Using permutation tests to enhance causal inference in interrupted time series analysis.

Interrupted time series analysis (ITSA) is an evaluation methodology in which a single treatment unit's outcome is studied over time and the intervention is expected to "interrupt" the level and/or trend of the outcome. The internal validity is strengthened considerably when the treated unit is contrasted with a comparable control group. In this paper, we introduce a robust evaluation framework that combines the synthetic controls method (SYNTH) to generate a comparable control group and ITSA regression to assess covariate balance and estimate treatment effects. We evaluate the effect of California's Proposition 99 for reducing cigarette sales, by comparing California to other states not exposed to smoking reduction initiatives. SYNTH is used to reweight nontreated units to make them comparable to the treated unit. These weights are then used in ITSA regression models to assess covariate balance and estimate treatment effects. Covariate balance was achieved for all but one covariate. While California experienced a significant decrease in the annual trend of cigarette sales after Proposition 99, there was no statistically significant treatment effect when compared to synthetic controls. The advantage of using this framework over regression alone is that it ensures that a comparable control group is generated. Additionally, it offers a common set of statistical measures familiar to investigators, the capability for assessing covariate balance, and enhancement of the evaluation with a comprehensive set of postestimation measures. Therefore, this robust framework should be considered as a primary approach for evaluating treatment effects in multiple group time series analysis.

Variation in the technical support of radiation oncology in different practice settings

On 11 March 2020, the World Health Organization declared coronavirus disease 19 (COVID-19) a global pandemic. This exceptional situation changed the world not only in terms of mortality and morbidity, but also in terms of epidemiology and health system resources consumption. The objective of this work was to analyze the consumption of antibiotics during the period around the pandemic in our region. A drug utilization study was performed comparing the antibiotic consumption in the community during the years 2018, 2019, 2020, and 2021. Quarterly antibiotic use (defined daily doses (DDD) per 1000 inhabitants per day (DID)) and number of patients treated were the outcomes. Interrupted time series regression analysis was performed to estimate the statistical significance of the change in level of consumption before and after the COVID-19 pandemic. The drop of global antibiotic consumption was statistically significant, both in number of patients and in DID when analyzing pre-pandemic period versus pandemic period. The use of strategic antibiotics for respiratory infections such as amoxicillin, amoxicillin-clavulanic acid, and levofloxacin also decreased significantly. Seasonal pattern of use of antibiotics disappeared due to the global measures imposed over the world to work against COVID-19.

Public awareness of calories in food sold in retail establishments is a primary objective of the menu labeling law. This study explores the extent to which we can use social media and internet search queries to understand whether the federal calorie labeling law increased awareness of calories. To evaluate the association of the federal menu labeling law with tweeting about calories we retrieved tweets that contained the term “calorie(s)” from the CompEpi Geo Twitter Database from 1 January through 31 December in 2016 and 2018. Within the same time period, we also retrieved time-series data for search queries related to calories via Google Trends (GT). Interrupted time-series analysis was used to test whether the federal menu labeling law was associated with a change in mentions of “calorie(s)” on Twitter and relative search queries to calories on GT. Before the implementation of the federal calorie labeling law on 7 May 2018, there was a significant decrease in the baseline trend of 4.37 × 10−8 (SE = 1.25 × 10−8, p < 0.001) mean daily ratio of calorie(s) tweets. A significant increase in post-implementation slope of 3.19 × 10−8 (SE = 1.34 × 10−8 , p < 0.018) mean daily ratio of calorie(s) tweets was seen compared to the pre-implementation slope. An interrupted time-series (ITS) analysis showed a small, statistically significant upward trend of 0.0043 (SE = 0.036, p < 0.001) weekly search queries for calories pre-implementation, with no significant level change post-implementation. There was a decrease in trend of 1.22 (SE = 0.27, p < 0.001) in search queries for calories post-implementation. The federal calorie labeling law was associated with a 173% relative increase in the trend of mean daily ratio of tweets and a -28381% relative change in trend for search queries for calories. Twitter results demonstrate an increase in awareness of calories because of the addition of menu labels. Google Trends results imply that fewer people are searching for the calorie content of their meal, which may no longer be needed since calorie information is provided at point of purchase. Given our findings, discussions online about calories may provide a signal of an increased awareness in the implementation of calorie labels.

Florida House Bill 21 (HB21) was implemented in July 2018 to limit Schedule II opioids prescriptions for patients with acute pain to a 3-day supply. Little is known about the potential unintended effects that such opioid restriction policies may have on chronic pain patients, who are exempt from the law. We aimed to evaluate the effect of HB21 on opioid utilization measures among a cohort of chronic opioid therapy (COT) patients. A quasi-experimental design with interrupted time series analyses. Pharmacy claims from January 1, 2015 to June 31, 2019 from a large employer-based health plan in Florida. COT patients were those who received a ≥ 70 days' supply of opioids in the prior 90 days, representing 15,310 patients. Interrupted time series analyses were conducted to compare the following monthly measures among COT patients before and after HB21 implementation: 1) number of COT patients, 2) daily Morphine Milligram Equivalents [MMEs], 3) days' supply of prescriptions. There was a significant 25% reduction in the trend (pre-HB21 RR: 0.95, 95% CI: 0.93, 0.96 versus post-HB21 RR: 0.70, 95% CI: 0.65, 0.76) and an 8% immediate decrease (RR: 0.92, 95% CI: 0.88, 0.97) in the monthly prevalence of COT patients after HB21 implementation. However, no significant change was observed in trends for monthly number of days supplied per prescription, monthly MMEs per COT patient-day, or total MMEs per prescription. Our study used data from employer-based private health insurance and did not include a longer post-policy period to adjust for implementation lag. Fewer patients received COT after HB21; however, patients who continued to receive COT experienced no significant changes in their regimen. The study did not assess whether COT patients were appropriately tapered or if therapeutic alternatives were initiated for new chronic pain patients.

Implementation of the 2015 American Thyroid Association guideline changes across a health system: A quality improvement opportunity

06: Supracervical or total hysterectomy at the time of a laparoscopic colpopexy: national trends in surgical practice

IntroductionThis study evaluates the impact of an Internet of Things (IoT) intervention in a hospital unit and provides empirical evidence on the effects of smart technologies on patient safety (patient falls and hand hygiene compliance rate) and staff experiences.MethodWe have conducted a post-intervention analysis of hand hygiene (HH) compliance rate, and a pre-and post-intervention interrupted time-series (ITS) analysis of the patient falls rates. Lastly, we investigated staff experiences by conducting semi-structured open-ended interviews based on Roger’s Diffusion of Innovation Theory.ResultsThe results showed that (i) there was no statistically significant change in the mean patient fall rates. ITS analysis revealed non-significant incremental changes in mean patient falls (− 0.14 falls/quarter/1000 patient-days). (ii) HH compliance rates were observed to increase in the first year then decrease in the second year for all staff types and room types. (iii) qualitative interviews with the nurses reported improvement in direct patient care time, and a reduced number of patient falls.ConclusionThis study provides empirical evidence of some positive changes in the outcome variables of interest and the interviews with the staff of that unit reported similar results as well. Notably, our observations identified behavioral and environmental issues as being particularly important for ensuring success during an IoT innovation implementation within a hospital setting.

To determine whether the Diabetes Inpatient Care and Education (DICE) programme, a whole-systems approach to managing inpatient diabetes, reduces length of stay, in-hospital mortality and readmissions. Diabetes Inpatient Care and Education initiatives included identification of all diabetes admissions, a novel DICE care-pathway, an online system for prioritizing referrals, use of web-linked glucose meters, an enhanced diabetes team, and novel diabetes training for doctors. Patient administration system data were extracted for people admitted to Ipswich Hospital from January 2008 to June 2016. Logistic regression was used to compare binary outcomes (mortality, 30-day readmissions) 6 months before and after the intervention; generalized estimating equations were used to compare lengths of stay. Interrupted time series analysis was performed over the full 7.5-year period to account for secular trends. Before-and-after analysis revealed a significant reduction in lengths of stay for people with and without diabetes: relative ratios 0.89 (95% CI 0.83, 0.97) and 0.93 (95% CI 0.90, 0.96), respectively; however, in interrupted time series analysis the change in long-term trend for length of stay following the intervention was significant only for people with diabetes (P=0.017 vs P=0.48). Odds ratios for mortality were 0.63 (0.48, 0.82) and 0.81 (0.70, 0.93) in people with and without diabetes, respectively; however, the change in trend was not significant in people with diabetes, while there was an apparent increase in those without diabetes. There was no significant change in 30-day readmissions, but interrupted time series analysis showed a rising trend in both groups. The DICE programme was associated with a shorter length of stay in inpatients with diabetes beyond that observed in people without diabetes.

BackgroundEarly diagnosis is one of the mainstay of rheumatoid arthritis (RA) management. Early diagnosis reflects on early treatment, better response with reduction of long-term detrimental disease outcomes. Early arthritis clinics...

Impact of an Inpatient Allergy Guideline on β-Lactam and Alternative Antibiotic Use.

Background Infective endocarditis (IE) is associated with high mortality and complex microbiological profile. The antibiotic prophylaxis guidelines underwent a major revision in 2009 to reduce unnecessary antibiotic exposure. Substantial geographic variations in microbiological profiles exist, of which the understanding in an Asian population is lacking. Purpose We aim to describe the trends in the microbiology of IE in Hong Kong in the past 2 decades. Methods All patients aged 20 or above diagnosed with incident IE with blood culture results from 2000–2019 were included from a well-validated territory-wide database in Hong Kong, and were classified as 7 groups of causative organisms as shown in Figure 1. To evaluate the association between microbiology and 1-year all-cause death, a multivariable Cox proportional-hazards model was used, adjusted with demographics and comorbidities. Temporal trends in the proportion of each organism were characterised using Poisson regression. Interrupted time series analysis was used to evaluate the change in the organism-specific incidence after the revision of guidelines. Results In a total of 5,657 patients (age 59.9±18.3 years, 37.2% females), there were 2,185 (38.6%) patients with culture-negative endocarditis. Staphylococcus aureus (22.4%) and Streptococci (20.5%) were the most common organisms identified. Over time, there was a significant reduction in the proportion of culture-negative endocarditis (annual percentage change [APC] −2.3% [−2.8 to −1.7], P&amp;lt;0.001), and a significant increase in the proportion of endocarditis due to Staphylococcus aureus (APC 1.6% [0.7 to 2.4], P&amp;lt;0.001) and Streptococci (APC 2.3% [1.4 to 3.3], P&amp;lt;0.001) (Figure 1). After guidelines revision in 2009, there was no significant change in organism-specific incidence (all P-values for relative change&amp;gt;0.05). Compared to patients with culture-negative endocarditis, those infected with Staphylococcus aureus (hazard ratio [HR] 2.19 [1.94–2.47], P&amp;lt;0.001), other Staphylococci (HR 1.56 [1.20–2.01], P&amp;lt;0.001), Enterococci (HR 1.60 [1.25–2.05], P&amp;lt;0.001), other microorganisms (HR 1.30 [1.05–1.60], P=0.015), and mixed microorganisms (HR 2.40 [2.02–2.84], P&amp;lt;0.001) had a higher risk of 1-year all-cause death (Figure 2). There was a significant increase in the proportion of methicillin-resistant Staphylococcus aureus (MRSA) endocarditis (APC 4.1% [1.9 to 6.3], P&amp;lt;0.001), with no significant interval change after 2009. Patients infected with MRSA had a higher all-cause death (HR 2.00 [1.70–2.36], P&amp;lt;0.001). Conclusions Different causative organisms carry variable mortality signals in infective endocarditis. Over time, there were fewer cases of culture-negative endocarditis, and the revision of antibiotic prophylaxis guidelines did not result in a significant change in the microbiological profile. There was an increasing trend for MRSA endocarditis, which was associated with a higher risk of death. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The Shenzhen Key Medical DisciplineThe Sanming Project of HKU-SZH Cardiology

We evaluated the effect of an antibiotic stewardship programme (ASP) on the use of antibiotics and resistance levels of Escherichia coli using a method that allowed direct comparison between an intervention hospital and a control hospital. The study was conducted as a retrospective controlled interrupted time series (ITS) at two university teaching hospitals, intervention and control, with 736 and 552 beds, respectively. The study period was between January 2008 and September 2014. We used ITS analysis to determine significant changes in antibiotic use and resistance levels of E. coli. Results were directly compared with data from the control hospital utilizing a subtracted time series (STS). Direct comparison with the control hospital showed that the ASP was associated with a significant change in the level of use of cephalosporins [-151 DDDs/1000 bed-days (95% CI -177, -126)] and fluoroquinolones [-44.5 DDDs/1000 bed-days (95% CI -58.9, -30.1)]. Resistance of E. coli showed a significant change in slope for cefuroxime [-0.13 percentage points/month (95% CI -0.21, -0.057)] and ciprofloxacin [-0.15 percentage points/month (95% CI -0.26, -0.038)]. The ASP significantly reduced the use of cephalosporins and fluoroquinolones, with concomitant decreasing levels of E. coli resistance to cefuroxime and ciprofloxacin. The same development was not observed at the control hospital.

inhibitor (PPI) esomeprazole in the third copayment tier on the TRICARE formulary on July 17, 2005. The change to nonpreferred formulary status for esomeprazole included a $13 copayment increase (from $9.00 to $22.00) for either a 30-day supply purchased from a community pharmacy or a 90-day supply purchased from the mail-order pharmacy and a $0 copayment if obtained from a military pharmacy but with a prior authorization (PA) requirement. The change to nonpreferred formulary status was designed to encourage the use of PPIs other than esomeprazole and to increase the use of the mail-order pharmacy for esomeprazole purchases. To quantify changes in (a) the TRICARE beneficiary utilization of esomeprazole relative to other PPIs and (b) the pharmacy settings used for filling esomeprazole prescriptions following implementation of a copayment increase and nonpreferred formulary status for esomeprazole. A census of outpatient pharmacy fill records for prescription acid-reducing medications (PPIs, histamine-2 blockers, misoprostol, and sucralfate) obtained by beneficiaries aged 18 years or older from January 1, 2005, through December 31, 2006, was examined. Interrupted time series regression analyses without a control group were used to compare the utilization of esomeprazole relative to other PPIs, as well as the pharmacy setting used to obtain esomeprazole, in the months before and after the formulary change. The rates of continued esomeprazole use, switching to other prescription PPIs (lansoprazole, omeprazole, pantoprazole, and rabeprazole), switching to non-PPI prescription acid-reducing drugs, and discontinued prescription acid-reducing medication use among existing esomeprazole users (i.e., beneficiaries who obtained esomeprazole as the last PPI fill before the formulary change) were calculated overall and for each pharmacy setting used prior to the formulary change. Over the 24-month study period from January 1, 2005, through December 31, 2006, the total numbers of PPI fills and PPI users increased by 8.5% and 9.0%, respectively, and the number of esomeprazole users decreased by 4.6%. Of esomeprazole users, the percentages of individuals obtaining esomeprazole from military pharmacies and community pharmacies, respectively, decreased from 1.7% to 1.1% and from 89.7% to 81.7%, while the percentage of individuals obtaining esomeprazole from the mail-order pharmacy increased from 8.8% to 17.6%. Time series analysis yielded a positive, statistically significant growth in esomeprazole fills (beta1=0.114; P=0.012) during the 6-month pre-intervention period (January through June 2005) and a significant reduction in August 2005 (beta2=-5.0%; P<0.001), the month immediately following the formulary change. During the 17-month post-intervention period (August 2005 through December 2006), no statistically significant change in trend for esomeprazole fills (beta3=-0.0265; P=0.534) was observed, although a small increase in the raw number of esomeprazole fills was noted. Among the 117,801 existing esomeprazole users, 86,386 (73.3%) continued using esomeprazole, 17,676 (15.0%) switched to other prescription PPIs, 679 (0.6%) used only non- PPI prescription therapy, and 13,060 (11.1%) discontinued all prescription acid-reducing pharmacotherapy after the formulary change. Significantly higher PPI switching and acid-reducing therapy discontinuation rates were observed among men aged 18-44 years and in TRICARE enrollees relative to women, those over 45 years of age, and those who used other health insurance (P<0.001). Individuals who used military pharmacies, where a PA requirement was implemented, were more likely to change pharmacy settings to obtain esomeprazole (43.8%) than were users of community pharmacies (11.9%) or the mail-order pharmacy (22.8%). Mail-order pharmacy users were less likely to discontinue acid-reducing pharmacotherapy (4.9%) than were community (11.9%) or military (12.9%) pharmacy users (P<0.05). After adjustment for serial correlation, the formulary change was associated with a migration of approximately 5% of all PPI fills and 25% of esomeprazole fills to the preferred PPIs in the first post-intervention month. Over the 17-month post-intervention period, the trend toward increased esomeprazole use was slowed and use of the mail-order pharmacy for esomeprazole fills nearly doubled. Our observed PPI switch rate of 15.0% resembled the rate observed for another insured population that experienced a similar formulary restructuring, but was substantially lower than the rates reported for more sizeable formulary changes. Thus, the present study's copayment differentials for third-tier medications ($19 compared with tier 1 and $13 compared with tier 2 copayments) may be less than the threshold amount required to optimize switching to preferred PPIs.

Media guidelines for reporting on suicides are a widely used means of preventing imitative suicides, but scientific accounts of their impact on suicide numbers are sparse. This report provides an evaluation of the Austrian guidelines that were introduced in 1987 as a natural experiment. The impact of the guidelines was tested by applying an autoregressive integrated moving average (ARIMA) model and a linear regression model. In addition to a nationwide evaluation, Austria was divided into three areas according to regional differences in coverage rates of the collaborating newspapers and the impact of the intervention was tested for each area separately. Main outcome measures were the overall annual suicide numbers, and the numbers of Viennese subway suicides that were exceptionally newsworthy for the mass media. In order to test intermediate impacts, also quantitative and qualitative changes in media reporting after the introduction of the guidelines were analysed. There was some evidence of a nationwide impact of the guidelines, calculated as a significant reduction of 81 suicides (95% confidence interval: -149 to -13; t = -2.32, df = 54, p <0.024) annually. This effect was particularly due to a significant reduction in the area with the highest coverage rates of the collaborating newspapers. Viennese subway suicides showed a highly significant level shift (t = -4.44, df = 19, p <0.001) and a highly significant trend change (t = -4.20, df = 19, p <0.001) after the introduction of the guidelines. These effects corresponded to significant changes in the quality and quantity of media reporting. The present results clearly support the hypothesis that the media guidelines have had an impact on the quality of reporting as well as on suicidal behaviour in Austria, and stress the importance of collaborating with nationwide, but also with regional media to achieve efficacy. Further research is needed to provide an international insight into this public health issue.