical and mental health conditions. METHODS: In this project we will investigate the effects of varenicline compared to nicotine replacement therapies on: (1) long-term smoking cessation and whether these effects differ by area level deprivation; and (2) the following clinically-important outcomes: rate of general practice and hospital attendance; all-cause mortality and death due to diseases of the respiratory system and cardiovascular disease; and a primary care diagnosis of respiratory illness, myocardial infarction or depression and anxiety. The study is based on a cohort of patients prescribed these smoking cessation medications from the Clinical Practice Research Datalink (CPRD). We will use three methods to overcome confounding: multivariable adjusted Cox regression, propensity score matched Cox regression, and instrumental variable regression. The total expected sample size for analysis will be at least 180 000. Follow-up will end with the earliest of either an ‘event’ or censoring due to the end of registration or death. ETHICS AND DISSEMINATION: Ethics approval was not required for this study. This project has been approved by the CPRD's Independent Scientific Advisory Committee (ISAC). We will disseminate our findings via publications in international peer-reviewed journals and presentations at international conferences