Interrupted time series

Invasive candidiasis is a severe opportunistic infection whose incidence may be influenced by major disruptive events. The COVID-19 pandemic substantially altered hospital dynamics in Colombia. This study aimed to evaluate temporal trends, seasonality, and potential changes in the incidence of invasive candidiasis between 2019 and 2024. We conducted an observational time-series study using confirmed cases of invasive candidiasis from medium- and high-complexity hospitals in three major Colombian cities. Cases were aggregated quarterly. An interrupted time-series (ITS) analysis was performed. A total of 1294 cases were analyzed. An increasing trend was observed until mid-2022, followed by a decline during 2023. Seasonal decomposition revealed persistent seasonality with recurrent peaks in the second and fourth quarters. The ITS analysis did not demonstrate statistically significant changes in level or slope after the interruption (p > 0.05), although clinically relevant fluctuations were observed. No significant differences in temporal trends were identified across Candida species. Invasive candidiasis in Colombia exhibited a complex temporal evolution during and after the COVID-19 pandemic characterized by sustained seasonality and an increase followed by a decline. Although the ITS analysis did not identify statistically significant post-pandemic changes, the findings support the use of time-series models as valuable tools for epidemiological surveillance and trend monitoring.

In an interrupted time series (ITS) design, data are collected at multiple instances over time before and after an intervention to detect whether the intervention has an effect significantly greater than the underlying secular trend. We critically reviewed the methodological quality of ITS designs using studies included in two systematic reviews (a review of mass media interventions and a review of guideline dissemination and implementation strategies). Quality criteria were developed, and data were abstracted from each study. If the primary study analyzed the ITS design inappropriately, we reanalyzed the results by using time series regression. Twenty mass media studies and thirty-eight guideline studies were included. A total of 66% of ITS studies did not rule out the threat that another event could have occurred at the point of intervention. Thirty-three studies were reanalyzed, of which eight had significant preintervention trends. All of the studies were considered "effective" in the original report, but approximately half of the reanalyzed studies showed no statistically significant differences. We demonstrated that ITS designs are often analyzed inappropriately, underpowered, and poorly reported in implementation research. We have illustrated a framework for appraising ITS designs, and more widespread adoption of this framework would strengthen reviews that use ITS designs.

Background Direct-acting oral anticoagulants (DOACs) were developed as an alternative to warfarin to treat and prevent thromboembolism, including stroke prevention in non-valvular atrial fibrillation patients. The COVID-19 pandemic could increase the risk of stroke and/or the risk of bleeding in patients due to nonadherence or sub/supra-optimal dosing. Objective To investigate DOAC prescription trends in England’s community settings during the complete first wave of COVID-19 pandemic. Methods Descriptive and interrupted time series (ITS) analyses were conducted to examine the prescription patterns of DOACs (dabigatran, rivaroxaban, apixaban and edoxaban) and warfarin for primary care patients in the English Prescribing Dataset from January 2019 to February 2021, with March 2020 as the cut-off point. Results A 19% increase in mean DOAC’s accompanied with 20% warfarin prescriptions decline was observed. ITS modelling showed an increase in DOAC prescription volume in March 2020 (+7 million items, p = 0.008). The pre-existing upward trend in DOAC prescriptions slowed during the period (-427,000 items, p = 0.007). Apixaban was the most frequently used DOAC and had the largest step-change in March 2020 (+5 million items, p = 0.010). The mean monthly combined cost of DOACs and warfarin was higher during the period. DOAC prescription trends were consistent across England’s regions. Conclusion: The overall oral anticoagulants use in this period was lower than expected, indicating a medical needs gap, possibly due to adherence issues. The potential clinical and logistical consequences warrant further study to identify contributing factors and mitigate avoidable risks.

BackgroundSouth Africa implemented universal test and treat (UTT) in September 2016 in an effort to encourage earlier initiation of antiretroviral therapy (ART).MethodsWe therefore conducted an interrupted time series (ITS) analysis to assess the impact of UTT on mean CD4 count at ART initiation among adults aged ≥16 years attending 17 public sector primary care clinics in rural South Africa, between July 2014 and March 2019.ResultsAmong 20 599 individuals (69% women), CD4 counts were available for 74%. Mean CD4 at ART initiation increased from 317.1 cells/μL (95% confidence interval [CI], 308.6 to 325.6) 1 to 8 months prior to UTT to 421.0 cells/μL (95% CI, 413.0 to 429.0) 1 to 12 months after UTT, including an immediate increase of 124.2 cells/μL (95% CI, 102.2 to 146.1). However, mean CD4 count subsequently fell to 389.5 cells/μL (95% CI, 381.8 to 397.1) 13 to 30 months after UTT but remained above pre-UTT levels. Men initiated ART at lower CD4 counts than women (–118.2 cells/μL, 95% CI, –125.5 to –111.0) throughout the study.ConclusionsAlthough UTT led to an immediate increase in CD4 count at ART initiation in this rural community, the long-term effects were modest. More efforts are needed to increase initiation of ART early in those living with human immunodeficiency virus, particularly men.

Trauma team leader and early mortality: An interrupted time series analysis

ObjectivesIn healthcare systems, practices and products of unproven value and cost-effectiveness can decrease value and increase waste. Using the management of complex wounds, this study investigates temporal trends in the...

Hebei Province is one of China’s high-incidence regions for hemorrhagic fever with renal syndrome (HFRS), posing significant public health challenges. This study aims to evaluate the efficacy of key Hemorrhagic Fever with Renal Syndrome (HFRS) control measures. This study analyzed annual incidence data (1981–2024) and monthly data (2004–2024) using interrupted time series (ITS) analysis and the X-12 seasonal adjustment method. The X-12 procedure decomposes the series into trend, seasonal, and irregular components and removes seasonal variation to produce seasonally adjusted data. Specifically, we assessed the impact of two interventions: the 2002 Hebei Epidemic Hemorrhagic Fever Prevention and Control Plan and the 2008 Vaccination Work Plan for Key HFRS-endemic Counties in Hebei Province. The results demonstrated that before 2002, the HFRS incidence rate increased significantly at 28.8% annually (β₁ = 0.25, p < 0.01). After policy implementation, the trend reversed, with an annual decline of 32.0% (β₁ + β₃ = −0.117, p < 0.05), indicating effective control. Notably, epidemic peaks temporarily elevated incidence levels (β₄ = 0.83, p < 0.01). Following the 2008 vaccination program, short-term incidence rate reductions of 1.229 cases per 100,000 (β₂ = -1.229, p = 0.044) and 0.351 cases per 100,000 (β₂ = -0.351, p = 0.10) were observed in Qinhuangdao and Tangshan, respectively, though the latter was not statistically significant. Long-term trends revealed slower monthly declines of 0.003 cases per 100,000 in Qinhuangdao (β₁ + β₃ = −0.003, p = 0.049) and 0.002 cases per 100,000 in Tangshan (β₁ + β₃ = −0.002, p = 0.019). These findings highlight the differential effects of policy interventions on HFRS incidence, with the 2002 plan achieving sustained reduction, while the 2008 vaccination program showed limited long-term impact. Not applicable.

Background: In March 2018, the European pregnancy prevention programme for oral retinoids was updated as part of risk minimisation measures (RMM), emphasising their contraindication in pregnant women. Objective: To measure the impact of the 2018 revision of the RMMs in Europe by assessing the utilisation patterns of isotretinoin, alitretinoin and acitretin, contraceptive measures, pregnancy testing, discontinuation, and pregnancy occurrence concomitantly with a retinoid prescription. Methods: An interrupted time series (ITS) analysis to compare level and trend changes after the risk minimisation measures implementation was conducted on a cohort of females of childbearing age (12-55years of age) from January 2010 to December 2020, derived from six electronic health data sources in four countries: Denmark, Netherlands, Spain, and Italy. Monthly utilisation figures (incidence rates [IR], prevalence rates [PR] and proportions) of oral retinoids were calculated, as well as discontinuation rates, contraception coverage, pregnancy testing, and rates of exposed pregnancies to oral retinoids, before and after the 2018 RMMs. Results: From 10,714,182 females of child-bearing age, 88,992 used an oral retinoid at any point during the study period (mean age 18.9-22.2years old). We found non-significant level and trend changes in incidence or prevalence of retinoid use in females of child-bearing age after the 2018 RMMs. The reason of discontinuation was unknown in >95% of cases. Contraception use showed a significant increase trend in Spain; for other databases this information was limited. Pregnancy testing was hardly recorded thus was not possible to model ITS analyses. After the 2018 RMM, rates of pregnancy occurrence during retinoid use, and start of a retinoid during a pregnancy varied from 0.0 to 0.4, and from 0.2 to 0.8, respectively. Conclusion: This study shows a limited impact of the 2018 RMMs on oral retinoids utilisation patterns among females of child-bearing age in four European countries. Pregnancies still occur during retinoid use, and oral retinoids are still prescribed to pregnant women. Contraception and pregnancy testing information was limited in most databases. Regulators, policymakers, prescribers, and researchers must rethink implementation strategies to avoid any pregnancy becoming temporarily related to retinoid use.

The Chinese government has launched six rounds of national drug price negotiation since 2016 to lower the price and expand access to innovative drugs, many of which are anticancer drugs. This study aims to examine the effect of the second round of negotiation at the provincial level on the expenditure, volume, and availability of anti-cancer drugs. Procurement data at the provincial level from January 2017 to September 2018 were extracted from the China Drug Supply Information Platform (CDSIP). The volume, expenditure, and availability of three targeted anti-cancer drugs, rituximab, trastuzumab, and recombinant human endostatin (RHE), in 11 provinces that implemented the policy in September 2017 were analyzed through a controlled interrupted time series (ITS) analysis. A significant 6.0% increase (p < 0.1) in monthly average expenditure, an increase in the volume of 99.51 DDDs (defined daily doses) (p < 0.1), and a 0.24% (p < 0.1) increase in availability were observed for rituximab following the implementation of the policy. The volume and availability of rituximab increased by 949.6 DDDs (p < 0.05) and 1.56%, respectively, immediately after implementation. The availability of trastuzumab increased by 5.14% (p < 0.01) immediately after the implementation while no instant changes in expenditure and volume were observed. A 15% (p < 0.01) increase in monthly expenditure, 3673.17 DDDs increase in volume, and 0.66% increase in availability were observed after the inclusion of Trastuzumab. However, for RHE, only a 0.32% (p < 0.01) increase was observed after its inclusion. Eastern and middle provinces benefited more than western provinces. National negotiation related to the drug price significantly increased the volume and expenditure of anti-cancer drugs and improved their availability. The effect of the policy might be different across different regions and across different anticancer drugs.

<title>Abstract</title> <bold>Background</bold> : Unexplained changes from a study’s analysis plan may increase the risk of bias in study results and undermine confidence in the findings. Discrepancies in methods between protocols and reports have not been examined in interrupted time series (ITS) studies. <bold>Methods</bold> : We searched for peer-reviewed protocols of ITS studies in 22 databases, and results reports addressing each protocol’s primary research question. We compared 20 design and analysis items between protocols and their reports, classifying an item as ‘discrepant’ when the report provided different details about the item compared to the protocol. We judged a discrepancy as ‘potentially important’ if it could have potentially impacted the results or the study conclusion. We recorded if authors provided justifications for discrepancies. <bold>Results</bold> : From 4,590 abstracts, after excluding ongoing studies, we identified 120 eligible ITS protocols, from which 44 protocols (37%) had at least one corresponding results report. Information about handling the complexities of time-series data were frequently missing from the protocol or report, or both, for example, methods of adjusting for autocorrelation (77% of studies, 34/44) and seasonality (82%, 36/44). Potentially important discrepancies were common for eligibility criteria (43%, 19/44), overall length of time series (39%, 17/44), length of each time segment (45%, 20/44), effect measures (25%, 11/44) and ITS analysis methods (23%, 10/44). Among studies with important discrepancies, justifications were missing in 50%-100% of cases. <bold>Conclusion</bold> : Study designs and analysis methods were often not, or insufficiently, reported in ITS studies. Changes to original analysis plans were also prevalent and often unjustified, precluding readers from judging the legitimacy of the changes. Protocols for ITS studies should provide detailed information about the design and analysis methods. Deviations from planned methods should be transparently reported with clear justifications.

Background: This paper aims to promote the use of interrupted time series analyses of routine data as a responsive feedback tool to improve public health programs on an ongoing basis. This methodology is demonstrated by measuring the effect of a radio campaign to promote a family planning call center in Nigeria on the demand for family planning information and explains how the results were used to adapt the program. Methods: We used a single group interrupted time series design (ITS) as a responsive feedback mechanism to determine whether the radio campaign influenced use of the Honey&amp;Banana call center. ITS is ideal when a control group is not available and assumes that an interruption of the trend in the outcome measure occurs after the intervention starts. ITS uses the pre-intervention trend to predict what would have happened if the intervention were absent. Results: After conducting ITS analyses, the results show that the number of calls requesting family planning information increased throughout the campaign period, with a gain of about 500 additional calls per month, and then decreased after the campaign ended. However, the number of calls gained from the campaign was substantially lower than anticipated. Conclusions: While end-of-project impact evaluations are necessary, there should be regular feedback system to provide program implementers with information about the status of the project, such as failures, successes, and areas of improvements. This would allow implementers to make necessary adjustments as needed throughout the intervention period. The finding that the radio campaign was not living up to expectations helped program implementers to end the campaign prematurely and re-allocate resources to a more promising activity. Our research shows that basic ITS analysis of routine data can be a useful tool for receiving regular feedback to guide programming improvements.

Chronic hepatitis B virus (HBV) infection remains a major burden. The "Hot Wave Project," a hospital-wide initiative launched in 2022, aims to enhance HBV care by integrating patient education with systematic screening, referral, diagnosis, treatment, and follow-up. We conducted a comparative analysis of hospital-wide HBV care metrics between 2021 (preintervention) and 2024 (postintervention). An interrupted time series (ITS) analysis was conducted on monthly data to evaluate the causal impact of the intervention. A decision-analytic Markov model was used to simulate the cost-effectiveness and epidemiological impact of the project on a hypothetical cohort of one million patients. From 2021 to 2024, the HBsAg screening rate hospital-wide increased from 11.75% to 15.25%. Referrals of HBsAg-positive patients from nonhepatology departments surged from 9.26% to 17.87% (p < 0.0001), and the overall antiviral treatment rate rose from 71.00% to 80.25%. ITS analysis confirmed that the intervention caused significant immediate increases in screening and referral rates and a sustained acceleration in treatment uptake. Regular follow-up rates increased modestly from 59.96% to 61.5%. The model projected that the 2024 intervention levels would avert 17.4 HBV-related deaths per 100,000 person-years, yielding an incremental cost-effectiveness ratio (ICER) of $5688 per quality-adjusted life year (QALY) gained. The "Hot Wave Project" is a cost-effective and scalable hospital-based model that significantly improves the HBV care continuum. By enhancing interdisciplinary coordination, this approach offers an adaptable framework to help China advance toward its viral hepatitis elimination targets.

Studying the effect of primary health care development when simultaneously implemented with health insurance schemes assesses effectiveness and use of health care services and gives us insight on how to develop such interventions in different countries. To analyze the impact of health insurance and the family physician program on total hospitalizations, and the relation between avoidable hospitalizations and access to family physicians among the rural population in Iran. We conducted an interrupted time series (ITS) analysis of monthly hospitalization rates between the years of 2003 and 2014 to assess the immediate and gradual effects of these reforms on total hospitalization rates in the rural areas of Tehran province. In addition, we used a sample of 22 570 hospitalizations between 2006 and 2013 to develop a logistic regression model to measure the association between access to a family physician and avoidable hospitalizations. ITS analysis showed that there was an immediate increase of about 1.96 hospitalizations per 1000 inhabitants (P<0.0001, CI=1.58, 2.34) hospitalization rates after the reforms. This was followed by a significant increase of about 0.089 per 1000 inhabitants (P<0.0001, CI=0.07, 0.1). Hospitalization increase continued up to four years after the policy implementation. Following that, hospitalization rates decreased among the rural population (a decrease of 0.066 per 1000, P<0.0001, CI=-0.084, -0.048). Studying the hospitalizations that occurred between 2006 and 2013 showed that there were 4106 avoidable hospitalizations from among a sample of 22 570 hospitalizations. Results of logistic regression models including gender, age and access to family physician variables showed that there was no statistical relation between access to a family physician and avoidable hospitalizations. Reforms had access effect and caused increased hospital services uses in people with unmet needs. Also the reforms did not decrease avoidable hospitalizations, and therefore had no efficiency effect.

Benchmarking is an effective strategy to improve antibiotic use but remains underutilized in long-term care(LTC). In 2018, the Massachusetts Department of Public Health, in partnership with Tufts Medical Center, launched the Antibiotic Start(AS) Reporting Program, a statewide initiative to monitor and improve antibiotic prescribing in LTC facilities through monthly reporting and feedback, alongside other stewardship interventions. LTC facilities voluntarily submitted monthly AS data through an online platform. AS rates were calculated as AS per 1,000 resident-days. Quarterly benchmarking reports and educational activities(introduced in 2022), including LTC office hours webinars, were conducted to support interpretation and engagement. We conducted an interrupted time series(ITS) analysis to assess changes in beta-lactam and fluoroquinolone prescribing from 2018 to 2024, and a stratified analysis comparing AS rates between facilities with and without honor roll recognition. A total of 217 LTC facilities submitted ≥1 month of AS data. The overall AS rate rose 7%, from 7.22 to 7.70 per 1,000 resident-days. Fluoroquinolone starts decreased 36%, while beta-lactam starts increased 26%. ITS analysis showed a significant rise in beta-lactam use following the October 2022 expansion of benchmarking reports and LTC office hours(p<0.001). A subgroup analysis showed higher total and beta-lactam AS rates among honor roll facilities compared with non-recognized facilities. The Massachusetts AS Reporting Program demonstrates that sustained, data-driven public health-academic collaboration can advance antimicrobial stewardship in LTC. By combining benchmarking, feedback, education, and recognition, public health agencies can support stewardship engagement and promote sustainable improvement in antibiotic use across resource-limited settings.

Infectious diseases (ID) consultation and optimal antibiotic therapy improve outcomes in Staphylococcus aureus bacteremia (SAB). Data on strategies to improve adherence to these practices in children are limited. This was a quasi-experimental study evaluating the impact of an electronic medical record (EMR)-based best practice advisory (BPA) for SAB, recommending ID consult and optimal antibiotic therapy based on rapid mecA gene detection. Inpatients < 21 years old with SAB before (January 2015-July 2017) and after (August 2017-December 2018) BPA implementation were included. Primary outcome was receipt of ID consult. Secondary outcomes included receipt of optimal therapy, time to ID consult and optimal therapy, recurrent SAB, and 30-day all-cause mortality. ID consultation rates pre- and postimplementation were compared using interrupted time series (ITS) analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) for time to optimal therapy were calculated using Cox regression. We included 99 SAB episodes (70 preintervention, 29 postintervention). Preintervention, 48 (68.6%) patients received an ID consult compared to 27 (93.1%) postintervention, but this was not statistically significant on ITS analysis due to a preexisting trend of increasing consultation. Median hours to optimal therapy decreased from 26.1 to 5.5 (P = .03), most notably in patients with methicillin-sensitive S. aureus (MSSA) (42.2 to 10.8; P < .01). On Cox regression, BPA implementation was associated with faster time to optimal therapy (HR, 3.22 [95% CI, 1.04-10.01]). Implementation of an EMR-based BPA for SAB resulted in faster time to optimal antibiotic therapy, particularly for patients with MSSA. ID consultation increased throughout the study period and was not significantly impacted by the BPA.