Long-term prescribed opioid use after hospitalization or emergency department presentation among opioid naïve adults (2014-2020)-A population-based descriptive cohort study.

AIMS: The aim of this work is to describe opioid initiation and long-term use after emergency department (ED) visits or hospitalizations in New South Wales, Australia, by patient, admission and clinical characteristics. METHODS: This is a population-based cohort study, including all hospitalizations and ED visits between 2014 and 2020, linked to medicine dispensings, deaths and cancer registrations (Medicines Intelligence Data Platform), among adults with no opioid dispensings in the previous year. Outcome measures were opioid initiations (dispensed within 7 days of discharge) and long-term use (90 days of continuous exposure, 90-270 days after initiation). RESULTS: The cohort included 16 153 096 admissions by 4.2 million opioid-naïve adults; 39.0% were ED presentations without hospital admission, 16.8% hospital admissions via ED and 44.2% direct hospital admissions. Opioids were initiated post-discharge for 6.2% of ED, 8.3% of hospital via ED and 10.0% of direct hospital admissions; of these 1.0%, 2.5% and 0.5% progressed to long-term opioid use, respectively. Initiation was lowest in obstetric admissions without surgery (1.0%), and highest among trauma admissions (25.4%), obstetric admissions with surgical intervention (19.8%) and non-trauma surgical admissions (12.0%). Long-term use was highest among medical admissions via ED (3.5%), trauma admissions (2.3%) and ED alone (1.0%). From 2014 to 2020, overall opioid initiations decreased 16% from 8.7% to 7.2%, and long-term opioid use decreased 33% from 1.3% to 0.8%. CONCLUSIONS: Both opioid initiation and long-term use decreased over time; however, the higher rates of long-term use following trauma, and medical admissions via ED, warrant further surveillance. Strategies supporting appropriate prescribing and access to multidisciplinary pain services will facilitate best practice care.

Oxycodone initiation in Australia (2014-2018): Sociodemographic factors and preceding health service use.

AIMS: Oxycodone is the most commonly prescribed strong opioid in Australia. This study describes health service antecedents and sociodemographic factors associated with oxycodone initiation. METHODS: Population-based new user cohort study linking medicine dispensings, hospitalizations, emergency department visits, medical services and cancer notifications from New South Wales (NSW) for 2014-2018. New users had no dispensings of any opioid in the preceding year. We analysed health service use in the 5 days preceding initiation and proportion of people on treatment over 1 year and fitted an area-based, multivariable initiation model with sociodemographic covariates. RESULTS: Oxycodone accounted for 30% of opioid initiations. Annually, 3% of the NSW population initiated oxycodone, and 5-6% were prevalent users; the new user cohort comprised 830 963 people. Discharge from hospital (39.3%), therapeutic procedures (21.4%) and emergency department visits (19.7%) were common; a hospital admission for injury (6.0%) or a past-year history of cancer (7.2%) were less common. At 1 year after initiation, 4.6% of people were using oxycodone. In the multivariable model, new use of oxycodone increased with age and was higher for people outside major cities, for example, an incidence rate ratio of 1.43 (95% confidence interval 1.36-1.51) for inner regional areas relative to major cities; there was no evidence of variation in rates of new use by social disadvantage. CONCLUSION: About half of new oxycodone use in NSW was preceded by a recent episode of hospital care or a therapeutic procedure. Higher rates of oxycodone initiation in rural and regional areas were not explained by sociodemographic factors.

Medicine utilization studies in Australian individual-level dispensing data: A blinded, multi-center replicated analysis.

PURPOSE: Medicine dispensing data require extensive preparation when used for research and decisions during this process may lead to results that do not replicate between independent studies. We conducted an experiment to examine the impact of these decisions on results of a study measuring discontinuation, intensification, and switching in a cohort of patients initiating metformin. METHODS: Four Australian sites independently developed a HARmonized Protocol template to Enhance Reproducibility (HARPER) protocol and executed their analyses using the Australian Pharmaceutical Benefits Scheme 10% sample dataset. Each site calculated cohort size and demographics and measured treatment events including discontinuation, switch to another diabetes medicine, and intensification (addition of another diabetes medicine). Time to event and hazard ratios for associations between cohort characteristics and each event were also calculated. Concordance was assessed by measuring deviations from the calculated median of each value across the sites. RESULTS: Good agreement was found across sites for the number of initiators (median: 53 127, range: 51 848-55 273), gender (56.9% female, range: 56.8%-57.1%) and age group. Each site employed different methods for estimating days supply and used different operational definitions for the treatment events. Consequently, poor agreement was found for incidence of discontinuation (median 55%, range: 34%-67%), switching (median 3.5%, range: 1%-7%), intensification (median 8%, range: 5%-12%), time to event estimates and hazard ratios. CONCLUSIONS: Differences in analytical decisions when deriving exposure from dispensing data affect replicability. Detailed analytical protocols, such as HARPER, are critical for transparency of operational definitions and interpretations of key study parameters.

A data-informed approach using individualised dispensing patterns to estimate medicine exposure periods and dose from pharmaceutical claims data.

Pharmaceutical claims data are often used as the primary information source to define medicine exposure periods in pharmacoepidemiological studies. However, often critical information on directions for use and the intended duration of medicine supply are not available. In the absence of this information, alternative approaches are needed to support the assignment of exposure periods. This study summarises the key methods commonly used to estimate medicine exposure periods and dose from pharmaceutical claims data; and describes a method using individualised dispensing patterns to define time-dependent estimates of medicine exposure and dose. This method extends on important features of existing methods and also accounts for recent changes in an individual's medicine use. Specifically, this method constructs medicine exposure periods and estimates the dose used by considering characteristics from an individual's prior dispensings, accounting for the time between prior dispensings and the amount supplied at prior dispensings. Guidance on the practical applications of this method is also provided. Although developed primarily for application to databases, which do not contain duration of supply or dose information, use of this method may also facilitate investigations when such information is available and there is a need to consider individualised and/or changing dosing regimens. By shifting the reliance on prescribed duration and dose to determine exposure and dose estimates, individualised dispensing information is used to estimate patterns of exposure and dose for an individual. Reflecting real-world individualised use of medicines with complex and variable dosing regimens, this method offers a pragmatic approach that can be applied to all medicine classes.

Diagnostic Accuracy of Assays Using Point-of-Care Testing or Dried Blood Spot Samples for the Determination of Hepatitis C Virus RNA: A Systematic Review.

BACKGROUND: Finger-stick point-of-care and dried blood spot (DBS) hepatitis C virus (HCV) RNA testing increases testing uptake and linkage to care. This systematic review evaluated the diagnostic accuracy of point-of-care testing and DBS to detect HCV RNA. METHODS: Bibliographic databases and conference presentations were searched for eligible studies. Meta-analysis was used to pool estimates. RESULTS: Of 359 articles identified, 43 studies were eligible and included. When comparing the Xpert HCV Viral Load Fingerstick assay to venous blood samples (7 studies with 987 samples), the sensitivity and specificity for HCV RNA detection was 99% (95% confidence interval [CI], 97%-99%) and 99% (95% CI, 94%-100%) and for HCV RNA quantification was 100% (95% CI, 93%-100%) and 100% (95% CI, 94%-100%). The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing was 6% (95% CI, 3%-11%). When comparing DBS to venous blood samples (28 studies with 3988 samples) the sensitivity and specificity for HCV RNA detection was 97% (95% CI, 95%-98%) and 100% (95% CI, 98%-100%) and for HCV RNA quantification was 98% (95% CI, 96%-99%) and 100% (95% CI, 95%-100%). CONCLUSIONS: Excellent diagnostic accuracy was observed across assays for detection of HCV RNA from finger-stick and DBS samples. The proportion of invalid results following Xpert HCV Viral Load Fingerstick testing highlights the importance of operator training and quality assurance programs.

Comparison of Collapsibility of the Human Upper Airway During Anesthesia and During Sleep.

BACKGROUND: The propensities for the upper airway to collapse during anesthesia and sleep are related, although much of our understanding of this relationship has been inferred from clinical observation and indirect measures such as the apnea-hypopnea index. The aim of this study was to use an identical, rigorous, direct measure of upper airway collapsibility (critical closing pressure of the upper airway) under both conditions to allow the magnitude of upper airway collapsibility in each state to be precisely compared. METHODS: Ten subjects (8 men and 2 women; mean ± SD: age, 40.4 ± 12.1 years; body mass index, 28.5 ± 4.0 kg/m) were studied. Critical closing pressure of the upper airway was measured in each subject on separate days during (1) propofol anesthesia and (2) sleep. RESULTS: Critical closing pressure of the upper airway measurements were obtained in all 10 subjects during nonrapid eye movement sleep and, in 4 of these 10 subjects, also during rapid eye movement sleep. Critical closing pressure of the upper airway during anesthesia was linearly related to critical closing pressure of the upper airway during nonrapid eye movement sleep (r = 0.64 [95% CI, 0.02-0.91]; n = 10; P = .046) with a similar tendency in rapid eye movement sleep (r = 0.80 [95% CI, -0.70 to 0.99]; n = 4; P = .200). However, critical closing pressure of the upper airway during anesthesia was systematically greater (indicating increased collapsibility) than during nonrapid eye movement sleep (2.1 ± 2.2 vs -2.0 ± 3.2 cm H2O, respectively, n = 10; within-subject mean difference, 4.1 cm H2O [95% CI, 2.32-5.87]; P < .001) with a similar tendency during rapid eye movement sleep (1.6 ± 2.4 vs -1.9 ± 4.3 cm H2O, respectively, n = 4; unadjusted difference, 3.5 cm H2O [95% CI, -0.95 to 7.96]; P = .087). CONCLUSIONS: These results demonstrate that the magnitude of upper airway collapsibility during anesthesia and sleep is directly related. However, the upper airway is systematically more collapsible during anesthesia than sleep, suggesting greater vulnerability to upper airway obstruction in the anesthetized state.

Birth-sex cohort alcohol use transitions in the general population: the cross-sectional PEGASUS-Murcia project. / Las transiciones en el uso de alcohol en una cohorte de nacimiento-sexo en la población general: el proyecto transversal PEGASUS-Murcia.

To examine the potential impact of prevalence of alcohol use in a birth-sex cohort on subsequent initiation and progression of alcohol use in the PEGASUS-Murcia project, a cross-sectional survey of a representative sample of non-institutionalized adults in Murcia (Spain). Data on lifetime history of alcohol use, DSM-IV use disorders, and remission were collected from 1,459 adults using face-to-face interviewers based on the Composite International Diagnostic Interview (CIDI 3.0). Life-table estimates based on survival functions for alcohol use age-of-onset and remission were used as time-varying predictors of subsequent individual-level alcohol use in discrete-time survival models. Nearly nine out of ten adults had a lifetime alcohol use history at time of interview. Of these lifetime users, 84.3% became regular users (>12 drinks a year) and 5.5-1.6% went on to meet criteria for DSM-IV alcohol abuse or dependence, respectively. By the age of 18, 70.9% of respondents had used alcohol, and one half (50.2%) had used regularly. Regular use sharply increased during early adulthood to reach 90.8% by age 22. Birth-sex cohort alcohol use was significantly and positively associated with increased odds of all subsequent transitions examined except for the transition from use to abuse. The findings highlight sensitive periods with rapid transitions to higher levels of alcohol use and emphasize the importance of cohort experiences in the full spectrum of stages of alcohol use. These results may contribute to predicting population-levels trends in alcohol-related problems in Spain.

Examinar el impacto potencial de la prevalencia de uso de alcohol en una cohorte de nacimiento-sexo en el inicio y progresión del uso de alcohol en el proyecto PEGASUS-Murcia, encuesta transversal en una muestra representativa de adultos no institucionalizados de Murcia (España). Se entrevistaron personalmente a 1.459 adultos sobre consumo de alcohol a lo largo de la vida, trastornos por uso de alcohol (criterios DSM-IV) y remisión utilizando la Entrevista Diagnóstica Internacional Compuesta (CIDI 3.0). Se calcularon estimaciones de tablas de vida basadas en las funciones de supervivencia para la edad de inicio en el uso de alcohol y su remisión en modelos de supervivencia de tiempo discreto. Casi nueve de cada diez adultos tuvieron una historia de uso de alcohol a lo largo de la vida. Entre ellos, 84,3% desarrolló un uso regular (>12 bebidas por año) y 5,5% y 1,6% cumplieron criterios DSM-IV de Abuso y Dependencia de alcohol, respectivamente. A los 18 años, 70,9% había usado alcohol, 50,2% de forma regular, con un aumento brusco en adultos jóvenes (90,8% a los 22 años). El uso de alcohol de la cohorte de nacimiento-sexo se asoció significativamente con mayores probabilidades para todas las transiciones examinadas, excepto en la transición uso-abuso. Se detectan períodos sensibles con transiciones rápidas a niveles más altos de uso de alcohol. Las experiencias de cohortes en todas las etapas del consumo de alcohol son importantes. Estos resultados podrían contribuir a la predicción de las tendencias poblacionales de los problemas con el alcohol en España.

The effect of temazepam on assessment of severity of obstructive sleep apnea by polysomnography.

PURPOSE: To determine the effect of temazepam on assessment of the severity of obstructive sleep apnea (OSA) by polysomnography (PSG). METHODS: Analysis of diagnostic laboratory-PSG studies was performed in OSA patients who were administered temazepam (10 mg) to facilitate sleep ("temazepam group", n = 73) and in OSA patients (matched for age, gender, body mass index and study date) in whom temazepam was not administered ("control group", n = 73). Sleep- and respiratory-related variables were compared between the groups for the (i) first 3 h of study following temazepam in the temazepam group (when peak blood concentration is expected) or following lights out in the control group, and (ii) entire study duration. RESULTS: Within the first 3 h, no differences in sleep-related variables were observed between the groups. Over the entire study duration, the temazepam group had a reduced total sleep time compared to the control group, likely due to the overnight sleep difficulties that led to its use. Whether measured during the first 3 h of study or over the entire study duration, no significant differences were detected between the groups for any respiratory-related variable, including apnea hypopnea index, arousal index, oxygen desaturation, apnea index, hypopnea index, and event duration. When patients were considered in terms of OSA severity, decreased arousal index was noted in the temazepam group over the entire study duration, but only in those with severe OSA. CONCLUSION: Oral administration of 10 mg of temazepam during the course of PSG does not systematically affect assessment of the severity of OSA by PSG.

Prevalence of obesity and the effect on length of mechanical ventilation and length of stay in intensive care patients: A single site observational study.

OBJECTIVES: To provide a snapshot of the prevalence of abnormal body mass index (BMI) in a sample of intensive care unit (ICU) patients; to identify if any medical specialty was associated with abnormal BMI and to explore associations between BMI and ICU-related outcomes. BACKGROUND: Obesity is an escalating public health issue across developed nations but there is little data pertaining to critically ill patients who require care that is expensive. METHODS: Retrospective observational audit of 735 adult patients (median age 58 years) admitted to the Sir Charles Gairdner Hospital 23 bed tertiary ICU between November 2012 and June 2014. Primary outcome measure was patient BMI: underweight (<18.5kg/m2), normal weight (18.5-24.99kg/m2), overweight (25-29.99kg/m2), obese (30-39.99kg/m2) or extreme obese (40kg/m2 or above). Other measures included gender, acute physiology and chronic health evaluation II score, admission specialty, length of mechanical ventilation (MV), length of stay (LOS) and mortality. RESULTS: Compared to the general population there was a higher proportion of obese patients within the cohort with the majority of patients overweight (33.9%) or obese (36.5%) and median BMI of 27.9 (IQR 7.9). There were no significant differences between specialties for BMI (p=0.103) and abnormal BMI was not found to impact negatively on mortality (ICU, p=0.373; hospital, p=0.330). Normal BMI patients had shorter length of MV than other BMI categories and the impact of BMI on ICU LOS was dependent on length of MV. Overweight patients ventilated for five days or more had a shorter LOS, and extremely obese non-ventilated patients had a longer LOS, compared to normal weight patients. CONCLUSIONS: Although the obesity-disease relationship is increasingly complex and data presented reflects categorical BMI for patients admitted to a single ICU site it may be important to consider the cost implications of caring for this cohort especially with regard to MV and LOS.

Clinicopathological and immunohistological features of polypoid endometriosis.

AIMS: To compare clinicopathological and immunohistochemical features of polypoid endometriosis (PE) and non-polypoid endometriosis (NPE). METHODS AND RESULTS: Fifteen cases of PE and 20 cases of NPE were assessed. All cases were stained immunohistochemically for CD10 and p16 and the proportion of p16-positive stromal and epithelial cells was estimated. On review, 10 PE cases resembled NPE histologically but occurred at mucosal or serosal surfaces, or within cyst cavities, that permitted polyp formation. These cases had a similar age distribution and immunohistochemical profile to NPE. The remaining five PE cases showed histological similarity to eutopic endometrial polyps; these occurred in older patients, and showed significantly greater stromal and epithelial p16 immunoreactivity. CONCLUSIONS: There are two main subgroups of PE. The majority of cases in this series showed similar histological features to NPE, but involved anatomical sites that facilitated exophytic or polypoid growth. The remaining PE cases resembled eutopic endometrial polyps histologically and immunophenotypically and they occurred in older patients. These findings suggest that such lesions are 'true' polyps sharing a pathogenetic relationship with similar lesions arising in the endometrium.

Isokinetic shoulder strength correlates with level of sports participation and functional activity after reverse total shoulder arthroplasty.

BACKGROUND: Reverse total shoulder arthroplasty (RTSA) is increasingly being performed. Many patients may wish to return to high levels of sporting activity. This study aimed to evaluate the correlation of isokinetic shoulder strength with level of participation in sport and recreation after RTSA. METHODS: We surveyed 51 patients at a mean of 29.5 months (range, 12-60 months) after surgery. Mean age was 74.1 years. Patient-reported sporting activity was classified as low, medium, or high demand. All patients completed the shortened Disabilities of the Arm, Shoulder, and Hand questionnaire and the Oxford Shoulder Score and underwent Biodex dynamometer testing of the RTSA evaluating isokinetic shoulder strength in flexion and extension, abduction and adduction, and internal and external rotation. RESULTS: Reported sporting activity was high demand in 35% and moderate demand in 43%. There was a large variation in shoulder isokinetic strength parameters especially for internal and external rotation. With the exception of abduction, a significant correlation was noted between strength and the level of sports participation that patients reported (P < .03). A significant correlation was also noted between strength and patient-reported outcome measures for internal rotation and arm flexion and abduction (P < .05). CONCLUSION: Most patients reported returning to moderate- or high-level sporting activity in the short term after RTSA. Isokinetic shoulder strength, especially in internal rotation and arm flexion, positively correlates with both patient-reported level of participation in sports and recreation and daily function.

Asynchronous glands in secretory pattern endometrium: clinical associations and immunohistological changes.

AIMS: The significance and pathogenesis of irregular or asynchronous maturation within endometrial glands remains uncertain. The aim of this study was to investigate differences in epithelial hormone receptor immunoreactivity and stromal cell calretinin, CD34 and p16 expression in morphologically normal secretory endometrium and in asynchronous (non-secretory) endometrial glands (AEGs). METHODS AND RESULTS: Nineteen consecutive endometrial specimens showing AEGs were examined. The mean age of the patients was 42.8 years, and the most common presenting symptom was menorrhagia. Immunohistological expression of oestrogen receptor (ER) α, of ERß and of progesterone receptor (PR) were compared in normal secretory glands and in AEGs. Stromal cell expression of calretinin, CD34 and p16 was also investigated. In contrast to normal secretory glands, the epithelial cells lining AEGs were usually ERα/PR-positive and showed significantly increased ERß expression. Altered calretinin and CD34 expression within functional layer stromal cells was seen in five and two cases, respectively, but there were no differences in stromal cell immunoreactivity around AEGs. CONCLUSIONS: The most common clinical symptom associated with AEGs in this study was menorrhagia. Aberrant hormone receptor expression in AEGs suggests a localized, possibly clonal, defect in epithelial maturation. There were no immunophenotypic changes to suggest that AEGs are related to a primary endometrial stromal deficiency.

Trends in use of medicines for opioid agonist treatment in Australia, 2013-2022.

BACKGROUND: There are limited longitudinal data on national patterns of opioid agonist treatment (OAT). This study describes 10-year trends in the sales of OAT medicines in Australia. METHODS: A descriptive and time-series analysis of methadone, sublingual (SL) buprenorphine (+/-naloxone), and long-acting injectable (LAI) buprenorphine sold in Australia between 2013 and 2022 was performed. Total units sold were converted into an estimate of the number of clients that could be treated over a 28-day period with that amount of medicine ('client-months'). RESULTS: Between January 2013 and December 2022, the estimated number of client-months on: any OAT increased by 50 % to 53,501, methadone decreased (-8.5%), SL buprenorphine increased (+78%), and LAI buprenorphine increased substantially after September 2019. In January 2013, 78 % of OAT client-months received methadone. By December 2022, 48 % received methadone, 26 % SL buprenorphine, and 26 % LAI buprenorphine. Between 2013 to 2022, OAT client-months per capita were highest in the state of New South Wales. Over the study period, greater increases in OAT were observed in very remote areas (88%) compared to major cities (53%). The number of client-months in non-community pharmacy settings remained stable from 2013 to 2019/20, before increasing markedly. The introduction of LAI buprenorphine was associated with an immediate, sustained increase of 1,636 OAT client-months, and further increases of 190 OAT client-months each month. CONCLUSION: Patterns of OAT have shifted over the last 10-years with buprenorphine (SL/LAI) now the most common OAT used in Australia. The introduction of LAI buprenorphine has expanded OAT access, particularly in non-community pharmacy settings, and in remote areas.

Prescription opioid use among people with opioid dependence and concurrent benzodiazepine and gabapentinoid exposure: An analysis of overdose and all-cause mortality.

BACKGROUND: Studies investigating mortality risk associated with use of opioid analgesics, benzodiazepines, gabapentinoids, and opioid agonist treatment (OAT) among people with opioid dependence (PWOD) are lacking. This study addresses this gap using a cohort of 37,994 PWOD initiating opioid analgesics between July 2003 and July 2018 in New South Wales, Australia. METHODS: Linked administrative records provided data on dispensings, sociodemographics, clinical characteristics, OAT, and mortality. Cox proportional hazards models assessed associations between time-varying measures of individual and concurrent medicine use and OAT with all-cause mortality, accidental opioid overdose, non-drug induced accidents, and non-drug-induced suicide. Opioid analgesic dose effects, expressed as oral morphine equivalents (OMEs) per day, were also examined. OUTCOMES: During the study period, 3167 individuals died. Compared with no use, all medicines of interest were associated with increased accidental opioid overdose risk; hazard ratios (HR) ranged from 1.33 (95 % CI: 1.05-1.68) for opioid analgesic use to 6.10 (95 % CI: 4.11-9.06) for opioid analgesic, benzodiazepine and gabapentinoid use. Benzodiazepine use was associated with increased non-drug-induced accidents and non-drug-induced suicides. For all-cause mortality, all combinations of benzodiazepines and gabapentinoids with opioid analgesics were associated with increased risk (aHRs ranged from 1.35 to 2.73). For most medicines/medicine combinations, all-cause mortality risk was reduced when in OAT compared to out of OAT. Higher opioid analgesic doses were associated with increased all-cause mortality (e.g., 90-199 mg vs 1-49 mg OME per day: HR 1.90 [95 % CI: 1.52-2.40]). INTERPRETATION: The increased mortality risk associated with benzodiazepines and gabapentinoids among PWOD appear to be reduced when engaged in OAT. A greater focus on encouraging OAT engagement, providing overdose prevention education, and access and coverage of overdose antidotes is necessary to minimise the unintended consequences of medicines use in this population.

Age-Related Risk of Serious Fall Events and Opioid Analgesic Use.

Importance: Opioid analgesics may be associated with increased risk of falls, particularly among older adults. Objective: To quantify the age-related risk of serious fall events among adults prescribed opioids by opioid exposure, time from initiation, and daily dose. Design, Setting, and Participants: This population-based cohort study conducted in New South Wales, Australia, used data linking national pharmaceutical claims to national and state datasets, including information on sociodemographic characteristics, clinical characteristics, medicines use, health services utilization, and mortality (POPPY II study). It included adults (18 years or older) who initiated prescription opioid treatment, which was defined as no prior dispensing during the preceding 365 days, between January 1, 2005, and December 31, 2018. Data were analyzed from February to June 2023. Exposure: Time-dependent periods of opioid exposure were evaluated from dispensing records. Main Outcome and Measures: Serious fall events identified from emergency department, hospitalization, and mortality records. Negative binomial models were used to assess associations between time-dependent opioid exposure (overall, by time from initiation, and by dose), age, and risk of fall events. Models were adjusted for known fall risk factors, including other fall risk-increasing drugs, frailty risk, and prior serious fall events. Results: The cohort comprised 3 212 369 individuals who initiated prescription opioid treatment (1 702 332 women [53%]; median [IQR] age at initiation, 49 [32-65] years). Overall, 506 573 serious fall events were identified, including 5210 fatal falls. During exposure to opioids, the risk of serious fall events was elevated among all age groups; compared with the group aged 18 to 44 years, this risk was highest among those 85 years or older (adjusted incident rate ratio, 6.35; 95% CI, 6.20-6.51). Across all age groups, the first 28 days following opioid initiation was a time of increased serious fall risk; this risk increased with age. Among individuals aged 18 to 84 years, associations were identified between higher daily opioid doses and serious fall events. Conclusions and Relevance: The results of this cohort study suggest that prescription opioids were associated with increased risk of serious fall events among adults of all ages, with individuals 85 years or older at greatest risk. These risks should be considered when prescribing opioids, particularly for individuals with preexisting risk factors or when opioids are prescribed at higher doses. Targeted falls prevention efforts may be most effective within the first month following opioid initiation.

Towards measuring effective coverage: critical bottlenecks in quality- and user-adjusted coverage for major depressive disorder in São Paulo metropolitan area, Brazil.

BACKGROUND: Major depressive disorder (MDD) contributes to a significant proportion of disease burden, disability, economic losses, and impact on need of treatment and health care in Brazil, but systematic information about its treatment coverage is scarce. This paper aims to estimate the gap in treatment coverage for MDD and identify key bottlenecks in obtaining adequate treatment among adult residents in the São Paulo Metropolitan area, Brazil. METHODS: A representative face-to-face household survey was conducted among 2942 respondents aged 18+ years to assess 12-month MDD, characteristics of 12-month treatment received, and bottlenecks to deliver care through the World Mental Health Composite International Diagnostic Interview. RESULTS: Among those with MDD (n = 491), 164 (33.3% [SE, 1.9]) were seen in health services, with an overall 66.7% treatment gap, and only 25.2% [SE, 4.2] received effective treatment coverage, which represents 8.5% of those in need, with a 91.5% gap in adequate care (66.4% due to lack of utilization and 25.1% due to inadequate quality and adherence). Critical service bottlenecks identified were: use of psychotropic medication (12.2 percentage points drop), use of antidepressants (6.5), adequate medication control (6.8), receiving psychotherapy (19.8). CONCLUSIONS: This is the first study demonstrating the huge treatment gaps for MDD in Brazil, considering not only overall coverage, but also identifying specific quality- and user-adjusted bottlenecks in delivering pharmacological and psychotherapeutic care. These results call for urgent combined actions focused in reducing effective treatment gaps within services utilization, as well as in reducing gaps in availability and accessibility of services, and acceptability of care for those in need.

Mortality during and after specialist alcohol and other drug treatment: Variation in rates according to principal drug of concern and treatment modality.

INTRODUCTION: For people accessing treatment for problems with drugs other than opioids, little is known about the relationship between treatment and mortality risk, nor how mortality risk varies across treatment modalities. We addressed these evidence gaps by determining mortality rates during and after treatment for people accessing a range of treatment modalities for several drugs of concern. METHODS: We conducted a cohort study using linked data on publicly funded specialist alcohol or other drug treatment service use and mortality for people receiving treatment in New South Wales between January 2012 and December 2018. We calculated and compared during-treatment and post-treatment crude mortality rates and age- and sex-standardised mortality rates, separately for each principal drug of concern and modality. RESULTS: Over the study period, 45,026 people accessed treatment for problems with alcohol, 26,407 for amphetamine-type stimulants, 23,047 for cannabinoids and 21,556 for opioids. People treated for alcohol or opioid problems had higher crude mortality rates (1.48, 1.91, 1.09 per 100 person years, respectively) than those with problems with amphetamine-type stimulants or cannabinoids (0.46, 0.30 per 100 person years, respectively). Mortality rates differed according to treatment status and modality only among people with alcohol or opioid problems. DISCUSSION AND CONCLUSIONS: The observed variation in mortality rates indicates there is scope to reduce mortality among people accessing treatment with alcohol or opioid problems. Future research on mortality among people accessing drug and alcohol treatment should account for the variation in mortality by drug of concern and treatment modality.

Five-Year Trajectories of Prescription Opioid Use.

Importance: There are known risks of using opioids for extended periods. However, less is known about the long-term trajectories of opioid use following initiation. Objective: To identify 5-year trajectories of prescription opioid use, and to examine the characteristics of each trajectory group. Design, Setting, and Participants: This population-based cohort study conducted in New South Wales, Australia, linked national pharmaceutical claims data to 10 national and state data sets to determine sociodemographic characteristics, clinical characteristics, drug use, and health services use. The cohort included adult residents (aged ≥18 years) of New South Wales who initiated a prescription opioid between July 1, 2003, and December 31, 2018. Statistical analyses were conducted from February to September 2022. Exposure: Dispensing of a prescription opioid, with no evidence of opioid dispensing in the preceding 365 days, identified from pharmaceutical claims data. Main Outcomes and Measures: The main outcome was the trajectories of monthly opioid use over 60 months from opioid initiation. Group-based trajectory modeling was used to classify these trajectories. Linked health care data sets were used to examine characteristics of individuals in different trajectory groups. Results: Among 3 474 490 individuals who initiated a prescription opioid (1 831 230 females [52.7%]; mean [SD] age, 49.7 [19.3] years), 5 trajectories of long-term opioid use were identified: very low use (75.4%), low use (16.6%), moderate decreasing to low use (2.6%), low increasing to moderate use (2.6%), and sustained use (2.8%). Compared with individuals in the very low use trajectory group, those in the sustained use trajectory group were older (age ≥65 years: 22.0% vs 58.4%); had more comorbidities, including cancer (4.1% vs 22.2%); had increased health services contact, including hospital admissions (36.9% vs 51.6%); had higher use of psychotropic (16.4% vs 42.4%) and other analgesic drugs (22.9% vs 47.3%) prior to opioid initiation, and were initiated on stronger opioids (20.0% vs 50.2%). Conclusions and relevance: Results of this cohort study suggest that most individuals commencing treatment with prescription opioids had relatively low and time-limited exposure to opioids over a 5-year period. The small proportion of individuals with sustained or increasing use was older with more comorbidities and use of psychotropic and other analgesic drugs, likely reflecting a higher prevalence of pain and treatment needs in these individuals.

Agreement between self-reported illicit drug use and biological samples: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Studies often rely upon self-report and biological testing methods for measuring illicit drug use, although evidence for their agreement is limited to specific populations and self-report instruments. We aimed to examine comprehensively the evidence for agreement between self-reported and biologically measured illicit drug use among all major illicit drug classes, biological indicators, populations and settings. METHODS: We systematically searched peer-reviewed databases (Medline, Embase and PsycINFO) and grey literature. Included studies reported 2 × 2 table counts or agreement estimates comparing self-reported and biologically measured use published up to March 2022. With biological results considered to be the reference standard and use of random-effect regression models, we evaluated pooled estimates for overall agreement (primary outcome), sensitivity, specificity, false omission rates (proportion reporting no use that test positive) and false discovery rates (proportion reporting use that test negative) by drug class, potential consequences attached to self-report (i.e. work, legal or treatment impacts) and time-frame of use. Heterogeneity was assessed by inspecting forest plots. RESULTS: From 7924 studies, we extracted data from 207 eligible studies. Overall agreement ranged from good to excellent (> 0.79). False omission rates were generally low, while false discovery rates varied by setting. Specificity was generally high but sensitivity varied by drug, sample type and setting. Self-report in clinical trials and situations of no consequences was generally reliable. For urine, recent (i.e. past 1-4 days) self-report produced lower sensitivity and false discovery rates than past month. Agreement was higher in studies that informed participants biological testing would occur (diagnostic odds ratio = 2.91, 95% confidence interval = 1.25-6.78). The main source of bias was biological assessments (51% studies). CONCLUSIONS: While there are limitations associated with self-report and biological testing to measure illicit drug use, overall agreement between the two methods is high, suggesting both provide good measures of illicit drug use. Recommended methods of biological testing are more likely to provide reliable measures of recent use if there are problems with self-disclosure.

Development and evaluation of a risk algorithm predicting alcohol dependence after early onset of regular alcohol use.

AIMS: Likelihood of alcohol dependence (AD) is increased among people who transition to greater levels of alcohol involvement at a younger age. Indicated interventions delivered early may be effective in reducing risk, but could be costly. One way to increase cost-effectiveness would be to develop a prediction model that targeted interventions to the subset of youth with early alcohol use who are at highest risk of subsequent AD. DESIGN: A prediction model was developed for DSM-IV AD onset by age 25 years using an ensemble machine-learning algorithm known as 'Super Learner'. Shapley additive explanations (SHAP) assessed variable importance. SETTING AND PARTICIPANTS: Respondents reporting early onset of regular alcohol use (i.e. by 17 years of age) who were aged 25 years or older at interview from 14 representative community surveys conducted in 13 countries as part of WHO's World Mental Health Surveys. MEASUREMENTS: The primary outcome to be predicted was onset of life-time DSM-IV AD by age 25 as measured using the Composite International Diagnostic Interview, a fully structured diagnostic interview. FINDINGS: AD prevalence by age 25 was 5.1% among the 10 687 individuals who reported drinking alcohol regularly by age 17. The prediction model achieved an external area under the curve [0.78; 95% confidence interval (CI) = 0.74-0.81] higher than any individual candidate risk model (0.73-0.77) and an area under the precision-recall curve of 0.22. Overall calibration was good [integrated calibration index (ICI) = 1.05%]; however, miscalibration was observed at the extreme ends of the distribution of predicted probabilities. Interventions provided to the 20% of people with highest risk would identify 49% of AD cases and require treating four people without AD to reach one with AD. Important predictors of increased risk included younger onset of alcohol use, males, higher cohort alcohol use and more mental disorders. CONCLUSIONS: A risk algorithm can be created using data collected at the onset of regular alcohol use to target youth at highest risk of alcohol dependence by early adulthood. Important considerations remain for advancing the development and practical implementation of such models.