Interrupted Time Series Studies Research Articles

Immediate effects of Ramadan on objective time asleep in male youth football players from the Middle East: an interrupted time-series study

ABSTRACT Objective To examine the abrupt effects of Ramadan onset on actigraphy-based time asleep in male youth Muslim football players. Methods We adopted a quasi-experimental, interrupted time-series research design and tracked objective time asleep over a minimum of 12 consecutive nights in the two weeks prior to and immediately after Ramadan onset, respectively. Twenty-two, male academy student-athletes (chronological age range: 12.6 to 16.2 years) participated in the study (464 individual observations). Segmented generalized mixed-effects modelling estimated the effects of Ramadan onset on time asleep during the first period of night sleep only. Results Ramadan onset led to an immediate mean reduction of 89 min (95% confidence interval [CI], 54 to 123 min) in time asleep during the first period of night sleep compared to pre-Ramadan sleep patterns. Model-adjusted estimated marginal means for time asleep were ~ 5.7 h (95%CI, 5.1 to 6.2 h) before and ~ 4.2 h (95%CI, 3.6 to 4.7 h) after Ramadan onset. Night sleep interruptions resulting in two or more fragmented periods accounted for 8% (95%CI, 2 to 21%) to 19% (95%, 11 to 29%) of sleep observations before and after Ramadan onset, respectively. Conclusions The onset of Ramadan determined an abrupt reduction in time asleep of ~ 1 h 30 min in the first period of a night cycle and contributed to additional problems of heterogeneous sleep fragmentation that can impact optimal school learning and youth athlete performance development processes.

Tobacco control policies and respiratory conditions among children presenting in primary care

Tobacco control policies can protect child health. We hypothesised that the parallel introduction in 2008 of smoke-free restaurants and bars in the Netherlands, a tobacco tax increase and mass media campaign, would be associated with decreases in childhood wheezing/asthma, respiratory tract infections (RTIs), and otitis media with effusion (OME) presenting in primary care. We conducted an interrupted time series study using electronic medical records from the Dutch Integrated Primary Care Information database (2000–2016). We estimated step and slope changes in the incidence of each outcome with negative binomial regression analyses, adjusting for underlying time-trends, seasonality, age, sex, electronic medical record system, urbanisation, and social deprivation. Analysing 1,295,124 person-years among children aged 0–12 years, we found positive step changes immediately after the policies (incidence rate ratio (IRR): 1.07, 95% CI: 1.01–1.14 for wheezing/asthma; IRR: 1.16, 95% CI: 1.13–1.19 for RTIs; and IRR: 1.24, 95% CI: 1.14–1.36 for OME). These were followed by slope decreases for wheezing/asthma (IRR: 0.95/year, 95% CI: 0.93–0.97) and RTIs (IRR: 0.97/year, 95% CI: 0.96–0.98), but a slope increase in OME (IRR: 1.05/year, 95% CI: 1.01–1.09). We found no clear evidence of benefit of changes in tobacco control policies in the Netherlands for the outcomes of interest. Our findings need to be interpreted with caution due to substantial uncertainty in the pre-legislation outcome trends.

Mandated rest breaks and occupational injuries and illnesses in Dallas County, TX construction workers: A quasi-experimental, comparative interrupted time series study.

We estimated associations of a rest break ordinance, implemented for construction workers in Dallas, Texas in 2016, with workplace injuries and illnesses. We used workers' compensation claims data to compare changes in rates of injuries and illnesses among Dallas, TX County construction (i.e., "treated") workers with changes in untreated workers, before (2013 - 2015) and after (2016 - 2018) a rest break ordinance was implemented. Immediately after the ordinance was implemented, rates of injuries/illnesses among treated workers were modestly lower than in comparison workers (Rate Ratio comparing post- versus pre-mandate rates, treated versus comparison workers: 0.89, 95% CI: 0.72 - 1.11). Post- vs pre-ordinance slope trends were similar in the treated versus the comparison group. Ten-minute rest breaks were associated with modestly lower rates of workplace injury/illnesses. More comprehensive standards may be needed for protection.

Studying the context of psychoses to improve outcomes in Ethiopia (SCOPE): Protocol paper

Background Global evidence on psychosis is dominated by studies conducted in Western, high-income countries. The objectives of the Study of Context Of Psychoses to improve outcomes in Ethiopia (SCOPE) are (1) to generate rigorous evidence of psychosis experience, epidemiology and impacts in Ethiopia that will illuminate aetiological understanding and (2) inform development and testing of interventions for earlier identification and improved first contact care that are scalable, inclusive of difficult-to-reach populations and optimise recovery. Methods The setting is sub-cities of Addis Ababa and rural districts in south-central Ethiopia covering 1.1 million people and including rural, urban and homeless populations. SCOPE comprises (1) formative work to understand care pathways and community resources (resource mapping); examine family context and communication (ethnography); develop valid measures of family communication and personal recovery; and establish platforms for community engagement and involvement of people with lived experience; (2a) a population-based incidence study, (2b) a case-control study and (2c) a cohort study with 12 months follow-up involving 440 people with psychosis (390 rural/Addis Ababa; 50 who are homeless), 390 relatives and 390 controls. We will test hypotheses about incidence rates in rural vs. urban populations and men vs. women; potential aetiological role of khat (a commonly chewed plant with amphetamine-like properties) and traumatic exposures in psychosis; determine profiles of needs at first contact and predictors of outcome; (3) participatory workshops to develop programme theory and inform co-development of interventions, and (4) evaluation of the impact of early identification strategies on engagement with care (interrupted time series study). Findings will inform development of (5) a protocol for (5a) a feasibility cluster randomised controlled trial of interventions for people with recent-onset psychosis in rural settings and (5b) two uncontrolled pilot studies to test acceptability, feasibility of co-developed interventions in urban and homeless populations.

Impact of capitation on physicians’ behavior among patients with hypertension: an interrupted time series study in rural China

ObjectiveThe purpose of this study is to explore the change in physicians’ hypertension treatment behavior before and after the reform of the capitation in county medical community.MethodsSpanning from January 2014 to December 2019, monthly data of outpatient and inpatient were gathered before and after the implementation of the reform in April 2015. We employed interrupted time series analysis method to scrutinize the instantaneous level and slope changes in the indicators associated with physicians’ behavior.ResultsSeveral indicators related to physicians’ behavior demonstrated enhancement. After the reform, medical cost per visit for inpatient exhibited a reverse trajectory (-53.545, 95%CI: -78.620 to -28.470, p < 0.01). The rate of change in outpatient drug combination decelerated (0.320, 95%CI: 0.149 to 0.491, p < 0.01). The ratio of infusion declined for both outpatient and inpatient cases (-0.107, 95%CI: -0.209 to -0.004, p < 0.1; -0.843, 95%CI: -1.154 to -0.532, p < 0.01). However, the results revealed that overall medical cost per visit and drug proportion for outpatient care continued their initial upward trend. After the reform, the decline of drug proportion for outpatient care was less pronounced compared to the period prior to the reform, and length of stay also had a similar trend.ConclusionTo some extent, capitation under the county medical community encourages physicians to control the cost and adopt a more standardized diagnosis and treatment behavior. This study provides evidence to consider the impact of policy changes on physicians’ behavior when designing payment methods and healthcare systems aimed at promoting PHC.

Impacts of pharmacist-led multifaceted antimicrobial stewardship on antibiotic use and clinical outcomes in urology department of a tertiary hospital in Guangzhou, China: an interrupted time series study

Limited research has explored the effectiveness of pharmacist-led antimicrobial stewardship programs (ASPs) in the urology department. To evaluate the impact of pharmacist-led multifaceted ASPs on antibiotic use and clinical outcomes. We conducted a prescription review of inpatients receiving one or more antibiotics in the urology department of a large teaching hospital in Guangzhou, China, from April 2019 to March 2023. The pharmacist-led multifaceted ASPs intervention included guidelines development, training, medication consultation, review of medical orders, indicator monitoring, and consultation. Our primary outcome was antibiotic consumption. The data was analysed using interrupted time series (ITS) analysis. Following the implementation of ASPs, we observed an immediate decrease in total antibiotic consumption (β = -32.42 DDDs/100PD and -36.24 DOT/100PD, P < 0.001), Antibiotic use rate (β = -7.87 %, P = 0.002), Second-generation cephalosporins (β = -12.43 DDDs/100PD and -15.18 DOT/100PD, P < 0.001), Third-generation cephalosporins (β = -5.13 DDDs/100PD, P = 0.001 and -6.16 DOT/100PD, P = 0.002), Fluoroquinolones (β = -12.26 DDDs/100PD and -12.70 DOT/100PD, P < 0.001), and WHO Watch category antibiotics (β = -32.07 DDDs/100PD and -34.96 DOT/100PD, P < 0.001). There were no differences observed in mortality rate before and after the intervention, and no significant short-term or long-term effects were found on length of hospital stay (LOS) using ITS. However, there was a significant short-term effect on average antibiotic cost (β = -446.83 RMB, P = 0.004). The implementation of pharmacist-led multifaceted ASPs had positive impacts on reducing antimicrobial consumption without increasing LOS, antibiotic cost, or mortality rate.

Trends in medication use after the onset of the COVID-19 pandemic in the Republic of Ireland: an interrupted time series study

Abstract Introduction The COVID-19 pandemic had a substantial impact on a range of health services, particularly in primary care. Research from Ireland suggests while community pharmacies remained open, restrictions for in-person healthcare appointments impacted patients.[1] Although there is evidence that the onset of the pandemic affected medicines utilisation internationally,[2] it is unclear how prescribing in Ireland changed following March 2020. Aim To evaluate how dispensing of medications in primary care in Ireland changed following the onset of the COVID-19 pandemic compared to expected trends. Methods This was an interrupted time series study, and the protocol was pre-registered (doi.org/10.17605/OSF.IO/WNQHR). It used publicly available data from the Health Service Executive Primary Care Reimbursement Services for each month between January 2016 and July 2022. Data covered dispensing on the General Medical Services (i.e. medical card) scheme for all medication therapeutic subgroups and commonly dispensed medications (based on the top 100 individual medications per month). Pre-pandemic data (January 2016-November 2019) was used to forecast expected trends from December 2019 onwards for each subgroup and medication with 99% prediction intervals. The Holt-Winters method was used, which decomposes time series data into seasonal, trend, and irregular components. Three months of observed data unaffected by the pandemic (December 2019-February 2020, validation period) were compared to the forecast to validate accuracy of predictions. Observed data were compared to forecasts in March 2020 (as the first month of pandemic restrictions in Ireland) and over the remainder of the study period from April 2020-July 2022. Statistical significance was defined as observed data outside the 99% prediction interval (p&amp;lt;0.01). Results The overall number of dispensings was 7.6% (99%CI 2.5% to 13.2%) higher than forecast in March 2020. Many (31/77) therapeutic subgroups had dispensing significantly different from forecast in March 2020. Drugs for obstructive airway disease had the largest difference, with dispensing 26.2% (99%CI 19.5%-33.6%) higher than forecasted. Other subgroups with dispensing significantly higher than forecasted included minerals, analgesics, thyroid therapy, serum lipid-reducing agents and diuretics. Dispensing was significantly lower than forecasted for other gynaecologicals (17.7% lower, 99%CI 6.3%-26.6%) and dressings (11.6%, 99%CI 9.4%-41.6%). Similarly, many individual medications had significantly higher dispensing in March 2020. Notably, dispensing of amoxicillin (with/without clavulanic acid) and oral prednisolone were lower than forecasted in the months following the onset of the pandemic, particularly during winter 2020/2021. Conclusion There was a peak in dispensing for many long-term medications in March 2020 suggesting patients obtained additional supplies of their regular medicines as pandemic restrictions were introduced. Exceptions were dispensing of two therapeutic subgroups (dressings/intrauterine devices) linked to in-person healthcare consultations, illustrating the disruption to service delivery. Lower than expected dispensing of antimicrobials and reduced seasonal peaks may be partly due to reduced infection transmission generally. Although we were limited by lacking data on the number of people dispensed each medication, this is the first study to examine changes in medication use during the COVID-19 pandemic in Ireland, considering all therapeutic areas. This study provides evidence to inform planning for medication demand and supply for future major health events.

Evaluating the impact of minimum unit pricing (MUP) on alcohol sales after 3years of implementation in Scotland: A controlled interrupted time-series study.

On 1May 2018, Scotland introduced minimum unit pricing (MUP), a strength-based floor price below which alcohol cannot be sold, throughout all alcoholic beverages. The legislation necessitates an evaluation of its impact across a range of outcomes that will inform whether MUP will continue beyond its sixth year. We measured the impact of MUP on per-adult alcohol sales (as a proxy for consumption) after 3 years of implementation. Controlled interrupted time-series regression was used to assess the impact of MUP on alcohol sales in Scotland after 3 years of implementation, with England and Wales (EW) being the control group. In adjusted analyses, we included household disposable income, on-trade alcohol sales (in off-trade analyses) and substitution between drink categories (in drink category analyses) as covariates. Weekly data were assessed on the volume of pure alcohol sold in Scotland and EW between January 2013 and May 2021, expressed as litres of pure alcohol per adult. The impact of MUP on total (on- and off-trade combined), off-trade and on-trade alcohol sales was assessed separately. The introduction of MUP in Scotland was associated with a 3.0% (95% confidence interval = 1.8-4.2%) net reduction in total alcohol sales per adult after adjustment for the best available geographical control, disposable income and substitution. This reflects a 1.1% fall in Scotland in contrast to a 2.4% increase in EW. The reduction in total alcohol sales in Scotland was driven by reduced sales of beer, spirits, cider and perry. The reduction in total sales was due to reductions in sales of alcohol through the off-trade. There was no evidence of any change in on-trade alcohol sales. Minimum unit pricing has been effective in reducing population-level alcohol sales in Scotland in the 3 years since implementation.

Impact of the COVID-19 Pandemic on Hepatitis C Treatment Initiation in British Columbia, Canada: An Interrupted Time Series Study.

We investigated the impacts of the COVID-19 pandemic on hepatitis C (HCV) treatment initiation, including by birth cohort and injection drug use status, in British Columbia (BC), Canada. Using population data from the BC COVID-19 Cohort, we conducted interrupted time series analyses, estimating changes in HCV treatment initiation following the introduction of pandemic-related policies in March 2020. The study included a pre-policy period (April 2018 to March 2020) and three follow-up periods (April to December 2020, January to December 2021, and January to December 2022). The level of HCV treatment initiation decreased by 26% in April 2020 (rate ratio 0.74, 95% confidence interval [CI] 0.60 to 0.91). Overall, no statistically significant difference in HCV treatment initiation occurred over the 2020 and 2021 post-policy periods, and an increase of 34.4% (95% CI 0.6 to 75.8) occurred in 2022 (equating to 321 additional people initiating treatment), relative to expectation. Decreases in HCV treatment initiation occurred in 2020 for people born between 1965 and 1974 (25.5%) and people who inject drugs (24.5%), relative to expectation. In summary, the pandemic was associated with short-term disruptions in HCV treatment initiation in BC, which were greater for people born 1965 to 1974 and people who inject drugs.

Medicare Transitional Care Management Program and Changes in Timely Postdischarge Follow-Up

In 2013, Medicare implemented payments for transitional care management (TCM) services, which provide increased reimbursement to clinicians providing ambulatory care to patients after discharge from medical facilities to the community. To determine whether the introduction of TCM payments was associated with an increase in timely postdischarge follow-up. This cross-sectional interrupted time-series study assessed quarterly postdischarge visit rates before (2010-2012) and after (2013-2019) TCM implementation 100% sample of Medicare fee-for-service beneficiaries discharged to the community after a hospital or skilled nursing facility stay. Data analyses were performed February 1 to December 15, 2023. Implementation of payments for TCM. Timely postdischarge primary care follow-up, defined as receipt of a primary care ambulatory visit within 14 days of discharge. Secondary outcomes included receipt of a TCM visit and specialty care follow-up. The study sample comprised 79 125 965 eligible discharges. Of these, 55.4% were female; 1.5% were Asian, 12.1% Black, 5.6% Hispanic, and 79.0% were White individuals; and 79.6% were beneficiaries aged 65 years and older. Timely primary care follow-up increased from 31.5% in 2010 to 38.8% in 2019 (absolute increase 7.3%), whereas specialist follow-up increased from 27.6% to 30.8% (absolute increase 3.2%). By 2019, 11.3% of eligible patients received TCM services. Interrupted time-series analyses demonstrated an increased slope of timely primary care follow-up after the introduction of TCM services (pre-TCM slope, 0.12% per quarter vs post-TCM slope, 0.29% per quarter; difference, 0.13%; 95% CI, 0.02% to 0.22%). Receipt of timely follow-up increased for all demographic groups; however, Black, Hispanic, and Medicaid dual-eligible patients and patients residing in urban areas and counties with high-level social deprivation were less likely to receive follow-up during the study period. These disparities widened for Black patients (difference-in-differences in pre-TCM vs post-TCM slope, -0.14%; 95% CI, -0.25% to -0.2%) and patients who were Medicaid dual-eligible (difference-in-differences pre-TCM vs post-TCM slope, -0.21%; 95% CI, -0.35% to -0.07%). These findings indicate that Medicare's introduction of payments for TCM services was associated with a persistent increase in the rate of timely postdischarge primary care but did not narrow demographic or socioeconomic disparities. Most beneficiaries did not receive timely primary care follow-up.

Antimicrobial Stewardship in the Emergency Department Observation Unit: Definition of a New Indicator and Evaluation of Antimicrobial Use and Clinical Outcomes.

We aimed to define a novel indicator for monitoring antimicrobial use specifically in the Emergency Department Observation Unit (EDOU) and to assess the long-term impact of an institutional education-based antimicrobial stewardship program (ASP) on the antimicrobial prescribing pattern and clinical outcomes in this setting. A quasi-experimental interrupted time-series study was performed from 2011 to 2022. An educational ASP was implemented at the EDOU in 2015. To estimate changes in antimicrobial use, we designed an indicator adjusted for patients at risk of antimicrobial prescribing: defined daily doses (DDDs) per 100 patients transferred from the Emergency Department to the Observation Unit (TOs) per quarter. The number of bloodstream infections (BSIs) and the crude all-cause 14-day mortality were assessed as clinical outcomes. Antimicrobial use showed a sustained reduction with a trend change of -1.17 DDD per 100 TO and a relative effect of -45.6% (CI95% -64.5 to -26.7), particularly relevant for meropenem and piperacillin-tazobactam, with relative effects of -80.4% (-115.0 to -45.7) and -67.9% (-93.9 to -41.9), respectively. The incidence density of all BSIs increased significantly during the ASP period, with a relative effect of 123.2% (41.3 to 284.7). The mortality rate remained low and stable throughout the study period, with an absolute effect of -0.7% (-16.0 to 14.7). The regular monitoring of antimicrobial use in the EDOU by using this new quantitative indicator was useful to demonstrate that an institutional education-based ASP successfully achieved a long-term reduction in overall antimicrobial use, with a low and steady BSI mortality rate.

The Effect of an Electronic Medical Record-Based Clinical Decision Support System on Adherence to Clinical Protocols in Inflammatory Bowel Disease Care: Interrupted Time Series Study.

Clinical decision support systems (CDSSs) embedded in electronic medical records (EMRs), also called electronic health records, have the potential to improve the adoption of clinical guidelines. The University of Alberta Inflammatory Bowel Disease (IBD) Group developed a CDSS for patients with IBD who might be experiencing disease flare and deployed it within a clinical information system in 2 continuous time periods. This study aims to evaluate the impact of the IBD CDSS on the adherence of health care providers (ie, physicians and nurses) to institutionally agreed clinical management protocols. A 2-period interrupted time series (ITS) design, comparing adherence to a clinical flare management protocol during outpatient visits before and after the CDSS implementation, was used. Each interruption was initiated with user training and a memo with instructions for use. A group of 7 physicians, 1 nurse practitioner, and 4 nurses were invited to use the CDSS. In total, 31,726 flare encounters were extracted from the clinical information system database, and 9217 of them were manually screened for inclusion. Each data point in the ITS analysis corresponded to 1 month of individual patient encounters, with a total of 18 months of data (9 before and 9 after interruption) for each period. The study was designed in accordance with the Statement on Reporting of Evaluation Studies in Health Informatics (STARE-HI) guidelines for health informatics evaluations. Following manual screening, 623 flare encounters were confirmed and designated for ITS analysis. The CDSS was activated in 198 of 623 encounters, most commonly in cases where the primary visit reason was a suspected IBD flare. In Implementation Period 1, before-and-after analysis demonstrates an increase in documentation of clinical scores from 3.5% to 24.1% (P<.001), with a statistically significant level change in ITS analysis (P=.03). In Implementation Period 2, the before-and-after analysis showed further increases in the ordering of acute disease flare lab tests (47.6% to 65.8%; P<.001), including the biomarker fecal calprotectin (27.9% to 37.3%; P=.03) and stool culture testing (54.6% to 66.9%; P=.005); the latter is a test used to distinguish a flare from an infectious disease. There were no significant slope or level changes in ITS analyses in Implementation Period 2. The overall provider adoption rate was moderate at approximately 25%, with greater adoption by nurse providers (used in 30.5% of flare encounters) compared to physicians (used in 6.7% of flare encounters). This is one of the first studies to investigate the implementation of a CDSS for IBD, designed with a leading EMR software (Epic Systems), providing initial evidence of an improvement over routine care. Several areas for future research were identified, notably the effect of CDSSs on outcomes and how to design a CDSS with greater utility for physicians. CDSSs for IBD should also be evaluated on a larger scale; this can be facilitated by regional and national centralized EMR systems.

Development of a search filter to retrieve reports of interrupted time series studies from MEDLINE and PubMed.

Interrupted time series (ITS) studies contribute importantly to systematic reviews of population-level interventions. We aimed to develop and validate search filters to retrieve ITS studies in MEDLINE and PubMed. A total of 1017 known ITS studies (published 2013-2017) were analysed using text mining to generate candidate terms. A control set of 1398 time-series studies were used to select differentiating terms. Various combinations of candidate terms were iteratively tested to generate three search filters. An independent set of 700 ITS studies was used to validate the filters' sensitivities. The filters were test-run in Ovid MEDLINE and the records randomly screened for ITS studies to determine their precision. Finally, all MEDLINE filters were translated to PubMed format and their sensitivities in PubMed were estimated. Three search filters were created in MEDLINE: a precision-maximising filter with high precision (78%; 95% CI 74%-82%) but moderate sensitivity (63%; 59%-66%), most appropriate when there are limited resources to screen studies; a sensitivity-and-precision-maximising filter with higher sensitivity (81%; 77%-83%) but lower precision (32%; 28%-36%), providing a balance between expediency and comprehensiveness; and a sensitivity-maximising filter with high sensitivity (88%; 85%-90%) but likely very low precision, useful when combined with specific content terms. Similar sensitivity estimates were found for PubMed versions. Our filters strike different balances between comprehensiveness and screening workload and suit different research needs. Retrieval of ITS studies would be improved if authors identified the ITS design in the titles.

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

IntroductionInterrupted 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.ObjectiveTo investigate design and statistical analysis characteristics of drug utilization studies using ITS design, and give recommendations for improvements.MethodsA 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.ResultsWe 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.ConclusionThe 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.

Investigation of reporting bias in interrupted time series (ITS) studies: a study protocol

Background Systematic reviews that aim to synthesize evidence on the effects of interventions targeted at populations often include interrupted time-series (ITS) studies. However, the suppression of ITS studies or results within these studies (known as reporting bias) has the potential to bias conclusions drawn in such systematic reviews, with potential consequences for healthcare decision-making. Therefore, we aim to determine whether there is evidence of reporting bias among ITS studies. Methods We will conduct a search for published protocols of ITS studies and reports of their results in PubMed, MEDLINE, and Embase up to December 31, 2022. We contact the authors of the ITS studies to seek information about their study, including submission status, data for unpublished results, and reasons for non-publication or non-reporting of certain outcomes. We will examine if there is evidence of publication bias by examining whether time-to-publication is influenced by the statistical significance of the study’s results for the primary research question using Cox proportional hazards regression. We will examine whether there is evidence of discrepancies in outcomes by comparing those specified in the protocols with those in the reports of results, and we will examine whether the statistical significance of an outcome’s result is associated with how completely that result is reported using multivariable logistic regression. Finally, we will examine discrepancies between protocols and reports of results in the methods by examining the data collection processes, model characteristics, and statistical analysis methods. Discrepancies will be summarized using descriptive statistics. Discussion These findings will inform systematic reviewers and policymakers about the extent of reporting biases and may inform the development of mechanisms to reduce such biases.

Reinforcing informed medication prescription for low back pain in the emergency department (RIME): a controlled interrupted time series implementation study protocol

IntroductionManagement guidelines for low back pain (LBP) recommend exclusion of serious pathology, followed by simple analgesics, superficial heat therapy, early mobilisation and patient education. An audit in a large metropolitan...

Differences in inpatient performance of public general hospitals following implementation of a points-counting payment based on diagnosis-related group: a robust multiple interrupted time series study in Wenzhou, China

ObjectivesThis study measures the differences in inpatient performance after a points-counting payment policy based on diagnosis-related group (DRG) was implemented. The point value is dynamic; its change depends on the...

Evaluation of an automated feedback intervention to improve antibiotic prescribing among primary care physicians (OPEN Stewardship): a multinational controlled interrupted time-series study.

Tools to advance antimicrobial stewardship in the primary health care setting, where most antimicrobials are prescribed, are urgently needed. The aim of this study was to evaluate OPEN Stewarship (Online Platform for Expanding aNtibiotic Stewardship), an automated feedback intervention, among a cohort of primary care physicians. We performed a controlled, interrupted time-series study of 32 intervention and 725 control participants, consisting of primary care physicians from Ontario, Canada and Southern Israel, from October 2020 to December 2021. Intervention participants received three personalized feedback reports targeting several aspects of antibiotic prescribing. Study outcomes (overall prescribing rate, prescribing rate for viral respiratory conditions, prescribing rate for acute sinusitis, and mean duration of therapy) were evaluated using multilevel regression models. We observed a decrease in the mean duration of antibiotic therapy (IRR = 0.94; 95% CI: 0.90, 0.99) in intervention participants during the intervention period. We did not observe a significant decline in overall antibiotic prescribing (OR = 1.01; 95% CI: 0.94, 1.07), prescribing for viral respiratory conditions (OR = 0.87; 95% CI: 0.73, 1.03), or prescribing for acute sinusitis (OR = 0.85; 95% CI: 0.67, 1.07). In this antimicrobial stewardship intervention among primary care physicians, we observed shorter durations of therapy per antibiotic prescription during the intervention period. The COVID-19 pandemic may have hampered recruitment; a dramatic reduction in antibiotic prescribing rates in the months before our intervention may have made physicians less amenable to further reductions in prescribing, limiting the generalizability of the estimates obtained.IMPORTANCEAntibiotic overprescribing contributes to antibiotic resistance, a major threat to our ability to treat infections. We developed the OPEN Stewardship (Online Platform for Expanding aNtibiotic Stewardship) platform to provide automated feedback on antibiotic prescribing in primary care, where most antibiotics for human use are prescribed but where the resources to improve antibiotic prescribing are limited. We evaluated the platform among a cohort of primary care physicians from Ontario, Canada and Southern Israel from October 2020 to December 2021. The results showed that physicians who received personalized feedback reports prescribed shorter courses of antibiotics compared to controls, although they did not write fewer antibiotic prescriptions. While the COVID-19 pandemic presented logistical and analytical challenges, our study suggests that our intervention meaningfully improved an important aspect of antibiotic prescribing. The OPEN Stewardship platform stands as an automated, scalable intervention for improving antibiotic prescribing in primary care, where needs are diverse and technical capacity is limited.

Effectiveness of IT-supported patient recruitment: study protocol for an interrupted time series study at ten German university hospitals

BackgroundAs part of the German Medical Informatics Initiative, the MIRACUM project establishes data integration centers across ten German university hospitals. The embedded MIRACUM Use Case “Alerting in Care - IT Support for Patient Recruitment”, aims to support the recruitment into clinical trials by automatically querying the repositories for patients satisfying eligibility criteria and presenting them as screening candidates. The objective of this study is to investigate whether the developed recruitment tool has a positive effect on study recruitment within a multi-center environment by increasing the number of participants. Its secondary objective is the measurement of organizational burden and user satisfaction of the provided IT solution.MethodsThe study uses an Interrupted Time Series Design with a duration of 15 months. All trials start in the control phase of randomized length with regular recruitment and change to the intervention phase with additional IT support. The intervention consists of the application of a recruitment-support system which uses patient data collected in general care for screening according to specific criteria. The inclusion and exclusion criteria of all selected trials are translated into a machine-readable format using the OHDSI ATLAS tool. All patient data from the data integration centers is regularly checked against these criteria. The primary outcome is the number of participants recruited per trial and week standardized by the targeted number of participants per week and the expected recruitment duration of the specific trial. Secondary outcomes are usability, usefulness, and efficacy of the recruitment support. Sample size calculation based on simple parallel group assumption can demonstrate an effect size of d=0.57 on a significance level of 5% and a power of 80% with a total number of 100 trials (10 per site). Data describing the included trials and the recruitment process is collected at each site. The primary analysis will be conducted using linear mixed models with the actual recruitment number per week and trial standardized by the expected recruitment number per week and trial as the dependent variable.DiscussionThe application of an IT-supported recruitment solution developed in the MIRACUM consortium leads to an increased number of recruited participants in studies at German university hospitals. It supports employees engaged in the recruitment of trial participants and is easy to integrate in their daily work.

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

BackgroundThe 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.MethodsWe 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.ResultsOf 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.ConclusionsOur 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.