Gabapentinoids in Ireland 2010 to 2020: An observational study of trends in gabapentinoid prescribing, law enforcement drug seizures and postmortem toxicology.

AIMS: We explored trends in gabapentinoid prescribing, drug seizures and postmortem toxicology using a national pharmacy claims database, law enforcement drug seizures data and a population-based postmortem toxicology database. METHODS: Gabapentinoid prescribing rates per 100 000 eligible population (2010-2020), annual number of drug seizures involving gabapentinoids (2012-2020) and gabapentinoid detection (positive) rates per 100 postmortem toxicology case (2013-2020) were calculated. Negative binomial regression models were used to evaluate longitudinal trends for gabapentin and pregabalin separately. RESULTS: Gabapentin (adjusted rate ratio [RR] 1.06, 95% confidence interval [CI] 1.05-1.06, P < .001) and pregabalin (adjusted RR 1.08, 95% CI 1.08-1.09, P < .001) prescribing increased annually, with higher rates of pregabalin (vs. gabapentin) observed every year. Drug seizures involving pregabalin also increased over time (RR 1.54 95% CI 1.25-1.90, P < .0001). Of the 26 317 postmortem toxicology cases, 0.92% tested positive for gabapentin, and 6.37% for pregabalin. Detection rates increased for both gabapentin (RR 1.28, 95% CI 1.11-1.48, P < .001) and pregabalin (RR 1.13, 95% CI 1.11-1.48, P < .001) between 2013 and 2020. A total of 1901 cases (7.2%) tested positive for heroin/methadone; this sub-group had a higher detection rate for pregabalin (n = 528, 27.8%) and gabapentin (n = 41, 2.2%) over the study period, with a high burden of codetections for pregabalin with benzodiazepines (peaking at 37.3% in 2018), and pregabalin with prescription opioids (peaking at 28.9% in 2020). CONCLUSION: This study raises concerns regarding the wide availability of pregabalin in Ireland, including a growing illicit supply, and the potential for serious harm arising from poly drug use involving pregabalin among people who use heroin or methadone.

Prescription drugs with potential for misuse in Irish prisons: analysis of national prison prescribing trends, by gender and history of opioid use disorder, 2012 to 2020.

BACKGROUND: Pharmacotherapy is essential for the delivery of an equivalent standard of care in prison. Prescribing can be challenging due to the complex health needs of prisoners and the risk of misuse of prescription drugs. This study examines prescribing trends for drugs with potential for misuse (opioids, benzodiazepines, Z-drugs, and gabapentinoids) in Irish prisons and whether trends vary by gender and history of opioid use disorder (OUD). METHODS: A repeated cross-sectional study between 2012 and 2020 using electronic prescribing records from the Irish Prison Services, covering all prisons in the Republic of Ireland was carried out. Prescribing rates per 1,000 prison population were calculated. Negative binomial (presenting adjusted rate ratios (ARR) per year and 95% confidence intervals) and joinpoint regressions were used to estimate time trends adjusting for gender, and for gender specific analyses of prescribing trends over time by history of OUD. RESULTS: A total of 10,371 individuals were prescribed opioid agonist treatment (OAT), opioids, benzodiazepines, Z-drugs or gabapentinoids during study period. History of OUD was higher in women, with a median rate of 597 per 1,000 female prisoners, compared to 161 per 1,000 male prisoners. Prescribing time trends, adjusted for gender, showed prescribing rates decreased over time for prescription opioids (ARR 0.82, 95% CI 0.80-0.85), benzodiazepines (ARR 0.99, 95% CI 0.98-0.999), Z-drugs (ARR 0.90, 95% CI 0.88-0.92), but increased for gabapentinoids (ARR 1.07, 95% CI 1.05-1.08). However, prescribing rates declined for each drug class between 2019 and 2020. Women were significantly more likely to be prescribed benzodiazepines, Z-drugs and gabapentinoids relative to men. Gender-specific analyses found that men with OUD, relative to men without, were more likely to be prescribed benzodiazepines (ARR 1.49, 95% CI 1.41-1.58), Z-drugs (ARR 10.09, 95% CI 9.0-11.31), gabapentinoids (ARR 2.81, 95% CI 2.66-2.97). For women, history of OUD was associated with reduced gabapentinoid prescribing (ARR 0.33, 95% CI 0.28-0.39). CONCLUSIONS: While the observed reductions in prescription opioid, benzodiazepine and Z-drug prescribing is consistent with guidance for safe prescribing in prisons, the increase in gabapentinoid (primarily pregabalin) prescribing and the high level of prescribing to women is concerning. Our findings suggest targeted interventions may be needed to address prescribing in women, and men with a history of OUD.

Impact of changes to the delivery of opioid agonist treatment, introduced during the COVID-19 pandemic, on treatment access and dropout in Ireland: An interrupted time series analysis.

BACKGROUND: Following the emergence of COVID-19, Ireland introduced national contingency guidelines to ensure rapid and uninterrupted access to opioid agonist treatment (OAT). This study aims to assess the impact of changes introduced to the delivery of OAT on the number of people accessing treatment and treatment dropout. METHODS: The study conducted interrupted time series analyses, with separate segmented regression models (March 2019-February 2020) vs (April 2020-March 2021), for (A) total number of people accessing OAT, (B) the number initiating treatment, and (C) the number dropping out of treatment, using data from the National OAT treatment register. The study examined immediate (change in level or intercept: ß2) and long-term impacts (change in slope; i.e., the difference between the slope before and after the intervention: ß3). We performed total and stratified analyses by gender, age group (<40/≥40 years), and OAT drug (methadone or buprenorphine). RESULTS: A total of 10,251 people accessed OAT in Ireland in March 2019 (2 % buprenorphine, n = 178), increasing to 11,441 (4 % buprenorphine, n = 471) in March 2021. The study observed an immediate (ß2 = 504.3, p < 0.001) and continued (ß3 = 31.9, p < 0.001) increase of people accessing treatment following the introduction of the OAT contingency guidelines. In contrast, observed changes in level and slope were not significant for treatment initiation or dropout. The study did find, however, a modest reduction in dropout among those receiving buprenorphine (ß3 = -0.6, p = 0.036). CONCLUSIONS: Changes introduced to the delivery of OAT, under the COVID-19 contingency guidelines, are associated with increased access to OAT in Ireland, with no evidence of increase in treatment dropout. Whether these effects will be maintained over time remains to be seen.

Prescription drugs with potential for misuse: protocol for a multi-indicator analysis of supply, detection and the associated health burden in Ireland between 2010 and 2020.

INTRODUCTION: There is an increasing concern about the misuse of prescription drugs. Misuse refers to the intentional repurposing of prescribed drugs and/or the use of illicitly sourced prescription drugs, which may be counterfeit or contaminated. Drugs with the greatest potential for misuse are prescription opioids, gabapentinoids, benzodiazepines, Z-drugs and stimulants. OBJECTIVE: The aim of this study is to provide a comprehensive analysis of the supply, patterns of use and health burden associated with prescription drugs with potential for misuse (PDPM) in Ireland between 2010 and 2020. Three inter-related studies will be carried out. The first study will describe trends in supply of PDPM using law enforcement drug seizures data and national prescription records from national community and prison settings. The second study aims to estimate trends in the detection of PDPM across multiple early warning systems using national forensic toxicology data. The third study aims to quantify the health burden associated with PDPM nationally, using epidemiological indicators of drug-poisoning deaths, non-fatal intentional drug overdose presentations to hospitals and drug treatment demand. METHODS AND ANALYSIS: A retrospective observational study design, with repeated cross-sectional analyses, using negative binomial regression models or, where appropriate, joinpoint regression. ETHICS AND DISSEMINATION: The study has received approval from the RCSI Ethics Committee (REC202202020). Results will be disseminated in peer-reviewed journals, scientific and drug policy meetings and with key stakeholders via research briefs.

Consensus recommendations for opioid agonist treatment following the introduction of emergency clinical guidelines in Ireland during the COVID-19 pandemic: A national Delphi study.

BACKGROUND: Emergency contingency guidelines for opioid agonist treatment (OAT) were introduced in Ireland in March 2020, to ensure rapid and uninterrupted access to treatment while mitigating COVID-19 risk. The contingency guidelines deviated, across multiple clinical domains, from pre-pandemic clinical guidelines published in 2016. The objectives of this study are to (1) identify changes introduced to OAT clinical guidelines in Ireland during the pandemic; and (2) develop consensus on whether the new recommendations should be retained beyond the pandemic, using a national Delphi consensus methodology. METHODS: Clinical guidance recommendations ('statements') were generated by comparing the newly established contingency guidelines with the national 2016 Clinical Guidelines for OAT. Over two rounds of on-line Delphi testing, a panel of experts (people currently accessing OAT, psychiatrists, general practitioners, community pharmacists, a nurse, a psychologist and support/key workers) independently rated their agreement with each statement and provided comments. Statements with a median score of 4 or 5 and a lower quartile of ≥4 were classified as having reached consensus. RESULTS: Forty-eight panel members were recruited, with a high participation level at Round 2 (90%, n=43). Consensus was achieved for 12 of the 19 statements at Round 1. The 7 remaining statements were revised, with 2 new statements, resulting in 9 statements at Round 2. Four statements reached consensus at Round 2. The final list includes 16 clinical guidance statements; 9 relating to assessment, 3 to OAT drug choice and dosing, 1 to take-away doses, 2 to overdose prevention and 1 to the continuation of e-prescriptions. CONCLUSIONS: A wide range of stakeholders involved in the delivery and receipt of OAT agreed on 16 clinical guidance statements for inclusion in OAT clinical guidelines as we move beyond the pandemic, rather than reverting to pre-pandemic guidelines. The agreed statements relate to facilitating safe access to OAT with minimal waiting time, supporting patient-centred care to promote health and well-being, and preventing drug overdose. Notably, consensus was not achieved for OAT drug dosage and frequency of urine testing during the stabilisation and maintenance phase of care.

Comparing characteristics of suicide to non-suicide drug poisoning deaths, by sex, in Ireland.

BACKGROUND: Suicide by drug poisoning is potentially preventable; however, evidence on associated risk factors by sex is limited. AIM: To assist in understanding how individual and social contextual factors, and specific drugs, influence risk of suicide compared to non-suicide drug poisoning deaths, and how this differs by sex. METHODS: Data were extracted from the National Drug-Related Deaths Index. Analysis included univariable and multivariable logistic regression to estimate unadjusted and adjusted odds ratios (OR) and 95% confidence intervals (CI) for factors associated with suicide drug poisoning deaths (SDPD) (primary outcome) compared with non-suicide drug poisoning deaths (NSDPD) and stratified by sex. RESULTS: SDPD accounted for 240 (22%) of 1114 poisoning deaths, the majority among men (n = 147, 61%). Increasing age, mental ill health (AOR 7.85, 95% CI: 5.46-11.28), chronic pain (AOR 5.57, 95% CI: 3.28-9.46), and history of previous overdose (AOR 5.06, 95% CI: 3.39-7.56) were associated with increased odds of SDPD, with similar results for both sexes. The main drugs associated with SDPD were non-opioid analgesics (OR 4.06 [95% CI 2.66-6.18]), antipsychotics (OR 2.42 [95% CI 1.63-3.60]) and antidepressants (OR 2.18 [95% CI 1.59-2.97]). Pregabalin was associated with SDPD among women only. LIMITATIONS: Secondary analysis of coronial data on drug poisoning deaths therefore findings may not be relevant to suicide deaths in general. CONCLUSIONS: Ongoing monitoring for signs of suicidal intent in individuals with mental illness, chronic pain, overdose, and/or prescribed mental health medications may identify individuals in need of additional intervention.

Trends in drug poisoning deaths, by sex, in Ireland: a repeated cross-sectional study from 2004 to 2017.

OBJECTIVE: To examine sex differences in age-standardised rates (ASR) of overall and drug-specific drug poisoning deaths in Ireland between 2004 and 2017. DESIGN: Repeated cross-sectional study. SETTING: Drug poisoning deaths in Ireland. PARTICIPANTS: National Drug-Related Deaths Index and pharmacy claims database (Primary Care Reimbursement Service-General Medical Services) data from 2004 to 2017. OUTCOME MEASURES: The primary outcome was trends in drug poisoning death rates by sex. The secondary outcomes were trends in drug poisoning death rates involving (1) any CNS (Central Nervous System) depressants, (2) ≥2 CNS depressants and (3) specific drugs/drug classes (eg, prescription opioids, benzodiazepines, antidepressants, alcohol, cocaine and heroin) by sex. Joinpoint regression was used to examine trends, stratified by sex, in the ASR of drug poisoning deaths (2004-2017), change points over time and average annual percentage changes (AAPCs) with 95% CI. RESULTS: Increased ASR for all drug poisoning deaths from 6.86 (95% CI 6.01 to 7.72) per 100 000 in 2004 to 8.08 (95% CI 7.25 to 8.91) per 100 000 in 2017 was mainly driven by increasing deaths among men (AAPC 2.6%, 95% CI 0.2 to 5.1), with no significant change observed among women. Deaths involving ≥2 CNS depressants increased for both men (AAPC 5.6%, 95% CI 2.4 to 8.8) and women (AAPC 4.0%, 95% CI 1.1 to 6.9). Drugs with the highest significant AAPC increases for men were cocaine (7.7%, 95% CI 2.2 to 13.6), benzodiazepines (7.2%, 95% CI 2.9 to 11.6), antidepressants (6.1%, 95% CI 2.4 to 10.0) and prescription opioids (3.5%, 95% CI 1.6 to 5.5). For women, the highest AAPC was for antidepressants (4.2%, 95% CI 0.2 to 8.3), benzodiazepines (3.3%, 95% CI 0.1 to 6.5) and prescription opioids (3.0%, 95% CI 0.7 to 5.3). CONCLUSION: Drugs implicated in drug poisoning deaths vary by sex. Policy response should include prescription monitoring programmes and practical harm reduction information on polydrug use, especially CNS depressant drugs.

Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence: A Systematic Review and Meta-analysis.

Importance: Mortality among people with opioid dependence is higher than that of the general population. Opioid agonist treatment (OAT) is an effective treatment for opioid dependence; however, there has not yet been a systematic review on the relationship between OAT and specific causes of mortality. Objective: To estimate the association of time receiving OAT with mortality. Data Sources: The Embase, MEDLINE, and PsycINFO databases were searched through February 18, 2020, including clinical trial registries and previous Cochrane reviews. Study Selection: All observational studies that collected data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving OAT were included. Randomized clinical trials (RCTs) were also included. Data Extraction and Synthesis: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data on study, participant, and treatment characteristics were extracted; person-years, all-cause mortality, and cause-specific mortality were calculated. Crude mortality rates and rate ratios (RRs) were pooled using random-effects meta-analyses. Main Outcomes and Measures: Overall all-cause and cause-specific mortality both by setting and by participant characteristics. Methadone and buprenorphine OAT were evaluated specifically. Results: Fifteen RCTs including 3852 participants and 36 primary cohort studies including 749 634 participants were analyzed. Among the cohort studies, the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR, 0.47; 95% CI, 0.42-0.53). This association was consistent regardless of patient sex, age, geographic location, HIV status, and hepatitis C virus status and whether drugs were taken through injection. Associations were not different for methadone (RR, 0.47; 95% CI, 0.41-0.54) vs buprenorphine (RR, 0.34; 95% CI, 0.26-0.45). There was lower risk of suicide (RR, 0.48; 95% CI, 0.37-0.61), cancer (RR, 0.72; 95% CI, 0.52-0.98), drug-related (RR, 0.41; 95% CI, 0.33-0.52), alcohol-related (RR, 0.59; 95% CI, 0.49-0.72), and cardiovascular-related (RR, 0.69; 95% CI, 0.60-0.79) mortality during OAT. In the first 4 weeks of methadone treatment, rates of all-cause mortality and drug-related poisoning were almost double the rates during the remainder of OAT (RR, 2.01; 95% CI, 1.55-5.09) but not for buprenorphine (RR, 0.58; 95% CI, 0.18-1.85). All-cause mortality was 6 times higher in the 4 weeks after OAT cessation (RR, 6.01; 95% CI, 4.32-8.36), remaining double the rate for the remainder of time not receiving OAT (RR, 1.81; 95% CI, 1.50-2.18). Opioid agonist treatment was associated with a lower risk of mortality during incarceration (RR, 0.06; 95% CI, 0.01-0.46) and after release from incarceration (RR, 0.09; 95% CI, 0.02-0.56). Conclusions and Relevance: This systematic review and meta-analysis found that OAT was associated with lower rates of mortality. However, access to OAT remains limited, and coverage of OAT remains low. Work to improve access globally may have important population-level benefits.

Factors associated with early and later dropout from methadone maintenance treatment in specialist addiction clinics: a six-year cohort study using proportional hazards frailty models for recurrent treatment episodes.

BACKGROUND: Retention in methadone maintenance treatment (MMT) is associated with reduced illicit drug use, criminal activity, and mortality; however, many clients move in and out of MMT. This study aims to identify determinants of time to dropout of MMT across multiple treatment episodes in specialist addiction services in Ireland. METHODS: Cohort study of persons attending specialist addiction clinics between 2010 and 2015. MMT episodes were periods of continuous treatment if there were no interruptions to treatment lasting > 7days. Proportional hazards frailty models were used to assess factors associated with time to dropout from recurrent MMT episodes at 3 (90 days) and 12 months (91-365 days). MMT episodes were right- censored at time of death, transfer to prison or primary care, and study end. RESULTS: A total of 2,035 individuals experienced 4,969 MMT episodes, with 2,724 dropout events during the six-year follow-up. Factors associated with dropout at 3 months included low dose methadone (<60 mg/day) (HR = 1.49, 95% CI 1.29-1.73) and previous dropout (HR = 1.65, 95% CI 1.41-1.92). Adherence was protective (HR = 0.91, 95% CI 0.90-0.92). Dropout at 12 months was associated with low dose methadone (HR = 1.44, 95% CI 1.23-1.68), previous dropout (HR = 1.37, 95% CI 1.16-1.61), males (HR 1.26, 95% CI 1.06-1.50), benzodiazepines (HR = 1.22, 95% CI 1.03-1.45) and number of comorbidities (HR = 1.12, 95% CI 1.05-1.20); adherence was protective (HR = 0.86, 95% CI 0.84-0.87). CONCLUSIONS: Clients with a previous history of treatment dropout and those on low dose methadone should be identified as high risk for both early and later dropout. Inversely, adherence to treatment, not missing methadone doses, is protective.

Sexual Behaviour and Human Papillomavirus-Positive Oral Cavity and Oropharyngeal Cancer: An Irish Perspective.

Background Characterization of the sexual behaviours and lifestyle factors associated with human papillomavirus (HPV)-positive oral cavity and oropharyngeal squamous cell carcinoma (OPSCC) is crucial to optimal counselling. Our study aims to investigate the relationship between sexual behaviours, lifestyle factors and HPV-positive OPSCC in an Irish population. Methods We performed a case-control study of 60 patients with newly diagnosed HPV-positive and HPV-negative oral cavity and OPSCC. Results Oral sexual activity was more common in the HPV-positive tumour subgroup; however, this association was insignificant on multivariate analysis. No association between age of onset of sexual activity, number of sexual partners or practicing anal sex and HPV-positivity was found. The HPV-positive tumour subgroup had significantly less tobacco use than their HPV-negative counterparts (OR 0.93, 95% CI 0.90-0.97). Conclusion The emergence of HPV-positive OPSCC means head and neck surgeons must adopt new roles as counsellors of sexually transmitted disease, in addition to their previous role of delivering a cancer diagnosis.

Drug Poisoning Deaths Among Women: A Scoping Review.

OBJECTIVE: Drug poisoning deaths among women remain a challenge for public health policy and have increased at a higher rate relative to men. Although biological, social, and psychological differences between men and women can have an influence on drug poisoning deaths, sex is rarely considered. The objective of this study is to explore the extent, range, and nature of evidence in relation to drug poisoning deaths among women. METHOD: A scoping review was conducted according to the Arksey and O'Malley framework. A comprehensive search was performed using MEDLINE, Embase, CINAHL, and Web of Science, supplemented by gray literature, including national and international reports and government documents and consultation with experts. Publications in English from June 1, 1998, to November 2, 2019, were included. Two reviewers independently screened publications for inclusion. RESULTS: The search identified 5,316 individual publications, and 61 met the inclusion criteria (46% from Europe; n = 28). The main candidate factors identified as contributing factors to drug poisoning deaths among women included age; opioid drugs, especially prescription opioids; other prescription drugs, particularly antidepressants; mental health issues; barriers to treatment; victim of violence; alcohol use; polydrug use; and history of imprisonment. CONCLUSIONS: The majority of studies on drug poisoning deaths among women involved descriptive epidemiological data, primarily prevalence estimates, with limited in-depth analyses of factors explaining these trends. To inform policies and practices to prevent drug poisoning deaths among women, more evidence is required on risk factors specifically related to women.

Prevalence of potentially serious alcohol-medication interactions in older adults in a community pharmacy setting: a cross-sectional study.

OBJECTIVE: Previous prevalence estimates of POtentially Serious Alcohol-Medication INteractions in Older adults (POSAMINO) are based on in-home inventories of medications; however, this method is associated with under-reporting of medications when compared with dispensing records. This study aims to estimate the prevalence of POSAMINO among community-dwelling older adults using drug dispensing data from the community pharmacy setting. DESIGN: Cross-sectional study. SETTING: Irish Community Pharmacy. PARTICIPANTS: 1599 consecutive older adults presenting with a prescription to 1 of 120 community pharmacies nationwide; community-dwelling, aged ≥65 years, able to speak and understand English, with no evidence of cognitive impairment. The mean age of sample was 75.5 years (SD 6.5); 55% (n=884) female. MEASURES: 38 POSAMINO criteria were identified using participants' pharmacy dispensing records linked to self-reported alcohol consumption (beverage-specific quantity and frequency measures) over the last 12 months. RESULTS: The overall prevalence of POSAMINO in the study population was 28%, with 10% at risk of at least one POSAMINO criteria and 18% at risk of two or more. Exposure to POSAMINO most commonly involved cardiovascular agents (19%) and central nervous system agents (15%). Exposure to a higher number of POSAMINO criteria was associated with younger age (adjusted incident rate ratio (AIRR): 0.97; 95% CI: 0.95 to 0.98), male sex (AIRR: 0.55; 95% CI: 0.45 to 0.67) and a higher number of comorbidities (AIRR: 1.05; 95% CI: 1.01 to 1.13). CONCLUSION: This study adds to the growing body of evidence, which suggests that older adults are vulnerable to potentially serious alcohol-medication interactions, particularly those involving cardiovascular and central nervous system agents, increasing their risk of orthostatic hypotension, gastrointestinal bleeds and increased sedation. Application of the POSAMINO criteria at the point of prescribing may facilitate the risk stratification of older adults and prioritise alcohol screening and brief alcohol interventions in those at greatest risk of harm.

Evaluation of the effect of insulin sensitivity-enhancing lifestyle- and dietary-related adjuncts on antidepressant treatment response: A systematic review and meta-analysis.

BACKGROUND: Depression is associated with insulin resistance (IR). However, the potential beneficial effect, on antidepressant treatment response, of adjunctive therapy with insulin sensitivity-enhancing lifestyle and dietary interventions (exercise; supplementation with: vitamin D, magnesium, zinc, probiotics or omega-3 fatty acids) has not been systematically explored. AIMS: To determine the effect of the above stated adjuncts on antidepressant treatment response in clinically depressed patients via a systematic review and meta-analysis. METHODS: RCTs which assessed the effect, on antidepressant treatment response of adjunctive therapy with any of the interventions in comparison with treatment as usual were included. RESULTS: The interventions had a significant antidepressant effect, with SMD for follow-up (end of study) scores and change (from baseline) scores being -0.88, [95% CI: -1.19 to -0.57; P < 0.001] and -1.98 [95% CI -2.86 to -1.10; P < 0.001], respectively. The odds ratio (OR) for remission was 2.28 (95% CI 1.42 to 3.66; P < 0.001). The number-needed-to-treat (NNT) for remission was 6. Subgroup analysis of the follow-up scores revealed age effect: SMD significant in those with mean age ≤50 (-1.02 SMD; 95% CI: -1.40 to -0.64; p < 0.001) and insignificant in those with mean age >50 (-0.38 SMD (95% CI: -0.82 to 0.05; P = 0.08)). Also, the interventions were more beneficial among outpatients- SMD: -0.97 (95% CI: -1.32 to -0.62; P < 0.001) compared to inpatients- SMD: -0.34 (95% CI: -0.88 to 0.20; P = 0.22). Sensitivity analysis did not change the results. CONCLUSION: The finding that antidepressant treatment response may be improved using insulin sensitivity-enhancing lifestyle and dietary adjuncts is worthy of further exploration.

Retention of patients in opioid substitution treatment: A systematic review.

BACKGROUND: Retention in opioid substitution (OST) treatment is associated with substantial reductions in all cause and overdose mortality. This systematic review aims to identify both protective factors supporting retention in OST, and risk factors for treatment dropout. METHODS: A systematic search was performed using MEDLINE, Embase, PsycInfo, CINAHL and Web of Science (January 2001 to October 2019). Randomised controlled trials (RCTs) and observational cohort studies reporting on retention rates and factors associated with retention in OST were included. Factors associated with treatment retention and dropout were explored according to the Maudsley Addiction Profile. A narrative synthesis is provided. RESULTS: 67 studies were included in this review (4 RCTs and 63 observational cohort studies; N = 294,592), all assessing factors associated with retention in OST or treatment dropout. The median retention rate across observational studies was approximately 57% at 12 months, which fell to 38.4% at three years. Studies included were heterogeneous in nature with respect to treatment setting, type of OST, risk factor assessment, ascertainment of outcome and duration of follow-up. While the presence of such methodological heterogeneity makes it difficult to synthesise results, there is limited evidence to support the influence of a number of factors on retention, including age, substance use, OST drug dose, legal issues, and attitudes to OST. CONCLUSIONS: Younger age, substance use particularly cocaine and heroin use, lower doses of methadone, criminal activity/incarceration, and negative attitudes to MMT appear to be associated with reduced retention in OST. A consensus definition of retention is required to allow for comparability across future studies.

Do interruptions to the continuity of methadone maintenance treatment in specialist addiction settings increase the risk of drug-related poisoning deaths? A retrospective cohort study.

AIMS: To examine the risk of mortality associated with interruptions to the continuity of methadone maintenance treatment (MMT), including transfers between services, in opioid-dependent individuals attending specialist addiction services. DESIGN: Retrospective cohort study using addiction services and primary care dispensing records, the National Methadone Register and National Drug-Related Death Index (NDRDI). SETTING: Geographically defined population in Dublin, Ireland. PARTICIPANTS: A total of 2899 people prescribed and dispensed methadone in specialist addiction services between January 2010 and December 2015. There were five exposure groups: weeks 1-4 following transfer between treatment providers; weeks 1-4 out of treatment; weeks 5-52 out of treatment; weeks 1-4 of treatment initiation; and weeks 5+ of continuous treatment (reference category). MEASUREMENTS: Primary outcome: drug-related poisoning (DRP) deaths. Secondary outcome: all-cause mortality (ACM). Mortality rates calculated by dividing number of deaths (DRP; ACM) in exposure groups by person-years exposure. Unadjusted and adjusted Poisson regression (covariates age, sex, incarceration, methadone dose and comorbidities) estimated differences in mortality rates. FINDINGS: There were 154 ACM deaths, 55 (35.7%) identified as DRP deaths. No deaths were observed in the first month following transfer between treatment providers. The risk of DRP mortality was highest in weeks 1-4 out of treatment [adjusted relative risk (aRR = 4.04, 95% confidence interval (CI) = 1.43-11.43, P = 0.009] and weeks 1-4 of treatment initiation (ARR = 3.4, 95% CI = 1.2-9.64, P = 0.02). Similarly, risk of ACM was highest in weeks 1-4 out of treatment (ARR = 11.78, 95% CI = 7.73-17.94, P < 0.001), weeks 1-4 of treatment initiation (aRR = 5.11, 95% CI = 2.95-8.83, P < 0.001) and weeks 5-52 off treatment (aRR = 2.04, 95% CI = 1.2-3.47, P = 0.009). CONCLUSIONS: Interruptions to the continuity of methadone maintenance treatment by treatment provider do not appear to be periods of risk for drug-related poisoning or all-cause mortality deaths. Risk of drug related poisoning and all-cause mortality deaths appears to be greatest during the first 4 weeks of treatment initiation/re-initiation and after treatment cessation.

A repeated cross-sectional study of factors associated with pregabalin-positive poisoning deaths in Ireland.

BACKGROUND: The increasing use of pregabalin and the presence of pregabalin in poisoning deaths, particularly with opioids, highlight it as a potential drug of abuse. In this study we examined factors associated with pregabalin-positive poisoning deaths (PPPD) between 2013 and 2016 in Ireland. METHODS: Data were extracted from the National Drug-Related Deaths Index (NDRDI). Analysis included univariate and multivariate logistic regression to estimate unadjusted and adjusted odds ratios (OR) and 95 % confidence intervals (CI) for factors associated with PPPD (primary outcome) by logistic regression models for the total sample and stratified by gender. RESULTS: Pregabalin was present on 240 (16 %) toxicology reports of 1489 poisoning deaths; significantly rising from 15 (4.5 %) in 2013 to 94 (26 %) in 2016. Women (AOR 2.69, 95 % CI: 1.95-3.70), opioid misuse (AOR 1.74, 95 % CI: 1.17-2.59), in receipt of treatment for problem drug use (AOR 1.95, 95 % CI: 1.33-2.86) and year of death (2016 vs 2013) (AOR 7.95, 95 % CI: 4.58-13.79) were associated with increased odds of PPPD. Alcohol dependence was associated with reduced odds of PPPD (AOR 0.59, 95 % CI: 0.41-0.85). For men, opioid misuse, in receipt of treatment for problem drug use, and year of death were associated with increased odds of PPPD, while alcohol dependence was associated with reduced odds of PPPD. For women, in receipt of treatment for problem drug use and year of death were associated with increased odds of PPPD. CONCLUSIONS: Enhanced training to prescribers and treatment providers on the potential risks associated with pregabalin, particularly among people who use drugs, is required.

Potentially serious alcohol-medication interactions and falls in community-dwelling older adults: a prospective cohort study.

OBJECTIVE: To investigate the association between potentially serious alcohol-medication interactions (POSAMINO criteria), hypothesised to increase the risk of falls in older adults, and falls in community-dwelling older adults at two and 4 years follow-up. DESIGN: A prospective cohort study. SETTING: The Irish Longitudinal Study on Ageing. SUBJECTS: A total of 1,457 community-dwelling older adults aged ≥65 years, with a complete alcohol and regular medication data to allow for the application of the POSAMINO criteria. OUTCOMES: Self-reported falls at 2 and 4 years follow-up, any falls (yes/no), injurious falls (yes/no) and number of falls (count variable). RESULTS: The number of participants who reported falling since their baseline interview at 2 and 4 years were 357 (24%) and 608 (41.8%), respectively; 145 (10%) reported an injurious fall at 2 years and 268 (18%) at 4 years. Median (IQR) number of falls was 1 (1-2) at 2 years and 2 (1-3) at 4 years. Exposure to CNS POSAMINO criteria, hypothesised to increase the risk of falls due primarily to increased sedation, was associated with a significantly increased risk for falling (adjusted relative risk (RR) 1.50, 95% confidence interval (CI) 1.21-1.88) and for injurious falls (adjusted RR 1.62, 95% CI: 1.03-2.55) at 4 years. These equate to an absolute risk of 19% for falling (95% CI: 5-33%) and 8% for injurious falls (95% CI, 4-20%) at 4 years. CONCLUSIONS: Assessment and management strategies to prevent falls in community-dwelling older adults should consider patients' alcohol consumption alongside their assessment of patient medications, particularly among those receiving CNS agents.

Determinants of intentions to monitor antihypertensive medication adherence in Irish community pharmacy: a factorial survey.

BACKGROUND: Community pharmacy represents an important setting to identify patients who may benefit from an adherence intervention, however it remains unclear whether it would be feasible to monitor antihypertensive adherence within the workflow of community pharmacy. The aim of this study was to identify facilitators and barriers to monitoring antihypertensive medication adherence of older adults at the point of repeat dispensing. METHODS: We undertook a factorial survey of Irish community pharmacists, guided by a conceptual model adapted from the Theory of Planned Behaviour (TPB). Respondents completed four sections, 1) five factorial vignettes (clinical scenario of repeat dispensing), 2) a medication monitoring attitude measure, 3) subjective norms and self-efficacy questions, and 4) demographic and workplace questions. Barriers and facilitators to adherence monitoring behaviour were identified in factorial vignette analysis using multivariate multilevel linear modelling, testing the effect of both contextual factors embedded within the vignettes (section 1), and respondent-level factors (sections 2-4) on likelihood to perform three adherence monitoring behaviours in response to the vignettes. RESULTS: Survey invites (n = 1543) were sent via email and 258 completed online survey responses were received; two-thirds of respondents were women, and one-third were qualified pharmacists for at least 15 years. In factorial vignette analysis, pharmacists were more inclined to monitor antihypertensive medication adherence by examining refill-patterns from pharmacy records than asking patients questions about their adherence or medication beliefs. Pharmacists with more positive attitudes towards medication monitoring and normative beliefs that other pharmacists monitored adherence, were more likely to monitor adherence. Contextual factors also influenced pharmacists' likelihood to perform the three adherence monitoring behaviours, including time-pressures and the number of days late the patient collected their repeat prescription. Pharmacists' normative beliefs and the number of days late the patient collected their repeat prescription had the largest quantitative influence on responses. CONCLUSIONS: This survey identified that positive pharmacist attitudes and normative beliefs can facilitate adherence monitoring within the current workflow; however contextual time-barriers may prevent adherence monitoring. Future research should consider these findings when designing a pharmacist-led adherence intervention to be integrated within current pharmacy workflow.