Natasa Gisev

Interrater agreement and interrater reliability: Key concepts, approaches, and applications

Evaluations of interrater agreement and interrater reliability can be applied to a number of different contexts and are frequently encountered in social and administrative pharmacy research. The objectives of this study were to highlight key differences between interrater agreement and interrater reliability; describe the key concepts and approaches to evaluating interrater agreement and interrater reliability; and provide examples of their applications to research in the field of social and administrative pharmacy. This is a descriptive review of interrater agreement and interrater reliability indices. It outlines the practical applications and interpretation of these indices in social and administrative pharmacy research. Interrater agreement indices assess the extent to which the responses of 2 or more independent raters are concordant. Interrater reliability indices assess the extent to which raters consistently distinguish between different responses. A number of indices exist, and some common examples include Kappa, the Kendall coefficient of concordance, Bland-Altman plots, and the intraclass correlation coefficient. Guidance on the selection of an appropriate index is provided. In conclusion, selection of an appropriate index to evaluate interrater agreement or interrater reliability is dependent on a number of factors including the context in which the study is being undertaken, the type of variable under consideration, and the number of raters making assessments.

The impact of opioid substitution therapy on mortality post-release from prison: retrospective data linkage study

AIMS Release from prison is a high-risk period for mortality. We examined the impact of opioid substitution therapy (OST), for opioid dependence during and after incarceration, upon mortality post-release. DESIGN A cohort was formed of all opioid-dependent people who entered OST between 1985 and 2010 and who, following first OST entry, were released from prison at least once between 2000 and 2012. We linked data on OST history, court and prison records and deaths. SETTING New South Wales (NSW), Australia. PARTICIPANTS A total of 16,453 people released from prison 60,161 times. MEASUREMENTS Crude mortality rates (CMRs) were calculated according to OST retention; multivariable Cox regressions for post-release periods were undertaken to examine the association between OST exposure (a time-dependent variable) and mortality post-release, for which covariates were updated per-release. FINDINGS There were 100,978 person-years (PY) post-release; 1050 deaths occurred. Most received OST while incarcerated (76.5%); individuals were receiving OST in 51% of releases. Lowest post-release mortality was among those continuously retained in OST post-release CMR 4 weeks post-release = 6.4 per 1000 PY; 95% confidence interval (CI) = 5.2, 7.8, highest among those with no OST (CMR = 36.7 per 1000 PY; 95% CI = 28.8, 45.9). Multi-factorial models showed OST exposure in the 4 weeks post-release reduced hazard of death by 75% (adjusted hazard ratio 0.25; 95% CI = 0.12, 0.53); OST receipt in prison had a short-term protective effect that decayed quickly across time. CONCLUSION In New South Wales, Australia, opioid substitution therapy in prison and post-release appears to reduce mortality risk in the immediate post-release period.

A synthesis of oral morphine equivalents (OME) for opioid utilisation studies

Oral Morphine Equivalent (OME) doses are increasingly being used as a metric to represent opioid use. Driven by a growing need from pharmacoepidemiological studies, the objective of this study was to develop a comprehensive OME conversion table that can be used by researchers to calculate OMEs in a consistent and systematic way.

Opioid substitution therapy as a strategy to reduce deaths in prison: retrospective cohort study

Objectives To describe deaths in prison among opioid-dependent people, and examine associations between receipt of opioid substitution therapy (OST) and risk of death in prison. Design Retrospective cohort study. Setting Adult prisons in New South Wales (NSW), Australia. Participants 16 715 opioid-dependent people who were received to prison between 2000 and 2012. Interventions Opioid substitution therapy. Primary outcome measures Natural and unnatural (suicide, drug-induced, violent and other injury) deaths in prison. Results Cohort members were in prison for 30 998 person-years (PY), during which time there were 51 deaths. The all-cause crude mortality rate (CMR) in prison was 1.6/1000 PY (95% CI 1.2 to 2.2/1000 PY), and the unnatural death CMR was 1.1/1000 PY (95% CI 0.8 to 1.6/1000 PY). Compared to time out of OST, the hazard of all-cause death was 74% lower while in OST (adjusted HR (AHR): 0.26; 95% CI 0.13 to 0.50), and the hazard of unnatural death was 87% lower while in OST (AHR: 0.13; 95% CI 0.05 to 0.35). The all-cause and unnatural death CMRs during the first 4 weeks of incarceration were 6.6/1000 PY (95% CI 3.8 to 10.6/1000 PY) and 5.5/1000 PY (95% CI 2.9 to 9.4/1000 PY), respectively. Compared to periods not in OST, the hazard of all-cause death during the first 4 weeks of incarceration was 94% lower while in OST (AHR: 0.06; 95% CI 0.01 to 0.48), and the hazard of unnatural death was 93% lower while in OST (AHR: 0.07; 95% CI 0.01 to 0.53). Conclusions Mortality of opioid-dependent prisoners was significantly lower while in receipt of OST.

Trends in heroin and pharmaceutical opioid overdose deaths in Australia

BACKGROUND There has been international concern over the rise in fatal pharmaceutical opioid overdose rates, driven by increased opioid analgesic prescribing. The current study aimed to examine trends in opioid overdose deaths by: 1) opioid type (heroin and pharmaceutical opioids); and 2) age, gender, and intent of the death assigned by the coroner. METHODS Analysis of data from the National Coronial Information System (NCIS) of opioid overdose deaths occurring between 2001 and 2012. RESULTS Deaths occurred predominantly (98%) among Australians aged 15-74 years. Approximately two-thirds of the decedents (68%) were male. The heroin overdose death rate remains unchanged over the period; these were more likely to occur among males. Pharmaceutical opioid overdose deaths increased during the study period (from 21.9 per million population in 2001-36.2), and in 2012 they occurred at 2.5 times the incident rate of heroin overdose deaths. Increases in pharmaceutical opioid deaths were largely driven by accidental overdoses. They were more likely to occur among males than females, and highest among Australians aged 45-54 years. Rates of fentanyl deaths in particular showed an increase over the study period (from a very small number at the beginning of the period) but in 2012 rates of morphine deaths were higher than those for oxycodone, fentanyl and tramadol. CONCLUSIONS Given the increase in rates of pharmaceutical opioid overdose deaths, it is imperative to implement strategies to reduce pharmaceutical opioid-related mortality, including more restrictive prescribing practices and increasing access to treatment for opioid dependence.

A longitudinal comparison of retention in buprenorphine and methadone treatment for opioid dependence in New South Wales, Australia

BACKGROUND AND AIMS To examine characteristics of first-time methadone and buprenorphine clients and factors associated with risk of leaving first treatment in New South Wales (NSW), Australia. DESIGN Retrospective linkage study of opioid substitution therapy (OST) treatment, court, custody and mortality data. SETTING NSW, Australia. PARTICIPANTS First-time OST entrants (August 2001-December 2010). MEASUREMENTS Characteristics of clients were examined. Time-dependent Cox models examined factors associated with the risk of leaving first treatment, with demographic, criminographic and treatment variables jointly considered. Interactions between medication and other variables upon risk of leaving treatment were examined. FINDINGS There were 15 600 treatment entrants: 7183 (46%) commenced buprenorphine, 8417 (54%) commenced methadone; the proportion entering buprenorphine increased over time. Those starting buprenorphine switched medications more frequently and had more subsequent treatment episodes. Buprenorphine retention was also poorer. On average, 44% spent 3+ months in treatment compared with 70% of those commencing methadone; however, buprenorphine retention for first-time entrants improved over time, whereas methadone retention did not. Multivariable Cox models indicated that in addition to sex, age, treatment setting and criminographic variables, the risk of leaving a first treatment episode was greater on any given day for those receiving buprenorphine, and was dependent on the year treatment was initiated. There was no interaction between any demographic variables and medication received, suggesting no clear evidence of any particular groups for whom each medication might be better suited in terms of improving retention. CONCLUSIONS Although retention rates for buprenorphine treatment have improved in New South Wales, Australia, individuals starting methadone treatment still show higher retention rates.

Mortality associated with benzodiazepines and benzodiazepine-related drugs among community-dwelling older people in Finland: a population-based retrospective cohort study.

Objective: To investigate the association between the use of benzodiazepines (BDZs) and BDZ-related drugs and mortality among community-dwelling people aged 65 years and older in Finland. Method: This was a population-based retrospective cohort study. Records of all reimbursed drugs purchased by all 2224 residents of Leppävirta, Finland, aged 65 years and older in 2000 were extracted from the Finnish National Prescription Register. Diagnostic data were extracted from the Special Reimbursement Register. All-cause mortality was assessed after 9 years using national registers. Cox proportional hazards models were used to compute unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals for mortality among prevalent users of BDZs and BDZ-related drugs in 2000 (n = 325), compared with nonusers of BDZs and BDZ-related drugs between 2000 and 2008 (n = 1520). Results: BDZs and BDZ-related drugs were used by 325 out of the 2224 residents (14.6%) in 2000. The 9-year mortality was 50.2% among BDZ and BDZ-related drug users in 2000 and 36.3% among BDZ and BDZ-related drug nonusers between 2000 and 2008 (HR 1.53; 95% CI 1.28 to 1.82). After adjusting for baseline age, sex, antipsychotic drug use, and diagnostic confounders, the HR was 1.01 (95% CI 0.84 to 1.21). Conclusions: Use of BDZs and BDZ-related drugs was associated with an increased mortality hazard in unadjusted analyses. However, after adjusting for age, sex, antipsychotic drug use, and diagnostic confounders, the use of BDZs and BDZ-related drugs was not associated with excess mortality.

The extent and correlates of community‐based pharmaceutical opioid utilisation in Australia

There has been concern regarding the increasing use of opioids and related harm. We present data on opioid utilisation across Australia and consider sociodemographic factors that may affect utilisation rates.

Imprisonment of opioid-dependent people in New South Wales, Australia, 2000–2012: a retrospective linkage study

Objective: There are few data about the incarceration of opioid‐dependent people involving large representative cohorts. We aimed to determine the prevalence and duration of incarceration in a large cohort of opioid‐dependent people in Australia using data linkage methods, and estimate the costs associated with their incarceration.

Effect of comorbidity on the risk of death associated with antipsychotic use among community-dwelling older adults.

BACKGROUND Antipsychotics are associated with adverse events and mortality among older adults with dementia. The objective of this study was to evaluate the risk of death associated with antipsychotic use among community-dwelling older adults with a range of comorbidities. METHODS This was a population-based cohort study of all 2,224 residents of Leppävirta, Finland, aged ≥65 years on 1 January 2000. Records of all reimbursed drug purchases were extracted from the Finnish National Prescription Register and diagnostic data were obtained from the Special Reimbursement Register. All-cause mortality was evaluated over a nine-year follow-up period. Time-dependent Cox proportional hazard models were used to compute unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality of antipsychotic use compared to non-use. RESULTS In total, 332 residents used antipsychotics between 2000 and 2008. The unadjusted HR for risk of death associated with antipsychotic use was 2.71 (95% CI = 2.3-3.2). After adjusting for baseline age, sex, antidepressant use, and diagnostic confounders, the HR was 2.07 (95% CI = 1.73-2.47). The adjusted HR was the highest among antipsychotic users with baseline respiratory disease (HR = 2.21, 95% CI = 1.30-3.76). CONCLUSIONS The increased risk of death associated with antipsychotic use was similar across diagnostic categories, the highest being among those with baseline respiratory disease. However, the results should be interpreted with caution, as the overall sample size of antipsychotic users was small. As in other observational studies, residual confounding may account for the higher mortality observed among antipsychotic users. Further research is needed to confirm these findings.