The Medicines Intelligence Data Platform: A Population-Based Data Resource From New South Wales, Australia.

BACKGROUND: The Medicines Intelligence (MedIntel) Data Platform is an anonymised linked data resource designed to generate real-world evidence on prescribed medicine use, effectiveness, safety, costs and cost-effectiveness in Australia. RESULTS: The platform comprises Medicare-eligible people who are ≥18 years and residing in New South Wales (NSW), Australia, any time during 2005-2020, with linked administrative data on dispensed prescription medicines (Pharmaceutical Benefits Scheme), health service use (Medicare Benefits Schedule), emergency department visits (NSW Emergency Department Data Collection), hospitalisations (NSW Admitted Patient Data Collection) plus death (National Death Index) and cancer registrations (NSW Cancer Registry). Data are currently available to 2022, with approval to update the cohort and data collections annually. The platform includes 7.4 million unique people across all years, covering 36.9% of the Australian adult population; the overall population increased from 4.8 M in 2005 to 6.0 M in 2020. As of 1 January 2019 (the last pre-pandemic year), the cohort had a mean age of 48.7 years (51.1% female), with most people (4.4 M, 74.7%) residing in a major city. In 2019, 4.4 M people (73.3%) were dispensed a medicine, 1.2 M (20.5%) were hospitalised, 5.3 M (89.4%) had a GP or specialist appointment, and 54 003 people died. Anti-infectives were the most prevalent medicines dispensed to the cohort in 2019 (43.1%), followed by nervous system (32.2%) and cardiovascular system medicines (30.2%). CONCLUSION: The MedIntel Data Platform creates opportunities for national and international research collaborations and enables us to address contemporary clinically- and policy-relevant research questions about quality use of medicines and health outcomes in Australia and globally.

Trajectories of Opioid Use Before and After Cancer Diagnosis: A Population-Based Cohort Study.

BACKGROUND: Opioid use prior to cancer diagnosis increases the likelihood of long-term use during survivorship, however, patterns of use before and after diagnosis are not understood. METHODS: We used population-based dispensing data linked with cancer and death notifications to identify two cohorts of adults residing in New South Wales initiating opioids within 24 months prior to a first cancer diagnosed between 2014 and 2016: 'survivors' (alive 24 months following diagnosis) and 'decedents' (died within 24 months). We used group-based trajectory modelling to identify trajectories of monthly opioid dispensings and dispensed oral morphine equivalent milligrams (OMEmg) during the 24 months before/after cancer diagnosis. RESULTS: There were 21,843 survivors with four prediagnosis opioid dispensing trajectories: infrequent (58% of the cohort), late increasing (26%), moderate (10%), and sustained dispensing (6%). We observed an overall increase in dispensed OMEmg of 83 OMEmg (95% CI: 76-91) during the month of diagnosis, with strong opioid formulations comprising most treatment postdiagnosis. Within each prediagnosis opioid trajectory group, we observed five to six postdiagnosis trajectory groups, including no opioid dispensing. Moderate and sustained prediagnosis groups had large proportions of people continuing or increasing opioid dispensing after diagnosis, while small proportions discontinued opioid treatment. We observed similar trajectories in the decedent cohort. CONCLUSIONS: There is considerable heterogeneity in opioid use before and after cancer diagnosis. Our findings suggest noncancer factors drive a significant proportion of postdiagnosis opioid use, but use increased significantly from the month of cancer diagnosis and never returned to prediagnosis levels.

The medical competence of health care providers in sub-Saharan Africa: Evidence from 16 127 providers across 11 countries.

Despite a consensus that quality of care is critically deficient in low-income countries, few nationally representative studies provide comparable measures of quality of care across countries. To address this gap, we used nationally representative data from in-person administrations of clinical vignettes to measure the competence of 16 127 health care providers across 11 sub-Saharan African countries. Rather than large variations across countries, we found that 81% of the variation in competence is within countries and the characteristics of health care providers do not explain most of this variation. Professional qualifications-including cadre and education-are only weakly associated with competence: across our sample, one-third of nurses are more competent than the average doctor in the same country and one-quarter of doctors are less competent than the average nurse. Finally, while younger cohorts do tend to be more competent, perhaps reflecting improvements in medical education, it would take 25 decades of turnover to improve care by 10 percentage points, on average, if we were to rely on such improvements alone. These patterns necessitate a fundamentally different approach to health care human resource management, calling into question typical staffing policies based on qualifications and seniority rather than directly measured quality.

Prevalence of long COVID symptoms in Haryana, India: a cross-sectional follow-up study.

Background: Emerging research indicates growing concern over long COVID globally, although there have been limited studies that estimate population burden. We aimed to estimate the burden of long COVID in three districts of Haryana, India, using an opportunity to link a seroprevalence study to follow-up survey of symptoms associated with long COVID. Methods: We used a population-based seroprevalence survey for COVID-19 conducted in September 2021 across Haryana, India. Adults from three purposively selected districts (Rohtak, Gurugram, and Jhajjar) were eligible to participate; 2205 of 3213 consented to participate in a survey on health status. Trained investigators administered a structured questionnaire that included demographic characteristics, self-reported symptoms of illness in the last six months before the survey, mental health, and history of COVID-19. Findings: Unadjusted regression estimates indicated positive correlations between symptomatic complaints and COVID-19 exposure, suggesting lingering effects of COVID-19 in this population. The overall physical morbidity index was higher among those who tested positive for COVID-19, as was the incidence of new cases. However, both morbidity and incidence became statistically insignificant after adjustment for multiple comparisons. Cough emerged as the only statistically significant individual persistent symptom. Sex-stratified analyses indicated significant estimates only for physical morbidity in women. Interpretation: This study is one of the first from India that uses a large population-based sample to examine longer term repercussions of COVID infections. The burden of long COVID should primarily be addressed in clinical settings, where specialised treatment for individual cases continues to evolve. Our analyses also provide insight into the size and nature of studies required to assess the population-level burden of long COVID. Funding: This paper was produced under the auspices of the Lancet COVID 19 Commission India Task Force, which was supported financially by the Reliance Foundation. The Lancet COVID 19 Commission was set up in July 2020 and submitted its final report by October 2022. This report by the India Task Force was prepared during the same period.

The impact of tightened prescribing restrictions for PBS-subsidised opioid medicines and the introduction of half-pack sizes, Australia, 2020-21: an interrupted time series analysis.

OBJECTIVES: To evaluate the impact of the tightened Pharmaceutical Benefits Scheme (PBS) prescribing rules for immediate release (IR) and controlled release (CR) opioid medicines (1 June 2020), which also eliminated repeat dispensing without authorisation for codeine/paracetamol and tramadol IR and introduced half-pack size item codes for IR formulations. DESIGN, SETTING: Population-based interrupted time series analysis of PBS dispensing data claims for a 10% sample of PBS-eligible residents and IQVIA national opioid medicine sales data (PBS-subsidised and private prescriptions), 28 May 2018 - 6 June 2021. MAIN OUTCOME MEASURES: Mean amount of PBS-subsidised opioid medicines dispensed per day and mean overall amount sold per day - each expressed as oral morphine equivalent milligrams (OME) - overall, by formulation type (IR, CR), and by specific formulation. RESULTS: During the twelve months following the PBS changes, daily PBS-subsidised opioid medicine dispensing was 81 565 OME lower (95% CI, -106 146 to -56 984 OME) than the mean daily level for 2018-20, a decline of 3.8% after adjusting for the pre-intervention trend; the relative reduction was greater for IR (8.4%) than CR formulations (2.6%). Total daily sales of all, IR formulation, and CR formulation opioid medicines did not change significantly after the PBS changes. Repeat dispensing of prescriptions comprised 7.4% of PBS-subsidised opioid dispensing before 1 June 2020, and 1.3% after the changes. Half-pack sizes comprised 8.4% of PBS-subsidised IR opioid medicine dispensing and 2.8% of all opioid medicines sold in the twelve months after the PBS changes. CONCLUSIONS: The introduction of new PBS rules for subsidised opioid medicines was followed by a decline in PBS-subsidised dispensing. Some people may have bypassed the new restrictions by switching to private prescriptions, but our findings suggest that opioid medicine use in Australia declined as a result of the new restrictions.

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.

Changes in systemic cancer therapy in Australia during the Delta and Omicron waves of the COVID-19 pandemic (2021-2022): a controlled interrupted time series analysis.

OBJECTIVES: Australian lockdowns in response to the initial coronavirus disease 2019 (COVID-19) outbreak in 2020 were associated with small and transient changes in the use of systemic cancer therapy. We aimed to investigate the impacts of the longer and more restrictive lockdowns in the Australian states of New South Wales (NSW) and Victoria during both the Delta subvariant lockdowns in mid-2021 and the Omicron subvariant outbreak in late 2021/early 2022. STUDY TYPE: Population-based, controlled interrupted time series analysis. METHODS: We conducted a national observational study using de-identified records of government-subsidised cancer medicines dispensed to a random 10% sample of Australians between July 2018 and July 2022. We used controlled interrupted time series analysis to investigate changes in the dispensing, initiation and discontinuation of all cancer medicines dispensed to residents of NSW and Victoria, using the rest of Australia as a control series. We used quasi-Poisson regression to model weekly counts and estimate incidence rate ratios (IRRs) for the effect of (each) the Delta phase lockdown and the Omicron outbreak on our systemic cancer therapy outcomes. RESULTS: Between July 2018 and July 2022, cancer medicines were dispensed 592 141 times to 33 198 people in NSW and Victoria. Overall, there were no changes to the rates of dispensing, initiation or discontinuation of antineoplastics during the Delta phase lockdowns. In both states during the Omicron outbreak, there were significant decreases in the dispensing of antineoplastics (NSW IRR 0.89; 95% confidence interval [CI] 0.84, 0.93. Victoria IRR 0.92; 95% CI 0.88, 0.96) and in the initiation of endocrine therapy (NSW IRR 0.85; 95% CI 0.74, 0.99. Victoria IRR 0.78; 95% CI 0.65, 0.94), and no changes in the discontinuation of any systemic cancer therapy. CONCLUSIONS: The 2021 lockdowns and 2021/2022 Omicron outbreaks in NSW and Victoria had significant impacts on the dispensing, initiation and discontinuation of systemic cancer therapies, however, the overall effects were minimal. The impacts of lockdowns were less significant than the Omicron outbreaks, suggesting COVID-19 infection, health system capacity, and patient and community concerns were important factors for treatment changes.

Microbiome composition and function within the Kellet's whelk perivitelline fluid.

Microbiomes have gained significant attention in ecological research, owing to their diverse interactions and essential roles within different organismal ecosystems. Microorganisms, such as bacteria, archaea, and viruses, have profound impact on host health, influencing digestion, metabolism, immune function, tissue development, and behavior. This study investigates the microbiome diversity and function of Kellet's whelk (Kelletia kelletii) perivitelline fluid (PVF), which sustains thousands of developing K. kelletii embryos within a polysaccharide and protein matrix. Our core microbiome analysis reveals a diverse range of bacteria, with the Roseobacter genus being the most abundant. Additionally, genes related to host-microbe interactions, symbiosis, and quorum sensing were detected, indicating a potential symbiotic relationship between the microbiome and Kellet's whelk embryos. Furthermore, the microbiome exhibits gene expression related to antibiotic biosynthesis, suggesting a defensive role against pathogenic bacteria and potential discovery of novel antibiotics. Overall, this study sheds light on the microbiome's role in Kellet's whelk development, emphasizing the significance of host-microbe interactions in vulnerable life history stages. To our knowledge, ours is the first study to use 16S sequencing coupled with RNA sequencing (RNA-seq) to profile the microbiome of an invertebrate PVF.IMPORTANCEThis study provides novel insight to an encapsulated system with strong evidence of symbiosis between the microbial inhabitants and developing host embryos. The Kellet's whelk perivitelline fluid (PVF) contains microbial organisms of interest that may be providing symbiotic functions and potential antimicrobial properties during this vulnerable life history stage. This study, the first to utilize a comprehensive approach to investigating Kellet's whelk PVF microbiome, couples 16S rRNA gene long-read sequencing with RNA-seq. This research contributes to and expands our knowledge on the roles of beneficial host-associated microbes.

Care pathways of individuals with tuberculosis before and during the COVID-19 pandemic in Bandung, Indonesia.

The COVID-19 pandemic is thought to have undone years' worth of progress in the fight against tuberculosis (TB). For instance, in Indonesia, a high TB burden country, TB case notifications decreased by 14% and treatment coverage decreased by 47% during COVID-19. We sought to better understand the impact of COVID-19 on TB case detection using two cross-sectional surveys conducted before (2018) and after the onset of the pandemic (2021). These surveys allowed us to quantify the delays that individuals with TB who eventually received treatment at private providers faced while trying to access care for their illness, their journey to obtain a diagnosis, the encounters individuals had with healthcare providers before a TB diagnosis, and the factors associated with patient delay and the total number of provider encounters. We found some worsening of care seeking pathways on multiple dimensions. Median patient delay increased from 28 days (IQR: 10, 31) to 32 days (IQR: 14, 90) and the median number of encounters increased from 5 (IQR: 4, 8) to 7 (IQR: 5, 10), but doctor and treatment delays remained relatively unchanged. Employed individuals experienced shorter delays compared to unemployed individuals (adjusted medians: -20.13, CI -39.14, -1.12) while individuals whose initial consult was in the private hospitals experienced less encounters compared to those visiting public providers, private primary care providers, and informal providers (-4.29 encounters, CI -6.76, -1.81). Patients who visited the healthcare providers >6 times experienced longer total delay compared to those with less than 6 visits (adjusted medians: 59.40, 95% CI: 35.04, 83.77). Our findings suggest the need to ramp up awareness programs to reduce patient delay and strengthen private provide engagement in the country, particularly in the primary care sector.

Impact of the COVID-19 pandemic on quality of tuberculosis care in private facilities in Bandung, Indonesia: a repeated cross-sectional standardized patients study.

BACKGROUND: Indonesia has the second highest incidence of tuberculosis in the world. While 74% of people with tuberculosis in Indonesia first accessed the private health sector when seeking care for their symptoms, only 18% of tuberculosis notifications originate in the private sector. Little is known about the impact of the COVID-19 pandemic on the private sector. Using unannounced standardized patient visits to private providers, we aimed to measure quality of tuberculosis care during the COVID-19 pandemic. METHODS: A cross-sectional study was conducted using standardized patients in Bandung City, West Java, Indonesia. Ten standardized patients completed 292 visits with private providers between 9 July 2021 and 21 January 2022, wherein standardized patients presented a presumptive tuberculosis case. Results were compared to standardized patients surveys conducted in the same geographical area before the onset of COVID-19. RESULTS: Overall, 35% (95% confidence interval (CI): 29.2-40.4%) of visits were managed correctly according to national tuberculosis guidelines. There were no significant differences in the clinical management of presumptive tuberculosis patients before and during the COVID-19 pandemic, apart from an increase in temperature checks (adjusted odds ratio (aOR): 8.05, 95% CI: 2.96-21.9, p < 0.001) and a decrease in throat examinations (aOR 0.16, 95% CI: 0.06-0.41, p = 0.002) conducted during the pandemic. CONCLUSIONS: Results indicate that providers successfully identify tuberculosis in their patients yet do not manage them according to national guidelines. There were no major changes found in quality of tuberculosis care due to the COVID-19 pandemic. As tuberculosis notifications have declined in Indonesia due to the COVID-19 pandemic, there remains an urgent need to increase private provider engagement in Indonesia and improve quality of care.

Decline in the Incidence of Distant Recurrence of Breast Cancer: A Population-Based Health Record Linkage Study, Australia 2001-2016.

BACKGROUND: We investigated differences in cumulative incidence of first distant recurrence (DR) following non-metastatic breast cancer over a time period when new adjuvant therapies became available in Australia. METHODS: We conducted a health record linkage study of females with localized (T1-3N0) or regional (T4 or N+) breast cancer in the New South Wales Cancer Registry in 2001 to 2002 and 2006 to 2007. We linked cancer registry records with administrative records from hospitals, dispensed medicines, radiotherapy services, and death registrations to estimate the 9-year cumulative incidence of DR and describe use of adjuvant treatment. RESULTS: The study included 13,170 women (2001-2002 n = 6,338, 2006-2007 n = 6,832). The 9-year cumulative incidence of DR was 3.6% [95% confidence interval (CI), 2.3%-4.9%] lower for 2006-2007 diagnoses (15.0%) than 2001-2002 (18.6%). Differences in the annual hazard of DR between cohorts were largest in year two. DR incidence declined for localized and regional disease. Decline was largest for ages <40 years (absolute difference, 14.4%; 95% CI, 8.3%-20.6%), whereas their use of adjuvant chemotherapy (2001-2002 49%, 2006-2007 75%) and HER2-targeted therapy (2001-2002 0%, 2006-2007 16%) increased. DR did not decline for ages ≥70 years (absolute difference, 0.9%; 95% CI, -3.6%-1.8%) who had low use of adjuvant chemotherapy and HER2-targeted therapy. CONCLUSIONS: This whole-of-population study suggests that DR incidence declined over time. Decline was largest for younger ages, coinciding with changes to adjuvant breast cancer therapy. IMPACT: Study findings support the need for trials addressing questions relevant to older people and cancer registry surveillance of DR to inform cancer control programs.

Characteristics and post-metastasis survival of recurrent metastatic breast cancer over time - An Australian population-based record linkage study, 2001-2016.

AIM: To assess population-level characteristics and post-metastasis survival of people with recurrent metastatic breast cancer (rMBC) during a period when new publicly-subsidised adjuvant and metastatic systemic therapies became available. METHODS: Record linkage study of females in NSW Cancer Registry (NSWCR) diagnosed with non-metastatic breast cancer (BC) in 2001-2002 (C1) and 2006-2007 (C2). We identified first rMBC from NSWCR, administrative hospital records, dispensed medicines and radiotherapy services (2001-2016). We used death registrations to estimate cumulative incidence of BC death. RESULTS: The analysis included 2267 women with rMBC (C1:1210, C2:1057). Compared to C1, C2 had access to adjuvant HER2-targeted therapy and were more likely to have received adjuvant chemotherapy (C1:38%, C2:47%) and aromatase inhibitors (C1:52%, C2:73%, of those dispensed endocrine therapy). Five-year probability of BC death was 65% (95%CI:62-68%) in C1 and 63% (95%CI:60-66%) in C2. Regional disease (T4 or N + ) at initial BC diagnosis (C1:62%, C2:68%), and age ≥ 70 years at first metastasis (C1:27%, C2:31%) were more common in C2 and had poorer prognosis. Five-year probability of BC death was lower in C2 than C1 for treatment-defined HER2-positive BC (C1:72% 95%CI:63-79%; C2:52% 95%CI 45-60%) and those dispensed chemotherapy alone (C1:76% 95%CI:69-82, C2:67% 95%CI:59-74%, p = 0.01), but not treatment-defined hormone receptor-positive HER2-negative BC (C1:60% 95%CI 56-63%, C2:64% 95%CI 60-68%). CONCLUSIONS: Despite less favourable prognostic characteristics in C2, BC-related survival following rMBC was similar between the two cohorts; and improved for women with HER2-positive tumours. These findings support the real-world benefits of newer treatments for rMBC.

Genomic DNA extraction optimization and validation for genome sequencing using the marine gastropod Kellet's whelk.

Next-generation sequencing technologies, such as Nanopore MinION, Illumina Hiseq and Novaseq, and PacBio Sequel II, hold immense potential for advancing genomic research on non-model organisms, including the vast majority of marine species. However, application of these technologies to marine invertebrate species is often impeded by challenges in extracting and purifying their genomic DNA due to high polysaccharide content and other secondary metabolites. In this study, we help resolve this issue by developing and testing DNA extraction protocols for Kellet's whelk (Kelletia kelletii), a subtidal gastropod with ecological and commercial importance, by comparing four DNA extraction methods commonly used in marine invertebrate studies. In our comparison of extraction methods, the Salting Out protocol was the least expensive, produced the highest DNA yields, produced consistent high DNA quality, and had low toxicity. We validated the protocol using an independent set of tissue samples, then applied it to extract high-molecular-weight (HMW) DNA from over three thousand Kellet's whelk tissue samples. The protocol demonstrated scalability and, with added clean-up, suitability for RAD-seq, GT-seq, as well as whole genome sequencing using both long read (ONT MinION) and short read (Illumina NovaSeq) sequencing platforms. Our findings offer a robust and versatile DNA extraction and clean-up protocol for supporting genomic research on non-model marine organisms, to help mediate the under-representation of invertebrates in genomic studies.

The family doctor: health, kin testing and primary care in Patna, India.

Private primary care providers are usually the first site where afflictions come under institutional view. In the context of poverty, the relationship between illness and care is more complex than a simple division of responsibilities between various actors-with care given by kin, and diagnosis and treatment being the purview of providers. Since patients would often visit the provider with family members, providers are attuned to the patients' web of kinship. Providers would take patients' kinship arrangements into account when prescribing diagnostic tests and treatments. This paper terms this aspect of the clinical encounter as 'kin testing' to refer to situations/clinical encounters when providers take into consideration that care provided by kin was conditional. 'Kin testing' allowed providers to manage the episode of illness that had brought the patient to the clinic by relying on clinical judgment rather than confirmed laboratory tests. Furthermore, since complaints of poor health also were an idiom to communicate kin neglect, providers had to also discern how to negotiate diagnoses and treatments. Kinship determined whether the afflicted bodies brought to the clinics were diagnosed, whether medicines reached the body, and adherence maintained. The providers' actions make visible the difference that kinship made in how health is imagined in the clinic and in standardized protocols. Focusing on primary care clinics in Patna, India, we contribute to research that shows that kinship determines care and management of illnesses at home by showing that relatedness of patients gets folded in the clinic by providers as well.

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.

Prevalence of Australians exposed to potentially cardiotoxic cancer medicines: a population-based cohort study.

Background: Cardiovascular disease (CVD) and cancer are leading causes of death and people with cancer are at higher risk of developing CVD than the general population. Many cancer medicines have cardiotoxic effects but the size of the population exposed to these potentially cardiotoxic medicines is not known. We aimed to determine the prevalence of exposure to potentially cardiotoxic cancer medicines in Australia. Methods: We identified potentially cardiotoxic systemic cancer medicines through searching the literature and registered product information documents. We conducted a retrospective cohort study of Australians dispensed potentially cardiotoxic cancer medicines between 2005 and 2021, calculating age-standardised annual prevalence rates of people alive with exposure to a potentially cardiotoxic medicine during or prior to each year of the study period. Findings: We identified 108,175 people dispensed at least one potentially cardiotoxic cancer medicine; median age, 64 (IQR: 52-74); 57% female. Overall prevalence increased from 49 (95%CI: 48.7-49.3)/10,000 to 232 (95%CI: 231.4-232.6)/10,000 over the study period; 61 (95%CI: 60.5-61.5)/10,000 to 293 (95%CI: 292.1-293.9)/10,000 for females; and 39 (95%CI: 38.6-39.4)/10,000 to 169 (95%CI: 168.3-169.7)/10,000 for males. People alive five years following first exposure increased from 29 (95%CI: 28.8-29.2)/10,000 to 134 (95%CI: 133.6-134.4)/10,000; and from 22 (95%CI: 21.8-22.2)/10,000 to 76 (95%CI: 75.7-76.3)/10,000 for those alive at least 10 years following first exposure. Most people were exposed to only one potentially cardiotoxic medicine, rates of which increased from 39 (95%CI: 38.7-39.3)/10,000 in 2005 to 131 (95%CI: 130.6-131.4)/10,000 in 2021. Interpretation: The number of people exposed to efficacious yet potentially cardiotoxic cancer medicines in Australia is growing. Our findings can support the development of service planning and create awareness about the magnitude of cancer treatment-related cardiotoxicities. Funding: NHMRC Centre for Research Excellence in Medicines Intelligence, Cancer Institute NSW Early Career Fellowship.

Do private providers initiate anti-tuberculosis therapy on the basis of chest radiographs? A standardised patient study in urban India.

Background: The initiation of anti-tuberculosis treatment (ATT) based on results of WHO-approved microbiological diagnostics is an important marker of quality tuberculosis (TB) care. Evidence suggests that other diagnostic processes leading to treatment initiation may be preferred in high TB incidence settings. This study examines whether private providers start anti-TB therapy on the basis of chest radiography (CXR) and clinical examinations. Methods: This study uses the standardized patient (SP) methodology to generate accurate and unbiased estimates of private sector, primary care provider practice when a patient presents a standardized TB case scenario with an abnormal CXR. Using multivariate log-binomial and linear regressions with standard errors clustered at the provider level, we analyzed 795 SP visits conducted over three data collection waves from 2014 to 2020 in two Indian cities. Data were inverse-probability-weighted based on the study sampling strategy, resulting in city-wave-representative results. Findings: Amongst SPs who presented to a provider with an abnormal CXR, 25% (95% CI: 21-28%) visits resulted in ideal management, defined as the provider prescribing a microbiological test and not offering a concurrent prescription for a corticosteroid or antibiotic (including anti-TB medications). In contrast, 23% (95% CI: 19-26%) of 795 visits were prescribed anti-TB medications. Of 795 visits, 13% (95% CI: 10-16%) resulted in anti-TB treatment prescriptions/dispensation and an order for confirmatory microbiological testing. Interpretation: One in five SPs presenting with abnormal CXR were prescribed ATT by private providers. This study contributes novel insights to empiric treatment prevalence based on CXR abnormality. Further work is needed to understand how providers make trade-offs between existing diagnostic practices, new technologies, profits, clinical outcomes, and the market dynamics with laboratories. Funding: This study was funded by the Bill & Melinda Gates Foundation (grant OPP1091843), and the Knowledge for Change Program at The World Bank.

Use of standardised patients to assess tuberculosis case management by private pharmacies in Patna, India: A repeat cross-sectional study.

As the first point of care for many healthcare seekers, private pharmacies play an important role in tuberculosis (TB) care. However, previous studies in India have showed that private pharmacies commonly dispense symptomatic treatments and broad-spectrum antibiotics over-the-counter (OTC), rather than referring patients for TB testing. Such inappropriate management by pharmacies can delaye TB diagnosis. We assessed medical advice and OTC drug dispensing practices of pharmacists for standardized patients presenting with classic symptoms of pulmonary TB (case 1) and for those with sputum smear positive pulmonary TB (case 2), and examined how practices have changed over time in an urban Indian site. We examined how and whether private pharmacies improved practices for TB in 2019 compared to a baseline study conducted in 2015 in the city of Patna, using the same survey sampling techniques and study staff. The proportion of patient-pharmacist interactions that resulted in correct or ideal management, as well as the proportion of interactions resulting in antibiotic, quinolone, and corticosteroid are presented, with standard errors clustered at the provider level. To assess the difference in case management and the use of drugs across the two cases by round, a difference in difference (DiD) model was employed. A total of 936 SP interactions were completed over both rounds of survey. Our results indicate that across both rounds of data collection, 331 of 936 (35%; 95% CI: 32-38%) of interactions were correctly managed. At baseline, 215 of 500 (43%; 95% CI: 39-47%) of interactions were correctly managed whereas 116 of 436 (27%; 95% CI: 23-31%) were correctly managed in the second round of data collection. Ideal management, where in addition to a referral, patients were not prescribed any potentially harmful medications, was seen in 275 of 936 (29%; 95% CI: 27-32%) of interactions overall, with 194 of 500 (39%; 95% CI: 35-43%) of interactions at baseline and 81 of 436 (19%; 95% CI: 15-22%) in round 2. No private pharmacy dispensed anti-TB medications without a prescription. On average, the difference in correct case management between case 1 vs. case 2 dropped by 20 percent points from baseline to the second round of data collection. Similarly, ideal case management decreased by 26 percentage points between rounds. This is in contrast with the dispensation of medicines, which had the opposite effect between rounds; the difference in dispensation of quinolones between case 1 and case 2 increased by 14 percentage points, as did corticosteroids by 9 percentage points, antibiotics by 25 percentage points and medicines generally by 30 percentage points. Our standardised patient study provides valuable insights into how private pharmacies in an Indian city changed their management of patients with TB symptoms or with confirmed TB over a 5-year period. We saw that overall, private pharmacy performance has weakened over time. However, no OTC dispensation of anti-TB medications occurred in either survey round. As the first point of contact for many care seekers, continued and sustained efforts to engage with Indian private pharmacies should be prioritized.

Psychotropic and other medicine use at time of death by suicide: a population-level analysis of linked dispensing and forensic toxicology data.

OBJECTIVES: To determine the numbers and types of medicines dispensed around the time of death to people who die by suicide; to compare the medicines recently dispensed and those recorded in post mortem toxicology reports. DESIGN, SETTING, PARTICIPANTS: Analysis of linked National Coronial Information System (NCIS) and Pharmaceutical Benefits Scheme (PBS) data from the Australian Suicide Prevention using Health Linked Data (ASHLi) study, a population-based case series study of closed coronial cases for deaths of people in Australia aged ten years or more during 1 July 2013 - 10 October 2019 deemed by coroners to be the result of intentional self-harm. MAIN OUTCOME MEASURES: Proportions of people to whom medicines were dispensed around the time of death, by medicine group, class, and specific medicine; comparison of medicines recently dispensed and those detected by post mortem toxicology. RESULTS: Toxicology reports were available for 13 541 of 14 206 people who died by suicide (95.3%; 10 246 men, 75.7%); poisoning with medicines contributed to 1163 deaths (8.6%). At least one PBS-subsidised medicine had been dispensed around the time of death to 7998 people (59.1%). For three medicine classes, the proportions of people in whom the medicines were detected post mortem and their death was deemed medicine-related were larger for those without records of recent dispensing than for people for whom they had been dispensed around the time of death: antidepressants (17.7% v 12.0%), anxiolytics (16.3% v 14.8%), and sedatives/hypnotics (24.3% v 16.5%). At least one recently dispensed medicine not detected post mortem was identified for 6208 people (45.8%). CONCLUSIONS: A considerable proportion of people who died by suicide were not taking psychotropic medicines recently dispensed to them, suggesting non-adherence to pharmacotherapy, and a smaller than expected proportion were using antidepressants. Conversely, medicines that had not recently been dispensed were detected post mortem in many people for whom poisoning with medicines was a contributing factor, suggesting medicine stockpiling.