Variations in Long-term Opioid Therapy Definitions: A Systematic Review of Observational Studies Using Routinely Collected Data (2000-2019)

Routinely collected data have been increasingly used to assess long-term opioid therapy (LTOT) patterns, with very little guidance on how to measure LTOT from these data sources. We conducted a systematic review of studies published between January 2000 and July 2019 to catalogue LTOT definitions, the rationale for definitions and LTOT rates in observational research using routinely collected data in nonsurgical settings. We screened 4056 abstracts, 210 full-text manuscripts and included 128 studies, mostly from the United States (81%) and published between 2015 and 2019 (69%). We identified 78 definitions of LTOT, commonly operationalised as 90 days of use within a year (23%). Studies often used multiple criteria to derive definitions (60%), mostly based on measures of duration, such as supply days/days of use (66%), episode length (21%) or prescription fills within specified time periods (12%). Definitions were based on previous publications (63%), clinical judgment (16%) or empirical data (3%); 10% of studies applied more than one definition. LTOT definition was not provided with enough details for replication in 14 studies and 38 studies did not specify the opioids evaluated. Rates of LTOT within study populations ranged from 0.2% to 57% according to study design and definition used. We observed a substantial rise in the last 5 years in studies evaluating LTOT with large variability in the definitions used and poor reporting of the rationale and implementation of definitions. This variation impacts on research reproducibility, comparability of findings and the development of strategies aiming to curb therapy that is not guideline-recommended

Reductions in emergency department presentations associated with opioid agonist treatment vary by geographic location: A retrospective study in New South Wales, Australia

Introduction and Aims: It is not known if the reduction in ED use during periods of OAT occurs across urgent and low acuity presentations. We aimed to compare the incidence and costs of urgent and low acuity ED presentations of people with opioid use disorder (OUD) in and out of opioid agonist treatment (OAT). Design and Methods: This was a retrospective cohort study (N=24,875), using linked administrative health data from New South Wales (NSW), Australia. Urgent and low acuity ED incidence and associated costs were calculated for periods in and out of OAT. GEE models estimated the adjusted incidence rate ratio (IRR) for ED presentations. Average costs per person-day were calculated with bootstrap confidence intervals. Results: Incidence of urgent presentations was lower in OAT compared to out of OAT [IRR (95%CI): 0.65 (0.61-0.69)]. In major cities, low acuity presentations were lower during OAT compared to timeout of OAT [IRR (95%CI): 0.82 (0.70-0.96)], in regional/remote areas, low acuity presentations were higher during OAT [IRR (95%CI): 2.65 (1.66-4.21)]. In major cities, average costs for low acuity presentations in OAT were 28% lower atA$0.50 (95$0.48-A$0.52) and A$0.69 (95%CI: A$0.66-A$0.71) out of OAT, but 103% higher in regional/remote NSW, at A$2.12 (95$1.91-A$2.34) in OAT and A$1.04 (95%CI: A$0.91-A$1.16) out of OAT. Discussion and Conclusions: OAT was associated with reductions in urgent ED presentations and associated costs among people with OUD. Geographical variation was evident for low acuity ED presentations, highlighting the need to increase access to OAT in regional/remote areas

Trends in transdermal fentanyl utilisation and fatal fentanyl overdose across Australia (2003–2015)

Introduction: Fentanyl-related overdose is an ongoing concern among countries with high prescription opioid utilisation. This study examines trends in transdermal fentanyl utilisation and fatal fentanyl overdose across Australia between 2003 and 2015, overall, and by age/sex. Methods: This was a retrospective nationwide study of prescription dispensings and coronial records. Transdermal fentanyl utilisation was examined using Pharmaceutical Benefits Scheme dispensing records. Details of fatal fentanyl overdoses were extracted from the National Coronial Information System. Results: Transdermal fentanyl utilisation increased 5.1-fold between 2003 and 2015, from 0.28 to 1.39 mg/1000 population/day and was consistently higher among females and adults aged ≥85 years. The utilisation of higher strength patches (75 and 100 mcg/h) was more common among males aged 25–44 years. A total of 291 fatal fentanyl overdoses were recorded, increasing from no recorded deaths in 2003 to 2.23 deaths/1 000 000 population in 2015. Rates were higher among males (increasing from 0 to 3.72 deaths/1 000 000 population) and for adults aged 25–44 years (increasing from 0 to 5.34 deaths/1 000 000 population). The number of deaths/kg fentanyl dispensed was highest among males aged <25 years (45.45, 95% confidence interval 21.80–83.59). Most deaths (70.1%) involved the intravenous administration of fentanyl from transdermal patches. Discussion and Conclusions: Rates of transdermal fentanyl utilisation and fatal fentanyl overdose across Australia increased between 2003 and 2015. Although transdermal fentanyl utilisation was consistently greater among females and older adults, rates of fatal fentanyl overdose were highest among younger males. Interventions to reduce extramedical use among this high-risk population group are necessary to minimise fentanyl-related harms

Combating escalating harms associated with pharmaceutical opioid use in Australia: The POPPY II study protocol

© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. Introduction Opioid prescribing has increased 15-fold in Australia in the past two decades, alongside increases in a range of opioid-related harms such as opioid dependence and overdose. However, despite concerns about increasing opioid use, extramedical use and harms, there is a lack of population-level evidence about the drivers of long-term prescribed opioid use, dependence, overdose and other harms. Methods and analysis We will form a cohort of all adult residents in New South Wales (NSW), Australia, who initiated prescribed opioids from 2002 using Pharmaceutical Benefits Scheme dispensing records. This cohort will be linked to a wide range of other datasets containing information on sociodemographic and clinical characteristics, health service use and adverse outcomes (eg, opioid dependence and non-fatal and fatal overdose). Analyses will initially examine patterns and predictors of prescribed opioid use and then apply regression and survival analysis to quantify the risks and risk factors of adverse outcomes associated with prescribed opioid use. Ethics and dissemination This study has received full ethical approval from the Australian Institute of Health and Welfare Ethics Committee, the NSW Population and Health Services Research Committee and the ACT Health Human Research Ethics Committee. This will be the largest postmarketing surveillance study of prescribed opioids undertaken in Australia, linking exposure and outcomes and examining risk factors for adverse outcomes of prescribed opioids. As such, this work has important translational promise, with direct relevance to regulatory authorities and agencies worldwide. Project findings will be disseminated at scientific conferences and in peer-reviewed journals. We will also conduct targeted dissemination with policy makers, professional bodies and peak bodies in the pain, medicine and addiction fields through stakeholder workshops and advisory groups. Results will be reported in accordance with the REporting of studies Conducted using Observational Routinely collected Data (RECORD) Statement

All-cause and cause-specific mortality in individuals with an alcohol-related emergency or hospital inpatient presentation: A retrospective data linkage cohort study

Background and Aims: Alcohol consumption is a leading risk factor for premature mortality globally, but there are limited studies of broader cohorts of people presenting with alcohol-related problems outside of alcohol treatment services. We used linked health administrative data to estimate all-cause and cause-specific mortality among individuals who had an alcohol-related hospital inpatient or emergency department presentation. Design: Observational study using data from the Data linkage Alcohol Cohort Study (DACS), a state-wide retrospective cohort of individuals with an alcohol-related hospital inpatient or emergency department presentation. Setting: Hospital inpatient or emergency department presentation in New South Wales, Australia, between 2005 and 2014. Participants: Participants comprised 188 770 individuals aged 12 and above, 66% males, median age 39 years at index presentation. Measurements: All-cause mortality was estimated up to 2015 and cause-specific mortality (by those attributable to alcohol and by specific cause of death groups) up to 2013 due to data availability. Age-specific and age–sex-specific crude mortality rates (CMRs) were estimated, and standardized mortality ratios (SMRs) were calculated using sex and age-specific deaths rates from the NSW population. Findings: There were 188 770 individuals in the cohort (1 079 249 person-years of observation); 27 855 deaths were recorded (14.8% of the cohort), with a CMR of 25.8 [95% confidence interval (CI) = 25.5, 26.1] per 1000 person-years and SMR of 6.2 (95% CI = 5.4, 7.2). Mortality in the cohort was consistently higher than the general population in all adult age groups and in both sexes. The greatest excess mortality was from mental and behavioural disorders due to alcohol use (SMR = 46.7, 95% CI = 41.4, 52.7), liver cirrhosis (SMR = 39.0, 95% CI = 35.5, 42.9), viral hepatitis (SMR = 29.4, 95% CI = 24.6, 35.2), pancreatic diseases (SMR = 23.8, 95% CI = 17.9, 31.5) and liver cancer (SMR = 18.3, 95% CI = 14.8, 22.5). There were distinct differences between the sexes in causes of excess mortality (all causes fully attributable to alcohol female versus male risk ratio = 2.5 (95% CI = 2.0, 3.1). Conclusions: In New South Wales, Australia, people who came in contact with an emergency department or hospital for an alcohol-related presentation between 2005 and 2014 were at higher risk of mortality than the general New South Wales population during the same period

Age at first alcohol-related hospital separation or emergency department presentation and rate of re-admission: A retrospective data linkage cohort of young Australians

Introduction: Alcohol is a leading risk factor for death and disease in young people. We compare age-specific characteristics of young people who experience their first (‘index’) alcohol-related hospitalisation or emergency department (ED) presentation, and whether age at index predicts 12-month rates of readmission. Methods: We used a retrospective linked-data cohort of 10,300 people aged 12–20 years with an index alcohol-related hospital and/or ED record in New South Wales, Australia from 2005 to 2013. Age group (early adolescent [12–14 years], late adolescent [15–17 years], young adult [18–20 years]) and diagnosis fields were used in logistic regression analyses and to calculate incidence rates with adjustment for year of index event, sex, socioeconomic disadvantage and residence remoteness. Results: People who experienced their index event in early adolescence (adjusted relative risk ratio [ARRR] 0.45 [95% confidence interval 0.39, 0.52]) or late adolescence (ARRR 0.82 [0.74, 0.90]) were less likely to be male compared to young adults. Early adolescents (ARRR 0.60 [0.51, 0.70]) and late adolescents (ARRR 0.84 [0.76, 0.93]) were less likely to have a hospitalisation index event. Early adolescents (adjusted incidence rate ratio 1.40 [1.15, 1.71]) and late adolescents (adjusted incidence rate ratio 1.16 [1.01, 1.34]) were more likely than young adults to have a subsequent 12-month non-poisoning injury ED presentation. Discussion and Conclusions: We identified preventable hospital events in young people who have previously experienced an alcohol-related ED presentation or hospitalisation, with age-specific characteristics and outcomes that can be used to inform future health policy and service planning

Antipsychotic prescribing for vulnerable populations: a clinical audit at an acute Australian mental health unit at two-time points

Background: Antipsychotics are recognised as a critical intervention for schizophrenia and bipolar disorder. Guidelines globally endorse the routine practice of antipsychotic monotherapy, at the minimum effective dose. Even in treatmentresistant schizophrenia, clozapine use is endorsed before combining antipsychotics. This aim of this study was to review antipsychotic polytherapy alone, high-dose therapy alone, polytherapy and highdose prescribing patterns in adults discharged from an inpatient mental health unit at two time-points, and the alignment of this prescribing with clinical guideline recommendations. Additionally, associations with polytherapy and high-dose antipsychotic prescribing, including patient and clinical characteristics, were explored. Methods: A retrospective clinical audit of 400 adults (200 patients at two different time-points) discharged with at least one antipsychotic. Preliminary findings and education sessions were provided to physicians between Cohorts. Outcomes (polytherapy alone, high-dose therapy alone, polytherapy and high-dose therapy) were compared between study Cohorts using chi-squared and rank-sum tests. Associations between outcomes and covariates were assessed using multivariable logistic regression. Results: Most patients (62.5%) were discharged on a single antipsychotic within the recommended dose range. There was a clear preference for prescribing second generation antipsychotics, and in this respect, prescribing is aligned with current evidence-based guidelines. However, sub-optimal prescribing practices were identified for both Cohorts in relation to polytherapy and high-dose antipsychotic rates. Involuntary treatment, frequent hospitalisations and previous clozapine use significantly increased the risk of all three prescribing outcomes at discharge. Conclusions: In a significant minority, antipsychotic prescribing did not align with clinical guidelines despite increased training, indicating that the education program alone was ineffective at positively influencing antipsychotic prescribing practices. Further consideration should be given when prescribing antipsychotics for involuntary patients, people with frequent hospitalisations, and those who have previously trialled clozapine

Mortality Risk of Hypnotics: Strengths and Limits of Evidence

Sleeping pills, more formally defined as hypnotics, are sedatives used to induce and maintain sleep. In a review of publications for the past 30 years, descriptive epidemiologic studies were identified that examined the mortality risk of hypnotics and related sedative-anxiolytics. Of the 34 studies estimating risk ratios, odds ratios, or hazard ratios, excess mortality associated with hypnotics was significant (p &lt; 0.05) in 24 studies including all 14 of the largest, contrasted with no studies at all suggesting that hypnotics ever prolong life. The studies had many limitations: possibly tending to overestimate risk, such as possible confounding by indication with other risk factors; confusing hypnotics with drugs having other indications; possible genetic confounders; and too much heterogeneity of studies for meta-analyses. There were balancing limitations possibly tending towards underestimates of risk such as limited power, excessive follow-up intervals with possible follow-up mixing of participants taking hypnotics with controls, missing dosage data for most studies, and over-adjustment of confounders. Epidemiologic association in itself is not adequate proof of causality, but there is proof that hypnotics cause death in overdoses; there is thorough understanding of how hypnotics euthanize animals and execute humans; and there is proof that hypnotics cause potentially lethal morbidities such as depression, infection, poor driving, suppressed respiration, and possibly cancer. Combining these proofs with consistent evidence of association, the great weight of evidence is that hypnotics cause huge risks of decreasing a patient's duration of survival

Analysis of TaqMan Array Cards Data by an Assumption-Free Improvement of the maxRatio Algorithm Is More Accurate than the Cycle-Threshold Method

<div><p>Quantitative PCR diagnostic platforms are moving towards increased sample throughput, with instruments capable of carrying out thousands of reactions at once already in use. The need for a computational tool to reliably assist in the validation of the results is therefore compelling. In the present study, 328 residual clinical samples provided by the Public Health England at Addenbrooke's Hospital (Cambridge, UK) were processed by TaqMan Array Card assay, generating 15 744 reactions from 54 targets. The amplification data were analysed by the conventional cycle-threshold (CT) method and an improvement of the <i>maxRatio</i> (MR) algorithm developed to filter out the reactions with irregular amplification profiles. The reactions were also independently validated by three raters and a consensus was generated from their classification. The inter-rater agreement by Fleiss' kappa was 0.885; the agreement between either CT or MR with the raters gave Fleiss' kappa 0.884 and 0.902, respectively. Based on the consensus classification, the CT and MR methods achieved an assay accuracy of 0.979 and 0.987, respectively. These results suggested that the assumption-free MR algorithm was more reliable than the CT method, with clear advantages for the diagnostic settings.</p></div