Impact of National Public-Private Mix and Medical Expense Support Program to Control Tuberculosis in South Korea: An Interrupted Time Series Analysis.

Tuberculosis (TB) remains a major threat to global public health. Various measures at the national level have been implemented to control TB, and no evidence with long-term effectiveness has yet been evaluated on TB control programs. We confirmed the long-term effectiveness of the TB control programs in reducing overall burden in South Korea using interrupted time series analysis. Our finding suggests that, along with the public-private mix, relieving the economic burden of people with TB may complement achieving the End TB Strategy. For countries currently developing strategies for TB control, results may provide important insights in effective TB control.

Estimated Population-Level Impact of Pneumococcal Conjugate Vaccines Against All-Cause Pneumonia Mortality Among Unvaccinated in 5 Latin American Countries.

BACKGROUND: Pneumococcal conjugate vaccines (PCVs) provide strong direct protection in children, while limited data are available on their indirect effect on mortality among older age groups. This multicountry study aimed to assess the population-level impact of pediatric PCVs on all-cause pneumonia mortality among children ≥5 years of age, and invasive pneumococcal disease (IPD) cases in Chile. METHODS: Demographic and mortality data from Argentina, Brazil, Chile, Colombia, and Mexico were collected considering the ≥ 5-year-old population, from 2000 to 2019, with 1 795 789 deaths due to all-cause pneumonia. IPD cases in Chile were also evaluated. Time series models were employed to evaluate changes in all-cause pneumonia deaths during the postvaccination period, with other causes of death used as synthetic controls for unrelated temporal trends. RESULTS: No significant change in death rates due to all-cause pneumonia was detected following PCV introduction among most age groups and countries. The proportion of IPD cases caused by vaccine serotypes decreased from 29% (2012) to 6% (2022) among people aged ≥65 years in Chile. DISCUSSION: While an effect of PCV against pneumonia deaths (a broad clinical definition that may not be specific enough to measure indirect effects) was not detected, evidence of indirect PCV impact was observed among vaccine-type-specific IPD cases.

Cholecystectomy and digestive cancer in Chile: Complementary results from interrupted time series and aggregated data analyses.

Gallbladder cancer (GBC) mortality in Chile is among the highest worldwide. In 2006, the Chilean government launched a programme guaranteeing access to gallbladder surgery (cholecystectomy) for patients aged 35-49 years. We evaluated the impact of this programme on digestive cancer mortality. After conducting an interrupted time series analysis of hospitalisation and mortality data from 2002 to 2018 publicly available from the Chilean Department of Health Statistics and Information, we calculated the change in the proportion of individuals without gallbladder since 10 years. We then estimated age, gender, region, and calendar-year standardised mortality ratios (SMRs) as a function of the change in the proportion of individuals without gallbladder. The cholecystectomy rate increased by 45 operations per 100,000 persons per year (95%CI 19-72) after the introduction of the health programme. Each 1% increase in the proportion of individuals without gallbladder since 10 years was associated with a 0.73% decrease in GBC mortality (95% CI -1.05% to -0.38%), but the negative correlation was limited to women, southern Chile and age over 60. We also found decreasing mortality rates for extrahepatic bile duct, liver, oesophageal and stomach cancer with increasing proportions of individuals without gallbladder. To conclude, 12 years after its inception, the Chilean cholecystectomy programme has markedly and heterogeneously changed cholecystectomy rates. Results based on aggregate data indicate a negative correlation between the proportion of individuals without gallbladder and mortality due to gallbladder and other digestive cancers, which requires validation using individual-level longitudinal data to reduce the potential impact of ecological bias.

A causal machine-learning framework for studying policy impact on air pollution: A case-study in COVID-19 lockdowns.

When studying the impact of policy interventions or natural experiments on air pollution, such as new environmental policies and opening or closing an industrial facility, careful statistical analysis is needed to separate causal changes from other confounding factors. Using COVID-19 lockdowns as a case-study, we present a comprehensive framework for estimating and validating causal changes from such perturbations. We propose using flexible machine learning-based comparative interrupted time series (CITS) models for estimating such a causal effect. We outline the assumptions required to identify causal effects, showing that many common methods rely on strong assumptions that are relaxed by machine learning models. For empirical validation, we also propose a simple diagnostic criterion, guarding against false effects in baseline years when there was no intervention. The framework is applied to study the impact of COVID-19 lockdowns on NO2 in the eastern US. The machine learning approaches guard against false effects better than common methods and suggest decreases in NO2 in Boston, New York City, Baltimore, and Washington D.C. The study showcases the importance of our validation framework in selecting a suitable method and the utility of a machine learning based CITS model for studying causal changes in air pollution time series.

Suicide mortality following the implementation of tobacco packaging and pricing policies in Korea: an interrupted time-series analysis.

BACKGROUND: To prevent tobacco use in Korea, the national quitline number was added to tobacco packages in December 2012, tobacco prices were raised by 80% in January 2015, and graphic health warning labels were placed on tobacco packages in December 2016. This study evaluated the association of these tobacco packaging and pricing policies with suicide mortality in Korea. METHODS: Monthly mortality from suicide was obtained from Cause-of-Death Statistics in Korea from December 2007 to December 2019. Interrupted time-series analysis was performed using segmented Poisson regression models. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated adjusted for suicide prevention strategies. RESULTS: Suicide mortality was 20 per 1,000,000 in December 2007 and showed a downward trend over the study period. After the implementation of tobacco packaging and pricing policies, suicide mortality immediately declined by - 0.09 percent points (95% CI = - 0.19 to 0.01; P > 0.05) for the national quitline number, - 0.22 percent points (95% CI = - 0.35 to - 0.09; P < 0.01) for tobacco prices, and - 0.30 percent points (95% CI = - 0.49 to - 0.11; P < 0.01) for graphic health warning labels. The corresponding RRs for these post-implementation changes compared with the pre-implementation level were 0.91 (95% CI = 0.83 to 1.00), 0.80 (95% CI = 0.70 to 0.91), and 0.74 (95% CI = 0.61 to 0.90), respectively. Significant associations between tobacco control policies and suicide mortality were observed even when stratified by sex and region. CONCLUSIONS: The findings of this study provide new evidence for an association between tobacco control policies and deaths by suicide. An array of effective tobacco control policies should be considered for prevention programs targeting suicide.

Potential impact of rotavirus vaccine introduction in India's Universal Immunisation Programme on private sector vaccine utilisation: an interrupted time series analysis.

BACKGROUND: Despite free immunisation services through the Universal Immunisation Programme (UIP), around 14% of Indian households seek immunisation in the private sector. We examined the potential impact of rotavirus vaccine (RVV) introduction in the Universal Immunisation Programme (UIP) on private-sector rotavirus vaccine utilisation. METHODS: We analysed nationally representative private-sector vaccine sales data. The intervention under consideration is RVV introduction in the UIP in selected Indian states. The outcome is the 'monthly RVV sales volume'-a proxy for vaccine utilisation. We performed a Poisson regression interrupted time series analysis to detect the pre-intervention trend, post-intervention level change and trend change relative to the pre-intervention for monthly rotavirus vaccine utilisation. RESULTS: Poisson segmented regression analysis showed that immediately after RVV introduction in the UIP private-sector RVV sales showed a decline in Rajasthan by 37.4% (Incidence Risk Ratio (IRR): 0.626; 95% CI: 0.504-0.779), in Tamil Nadu by 26% (IRR: 0.740; 95% CI: 0.513-1.068), in Uttar Pradesh-East by 72.2% (IRR: 0.278; 95% CI: 0.178-0.436) and in Kerala by 3% (IRR: 0.970; 95% CI: 0.651-1.447). Rajasthan, Tamil Nadu and Kerala had sustained reduction in the postintervention trend relative to the preintervention trend by 20.1% (IRR: 0.799; 95% CI: 0.763-0.836), 6.4% (IRR: 0.936; 95% CI: 0.906-0.967) and 3.3% (IRR: 0.967; 95% CI: 0.926-0.960) per month, respectively. However, in Haryana and UP-west, in the first-month post-UIP introduction, the private-sector RVV sales increased by 101% and 3.8%, respectively which was followed by a sustained decrease of 14.2% (IRR: 0.858; 95% CI: 0.688-1.070) and 5.8% (IRR: 0.942; 95% CI: 0.926-0.960) per month, respectively. In terms of long-term impact, the private sector RVV sales post-UIP introduction decreased at a monthly rate of 4.4% (IRR: 0.956, 95% CI: 0.939-0.974) in Rajasthan but increased by 5.5% (IRR: 1.055; 95% CI: 1.040-1.070) in UP-east, 0.3% (IRR: 1.003, 95% CI: 0.976-1.031)) in Kerala and 0.2% (IRR: 1.002, 95% CI: 0.993-1.011) in Tamil Nadu whereas Haryana and UP-west had a reduction in RVV utilisation by 2.8% (IRR: 0.972; 95% CI: 0.955-0.990) and 1% (IRR: 0.990; 95% CI: 0.982-0.998), respectively. CONCLUSIONS: The study provides evidence that access to RVV through UIP leads to a reduction in private-sector RVV utilisation. We recommend strengthening UIP to expand the basket of new vaccines.

Impact of COVID-19 pandemic on depression incidence and healthcare service use among patients with depression: an interrupted time-series analysis from a 9-year population-based study.

BACKGROUND: Most studies on the impact of the COVID-19 pandemic on depression burden focused on the earlier pandemic phase specific to lockdowns, but the longer-term impact of the pandemic is less well-studied. In this population-based cohort study, we examined the short-term and long-term impacts of COVID-19 on depression incidence and healthcare service use among patients with depression. METHODS: Using the territory-wide electronic medical records in Hong Kong, we identified all patients aged ≥ 10 years with new diagnoses of depression from 2014 to 2022. We performed an interrupted time-series (ITS) analysis to examine changes in incidence of medically attended depression before and during the pandemic. We then divided all patients into nine cohorts based on year of depression incidence and studied their initial and ongoing service use patterns until the end of 2022. We applied generalized linear modeling to compare the rates of healthcare service use in the year of diagnosis between patients newly diagnosed before and during the pandemic. A separate ITS analysis explored the pandemic impact on the ongoing service use among prevalent patients with depression. RESULTS: We found an immediate increase in depression incidence (RR = 1.21, 95% CI: 1.10-1.33, p < 0.001) in the population after the pandemic began with non-significant slope change, suggesting a sustained effect until the end of 2022. Subgroup analysis showed that the increases in incidence were significant among adults and the older population, but not adolescents. Depression patients newly diagnosed during the pandemic used 11% fewer resources than the pre-pandemic patients in the first diagnosis year. Pre-existing depression patients also had an immediate decrease of 16% in overall all-cause service use since the pandemic, with a positive slope change indicating a gradual rebound over a 3-year period. CONCLUSIONS: During the pandemic, service provision for depression was suboptimal in the face of increased demand generated by the increasing depression incidence during the COVID-19 pandemic. Our findings indicate the need to improve mental health resource planning preparedness for future public health crises.

Evaluating the long-term impact of COVID-19-associated public health interventions on zoonotic and vector-borne diseases in China: an interrupted time series analysis.

BACKGROUND: The long-term impact of COVID-19-associated public health interventions on zoonotic and vector-borne infectious diseases (ZVBs) remains uncertain. This study sought to examine the changes in ZVBs in China during the COVID-19 pandemic and predict their future trends. METHODS: Monthly incidents of seven ZVBs (Hemorrhagic fever with renal syndrome [HFRS], Rabies, Dengue fever [DF], Human brucellosis [HB], Leptospirosis, Malaria, and Schistosomiasis) were gathered from January 2004 to July 2023. An autoregressive fractionally integrated moving average (ARFIMA) by incorporating the COVID-19-associated public health intervention variables was developed to evaluate the long-term effectiveness of interventions and forecast ZVBs epidemics from August 2023 to December 2025. RESULTS: Over the study period, there were 1,599,647 ZVBs incidents. HFRS and rabies exhibited declining trends, HB showed an upward trajectory, while the others remained relatively stable. The ARFIMA, incorporating a pulse pattern, estimated the average monthly number of changes of - 83 (95% confidence interval [CI] - 353-189) cases, - 3 (95% CI - 33-29) cases, - 468 (95% CI - 1531-597) cases, 2191 (95% CI 1056-3326) cases, 7 (95% CI - 24-38) cases, - 84 (95% CI - 222-55) cases, and - 214 (95% CI - 1036-608) cases for HFRS, rabies, DF, HB, leptospirosis, malaria, and schistosomiasis, respectively, although these changes were not statistically significant besides HB. ARFIMA predicted a decrease in HB cases between August 2023 and December 2025, while indicating a relative plateau for the others. CONCLUSIONS: China's dynamic zero COVID-19 strategy may have exerted a lasting influence on HFRS, rabies, DF, malaria, and schistosomiasis, beyond immediate consequences, but not affect HB and leptospirosis. ARFIMA emerges as a potent tool for intervention analysis, providing valuable insights into the sustained effectiveness of interventions. Consequently, the application of ARFIMA contributes to informed decision-making, the design of effective interventions, and advancements across various fields.

Temporal trends in hemodialysis access creation during the fistula first era.

OBJECTIVE: Although forearm arteriovenous fistulas (AVFs) are the preferred initial vascular access for hemodialysis based on national guidelines, there are no population-level studies evaluating trends in creation of forearm vs upper arm AVFs and arteriovenous grafts (AVGs). The purpose of this study was to report temporal trends in first-time permanent hemodialysis access type, and to assess the effect of national initiatives on rates of AVF placement. METHODS: Retrospective cross-sectional study (2012-2022) utilizing the Vascular Quality Initiative database. All patients older than 18 years with creation of first-time upper extremity surgical hemodialysis access were included. Anatomic location of the AVF or AVG (forearm vs upper arm) was defined based on inflow artery, outflow vein, and presumed cannulation zone. Primary analysis examined temporal trends in rates of forearm vs upper arm AVFs and AVGs using time series analyses (modified Mann-Kendall test). Subgroup analyses examined rates of access configuration stratified by age, sex, race, dialysis, and socioeconomic status. Interrupted time series analysis was performed to assess the effect of the 2015 Fistula First Catheter Last initiative on rates of AVFs. RESULTS: Of the 52,170 accesses, 57.9% were upper arm AVFs, 25.2% were forearm AVFs, 15.4% were upper arm AVGs, and 1.5% were forearm AVGs. From 2012 to 2022, there was no significant change in overall rates of forearm or upper arm AVFs. There was a numerical increase in upper arm AVGs (13.9 to 18.2 per 100; P = .09), whereas forearm AVGs significantly declined (1.8 to 0.7 per 100; P = .02). In subgroup analyses, we observed a decrease in forearm AVFs among men (33.1 to 28.7 per 100; P = .04) and disadvantaged (Area Deprivation Index percentile ≥50) patients (29.0 to 20.7 per 100; P = .04), whereas female (17.2 to 23.1 per 100; P = .03), Black (15.6 to 24.5 per 100; P < .01), elderly (age ≥80 years) (18.7 to 32.5 per 100; P < .01), and disadvantaged (13.6 to 20.5 per 100; P < .01) patients had a significant increase in upper arm AVGs. The Fistula First Catheter Last initiative had no effect on the rate of AVF placement (83.2 to 83.7 per 100; P=.37). CONCLUSIONS: Despite national initiatives to promote autogenous vascular access, the rates of first-time AVFs have remained relatively constant, with forearm AVFs only representing one-quarter of all permanent surgical accesses. Furthermore, elderly, Black, female, and disadvantaged patients saw an increase in upper arm AVGs. Further efforts to elucidate factors associated with forearm AVF placement, as well as potential physician, center, and regional variation is warranted.

Time series analysis of malaria cases to assess the impact of various interventions over the last three decades and forecasting malaria in India towards the 2030 elimination goals.

BACKGROUND: Despite the progress made in this decade towards malaria elimination, it remains a significant public health concern in India and many other countries in South Asia and Asia Pacific region. Understanding the historical trends of malaria incidence in relation to various commodity and policy interventions and identifying the factors associated with its occurrence can inform future intervention strategies for malaria elimination goals. METHODS: This study analysed historical malaria cases in India from 1990 to 2022 to assess the annual trends and the impact of key anti-malarial interventions on malaria incidence. Factors associated with malaria incidence were identified using univariate and multivariate linear regression analyses. Generalized linear, smoothing, autoregressive integrated moving averages (ARIMA) and Holt's models were used to forecast malaria cases from 2023 to 2030. RESULTS: The reported annual malaria cases in India during 1990-2000 were 2.38 million, which dropped to 0.73 million cases annually during 2011-2022. The overall reduction from 1990 (2,018,783) to 2022 (176,522) was 91%. The key interventions of the Enhanced Malaria Control Project (EMCP), Intensified Malaria Control Project (IMCP), use of bivalent rapid diagnostic tests (RDT-Pf/Pv), artemisinin-based combination therapy (ACT), and involvement of the Accredited Social Health Activists (ASHAs) as front-line workers were found to result in the decline of malaria significantly. The ARIMA and Holt's models projected a continued decline in cases with the potential for reaching zero indigenous cases by 2027-2028. Important factors influencing malaria incidence included tribal population density, literacy rate, health infrastructure, and forested and hard-to-reach areas. CONCLUSIONS: Studies aimed at assessing the impact of major commodity and policy interventions on the incidence of disease and studies of disease forecasting will inform programmes and policymakers of steps needed during the last mile phase to achieve malaria elimination. It is proposed that these time series and disease forecasting studies should be performed periodically using granular (monthly) and meteorological data to validate predictions of prior studies and suggest any changes needed for elimination efforts at national and sub-national levels.

Impact of codeine rescheduling on prescribing of codeine and other opioids: Interrupted time series analyses using Australian general practice data.

AIMS: We aimed to determine the impact of codeine rescheduling on prescribing of codeine and other opioids, with a focus on demographic and diagnoses associated with codeine prescribing before and after rescheduling of codeine to prescription-only in February 2018. METHODS: We used interrupted time series analysis (February 2016-February 2020) and probit regression to examine prescribing of codeine and other opioids according to primary care data from 464 general practice clinics in Victoria, Australia. RESULTS: The rate of codeine prescribing increased in the month following rescheduling (additional 76 people/10000, 95% confidence interval [CI] 49-103), then declined to baseline rates (slope -2.02, 95% CI 3.79, -0.25). Prescribing of other opioids did not change. Post rescheduling, females were more likely to receive codeine prescriptions compared to males (ß = 0.094, 95% CI 0.08-0.108) and those aged 70-79 years were more likely to receive codeine compared to those aged <30 years. Those residing in the least disadvantaged areas had a greater probability of being prescribed codeine than those in more disadvantaged areas after rescheduling (ß = 0.154, 95% CI 0.129-0.179). A documented mental health diagnosis (ß = 0.067, 95% CI 0.052-0.082) or migraine diagnosis (ß = 0.057, 95% CI 0.037-0.078) was associated with increased likelihood of receiving a codeine prescription after rescheduling compared to before in contrast to those without such a diagnosis. CONCLUSION: Codeine rescheduling did not result in a sustained increase in codeine prescribing nor a change in the prescribing of other opioids. Patient factors associated with increased codeine prescribing after compared to before rescheduling included female sex, older age, migraine diagnosis and comorbid mental health conditions. REGISTRATION: EU PAS Register (EUPAS43218).

Impact of narcotics information management system on inappropriate benzodiazepine receptor agonist prescriptions: A quasi-experimental analysis in South Korea.

AIMS: The South Korean government implemented the narcotics information management system (NIMS) on 18 May 2018 to manage benzodiazepine receptor agonists (BzRAs) and narcotics effectively and establish a reporting mechanism for these drugs. This study assessed the effects of NIMS on inappropriate use of BzRAs. METHODS: Using national patient sample data from 2016 to 2020, we analysed adult outpatients who were prescribed oral BzRAs. We conducted a time series and segmented regression analysis using selected indicators to analyse the monthly variations related to the inappropriate use of these medications. RESULTS: The study revealed no significant changes in the indicators of inappropriate BzRA use following the NIMS implementation. Contrary to expectations, there was a significant increase in the proportion of patients exceeding defined daily dose (DDD) and in those receiving concurrent prescriptions of multiple BzRAs, following the implementation of NIMS. The immediate impact of the COVID-19 pandemic was an increase in DDD exceedance; however, overall, this did not significantly affect BzRA use. CONCLUSIONS: The introduction of NIMS did not significantly enhance the management of BzRA misuse. Additional measures, including continuous monitoring, system improvements and comprehensive education for prescribers and patients, are recommended to ensure the appropriate use of psychotropic medications.

Impact of the pandemic on surgical oncology in Piedmont, Italy: A retrospective observational study.

BACKGROUND AND METHODS: This retrospective observational study analyzes how the COVID-19 pandemic affected surgical oncology healthcare in a large sample from Piedmont, Northern Italy. Patients admitted for regular hospitalization were included (n = 99 651). Data from 2020 were compared to the averages from 2016 to 2019, stratified by tumor site, year, month, and admission method, using interrupted time series analysis post-March 2020. RESULTS: In 2020, oncological surgeries decreased by 12.3% (n = 17 923) compared to the 2016-2019 average (n = 20 432), notably dropping post-March (incidence rate ratio = 0.858; p < 0.001). The greatest reduction was observed for breast (-19.2%), colon (-18.2%), bladder (-17.5%), kidney (-14.2%), and prostate (-14%) surgeries. There was a huge reduction in nonemergency admissions (-13.6%), especially for colon (-23.8%), breast (-19.4%), and bladder (-18.7%). The proportion of hospitalizations with emergency access increased (p < 0.001). CONCLUSIONS: The COVID-19 pandemic led to a significant decrease in cancer surgeries in Piedmont in 2020, with an increase in the proportion of admissions through emergency access. DISCUSSION: The research provides valuable insights for comparing data with other regions and evaluating the effectiveness of efforts to recover lost surgical procedures. These findings can be useful to policymakers in developing coordinated measures and more efficient access strategies to healthcare services in any future emergency situations.

Health guidance intervention mitigates the escalation of predicted comprehensive cardiovascular disease risk: Interrupted time series design.

INTRODUCTION: Metabolic syndrome increases the risk of cardiovascular events. Despite the Japanese healthcare system's efforts in early detection and intervention, particularly through Specific Health Checkup and Guidance programs, research on their effectiveness is limited. This study evaluated the impact of Specific Health Guidance on the predicted risk of atherosclerotic cardiovascular disease (ASCVD) in working-age Japanese individuals. METHODS: Employing an Interrupted Time Series (ITS) design, this study compared the trends in predicted ASCVD risk and each individual risk factor used for the prediction of ASCVD risk before and after intervention in individuals participating in the guidance. RESULTS: Analyses based on the ITS design indicated that participation in Specific Health Guidance programs, specifically the intensive level program, mitigates the increase trend of the predicted ASCVD risk. On the other hand, the impact on the trends of individual cardiovascular risk factors was minimal. CONCLUSIONS: The intensive level Specific Health Guidance appeared to reduce the increasing trend in ASCVD risk, emphasizing the importance of comprehensive risk assessment in evaluating health interventions. However, the results are limited owing to the specific demographics and short evaluation period. Further research is necessary to understand the long-term impacts and broader applicability.

Comparison of statistical methods used to meta-analyse results from interrupted time series studies: an empirical study.

BACKGROUND: The Interrupted Time Series (ITS) is a robust design for evaluating public health and policy interventions or exposures when randomisation may be infeasible. Several statistical methods are available for the analysis and meta-analysis of ITS studies. We sought to empirically compare available methods when applied to real-world ITS data. METHODS: We sourced ITS data from published meta-analyses to create an online data repository. Each dataset was re-analysed using two ITS estimation methods. The level- and slope-change effect estimates (and standard errors) were calculated and combined using fixed-effect and four random-effects meta-analysis methods. We examined differences in meta-analytic level- and slope-change estimates, their 95% confidence intervals, p-values, and estimates of heterogeneity across the statistical methods. RESULTS: Of 40 eligible meta-analyses, data from 17 meta-analyses including 282 ITS studies were obtained (predominantly investigating the effects of public health interruptions (88%)) and analysed. We found that on average, the meta-analytic effect estimates, their standard errors and between-study variances were not sensitive to meta-analysis method choice, irrespective of the ITS analysis method. However, across ITS analysis methods, for any given meta-analysis, there could be small to moderate differences in meta-analytic effect estimates, and important differences in the meta-analytic standard errors. Furthermore, the confidence interval widths and p-values for the meta-analytic effect estimates varied depending on the choice of confidence interval method and ITS analysis method. CONCLUSIONS: Our empirical study showed that meta-analysis effect estimates, their standard errors, confidence interval widths and p-values can be affected by statistical method choice. These differences may importantly impact interpretations and conclusions of a meta-analysis and suggest that the statistical methods are not interchangeable in practice.

Design and statistical analysis reporting among interrupted time series studies in drug utilization research: a cross-sectional survey.

INTRODUCTION: Interrupted time series (ITS) design is a commonly used method for evaluating large-scale interventions in clinical practice or public health. However, improperly using this method can lead to biased results. OBJECTIVE: To investigate design and statistical analysis characteristics of drug utilization studies using ITS design, and give recommendations for improvements. METHODS: A literature search was conducted based on PubMed from January 2021 to December 2021. We included original articles that used ITS design to investigate drug utilization without restriction on study population or outcome types. A structured, pilot-tested questionnaire was developed to extract information regarding study characteristics and details about design and statistical analysis. RESULTS: We included 153 eligible studies. Among those, 28.1% (43/153) clearly explained the rationale for using the ITS design and 13.7% (21/153) clarified the rationale of using the specified ITS model structure. One hundred and forty-nine studies used aggregated data to do ITS analysis, and 20.8% (31/149) clarified the rationale for the number of time points. The consideration of autocorrelation, non-stationary and seasonality was often lacking among those studies, and only 14 studies mentioned all of three methodological issues. Missing data was mentioned in 31 studies. Only 39.22% (60/153) reported the regression models, while 15 studies gave the incorrect interpretation of level change due to time parameterization. Time-varying participant characteristics were considered in 24 studies. In 97 studies containing hierarchical data, 23 studies clarified the heterogeneity among clusters and used statistical methods to address this issue. CONCLUSION: The quality of design and statistical analyses in ITS studies for drug utilization remains unsatisfactory. Three emerging methodological issues warranted particular attention, including incorrect interpretation of level change due to time parameterization, time-varying participant characteristics and hierarchical data analysis. We offered specific recommendations about the design, analysis and reporting of the ITS study.

Population-level changes in perinatal death for pregnancies prior to and during the COVID-19 pandemic: A pregnancy cohort analysis.

BACKGROUND: Results of population-level studies examining the effect of the COVID-19 pandemic on the risks of perinatal death have varied considerably. OBJECTIVES: To explore trends in the risk of perinatal death among pregnancies beginning prior to and during the pandemic using a pregnancy cohort approach. METHODS: This secondary analysis included data from singleton pregnancies ≥20 weeks' gestation in Alberta, Canada, beginning between 5 March 2017 and 4 March 2021. Perinatal death (i.e. stillbirth or neonatal death) was the primary outcome considered. The risk of this outcome was calculated for pregnancies with varying gestational overlap with the pandemic (i.e. none, 0-20 weeks, entire pregnancy). Interrupted time series analysis was used to further determine temporal trends in the outcome by time period of interest. RESULTS: There were 190,853 pregnancies during the analysis period. Overall, the risk of perinatal death decreased with increasing levels of pandemic exposure; this outcome was experienced in 1.0% (95% confidence interval [CI] 0.9, 1.0), 0.9% (95% CI 0.8, 1.1) and 0.8% (95% CI 0.7, 0.9) of pregnancies with no overlap, partial overlap and complete pandemic overlap respectively. Pregnancies beginning during the pandemic that had high antepartum risk scores less frequently led to perinatal death compared to those beginning prior; 3.3% (95% CI 2.7, 3.9) versus 5.7% (95% CI 5.0, 6.5) respectively. Interrupted time-series analysis revealed a decreasing temporal trend in perinatal death for pregnancies beginning ≤40 weeks prior to the start of the COVID-19 pandemic (i.e. with pandemic exposure), with no trend for pregnancies beginning >40 weeks pre-pandemic (i.e. no pandemic exposure). CONCLUSION: We observed a decrease in perinatal death for pregnancies overlapping with the COVID-19 pandemic in Alberta, particularly among those at high risk of these outcomes. Specific pandemic control measures and government response programmes in our setting may have contributed to this finding.

Drug utilisation in children and adolescents before and after the start of the COVID-19 pandemic: Interrupted time-series analyses in three European countries.

BACKGROUND: The COVID-19 pandemic has affected children and adolescents in several ways, including worsened mental health, improvement of asthma, and increases in diabetes ketoacidosis. Less is known about how medication use in children and adolescents has been affected by the pandemic. OBJECTIVES: To explore how the COVID-19 pandemic affected drug utilisation in children and adolescents in Norway, Sweden, and Italy, by child age. METHODS: We conducted a longitudinal drug utilisation study among all children and adolescents (<18 years old) in Norway and Sweden and a nationwide paediatric database covering 3% of the paediatric population in Italy. We conducted an interrupted time-series analysis from January 2018 to December 2021, with March 2020 as the interruption point. Dispensing or prescription rates of antidepressants, anxiolytics, sleep medications, attention-deficit/hyperactivity disorder (ADHD) medications, insulin, and asthma medications were examined. RESULTS: The study population in January 2018 consisted of 3,455,521 children and adolescents (136,188 from Italy, 1,160,431 from Norway, and 2,158,902 from Sweden). For sleep medications and insulin, there were only minor changes in level or trend in some age groups after March 2020. For asthma medications, the pandemic was associated with an immediate decrease in dispensing in Norway and Sweden (range of change in level: -19.2 to -3.7 dispensings per 1000 person-months), and an increasing trend in all countries afterward (range of change in trend: 0.3-6.4 dispensings per 1000 person-months), especially for the youngest age groups. Among adolescents, the pandemic was associated with an increased trend for ADHD medications, antidepressants, and anxiolytics in Norway and Sweden, but not in Italy. CONCLUSIONS: The increasing trend of psychotropic medication dispensing, especially among adolescents after the start of the pandemic, is concerning and should be investigated further. Aside from a temporary effect on asthma medication dispensing, the pandemic did not greatly affect the dispensing of the medications investigated.

Changes in surgery rates among hospitalized patients with inflammatory bowel disease in Japan from 2015 to 2019: A nationwide administrative database analysis.

BACKGROUND AND AIM: Treatment of inflammatory bowel disease (IBD), consisting of ulcerative colitis (UC) and Crohn's disease (CD), has advanced with the application of biologics or Janus kinase inhibitor (JAKi); however, some patients still need surgery. We assessed time trends of surgery and biologics or JAKi variety in Japan. METHODS: Patients hospitalized due to IBD were analyzed using Diagnosis Procedure Combination data between 2015 and 2019. Longitudinal trend analysis was performed for demographics, and interrupted time-series analysis was performed to examine the association between surgery rates and an increase in the types of biologics or JAKi. RESULTS: Totally, 37 867 cases with UC and 35 493 cases with CD were analyzed. Over 5 years, the surgery rate decreased in both UC and CD. The proportion of biologics and JAKi usage increased in UC and stabilized in CD. Between decreasing surgery and expanding treatment options of biologic or JAKi, interrupted time-series analysis results showed no significant correlation (level change in UC, -1.13, 95% confidence interval [CI]: -2.11 to -0.16, P = 0.0235; slope change in UC, -0.05, 95% CI: -0.26 to 0.16, P = 0.6372; level change in CD, -0.55, 95% CI: -1.82 to 0.71, P = 0.3815; slope change in CD, -0.22, 95% CI: -0.63 to 0.19, P = 0.2892). CONCLUSIONS: In Japan, from 2015 to 2019, the use of biologics or JAKi increased for UC and slightly decreased for CD, while the number of surgeries decreased in both. Our findings suggest that more widespread use of biologics or JAKi therapy could reduce surgeries in patients with IBD.

Potential impact of blood cholesterol guidelines on statin treatment in the U.S. population using interrupted time series analysis.

BACKGROUND: The 2013 ACC/AHA Guideline was a paradigm shift in lipid management and identified the four statin-benefit groups. Many have studied the guideline's potential impact, but few have investigated its potential long-term impact on MACE. Furthermore, most studies also ignored the confounding effect from the earlier release of generic atorvastatin in Dec 2011. METHODS: To evaluate the potential (long-term) impact of the 2013 ACC/AHA Guideline release in Nov 2013 in the U.S., we investigated the association of the 2013 ACC/AHA Guideline with the trend changes in 5-Year MACE survival and three other statin-related outcomes (statin use, optimal statin use, and statin adherence) while controlling for generic atorvastatin availability using interrupted time series analysis, called the Chow's test. Specifically, we conducted a retrospective study using U.S. nationwide de-identified claims and electronic health records from Optum Labs Database Warehouse (OLDW) to follow the trends of 5-Year MACE survival and statin-related outcomes among four statin-benefit groups that were identified in the 2013 ACC/AHA Guideline. Then, Chow's test was used to discern trend changes between generic atorvastatin availability and guideline potential impact. RESULTS: 197,021 patients were included (ASCVD: 19,060; High-LDL: 33,907; Diabetes: 138,159; High-ASCVD-Risk: 5,895). After the guideline release, the long-term trend (slope) of 5-Year MACE Survival for the Diabetes group improved significantly (P = 0.002). Optimal statin use for the ASCVD group also showed immediate improvement (intercept) and long-term positive changes (slope) after the release (P < 0.001). Statin uses did not have significant trend changes and statin adherence remained unchanged in all statin-benefit groups. Although no other statistically significant trend changes were found, overall positive trend change or no changes were observed after the 2013 ACC/AHA Guideline release. CONCLUSIONS: The 2013 ACA/AHA Guideline release is associated with trend improvements in the long-term MACE Survival for Diabetes group and optimal statin use for ASCVD group. These significant associations might indicate a potential positive long-term impact of the 2013 ACA/AHA Guideline on better health outcomes for primary prevention groups and an immediate potential impact on statin prescribing behaviors in higher-at-risk groups. However, further investigation is required to confirm the causal effect of the 2013 ACA/AHA Guideline.