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.

The Effectiveness of α2 Agonists As Sedatives in Pediatric Critical Care: A Propensity Score-Matched Cohort Study.

OBJECTIVES: There is limited evidence supporting the widespread use of α2 agonists (clonidine and dexmedetomidine) in pediatric critical care sedation. This study sought to test the association between the use of α2 agonists and enhanced sedation. DESIGN: A retrospective observational cohort study was conducted. Noninferiority of time adequately sedated (COMFORT Behavior Score 11-16) while mechanically ventilated was assessed. Secondarily, dosing of opioids and benzodiazepines was examined. SETTING: Two tertiary PICUs. PATIENTS: Children were classified into an exposed group, who received an α2 agonist as part of their sedation regimen, and an unexposed group. Groups were matched using propensity score analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-thousand eighty-five patients were included. The exposed group were adequately sedated 74% (95% CI, 72-75%) of the study time compared with the unexposed group at 70% (95% CI, 67-72%) giving a ratio of 1.06 (95% CI, 1.02-1.10) and a noninferior time adequately sedated. A decrease in time oversedated was observed with 8.1% (95% CI, 4.3-11.9%) less time classified as oversedated in the exposed group. Reduction in morphine use of 0.25 µg/kg/hr (95% CI, -0.68 to 1.18 µg/kg/hr) was not statistically significant. Midazolam use did not decrease and was statistically higher. CONCLUSIONS: Use of α2 agonists was associated with similar time adequately sedated as a matched unexposed group although no reduction in morphine or benzodiazepine coadministration was observed. There was a shift toward lighter sedation with α2 agonist use.

Longitudinal prevalence of potentially serious alcohol-medication interactions in community-dwelling older adults: a prospective cohort study.

PURPOSE: This study aims to estimate (i) the prevalence of potentially serious alcohol-medication interactions in a nationally representative sample of older adults using the Potentially Serious Alcohol-Medication Interactions in Older adults (POSAMINO) criteria, and (ii) whether POSAMINO prevalence changes over time. METHODS: A prospective cohort study of adults aged ≥ 65 years, using data from the first three waves of The Irish Longitudinal Study on Ageing (TILDA). All 38 POSAMINO criteria were applied at each wave using respondents' information on regular medications and alcohol consumption. Multilevel logistic regression and negative binomial models were used to investigate whether the prevalence of POSAMINO varied over time. RESULTS: The overall prevalence of POSAMINO was 18% at baseline, with 8% at risk of one potentially serious alcohol-medication interaction, and 10% at risk of two or more. The most common POSAMINO involved cardiovascular (CVS) agents (15% baseline; 11% wave 2; 14% wave 3), followed by central nervous system (CNS) agents (4% baseline; 4% wave 2; 5% wave 3). Prevalence of any POSAMINO (AOR 0.94, 95% CI 0.81, 1.08) or number of POSAMINO criteria (AIRR 0.97, 95% CI 0.91, 1.04) did not change over time. Any POSAMINO and number of POSAMINO were associated with younger age, male sex and number of medications and chronic conditions. CONCLUSIONS: Potentially serious alcohol-medication interactions occurred in 18% of older adults in this study. Alcohol screening and brief interventions should be considered for high-risk groups at the point of prescribing, particularly among younger older adults, men and as patients receive more medications or develop additional illnesses.

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.

Optimizing clonidine dosage for sedation in mechanically ventilated children: A pharmacokinetic simulation study.

BACKGROUND: Clonidine is in widespread off-label use as a sedative in mechanically ventilated children, despite limited evidence of efficacy. A variety of dosage regimens have been utilized in clinical practice and in research studies. Within these studies, clonidine has inconsistently shown useful sedation properties. One of the reasons attributed to the inconsistent signs of efficacy is suboptimal clonidine dosing. AIMS: This study aims to propose a target plasma concentration and simulate clonidine pharmacokinetics (PK) in a cohort of mechanically ventilated children to evaluate the adequacy of clonidine dosage regimens used in clinical practice and research studies. METHODS: A literature search was undertaken to identify a clonidine pharmaockinetic-pharmacodynamics (PKPD) model, from which a target concentration for sedation was defined. Using a previously published PK model, the projected plasma concentrations of 692 mechanically ventilated children (demographics taken from a recent study) were generated. Doses from recently published clinical studies were investigated. Adequacy of each regimen to attain therapeutic clonidine plasma concentrations was assessed. RESULTS: A target plasma concentration of above 2 µg/L was proposed. Nine dosage regimens (four intravenous boluses, four intravenous infusions, and one nasogastric route boluses) were evaluated ranging from 1 µg/kg eight hourly intravenous boluses to a regimen up to 3 µg/kg/hr continuous intravenous infusion. Regimens with a loading dose of 2 µg/kg followed by variable continuous infusion of up to 2 µg/kg/hr titrated according to sedation score appear most suitable. Doses should be halved in neonates. CONCLUSION: The variety of dosage regimens in the previous studies of clonidine along with difficulties in the conduct of interventional studies may have contributed to the lack of efficacy data to support its use. Simulations of clonidine plasma concentrations based on known population pharmacokinetic parameters suggest a loading dose followed by higher than current practice maintenance dose infusion is required to achieve adequate steady-state concentrations early in treatment. Further PKPD studies will aid in the determination of the optimal clonidine dosage regimen.

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.

Assessing the Multidimensional Relationship Between Medication Beliefs and Adherence in Older Adults With Hypertension Using Polynomial Regression.

Background: The Necessity-Concerns Framework (NCF) is a multidimensional theory describing the relationship between patients' positive and negative evaluations of their medication which interplay to influence adherence. Most studies evaluating the NCF have failed to account for the multidimensional nature of the theory, placing the separate dimensions of medication "necessity beliefs" and "concerns" onto a single dimension (e.g., the Beliefs about Medicines Questionnaire-difference score model). Purpose: To assess the multidimensional effect of patient medication beliefs (concerns and necessity beliefs) on medication adherence using polynomial regression with response surface analysis. Methods: Community-dwelling older adults >65 years (n = 1,211) presenting their own prescription for antihypertensive medication to 106 community pharmacies in the Republic of Ireland rated their concerns and necessity beliefs to antihypertensive medications at baseline and their adherence to antihypertensive medication at 12 months via structured telephone interview. Results: Confirmatory polynomial regression found the difference-score model to be inaccurate; subsequent exploratory analysis identified a quadratic model to be the best-fitting polynomial model. Adherence was lowest among those with strong medication concerns and weak necessity beliefs, and adherence was greatest for those with weak concerns and strong necessity beliefs (slope ß = -0.77, p<.001; curvature ß = -0.26, p = .004). However, novel nonreciprocal effects were also observed; patients with simultaneously high concerns and necessity beliefs had lower adherence than those with simultaneously low concerns and necessity beliefs (slope ß = -0.36, p = .004; curvature ß = -0.25, p = .003). The difference-score model fails to account for the potential nonreciprocal effects. Conclusion: Results extend evidence supporting the use of polynomial regression to assess the multidimensional effect of medication beliefs on adherence.

Impact of financial burden, resulting from prescription co-payments, on antihypertensive medication adherence in an older publically insured population.

INTRODUCTION: Medication co-payments represent a financial barrier to antihypertensive medication adherence. The introduction of co-payments for Irish publically insured patients was associated with a 5% reduction in adherence. However there is socioeconomic variability within this population, and the impact may be greater for those on lower income. We evaluated medication-related financial burden of the co-payment in a cohort of Irish publically insured antihypertensive users and tested its association with adherence at 12 months. METHODS: This was a prospective cohort study of community dwelling older (> 65 yrs) adults (n = 1152) from 106 Irish community pharmacies. Participants completed a structured telephone interview at baseline, and a follow-up interview at 12-months, which we linked to pharmacy records. We assessed medication-related financial burden at baseline using a single questionnaire item, and adherence at 12 months via questionnaire and refill-adherence as Proportion of Days Covered (PDC). RESULTS: A third of participants (30.1%) reported financial burden due to medication costs. In adjusted linear regression models financially burdened participants had significantly lower self-reported adherence (ß = - 0.29, 95% CI -0.48 to - 0.11), although this was not evident with PDC (ß = - 2.76, 95% CI -5.65 to 0.14). CONCLUSION: This co-payment represents a financial barrier to antihypertensive adherence for many older Irish publically insured patients. The negative impact to adherence will potentially increase the risk of adverse outcomes, such as stroke, and increase long-term healthcare costs.

Adverse outcomes in older adults attending emergency departments: a systematic review and meta-analysis of the Identification of Seniors At Risk (ISAR) screening tool.

Background: older adults are frequent users of emergency services and demonstrate high rates of adverse outcomes following emergency care. Objective: to perform a systematic review and meta-analysis of the Identification of Seniors At Risk (ISAR) screening tool, to determine its predictive value in identifying adults ≥65 years at risk of functional decline, unplanned emergency department (ED) readmission, emergency hospitalisation or death within 180 days after index ED visit/hospitalisation. Methods: a systematic literature search was conducted in PubMed, EMBASE, CINAHL, EBSCO and the Cochrane Library to identify validation and impact analysis studies of the ISAR tool. A pre-specified ISAR score of ≥2 (maximum score 6 points) was used to identify patients at high risk of adverse outcomes. A bivariate random effects model generated pooled estimates of sensitivity and specificity. Statistical heterogeneity was explored and methodological quality was assessed using validated criteria. Results: thirty-two validation studies (n = 12,939) are included. At ≥2, the pooled sensitivity of the ISAR for predicting ED return, emergency hospitalisation and mortality at 6 months is 0.80 (95% confidence interval (CI) 0.70-0.87), 0.82 (95% CI 0.74-0.88) and 0.87 (95% CI 0.75-0.94), respectively, with a pooled specificity of 0.31 (95% CI 0.24-0.38), 0.32 (95% CI 0.24-0.41) and 0.35 (95% CI 0.26-0.44). Similar values are demonstrated at 30 and 90 days. Three heterogeneous impact analysis studies examined the clinical implementation of the ISAR and reported mixed findings across patient and process outcomes. Conclusion: the ISAR has modest predictive accuracy and may serve as a decision-making adjunct when determining which older adults can be safely discharged.

Shared care across the interface between primary and specialty care in management of long term conditions.

BACKGROUND: Shared care has been used in the management of many chronic conditions with the assumption that it delivers better care than primary or specialty care alone; however, little is known about the effectiveness of shared care. OBJECTIVES: To determine the effectiveness of shared care health service interventions designed to improve the management of chronic disease across the primary/specialty care interface. This is an update of a previously published review.Secondary questions include the following:1. Which shared care interventions or portions of shared care interventions are most effective?2. What do the most effective systems have in common? SEARCH METHODS: We searched MEDLINE, Embase and the Cochrane Library to 12 October 2015. SELECTION CRITERIA: One review author performed the initial abstract screen; then two review authors independently screened and selected studies for inclusion. We considered randomised controlled trials (RCTs), non-randomised controlled trials (NRCTs), controlled before-after studies (CBAs) and interrupted time series analyses (ITS) evaluating the effectiveness of shared care interventions for people with chronic conditions in primary care and community settings. The intervention was compared with usual care in that setting. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included studies, evaluated study quality and judged the certainty of the evidence using the GRADE approach. We conducted a meta-analysis of results when possible and carried out a narrative synthesis of the remainder of the results. We presented the results in a 'Summary of findings' table, using a tabular format to show effect sizes for all outcome types. MAIN RESULTS: We identified 42 studies of shared care interventions for chronic disease management (N = 18,859), 39 of which were RCTs, two CBAs and one an NRCT. Of these 42 studies, 41 examined complex multi-faceted interventions and lasted from six to 24 months. Overall, our confidence in results regarding the effectiveness of interventions ranged from moderate to high certainty. Results showed probably few or no differences in clinical outcomes overall with a tendency towards improved blood pressure management in the small number of studies on shared care for hypertension, chronic kidney disease and stroke (mean difference (MD) 3.47, 95% confidence interval (CI) 1.68 to 5.25)(based on moderate-certainty evidence). Mental health outcomes improved, particularly in response to depression treatment (risk ratio (RR) 1.40, 95% confidence interval (CI) 1.22 to 1.62; six studies, N = 1708) and recovery from depression (RR 2.59, 95% CI 1.57 to 4.26; 10 studies, N = 4482) in studies examining the 'stepped care' design of shared care interventions (based on high-certainty evidence). Investigators noted modest effects on mean depression scores (standardised mean difference (SMD) -0.29, 95% CI -0.37 to -0.20; six studies, N = 3250). Differences in patient-reported outcome measures (PROMs), processes of care and participation and default rates in shared care services were probably limited (based on moderate-certainty evidence). Studies probably showed little or no difference in hospital admissions, service utilisation and patient health behaviours (with evidence of moderate certainty). AUTHORS' CONCLUSIONS: This review suggests that shared care improves depression outcomes and probably has mixed or limited effects on other outcomes. Methodological shortcomings, particularly inadequate length of follow-up, may account in part for these limited effects. Review findings support the growing evidence base for shared care in the management of depression, particularly stepped care models of shared care. Shared care interventions for other conditions should be developed within research settings, with account taken of the complexity of such interventions and awareness of the need to carry out longer studies to test effectiveness and sustainability over time.

Concurrent use of alcohol interactive medications and alcohol in older adults: a systematic review of prevalence and associated adverse outcomes.

BACKGROUND: Older adults are susceptible to adverse effects from the concurrent use of medications and alcohol. The aim of this study was to systematically review the prevalence of concurrent use of alcohol and alcohol-interactive (AI) medicines in older adults and associated adverse outcomes. METHODS: A systematic search was performed using MEDLINE (PubMed), Embase, Scopus and Web of Science (January 1990 to June 2016), and hand searching references of retrieved articles. Observational studies reporting on the concurrent use of alcohol and AI medicines in the same or overlapping recall periods in older adults were included. Two independent reviewers verified that studies met the inclusion criteria, critically appraised included studies and extracted relevant data. A narrative synthesis is provided. RESULTS: Twenty studies, all cross-sectional, were included. Nine studies classified a wide range of medicines as AI using different medication compendia, thus resulting in heterogeneity across studies. Three studies investigated any medication use and eight focused on psychotropic medications. Based on the quality assessment of included studies, the most reliable estimate of concurrent use in older adults ranges between 21 and 35%. The most reliable estimate of concurrent use of psychotropic medications and alcohol ranges between 7.4 and 7.75%. No study examined longitudinal associations with adverse outcomes. Three cross-sectional studies reported on falls with mixed findings, while one study reported on the association between moderate alcohol consumption and adverse drug reactions at hospital admission. CONCLUSIONS: While there appears to be a high propensity for alcohol-medication interactions in older adults, there is a lack of consensus regarding what constitutes an AI medication. An explicit list of AI medications needs to be derived and validated prospectively to quantify the magnitude of risk posed by the concurrent use of alcohol for adverse outcomes in older adults. This will allow for risk stratification of older adults at the point of prescribing, and prioritise alcohol screening and brief alcohol interventions in high-risk groups.

Estimating Risk of Alcohol Dependence Using Empirically Validated Ordinal Risk Zones Versus Recommended Binary Risk Zones of the RAPS4: A Validation Study Using Stratum-Specific Likelihood Ratio Analysis.

BACKGROUND: Effective treatment options for alcohol dependence exist; yet, only 10% of people with alcohol dependence receive treatment. The objective of the current study was to examine the performance of previously recommended Rapid Alcohol Problem Screen 4 (RAPS4) risk zones, based on single binary cut-points (RAPS4 ≥ 1; RAPS4 ≥ 2), and empirically identified RAPS4 risk zones to identify people with alcohol dependence so that further diagnostic assessment or interventions can be offered. METHOD: Stratum-specific likelihood ratio (SSLR) and receiver operating characteristic analyses were used to compare the screening performance of empirically identified "risk zones" on the RAPS4 to previously recommended binary cut-points in a general population sample of current drinkers in Ireland (N = 4,267). SSLRs were also used along with the pretest prevalence of alcohol dependence to estimate posttest probabilities of alcohol dependence for the recommended and empirically identified risk zones. RESULTS: The weighted prevalence estimate of alcohol dependence among current drinkers was 6.9% (9.3% men; 4.5% women). The SSLR analysis identified multiple risk zones in the RAPS4, with each of the individual scores (0, 1, 2, 3, 4) retained as 5 separate ordinal risk zones for both men and women. A comparison of the area under the receiver operating characteristic curve showed that the ordinal RAPS4 risk zones performed better than recommended binary thresholds for both men and women. Based on the pretest probability of 9.3% and the identified SSLRs for the ordinal risk zones, the posttest probability of alcohol dependence for men ranged from 1.6% for those in the lower risk zone (RAPS4 = 0) to 86.7% for those in the highest risk zone (RAPS4 = 4). The posttest probability of alcohol dependence for women ranged from 0.4% for those in the lower risk zone to 80% for those in the higher risk zone. CONCLUSIONS: The detection of alcohol dependence may be improved using the empirically identified ordinal RAPS4 risk zones for both men and women. The application of the identified SSLRs, particularly if integrated into a clinical decision support system, may be helpful for clinicians in providing feedback to patients regarding their risk of alcohol dependence.

Potential Impact of Minimum Unit Pricing for Alcohol in Ireland: Evidence from the National Alcohol Diary Survey.

AIM: One of the main provisions of the Irish Public Health (Alcohol) Bill is the introduction of a minimum unit price (MUP) for alcohol in Ireland, set at €1.00/standard drink. We sought to identify who will be most affected by the introduction of a MUP, examining the relationship between harmful alcohol consumption, personal income, place of purchase and price paid for alcohol. METHOD: A nationally representative survey of 3187 respondents aged 18-75 years, completing a diary of their previous week's alcohol consumption. The primary outcome was purchasing alcohol at <€1.00/standard drink; secondary outcome was purchasing alcohol at <€1.00/standard drink off-sales. Primary exposures were harmful alcohol consumption (AUDIT-C > 5), low personal annual income (<€20,000) and place of purchase (off- or- on-sales). RESULTS: One in seven respondents (14%) spent <€1.00/standard drink, with a median spend of 0.78/standard drink. High-risk drinkers (OR 1.56, 95% CI 1.09-2.23), men (OR 1.95, 95% CI 1.43-2.66), people on low income (OR 1.64, 95% CI 1.20-2.23) and those purchasing alcohol off-sales (OR 21.9, 95% CI 12.5-38.1) were most likely to report purchasing alcohol at <€1.00/standard drink. Forty-four per cent of alcohol consumed was purchased off-sales. Of those purchasing off-sales, 30% bought cheap alcohol. High-risk drinkers, men and those on low income were most likely to report paying < €1.00/standard drink off-sales. CONCLUSION: Heavy drinkers, men and those on low income seek out the cheapest alcohol. The introduction of a MUP in Ireland is likely to target those suffering the greatest harm, and reduce alcohol-attributable mortality in Ireland. Further prospective studies are needed to monitor consumption trends and associated harms following the introduction of minimum unit pricing of alcohol.

Efficacy of α2-Agonists for Sedation in Pediatric Critical Care: A Systematic Review.

OBJECTIVE: Children in PICUs normally require analgesics and sedatives to maintain comfort, safety, and cooperation with interventions. α2-agonists (clonidine and dexmedetomidine) have been described as adjunctive (or alternative) sedative agents alongside opioids and benzodiazepines. This systematic review aimed to determine whether α2-agonists were effective in maintaining patients at a target sedation score over time compared with a comparator group. We also aimed to determine whether concurrent use of α2-agonists provided opioid-sparing effects. DATA SOURCES: A systematic search was performed using the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, CINAHL, and LILACS. STUDY SELECTION: We included randomized controlled trials of children in PICU treated with clonidine or dexmedetomidine for the indication of sedation. DATA EXTRACTION: Two authors independently screened articles for inclusion. DATA SYNTHESIS: Six randomized controlled trials with sufficient data were identified and critically appraised. Three clonidine trials (two vs placebo and one vs midazolam) and three dexmedetomidine trials (two vs fentanyl, one vs midazolam) were included. Due to study heterogeneity it was not possible to pool studies. A narrative synthesis is provided. CONCLUSIONS: Reporting of study results using the outcome "time maintained at target sedation score' for clonidine or dexmedetomidine was poor. Only one trial compared clonidine with midazolam using a sedation score outcome. This study was underpowered to demonstrate equivalence to midazolam as a sedative. The adjunctive use of clonidine demonstrated significant decreases in opioid use in neonates but not in older groups. Clonidine dose was inconsistent between studies. Dexmedetomidine demonstrated an opioid-sparing effect in two small trials. Further studies, including dose-finding studies and studies with sedation score-based outcomes, are needed.

Does EUS-FNA molecular analysis carry additional value when compared to cytology in the diagnosis of pancreatic cystic neoplasm? A systematic review.

BACKGROUND: Endoscopic ultrasonography with fine needle aspiration (EUS-FNA) has become an integral tool in the diagnosis of pancreatic cystic lesions (PCLs) and the analysis of molecular/DNA abnormalities might improve the accuracy of pre-operative diagnosis. A review was conducted of all studies using EUS-FNA aspirates of PCLs to assess the accuracy and added benefit that molecular analysis provides to cytological analysis. METHODS: A systematic review of the literature was conducted using PRISMA guidelines and electronic databases: PubMed/SCOPUS/EMBASE/Cochrane/CINAHL. Surgical pathology was used as the definitive reference standard. The QUADAS-2 tool was used for quality assessment. RESULTS: In total, 162 articles were identified; 12 articles met inclusion/exclusion criteria. Ten studies reported on cytology and 8 studies reported k-ras mutational analysis. 362 patients (of 1115 total) had surgical pathology available. The sensitivity and specificity of cytology was 0.42 and 0.99; the sensitivity and specificity of k-ras was 0.39 and 0.95; and the sensitivity and specificity of the combined test of cytology and k-ras was 0.71 and 0.88, respectively. CONCLUSIONS: k-ras mutational analysis used as an individual screening test has a poor diagnostic accuracy, as does cytology when used alone. The benefit comes with utilization in a combined fashion. More studies are needed to evaluate the correct sequence and utility of these tests for cyst differentiation.

Systematic review and meta-analysis of the impact of depression on subsequent smoking cessation in patients with coronary heart disease: 1990 to 2013.

OBJECTIVE: Smoking cessation is crucial for patients with coronary heart disease (CHD), yet depression may impede cessation success. We systematically reviewed the prospective association between depression and subsequent smoking cessation in individuals with CHD to quantify this effect. METHODS: Electronic databases (PsychInfo, PubMed, CINAHL) were searched for prospective studies of patients with CHD that measured depression at baseline (scales, diagnostic interview, or antidepressant prescription) and reported smoking continuation/cessation at follow-up. Inclusive dates were January 1, 1990, to May 22, 2013. Standardized mean differences (SMDs) and associated 95% confidence intervals were estimated using random-effects meta-analysis. Sensitivity analysis explored the impact of limiting meta-analysis to studies using different depression measures (validated scales, diagnostic interviews, antidepressant prescription), different durations of follow-up, or higher-quality studies. RESULTS: From 1185 citations retrieved, 28 relevant articles were identified. Meta-analysis of all available data from 20 unique data sets found that depressed patients with CHD were significantly less likely to quit smoking at follow-up (SMD = -0.39, 95% confidence interval = -0.50 to -0.29; I(2) = 51.2%, p = .005). Estimates remained largely unchanged for each sensitivity analysis, except for two studies that used antidepressants, which showed a much larger effect (SMD = -0.94, -1.38 to -0.51; I(2) = 57.7%, p = .124). CONCLUSIONS: Patients with CHD and depressive symptoms are significantly less likely to quit smoking than their nondepressed counterparts. This may have implications for cardiovascular prognosis, and CHD smokers may require aggressive depression treatment to enhance their chances of quitting.

Developing an international register of clinical prediction rules for use in primary care: a descriptive analysis.

PURPOSE: We describe the methodology used to create a register of clinical prediction rules relevant to primary care. We also summarize the rules included in the register according to various characteristics. METHODS: To identify relevant articles, we searched the MEDLINE database (PubMed) for the years 1980 to 2009 and supplemented the results with searches of secondary sources (books on clinical prediction rules) and personal resources (eg, experts in the field). The rules described in relevant articles were classified according to their clinical domain, the stage of development, and the clinical setting in which they were studied. RESULTS: Our search identified clinical prediction rules reported between 1965 and 2009. The largest share of rules (37.2%) were retrieved from PubMed. The number of published rules increased substantially over the study decades. We included 745 articles in the register; many contained more than 1 clinical prediction rule study (eg, both a derivation study and a validation study), resulting in 989 individual studies. In all, 434 unique rules had gone through derivation; however, only 54.8% had been validated and merely 2.8% had undergone analysis of their impact on either the process or outcome of clinical care. The rules most commonly pertained to cardiovascular disease, respiratory, and musculoskeletal conditions. They had most often been studied in the primary care or emergency department settings. CONCLUSIONS: Many clinical prediction rules have been derived, but only about half have been validated and few have been assessed for clinical impact. This lack of thorough evaluation for many rules makes it difficult to retrieve and identify those that are ready for use at the point of patient care. We plan to develop an international web-based register of clinical prediction rules and computer-based clinical decision support systems.

Prevalence of potentially inappropriate prescribing and prescribing omissions in older Irish adults: findings from The Irish LongituDinal Study on Ageing study (TILDA).

PURPOSE: We sought to estimate the prevalence of potentially inappropriate prescriptions (PIP) and potential prescribing omissions (PPOs) using a subset of the STOPP/START criteria in a population based sample of Irish adults aged ≥ 65 years using data from The Irish LongituDinal Study on Ageing (TILDA). METHODS: A subset of 26 PIP indicators and 10 PPO indicators from the STOPP/START criteria were applied to the TILDA dataset. PIP/PPO prevalence according to individual STOPP/START criteria and the overall prevalence of PIP/PPO were estimated. The relationship between PIP and PPOs and polypharmacy, age, gender and multimorbidity was examined using logistic regression. RESULTS: The overall prevalence of PIP in the study population (n=3,454) was 14.6 %. The most common examples of PIP identified were NSAID with moderate-severe hypertension (200 participants; 5.8 %) and aspirin with no history of coronary, cerebral, or peripheral vascular symptoms or occlusive event (112 participants; 3.2 %). The overall prevalence of PPOs was 30 % (n=1,035). The most frequent PPO was antihypertensive therapy where systolic blood pressure consistently >160 mmHg (n=341, 9.9 %), There was a significant association between PIP and PPO and polypharmacy when adjusting for age, sex and multimorbidity (adjusted OR 2.62, 95 % CI 2.05-3.33 for PIP and adjusted OR 1.46, 95 % CI 1.23-1.75 for prescribing omissions). CONCLUSION: Our findings indicate prescribing omissions are twice as prevalent as PIP in the elderly using a subset of the STOPP/START criteria as an explicit process measure of potentially inappropriate prescribing and prescribing omissions. Polypharmacy was independently associated with both PPO and PIP. Application of such screening tools to prescribing decisions may reduce unnecessary medication, related adverse events, healthcare utilisation and cost.

Potential for alcohol and drug interactions in older adults: evidence from the Irish longitudinal study on ageing.

BACKGROUND: Older adults are susceptible to adverse effects from the concomitant use of prescription medications and alcohol. This study estimates the prevalence of exposure to alcohol interactive (AI) medications and concomitant alcohol use by therapeutic class in a large, nationally representative sample of older adults. METHODS: Cross-sectional analysis of a population based sample of older Irish adults aged ≥60 years using data from The Irish Longitudinal Study on Ageing (TILDA) (N = 3,815). AI medications were identified using Stockley's Drug Interactions, the British National Formulary and the Irish Medicines Formulary. An in-home inventory of medications was used to characterise AI drug exposure by therapeutic class. Self-reported alcohol use was classified as non-drinker, light/moderate and heavy drinking. Comorbidities known to be exacerbated by alcohol were also recorded (diabetes mellitus, hypertension, peptic ulcer disease, liver disease, depression, gout or breast cancer), as well as sociodemographic and health factors. RESULTS: Seventy-two per cent of participants were exposed to AI medications, with greatest exposure to cardiovascular and CNS agents. Overall, 60% of participants exposed to AI medications reported concomitant alcohol use, compared with 69.5% of non-AI exposed people (p < 0.001). Almost 28% of those reporting anti-histamine use were identified as heavy drinkers. Similarly almost one in five, combined heavy drinking with anti-coagulants/anti-platelets and cardiovascular agents, with 16% combining heavy drinking with CNS agents. Multinomial logistic regression showed that being male, younger, urban dwelling, with higher levels of education and a history of smoking, were associated with an increased risk for concomitant exposure to alcohol consumption (both light/moderate and heavier) and AI medications. Current smokers and people with increasing co-morbidities were also at greatest risk for heavy drinking in combination with AI medications. CONCLUSIONS: The concurrent use of alcohol with AI medications, or with conditions known to be exacerbated by alcohol, is common among older Irish adults. Prescribers should be aware of potential interactions, and screen patients for alcohol use and provide warnings to minimize patient risk.