Interrupted Time Series Studies Research Articles

Evaluation of a pilot program that integrated prenatal screening into routine antenatal care in western rural China: an interrupted time-series study

BackgroundWe evaluated a large-scale pilot program in Shaanxi Province, western rural China, which integrated prenatal screening interventions for congenital abnormalities into routine antenatal programs. MethodsWe surveyed 1,597 mothers who gave birth between 2009 and 2016. Adopting the interrupted time-series design, we evaluated the program's impact on awareness, coverage, and cost, by comparing two counties with only supply-side policies, and two counties from the neighbouring province with no policies; and among the two counties with both supply- and demand-side policies and the two counties with only supply-side policies. We adjusted the sampling procedure and women's background characteristics. We conducted subgroup analyses by women's education. FindingsAfter one year of implementation, the coverage of prenatal foetal aneuploidies and B-ultrasound screening rose by 25.0% and 23.5%. The program's supply-side policies attributed to 17.2 percentage points (90%CI 7.8–26.6%) and 27.3 percentage points (90%CI 16.2–38.5%) in coverage, and contributed to a higher median cost of 796.5RMB (90%CI 595.5–997.5). These significantly affected women with secondary education and above. However, the program's demand-side measures, that is, vouchers, seemed to be effective only in the mountainous regions, which raised awareness, and increased coverage of prenatal foetal aneuploidies screening by 28.6 percentage points (90%CI 13.4–43.8%), while not increasing costs. These significantly affected women with primary education and below. Education-related inequalities widened post-program in counties with only supply-side policies, but no inequalities existed in counties with demand-side policies. InterpretationShaanxi's program made a pilot study to other provinces of China to integrate antenatal services. Government subsidies might be more effective in targeting specific geographic locations and people with primary education and lower.

Assessing antiretroviral therapy success in HIV/AIDS morbidity and mortality trends in Brazil, 1990-2017: an interrupted time series study.

To describe the trends of HIV/AIDS metrics related to the burden of disease for Brazil between 1990 and 2017 we conducted a timeseries analysis for HIV/AIDS indicators by extracting data from the Global Burden of Disease study. We calculated traditional prevalence, incidence and mortality rates, the number of years lost by HIV-related deaths (YLL) and disability (YLD), and disability-adjusted life years (DALY). We estimated time series models and assessed the impact of highly active antiretroviral therapy (HAART) on the same indicators. In the set of disability-adjusted life years (DALY), the highest weight of its magnitude was due to YLL. There was a decline, especially after 1996, of DALY, mortality and YLL for HIV/AIDS. However, YLD, incidence, and prevalence increased over the same period. Also, the analysis of interrupted time series showed that the introduction of HAART into health policy had a significant impact on indicators, especially for DALY and YLL. We need to assess the quality of life of people living with HIV, especially among older adults. In addition, we need to focus on primary prevention, emphasizing methods to avoid infection and public policies should reflect this.

Methods used to meta-analyse results from interrupted time series studies: A methodological systematic review protocol.

Background: Systematic reviews are used to inform healthcare decision making. In reviews that aim to examine the effects of organisational, policy change or public health interventions, or exposures, evidence from interrupted time series (ITS) studies may be included. A core component of many systematic reviews is meta-analysis, which is the statistical synthesis of results across studies. There is currently a lack of guidance informing the choice of meta-analysis methods for combining results from ITS studies, and there have been no studies examining the meta-analysis methods used in practice. This study therefore aims to describe current meta-analysis methods used in a cohort of reviews of ITS studies. Methods: We will identify the 100 most recent reviews (published between 1 January 2000 and 11 October 2019) that include meta-analyses of ITS studies from a search of eight electronic databases covering several disciplines (public health, psychology, education, economics). Study selection will be undertaken independently by two authors. Data extraction will be undertaken by one author, and for a random sample of the reviews, two authors. From eligible reviews we will extract details at the review level including discipline, type of interruption and any tools used to assess the risk of bias / methodological quality of included ITS studies; at the meta-analytic level we will extract type of outcome, effect measure(s), meta-analytic methods, and any methods used to re-analyse the individual ITS studies. Descriptive statistics will be used to summarise the data. Conclusions: This review will describe the methods used to meta-analyse results from ITS studies. Results from this review will inform future methods research examining how different meta-analysis methods perform, and ultimately, the development of guidance.

Impact of class-level labelling change on prescriptions of antidepressants for adolescents: An interrupted time-series study using a health insurance claims database in Japan, 2005-2013.

BackgroundIn October 2007, the Japanese Health Authority directed that precautions be added to antidepressants (ADs) labelling regarding suicide risk among young people.This study evaluates the impact of the labelling change on AD prescriptions and Japanese adolescent suicide rates.MethodsWe compared AD prescription rates per 100,000 population as a primary outcome. The intervention group comprised adolescents (10–24 years), while the control group comprised adults (25–64 years). We defined the pre-intervention period as January 2005 to October 2007 and post-intervention as November 2007 to February 2013. Monthly prescription rate data from a commercial claims database were triangulated with annual suicide rates in Japan. We performed segmented regression analysis for the prescription rates, using a quasi-Poisson model, and tested for level and trend changes.ResultsThe commercial claims database included 152,686 adolescents and 195,251 adults during the pre-intervention period and 846,367 adolescents and 1,352,453 adults during post-intervention. Post-intervention, the overall AD prescription rates decreased only in adult males (-95.8 prescription per 100,000) but increased in all other groups. The mean annual suicide rate increased in adolescent males (+1.5 suicides per 100,000) but decreased in all other groups. Overall, the upward trend became moderate or inverse in all groups post-intervention but with a large difference between males and females. The suicide rates rose slightly in adolescents but began declining in adults a year post-intervention. In females, changes in level, trend, and suicide rates were very small in both adolescents and adults.ConclusionsContrary to expectations, the mean prescription rates only decreased in adult males, but not in adolescents, regardless of gender. Downward level and trend change were clearly observed in adult males but not in adolescents, the original target of the updated warning. There were no clear temporal associations between suicide rates and the labelling change in either group.

Impact of co-payment level increase of antidiabetic medications on glycaemic control: an interrupted time-series study among Finnish patients with type 2 diabetes

BackgroundA new special reimbursement scheme (SRS) for non-insulin medications used for treatment of hyperglycaemia in type 2 diabetes (T2D) was implemented in Finland on January 1, 2017. The new SRS affected all community-dwelling Finnish T2D patients as all community-dwelling residents are eligible for reimbursement for prescription medications. The aim of the study was to evaluate the impact of this co-payment increase on glycaemic control among Finnish T2D patients.MethodsData on glycaemic control were collected with HbA1c measures from electronic health records from primary health care and specialized care in the North Karelia region, Finland, from patients with a confirmed T2D diagnosis in 2012 who were alive on January 1, 2017 (n = 8436). Average HbA1c levels were measured monthly 36 months before and 33 months after the policy change. Consumption of diabetes medications was measured with defined daily doses (DDDs) based on reimbursed medication purchases. Interrupted time series design analysed with segmented regression model was applied to examine the effect of the policy change on average HbA1c levels.ResultsEight thousand one hundred forty-three T2D patients had at least one HbA1c measurement within 01/2014–9/2019. Mean age of the patients was 68.1 (SD 11.3) years and 53.0% were women. Average time since T2D diagnosis was 11.5 (SD 6.1) years. An estimated increase of 0.81 (95% confidence interval, CI, 0.04–1.58) mmol/mol in average HbA1c levels was detected at the time of the policy change. In subgroup analyses, strongest effects were detected among patients who used only other diabetes medications than insulin or metformin in 2016 (3.56 mmol/mol, 95% CI 2.50–4.62). Meanwhile, yearly consumption of diabetes medications decreased slightly from 618.9 (SD 487.8) DDDs/patient in 2016 to 602.9 (SD 475.6) DDDs/patient in 2017 (p = 0.048).ConclusionsSimultaneously with the increase of the co-payment level, the average HbA1c level increased among T2D patients from the North Karelia region, Finland. This may be explained by the decreased consumption of diabetes medications between 2016 and 2017. Special attention should be allocated to glycaemic control of patients utilizing only other antidiabetic medications than metformin or insulin.

The Medium-Term Impact of COVID-19 Lockdown on Referrals to Secondary Care Mental Health Services: A Controlled Interrupted Time Series Study.

To date, there is a paucity of information regarding the effect of COVID-19 or lockdown on mental disorders. We aimed to quantify the medium-term impact of lockdown on referrals to secondary care mental health clinical services. We conducted a controlled interrupted time series study using data from Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), UK (catchment population ~0.86 million). The UK lockdown resulted in an instantaneous drop in mental health referrals but then a longer-term acceleration in the referral rate (by 1.21 referrals per day per day, 95% confidence interval [CI] 0.41–2.02). This acceleration was primarily for urgent or emergency referrals (acceleration 0.96, CI 0.39–1.54), including referrals to liaison psychiatry (0.68, CI 0.35–1.02) and mental health crisis teams (0.61, CI 0.20–1.02). The acceleration was significant for females (0.56, CI 0.04–1.08), males (0.64, CI 0.05–1.22), working-age adults (0.93, CI 0.42–1.43), people of White ethnicity (0.98, CI 0.32–1.65), those living alone (1.26, CI 0.52–2.00), and those who had pre-existing depression (0.78, CI 0.19–1.38), severe mental illness (0.67, CI 0.19–1.15), hypertension/cardiovascular/cerebrovascular disease (0.56, CI 0.24–0.89), personality disorders (0.32, CI 0.12–0.51), asthma/chronic obstructive pulmonary disease (0.28, CI 0.08–0.49), dyslipidemia (0.26, CI 0.04–0.47), anxiety (0.21, CI 0.08–0.34), substance misuse (0.21, CI 0.08–0.34), or reactions to severe stress (0.17, CI 0.01–0.32). No significant post-lockdown acceleration was observed for children/adolescents, older adults, people of ethnic minorities, married/cohabiting people, and those who had previous/pre-existing dementia, diabetes, cancer, eating disorder, a history of self-harm, or intellectual disability. This evidence may help service planning and policy-making, including preparation for any future lockdown in response to outbreaks.

Recreational Cannabis Legalization and Alcohol Purchasing: An Interrupted Time Series Study

Recreational Cannabis Legalization and Alcohol Purchasing: An Interrupted Time Series Study

The use of segmented regression for evaluation of an interrupted time series study involving complex intervention: the CaPSAI project experience

An interrupted time series with a parallel control group (ITS-CG) design is a powerful quasi-experimental design commonly used to evaluate the effectiveness of an intervention, on accelerating uptake of useful public health products, and can be used in the presence of regularly collected data. This paper illustrates how a segmented Poisson model that utilizes general estimating equations (GEE) can be used for the ITS-CG study design to evaluate the effectiveness of a complex social accountability intervention on the level and rate of uptake of modern contraception. The intervention was gradually rolled-out over time to targeted intervention communities in Ghana and Tanzania, with control communities receiving standard of care, as per national guidelines. Two ITS GEE segmented regression models are proposed for evaluating of the uptake. The first, a two-segmented model, fits the data collected during pre-intervention and post-intervention excluding that collected during intervention roll-out. The second, a three-segmented model, fits all data including that collected during the roll-out. A much simpler difference-in-difference (DID) GEE Poisson regression model is also illustrated. Mathematical formulation of both ITS-segmented Poisson models and that of the DID Poisson model, interpretation and significance of resulting regression parameters, and accounting for different sources of variation and lags in intervention effect are respectively discussed. Strengths and limitations of these models are highlighted. Segmented ITS modelling remains valuable for studying the effect of intervention interruptions whether gradual changes, over time, in the level or trend in uptake of public health practices are attributed by the introduced intervention.Trial Registration: The Australian New Zealand Clinical Trials registry.Trial registration number: ACTRN12619000378123.Trial Registration date: 11-March-2019.

Interventions to support the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic: a mixed methods systematic review.

Interventions to support the resilience and mental health of frontline health and social care professionals during and after a disease outbreak, epidemic or pandemic: a mixed methods systematic review.

Length of Initial Prescription at Hospital Discharge and Long-Term Medication Adherence for Elderly, Post-Myocardial Infarction Patients: Protocol for an Interrupted Time Series Study.

BackgroundBased on high-quality evidence, guidelines recommend the long-term use of secondary prevention medications post-myocardial infarction (MI) to avoid recurrent cardiovascular events and death. Unfortunately, discontinuation of recommended medications post-MI is common. Observational evidence suggests that prescriptions covering a longer duration at discharge from hospital are associated with greater long-term medication adherence. The following is a proposal for the first interventional study to evaluate the impact of longer prescription duration at discharge post-MI on long-term medication adherence.ObjectiveThe overarching goal of this study is to reduce morbidity and mortality among post-MI patients through improved long-term cardiac medication adherence. The specific objectives include the following. First, we will assess whether long-term cardiac medication adherence improves among elderly, post-MI patients following the implementation of (1) standardized discharge prescription forms with 90-day prescriptions and 3 repeats for recommended cardiac medication classes, in combination with education and (2) education alone compared to (3) usual care. Second, we will assess the cost implications of prolonged initial discharge prescriptions compared with usual care. Third, we will compare clinical outcomes between longer (>60 days) versus shorter prescription durations. Fourth, we will collect baseline information to inform a multicenter interventional study.MethodsWe will conduct a quasiexperimental, interrupted time series design to evaluate the impact of a multifaceted intervention to implement longer duration prescriptions versus usual care on long-term cardiac medication adherence among post-MI patients. Intervention groups and their corresponding settings include: (1) intervention group 1: 1 cardiac center and 1 noncardiac hospital allocated to receive standardized discharge prescription forms supporting the dispensation of 90 days’ worth of cardiac medications with 3 repeats, coupled with education; (2) intervention group 2: 4 sites (including 1 cardiac center) allocated to receive education only; and (3) control group: all remaining hospitals within the province that did not receive an intervention (ie, usual care). Administrative databases will be used to measure all outcomes. Adherence to 4 classes of cardiac medications — statins, beta blockers, angiotensin system inhibitors, and secondary antiplatelets (ie, prasugrel, clopidogrel, or ticagrelor) — will be assessed.ResultsEnrollment began in September 2017, and results are expected to be analyzed in late 2020.ConclusionsThe results have the potential to redefine best practices regarding discharge prescribing policies for patients post-MI. A policy of standardized maximum-duration prescriptions at the time of discharge post-MI is a simple intervention that has the potential to significantly improve long-term medication adherence, thus decreasing cardiac morbidity and mortality. If effective, this low-cost intervention to implement longer duration prescriptions post-MI could be easily scaled.Trial RegistrationClinicalTrials.gov NCT03257579; https://clinicaltrials.gov/ct2/show/NCT03257579International Registered Report Identifier (IRRID)DERR1-10.2196/18981

Impact of the zero-mark-up drug policy on drug-related expenditures and use in public hospitals, 2016–2018: an interrupted time series study in Shaanxi

ObjectiveThe aim of this study was to measure the impact of zero-mark-up drug policy (ZMDP) on drug-related expenditures and use in urban hospitals.DesignThis was a retrospective observational study of trends...

Tracking health commodity inventory and notifying stock levels via mobile devices: a mixed methods systematic review.

Tracking health commodity inventory and notifying stock levels via mobile devices: a mixed methods systematic review.

Implementation interventions to promote the uptake of evidence-based practices in stroke rehabilitation.

Rehabilitation based upon research evidence gives stroke survivors the best chance of recovery. There is substantial research to guide practice in stroke rehabilitation, yet uptake of evidence by healthcare professionals is typically slow and patients often do not receive evidence-based care. Implementation interventions are an important means to translate knowledge from research to practice and thus optimise the care and outcomes for stroke survivors. A synthesis of research evidence is required to guide the selection and use of implementation interventions in stroke rehabilitation. To assess the effects of implementation interventions to promote the uptake of evidence-based practices (including clinical assessments and treatments recommended in evidence-based guidelines) in stroke rehabilitation and to assess the effects of implementation interventions tailored to address identified barriers to change compared to non-tailored interventions in stroke rehabilitation. We searched CENTRAL, MEDLINE, Embase, and eight other databases to 17 October 2019. We searched OpenGrey, performed citation tracking and reference checking for included studies and contacted authors of included studies to obtain further information and identify potentially relevant studies. We included individual and cluster randomised trials, non-randomised trials, interrupted time series studies and controlled before-after studies comparing an implementation intervention to no intervention or to another implementation approach in stroke rehabilitation. Participants were qualified healthcare professionals working in stroke rehabilitation and the patients they cared for. Studies were considered for inclusion regardless of date, language or publication status. Main outcomes were healthcare professional adherence to recommended treatment, patient adherence to recommended treatment, patient health status and well-being, healthcare professional intention and satisfaction, resource use outcomes and adverse effects. Two review authors independently selected studies for inclusion, extracted data, and assessed risk of bias and certainty of evidence using GRADE. The primary comparison was any implementation intervention compared to no intervention. Nine cluster randomised trials (12,428 patient participants) and three ongoing trials met our selection criteria. Five trials (8865 participants) compared an implementation intervention to no intervention, three trials (3150 participants) compared one implementation intervention to another implementation intervention, and one three-arm trial (413 participants) compared two different implementation interventions to no intervention. Eight trials investigated multifaceted interventions; educational meetings and educational materials were the most common components. Six trials described tailoring the intervention content to identified barriers to change. Two trials focused on evidence-based stroke rehabilitation in the acute setting, four focused on the subacute inpatient setting and three trials focused on stroke rehabilitation in the community setting. We are uncertain if implementation interventions improve healthcare professional adherence to evidence-based practice in stroke rehabilitation compared with no intervention as the certainty of the evidence was very low (risk ratio (RR) 1.19, 95% confidence interval (CI) 0.53 to 2.64; 2 trials, 39 clusters, 1455 patient participants; I2 = 0%). Low-certainty evidence indicates implementation interventions in stroke rehabilitation may lead to little or no difference in patient adherence to recommended treatment (number of recommended performed outdoor journeys adjusted mean difference (MD) 0.5, 95% CI -1.8 to 2.8; 1 trial, 21 clusters, 100 participants) and patient psychological well-being (standardised mean difference (SMD) -0.02, 95% CI -0.54 to 0.50; 2 trials, 65 clusters, 1273 participants; I2 = 0%) compared with no intervention. Moderate-certainty evidence indicates implementation interventions in stroke rehabilitation probably lead to little or no difference in patient health-related quality of life (MD 0.01, 95% CI -0.02 to 0.05; 2 trials, 65 clusters, 1242 participants; I2 = 0%) and activities of daily living (MD 0.29, 95% CI -0.16 to 0.73; 2 trials, 65 clusters, 1272 participants; I2 = 0%) compared with no intervention. No studies reported the effects of implementation interventions in stroke rehabilitation on healthcare professional intention to change behaviour or satisfaction. Five studies reported economic outcomes, with one study reporting cost-effectiveness of the implementation intervention. However, this was assessed at high risk of bias. The other four studies did not demonstrate the cost-effectiveness of interventions. Tailoring interventions to identified barriers did not alter results. We are uncertain of the effect of one implementation intervention versus another given the limited very low-certainty evidence. We are uncertain if implementation interventions improve healthcare professional adherence to evidence-based practice in stroke rehabilitation compared with no intervention as the certainty of the evidence is very low.

Impact of DRGs-based inpatient service management on the performance of regional inpatient services in Shanghai, China: an interrupted time series study, 2013\u20132019

BackgroundThe asymmetry of information brings difficulty for government to manage public hospitals. Therefore, Jiading District of Shanghai has been establishing DRGs-based inpatient service management system (ISMS) to effectively compare the output of different hospitals through DRGs, reward desired hospital performance and enhance inpatient service capacity. However, the impact of the implementation of DRGs-based inpatient service management (ISM) policy in Jiading district is still unknow. We therefore conducted this study to evaluate the impact of DRGs-based ISM policy on the performance of inpatient service since its implementation in Jiading District, Shanghai, China in 2017.MethodsUsing an interrupted time series design, we analyzed quarterly data of seven DRGs-based performance measures from the ISMS which covered all five public hospitals in Jiading District from 2013 to 2019. We utilized the segmented linear regression model to assess the change of level and trend of performance indicators before and after ISM policy. Dickey–Fuller test was used to examine the stationary of the data. Durbin-Watson test was performed to check the series autocorrelation of indicators.ResultsSignificant changes in the following indicators were observed since the implementation of ISM policy. The case-mix index (CMI) level decreased by 0.103 (P < 0.05), the trend increased by 0.008 (P < 0.05). The total weight level decreased by 3719.05 (P < 0.05), and the trend increased by 250.13 (P < 0.05). The time efficiency index (TEI) level increased by 0.12 (P < 0.05), and the trend decreased by 0.01 (P < 0.05). The cost efficiency index (CEI) level increased by 0.31 (P < 0.05), and the trend decreased by 0.02 (P < 0.05). No significant difference was found in the change of DRGs number, inpatient mortality of low-risk group cases (IMLRG) and inpatient mortality of medium-to-low risk group cases (IMMLRG).ConclusionsFindings highlight the role of ISM policy in improving the capacity and efficiency of regional inpatient service. Three prerequisites, including a good information system, high-quality EMR data, and a management team, are needed for other countries to implement their own ISM policy to help government manage public hospitals and improve the performance of regional inpatient service.

Increases in Suicide Deaths Among Adolescents and Young Adults Following US Food and Drug Administration Antidepressant Boxed Warnings and Declines in Depression Care.

ObjectiveStudies show decreased depression diagnosis, psychotherapy, and medications and increased suicide attempts following US Food and Drug Administration antidepressant warnings regarding suicidality risk among youth. Effects on care spilled over to older adults. This study investigated whether suicide deaths increased following the warnings and declines in depression care.MethodsWe conducted an interrupted time series study of validated death data (1990–2017) to estimate changes in trends of US suicide deaths per 100,000 adolescents (ages 10–19) and young adults (ages 20–24) after the warnings, controlling for baseline trends.ResultsBefore the warnings (1990–2002), suicide deaths decreased markedly. After the warnings (2005–2017) and abrupt declines in treatment, this downward trend reversed. There was an immediate increase of 0.49 suicides per 100,000 adolescents, 95% confidence interval [CI]: 0.12, 0.86) and a trend increase of 0.03 suicides per 100,000 adolescents per year (95% CI: 0.026, 0.031). Similarly, there was an immediate increase of 2.07 suicides per 100,000 young adults (95% CI: 1.04, 3.10) and a trend increase of 0.05 suicides per 100,000 young adults per year (95% CI: 0.04, 0.06). Assuming baseline trends continued, there may have been 5958 excess suicides nationally by 2010 among yearly cohorts of 43 million adolescents and 21 million young adults.ConclusionsWe observed increases in suicide deaths among youth following the warnings and declines in depression care. Alternative explanations were explored, including substance use, economic recessions, smart phone use, and unintentional injury deaths. Additional factors may have contributed to continued increases in youth suicide during the last decade. Combined with previous research on declining treatment, these results call for re‐evaluation of the antidepressant warnings.

Impact of the Requirement of Bone Mineral Density Evidence on Utilization of Anti-osteoporosis Medications, Clinical Outcome and Medical Expenditures of Patient With Hip Fracture in Taiwan.

Background: Since 2011, Taiwan’s National Health Insurance Administration (NHIA) issued a regulation on the reimbursement to anti-osteoporosis medications (AOMs). This study aimed to evaluate the impact of this regulation in reimbursement on the utilization of AOMs, clinical outcomes and associated medical expenditures of patients with incident hip fractures. Methods: By using the National Health Insurance Research Database (NHIRD), patients with incident hip fracture from 2006 to 2015 were identified as our study cohort. Patients younger than 50 years old or prescribed with AOMs within one year prior to incident fracture were excluded. Outcomes of interest were quarterly estimates of the proportion of patients who received bone mineral density (BMD) examination, who were prescribed AOMs, as well as who encountered subsequent osteoporotic fracture-related visits and associated medical expenditures. Particularly, age- and gender specific estimates were reported. An interrupted time series study design with segmented regression model was used to quantitatively explore the impact of the changes of the reimbursement criteria on the level (immediate) and trend (long-term) changes of these outcomes. Results: Our study enrolled 118 493 patients with incident hip fracture with those patients aged older than 80 years old accounting for the largest proportion. A significantly decreased trend of AOMs prescription rates was observed immediately post regulation except for female aged between 65 and 80, while the long-term pattern showed no significant difference. However, the percentage of patients encountered subsequent osteoporotic fracture-related visit was not statistically different between pre- and post-regulation periods. Noteworthy, the policy regulation was associated with an increasing trend of osteoporotic fracture associated medical expenditures, especially for patients older than 80 years old.Conclusion: The regulation on the reimbursement for AOMs decreased the prescribing rate of AOMs immediately although the effect did not sustain thereafter. However, higher subsequent osteoporotic fracture-related medical expenditures were introduced, especially among those very old population.

Can synthetic controls improve causal inference in interrupted time series evaluations of public health interventions?

Interrupted time series designs are a valuable quasi-experimental approach for evaluating public health interventions. Interrupted time series extends a single group pre-post comparison by using multiple time points to control for underlying trends. But history bias-confounding by unexpected events occurring at the same time of the intervention-threatens the validity of this design and limits causal inference. Synthetic control methodology, a popular data-driven technique for deriving a control series from a pool of unexposed populations, is increasingly recommended. In this paper, we evaluate if and when synthetic controls can strengthen an interrupted time series design. First, we summarize the main observational study designs used in evaluative research, highlighting their respective uses, strengths, biases and design extensions for addressing these biases. Second, we outline when the use of synthetic controls can strengthen interrupted time series studies and when their combined use may be problematic. Third, we provide recommendations for using synthetic controls in interrupted time series and, using a real-world example, we illustrate the potential pitfalls of using a data-driven approach to identify a suitable control series. Finally, we emphasize the importance of theoretical approaches for informing study design and argue that synthetic control methods are not always well suited for generating a counterfactual that minimizes critical threats to interrupted time series studies. Advances in synthetic control methods bring new opportunities to conduct rigorous research in evaluating public health interventions. However, incorporating synthetic controls in interrupted time series studies may not always nullify important threats to validity nor improve causal inference.

Effect of a Nationwide Real-Time Drug Utilization Review System on Duplicated Nonsteroidal Antiinflammatory Drug Prescriptions in Korea.

Since January 2013, a nationwide drug utilization review (DUR) system for therapeutic duplication (TD) of nonsteroidal antiinflammatory drugs (NSAIDs) has been implemented in Korea. Our objective was to perform an interrupted time series study to assess changes in the pattern of NSAIDs use in knee osteoarthritis patients after implementation of the regulations. We compared the prescribing patterns in 2012 and 2013 by means of an interrupted time series study, using the Health Insurance Review and Assessment Service database. TD was defined as use of concurrent NSAIDs either on the same or on different prescriptions for >3 days in a patient. Level change and trend change (with 95% confidence intervals [95% CIs]), and absolute and relative changes in the proportion of TDs, were estimated using segmented regression models. Multivariable logistic regression models were used to explore patient and provider characteristics associated with the TDs. Approximately 2.5 million patients were prescribed NSAIDs in both 2012 and 2013. The proportion of TDs before and after introduction of the DUR system was 7.4% and 5.6%, respectively. Overall, an absolute reduction of 89% and a relative reduction of 30% in TDs were observed. In the postregulation period, older patients, medical aid subscribers (odds ratio [OR] 1.87 [95% CI 1.84, 1.90]), and veterans (OR 3.28 [95% CI 3.10, 3.46]) were most likely to receive NSAID TDs. The prescription of NSAID TDs decreased with the introduction of the nationwide DUR system. Continuous adherence to the DUR regulations and safety monitoring are needed, especially with the elderly, medical aid subscribers, and veterans.

Effectiveness of the non-pharmaceutical public health interventions against COVID-19; a protocol of a systematic review and realist review.

BackgroundWithout any pharmaceutical intervention and vaccination, the only way to combat Coronavirus Disease 2019 (COVID-19) is to slow down the spread of the disease by adopting non-pharmaceutical public health interventions (PHIs). Patient isolation, lockdown, quarantine, social distancing, changes in health care provision, and mass screening are the most common non-pharmaceutical PHIs to cope with the epidemic. However, there is neither systematic evidence on the effectiveness of non-pharmaceutical PHIs in controlling the COVID-19 nor on how these interventions work in different contexts. Therefore, in this study we will address two main objectives: 1) to assess the effectiveness of the non-pharmaceutical PHIs in controlling the spread of COVID-19 using a systematic review and meta-analyses; 2) to explore why, how, and for whom these interventions work using a realist review.Materials and methodsThis review study has two main phases. In the first phase of this study, we will extract data from two main types of studies including quasi-experimental studies (such as quasi-randomized trials, controlled before-after studies (CBAs) and interrupted time series studies (ITSs)) and observational studies (such as cohort, case-control, and cross-sectional studies), written in the English language. We will explore effectiveness of the non-pharmaceutical PHIs targeted either suppression or mitigation strategies (or a combination of both) in controlling the COVID-19 epidemics in the community level. Effectiveness will be considered as the changes in mortality rate, incidence rate, basic reproduction number rate, morbidity rate, rates of hospitalization, rates of intensive care unit (ICU) hospitalization, and other health outcomes where possible. We will perform random-effects meta-analyses, if possible, using CMA software. In the second phase, we will conduct a realist review to find out how, why, for whom, and in what circumstances the non-pharmaceutical PHIs work. At the realist review, we will identify and explore Context-Mechanism-Outcome configurations to provide a robust explanation on the effectiveness of the interventions in different contexts using Pawson's 5-step realist review template including: "clarify scope; search for evidence; appraise primary studies and extract data; synthesize evidence and draw conclusions; and disseminate, implement and evaluate". Although the steps are presented in a linear manner, in practice, we will follow them in iterative stages to fill any potential overlap.DiscussionThe findings of this research will provide a crucial insight into how and in which context the non-pharmaceutical PHIs work in controlling the spread of COVID-19. Conducting a systematic review and meta-analysis in line with a realist review will allow us to draw a robust conclusion on the effects and the way in which the interventions work. Understanding the role of contextual factors in the effectiveness of non-pharmaceutical PHIs and the mechanism of this process could enable policymakers to implement appropriate policies and manage the COVID-19 epidemics more efficiently.Systematic review registrationCRD42020186855.

Improving adherence to guideline recommendations in dementia care through establishing a quality improvement collaborative of agents of change: an interrupted time series study

BackgroundNon-pharmacological interventions including physical activity programmes, occupational therapy and caregiver education programmes have been shown to lead to better outcomes for people with dementia and their care partners. Yet, there are gaps between what is recommended in guidelines and what happens in practice. The aim of this study was to bring together clinicians working in dementia care and establish a quality improvement collaborative. The aim of the quality improvement collaborative was to increase self-reported guideline adherence to three guideline recommendations.MethodsInterrupted time series. We recruited health professionals from community, hospital and aged care settings across Australia to join the collaborative. Members of the collaborative participated in a start-up meeting, completed an online learning course with clinical and quality improvement content, formed a quality improvement plan which was reviewed by a team of experts, received feedback following an audit of their current practice and were able to share experiences with their peers. The primary outcome was self-reported adherence to their guideline recommendation of interest which was measured using checklists. Data were collected monthly over a period of 18 months, and the study used an interrupted time series design and multilevel Poisson regression analysis to evaluate changes in self-reported adherence.ResultsA total of 45 health professionals (78% therapists) from different sites joined the collaborative and 28 completed all requirements. Data from 1717 checklists were included in the analyses. Over the duration of the project, there was a significant increase in clinician self-reported adherence to guideline recommendations with a 42.1% immediate increase in adherence (incidence rate ratio = 1.42; 95% confidence interval = 1.08–1.87; p = 0.012).ConclusionHealth professionals working with people with dementia are interested in and willing to join a quality improvement collaborative with the goal of improving non-pharmacological aspects of care. Participation in the collaborative improved the quality of care for people with dementia as measured through self-reported adherence to guideline recommendations. Although there are challenges in implementation of guideline recommendations within dementia care, the quality improvement collaborative method was considered successful. A strength was that it equipped and empowered clinicians to lead improvement activities and allowed for heterogeneity in terms of service and setting.Trial registrationACTRN12618000268246