Segmented Time-series Analysis Research Articles

Long-term effect of intravenous antimicrobial use in a pharmacist-led ASP at a small Japanese acute care hospital

Background: Antimicrobial resistance (AMR) remains a crucial, healthcare issue for which many countries have devised a national action plan. In Japan as well, antimicrobial stewardship programs (ASP) are being implemented in acute care hospitals under this policy framework. Clinical pharmacists play a central role in ASP, often jointly with infectious disease (ID) physicians. However, in Japan, a shortage of ID physicians has resulted in some ASP being led solely by pharmacists. While reports of the short-term effects of this situation are emerging, the long-term impact of pharmacist-led ASP is still largely unknown in Japan. The present study retrospectively examined the long-term effects of pharmacist-led ASP in a small, Japanese, acute care hospital. Method: The present study examined a pharmacist-led ASP in an acute care hospital (287 beds) in Japan which was launched in August 2015 and assessed the duration of therapy per 1000 patient-days (DOT) as the primary outcome by comparing the pre-intervention period (April 2013-July 2015) with the intervention period (August 2015-March 2023) using linear regression analysis. Additionally, segmented time-series analysis was conducted for each, additional intervention, and the impact of reduced activity due to the coronavirus disease 2019 (COVID-19) pandemic during the intervention. The DOT at the study center were compared with the national average of facilities implementing ASP. Result: While the DOT for all intravenous antimicrobials showed a slight increase on linear regression (r=0.01; P=0.1), the DOT of antipseudomonal intravenous antimicrobials significantly decreased (r=-0.027; P < 0 .01). Moreover, a significant reduction in DOT was observed immediately after the initiation of prospective review and feedback for carbapenems and daily prospective review and feedback for all intravenous antimicrobials (-3.2 and -2.4; P < 0 .001 for the intercept). An increase in DOT was observed during the COVID-19 pandemic-related reduction in activity time, and a rapid decline was observed upon the resumption of activities. Conversely, the average, nationwide DOT significantly increased for all intravenous antimicrobials as well as for antipseudomonal intravenous antimicrobials (r=0.02 and r=0.004; P < 0 .01) Conclusion: Sustaining an effective, pharmacist-led antimicrobial stewardship program led to a continual decrease in the DOT of antipseudomonal intravenous antimicrobials in a small, Japanese, acute care hospital despite a nationwide increase in their use following implementation of the national AMR action plan. Detailed analysis of pharmacists’ activities across multiple facilities is necessary to verify these effects.

Impact of COVID-19 pandemic on the utilization and quality of antibiotic use in the primary care setting in England, March 2019–March 2023: a segmented interrupted time series analysis of over 53 million individuals

ABSTRACT Background Amid the COVID-19 pandemic, we evaluated the short-term impact of COVID-19 on antibiotic use in primary care in England, focusing on both antibiotic quantity (overuse) and quality (misuse) of use. Research design and methods A population-based segmented interrupted analysis was applied on monthly dispensed antibiotics prescriptions using the Prescription Cost Analysis dataset (March/2019–March/2023). The quantity was assessed using number of items dispensed per 1000 inhabitants (NTI) and defined daily doses per 1000 inhabitants per day (DID), while quality was evaluated using WHO’s Access Watch Reserve (AWaRe) classification, the proportion of ‘4C’ antibiotics and the percentage of broad- to narrow-spectrum antibiotics. Results Findings indicate 8.6 (17.2%) and 0.4 (2.6%) increase in the NTI and DID, respectively, with a statistically significant uptick in trend noted after the second lockdown (β5) for ‘total antibiotics’ for NTI only (β5 = 1.6; 95% CI:0.17, 3.1). Quality assessment showed an increase in ‘Access’ antibiotics from 77% in March/2019 to 86% in March/2023; however, COVID-19 had no significant impact on WHO AWaRe classes. Conclusion COVID-19’s impact on antibiotic use quality and quantity appeared to be minimal, though an increase in utilization post-second lockdown coincided with healthcare system recovery. This suggests a nuanced impact of the pandemic, highlighting the importance of continued antimicrobial stewardship.

Learning design thinking well: organizing (introductory) workshops for optimal participant experience

A better understanding of the implementation of design thinking (DT) as a means to increase the assimilation of its practices is an important concern for R&D and innovation managers because more frequent use of DT practices raises organizational innovative capabilities. Introducing DT practices in workshops is a common, but also challenging approach to learning DT. Participants often have little to no prior encounters with the tools, techniques and principles used to practice DT and often mistrust or misinterpret the DT concept after a bad experience during the first exposure. For that reason, a suboptimal experience in introductory workshops can prevent or reduce the assimilation of DT practices. This study investigates how participant experience during first exposure as a vital precursor to the assimilation of DT practices can be improved via the organization of introductory workshops. We examine flow as the core experience measure in a quantitative‐inductive, quasi‐experimental study of two 3‐day DT workshops and compare periods with step‐by‐step acquisition of DT practices under guidance, periods of flexible, independent application of DT practices and periods of recovery. Our research employs a segmented time series analysis on more than 1100 real‐time observations collected with the experience sampling method (ESM). This study contributes to the scarce empirical research on improving the implementation of DT practices by indicating that a positive initial experience depends on workshop length, the logic of guided periods, the combination of guided and unguided periods, timing and type of recovery, as well as on team formation. Our results lead to five organizing principles, which can be used as testable propositions for future research, as well as in the planning and execution of (introductory) DT workshops.

Time series analysis of daily reported number of new positive cases of COVID-19 in Japan from January 2020 to February 2023.

This study investigated temporal variations of the COVID-19 pandemic in Japan using a time series analysis incorporating maximum entropy method (MEM) spectral analysis, which produces power spectral densities (PSDs). This method was applied to daily data of COVID-19 cases in Japan from January 2020 to February 2023. The analyses confirmed that the PSDs for data in both the pre- and post-Tokyo Olympics periods show exponential characteristics, which are universally observed in PSDs for time series generated from nonlinear dynamical systems, including the so-called susceptible/exposed/infectious/recovered (SEIR) model, well-established as a mathematical model of temporal variations of infectious disease outbreaks. The magnitude of the gradient of exponential PSD for the pre-Olympics period was smaller than that of the post-Olympics period, because of the relatively high complex variations of the data in the pre-Olympics period caused by a deterministic, nonlinear dynamical system and/or undeterministic noise. A 3-dimensional spectral array obtained by segment time series analysis indicates that temporal changes in the periodic structures of the COVID-19 data are already observable before the commencement of the Tokyo Olympics and immediately after the introduction of mass and workplace vaccination programs. Additionally, the possibility of applying theoretical studies for measles control programs to COVID-19 is discussed.

National increase in the community supply of take‐home naloxone associated with a mass media campaign in Scotland: a segmented time series analysis

BackgroundTake-home naloxone (THN) programmes have been associated with reductions in opioid-related mortality. In response to high rates of drug-related deaths in Scotland, the Scottish Government commissioned the ‘How to save a life’ (HTSAL) mass media campaign to: (1) increase awareness of drug-related deaths and how to respond to an overdose, and (2) increase the supply of THN. The aim of this study was to assess the effect of the campaign on the supply of THN. MethodsWe used an interrupted time series design to assess the effect of the HTSAL mass media campaign on the national community supply of THN. The study time period was August 2020–December 2021. We modelled two key dates: the start of the campaign (week beginning (w/b) 30th of August 2021) and after the end of the main campaign (w/b 25th of October 2021). ResultsThe total number of THN kits distributed in the community in Scotland during the study period was 27,064. The mean number of THN kits distributed per week (relative to the pre-campaign period), increased by 126% during the campaign and 57% post-campaign. In segmented regression analyses, the pre-campaign trend in the number of THN kits supplied was increasing by an average of 1% each week (RR=1.01, 95% CI 1.01 to 1.01, p<0.001). Once the campaign started, a significant change in level was observed, and the number of kits increased by 75% (RR=1.75, 95% CI 1.29 to 2.40, p<0.001). The trend during the campaign was stable (i.e. not increasing or decreasing) but a significant change in level was observed when the campaign ended, and the number of THN kits supplied decreased by 32% (RR=0.68, 95% CI 0.46 to 0.98, p = 0.042). The trend during the post-campaign period was stable. ConclusionsThe HTSAL campaign had a short term, but large and significant impact, on the community supply of THN in Scotland. Mass media campaigns could be combined with other interventions and strategies to maintain the increased uptake of THN outside of campaign periods.

Evaluation of duration of antibiotic therapy across hospitals in Scotland including the impact of COVID-19 pandemic: a segmented interrupted time series analysis

Background Little is known about the duration of antibiotic use in hospital settings. We evaluated the duration of hospital antibiotic therapy (as a quality indicator proxy) for four commonly prescribed antibiotics (amoxicillin, co-amoxiclav, doxycycline and flucloxacillin) including the assessment of COVID-19 impact. Methods A repeated, cross-sectional study using the Hospital Electronic Prescribing and Medicines Administration system (January/2019-March/2022). Monthly median duration of therapy/duration categories were calculated, stratified by routes of administration, age and sex. Impact of COVID-19 was assessed using segmented time-series analysis. Results There were significant variations in the median duration of therapy across routes of administration (P<0.05), with the highest value among those antibiotic courses comprised of both oral and IV antibiotics (“Both” group). Significantly higher proportions of prescriptions within the “Both” group had a duration of > 7 days compared to oral or IV. Duration of therapy overall differed significantly by age. Some small statistically significant changes in the level/trends of duration of therapy were observed in the post- COVID-19 period. Conclusions No evidence for prolonged duration of therapy were observed, even during COVID-19 pandemic. Duration of IV therapy was relatively short suggesting timely clinical review and consideration of IV to oral switch. Longer duration of therapy was observed among older patients.

COVID-19-related healthcare impacts: an uncontrolled, segmented time-series analysis of tuberculosis diagnosis services in Mozambique, 2017–2020

IntroductionCurrently, COVID-19 dominates the public health agenda and poses a permanent threat, leading to health systems’ exhaustion and unprecedented service disruption. Primary healthcare services, including tuberculosis services, are at increased...

Clinical Trials Increase Off-Study Drug Use: A Segmented Time-Series Analysis.

BackgroundThe effect of participation in a clinical trial on concomitant off-study investigational drug use has not been described. We sought to determine if participation in the Daptomycin as Adjunctive Therapy for Staphylococcus aureus bacteremia (DASH) trial increased overall daptomycin prescribing at study sites.MethodsWe retrospectively analyzed daptomycin use for 8 years preceding the trial, off-study daptomycin use during the trial itself (31 months), and daptomycin use for 6 fiscal months after trial completion. We used a segmented linear regression analysis of an interrupted time series to analyze changes in each drug’s defined daily doses (DDD) per 1000 patient-days. As a control, we analyzed use of linezolid over these periods and also accounted for rates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) infections.ResultsFor 1.5 years before the DASH trial, daptomycin use was decreasing by –0.30 DDD per 1000 patient-days per fiscal period (95% CI, –0.52 to –0.07). Following the initiation of the study, there was a statistically significant increase in daptomycin use of 0.28 DDD per 1000 patient-days per fiscal period (95% CI, 0.03 to 0.52), despite low, stable rates of MRSA and VRE infections. Following trial completion, daptomycin use decreased back toward prestudy rates. Use of linezolid remained stable throughout.ConclusionsDespite the DASH trial being a negative study, it impacted the prescribing habits of local clinicians during recruitment. Trialists should be aware of potential off-target study effects, and prescribers should be wary of early uptake of interventions before definitive study results.

Sustainability of Handshake Stewardship: Extending a Hand Is Effective Years Later.

Children's Hospital Colorado created a unique method of antimicrobial stewardship, called handshake stewardship, that effectively decreased hospital anti-infective use and costs in its pilot year (2013). Handshake stewardship is distinguished by: (1) the lack of prior authorization; (2) a review of all prescribed anti-infectives; (3) a shared review by the physician and the pharmacist; and (4) a daily, rounding-based, in-person approach to supporting providers. We sought to reevaluate the outcomes of the program after 5 years of experience, totaling 8 years of data. We retrospectively measured anti-infective (antibiotic, antiviral, antifungal) use hospital-wide by unit and by drug for an 8-year period spanning October 2010 to October 2018. Aggregated monthly use was measured in days of therapy per thousand patient days (DOT/1000 PD). The percentage of children admitted ever receiving an anti-infective was also measured, as well as severity-adjusted mortality, readmissions, and lengths of stay. Hospital-wide mean anti-infective use significantly decreased, from 891 (95% confidence interval [CI] 859-923) in the pre-implementation phase to 655 (95% CI 637-694) DOT/1000 PD in post-implementation Year 5; in a segmented regression time series analysis, this was a rate of -2.6 DOT/1000 PD (95% CI -4.8 to -0.4). This is largely attributable to decreased antibacterial use, from 704 (95% CI 686-722) to 544 (95% CI 525 -562) DOT/1000 PD. The percentage of children ever receiving an anti-infective during admission likewise declined, from 65% to 52% (95% CI 49-54). There were no detrimental effects on severity adjusted mortality, readmissions, or lengths of stay. The handshake method is an effective and sustainable approach to stewardship.

How to assess the impact of process improvement interventions with routinely collected longitudinal hospital data

Objective: To show how interrupted time series can be used to isolate and measure the impact of process improvement while accounting for confounders often present in complex hospital operations. Methods: Retrospective cohort study comparing the volume of operating room exit delays (OR holds) 52 weeks before and 62 weeks after implementation of a surgical patient throughput optimization program at a tertiary academic hospital. Time-stamped electronic medical records data were collected and analyzed using interrupted time-series design. Segmented regression and Box-Jenkins time series analysis were used to measure OR hold volume pre- and post-implementation, controlling for secular trends in surgical volume, downstream capacity, and the loss of high-volume surgeons. Results: A total of 8,983 surgical patients were discharged during the pre-intervention period and 9,855 during the post-intervention period. The median weekly discharge volume pre-intervention was 175 (interquartile range [IQR] 164–180), and the median bed occupancy was 86% (IQR 84.6–88.1%). The median weekly discharge volume post-intervention was 163 (IQR 150.5–169.8), and the median bed occupancy was 82.1% (IQR 78.9–84.7%). Post-intervention, there was an immediate 60% (95% confidence interval, 54–70%) reduction in the number of OR holds that was sustained over the 14-month post-intervention period.

1841. Implementation of an Outpatient Antimicrobial Stewardship Program to Reduce Fluoroquinolone Overprescribing at a Veterans Affairs Medical Center (VAMC)

BackgroundFluoroquinolones are often overprescribed in outpatient settings; however, stewardship programs designed to prevent overuse are not well described. The primary purpose of this study was to evaluate the change in overall and appropriate fluoroquinolone prescribing rates by primary care providers within internal medicine primary care clinics at the Houston VAMC before and after implementation of an audit and feedback intervention.MethodsAll fluoroquinolone prescriptions written by internal medicine primary care providers were included in this study. A medical chart audit to assess the appropriateness of fluoroquinolone prescriptions was conducted, and face to face feedback was given to providers regarding prescribing patterns. Aggregate monthly fluoroquinolone utilization data were also provided. Monthly face to face academic detailing sessions were provided regarding the treatment of common outpatient infectious diseases, appropriate fluoroquinolone use, and suggested alternatives. Study objectives were assessed before and after the intervention time period using segmented regression time series analysis including non-intervention internal medicine primary care comparator clinics.ResultsIn the intervention clinics, rates of fluoroquinolone orders decreased from 9.4 ± 5.8 orders per week per 1,000 patient visits in the pre-intervention time period to 6.9 ± 6.6 orders per week per 1,000 patient visits in the post-intervention time periods. Using segmented regression analysis, controlling for change in prescribing rates in the non-intervention clinics, and changes in the rate of prescribing over time, the intervention was associated with a 3.1 ± 0.99 decrease in fluoroquinolone orders per week per 1,000 patient visits (P = 0.0019). The percentage of orders deemed appropriate increased from 50 ± 31% in the pre-intervention time period to 66 ± 53% in the post-intervention time period (P = 0.06). Rates of fluoroquinolone orders did not change in the non-intervention clinics.ConclusionAn audit and feedback intervention in ambulatory care clinics was able to reduce the rate of fluoroquinolone orders and increase the percent of orders deemed appropriate.Disclosures All authors: No reported disclosures.

Effectiveness of India's National Programme to save the girl child: experience of Beti Bachao Beti Padao (B3P) programme from Haryana State.

The Government of India launched a nationwide programme to save and educate the girl child, Beti Bachao Beti Padhao (B3P), by stringent prohibition of sex-selective abortion, enforcement of Preconception and Prenatal Diagnostic Technique (PC-PNDT) and Medical Termination of Pregnancy (MTP) Acts, and social mobilization. We undertook this study to assess the effectiveness of intervention in Haryana state to improve sex ratio at birth (SRB). The monthly data on SRB (represented as girls per 1000 boys) were collected from civil registration system for the entire state of Haryana to evaluate the impact of B3P programme. The segmented time-series regression analysis was used to estimate the change in SRB after B3P programme. In this process, the seasonal auto regressive integrated moving average model was used to control the seasonality, autocorrelation and secular trend imbibed in the data before calculating the estimate of change in slope using regression equation. Overall, the sex ratio at birth in Haryana increased from 827 girls per 1000 boys in January 2005 to 900 girls per 1000 boys in September 2016. The estimates from segmented time-series regression analysis show that there was an insignificant change in SRB of -0.012 units before the intervention. Post slope was estimated to be 1.684, which suggested an increase in SRB of 1.696 [(confidence interval: 0.23, 3.15), P = 0.025] in terms of the difference between pre- and post-slope. This indicates a statistically significant increase of SRB by 1.696 per month attributable to B3P programme. B3P programme has resulted in an improvement of SRB in Haryana.

Quasi-experimental Studies in the Fields of Infection Control and Antibiotic Resistance, Ten Years Later: A Systematic Review.

OBJECTIVE A systematic review of quasi-experimental studies in the field of infectious diseases was published in 2005. The aim of this study was to assess improvements in the design and reporting of quasi-experiments 10 years after the initial review. We also aimed to report the statistical methods used to analyze quasi-experimental data. DESIGN Systematic review of articles published from January 1, 2013, to December 31, 2014, in 4 major infectious disease journals. METHODS Quasi-experimental studies focused on infection control and antibiotic resistance were identified and classified based on 4 criteria: (1) type of quasi-experimental design used, (2) justification of the use of the design, (3) use of correct nomenclature to describe the design, and (4) statistical methods used. RESULTS Of 2,600 articles, 173 (7%) featured a quasi-experimental design, compared to 73 of 2,320 articles (3%) in the previous review (P<.01). Moreover, 21 articles (12%) utilized a study design with a control group; 6 (3.5%) justified the use of a quasi-experimental design; and 68 (39%) identified their design using the correct nomenclature. In addition, 2-group statistical tests were used in 75 studies (43%); 58 studies (34%) used standard regression analysis; 18 (10%) used segmented regression analysis; 7 (4%) used standard time-series analysis; 5 (3%) used segmented time-series analysis; and 10 (6%) did not utilize statistical methods for comparisons. CONCLUSIONS While some progress occurred over the decade, it is crucial to continue improving the design and reporting of quasi-experimental studies in the fields of infection control and antibiotic resistance to better evaluate the effectiveness of important interventions. Infect Control Hosp Epidemiol 2018;39:170-176.

Impact of the Mass Drug Administration for malaria in response to the Ebola outbreak in Sierra Leone.

BackgroundAs emergency response to the Ebola epidemic, the Government of Sierra Leone and its partners implemented a large-scale Mass Drug Administration (MDA) with artesunate–amodiaquine (ASAQ) covering >2.7 million people in the districts hardest hit by Ebola during December 2014–January 2015. The World Health Organization (WHO) and the National Malaria Control Programme (NMCP) evaluated the impact of the MDA on malaria morbidity at health facilities and the number of Ebola alerts received at District Ebola Command Centres.MethodsThe coverage of the two rounds of MDA with ASAQ was estimated by relating the number anti-malarial medicines distributed to the estimated resident population. Segmented time-series analysis was applied to weekly data collected from 49 primary health units (PHUs) and 11 hospitals performing malaria parasitological testing during the study period, to evaluate trends of malaria cases and Ebola alerts during the post-MDA weeks compared to the pre-MDA weeks in MDA- and non-MDA-cheifdoms.ResultsAfter two rounds of the MDA, the number of suspected cases tested with rapid diagnostic test (RDT) decreased significantly by 43 % (95 % CI 38–48 %) at week 1 and remained low at week 2 and 3 post-first MDA and at week 1 and 3 post-second MDA; RDT positive cases decreased significantly by 47 % (41–52 %) at week 1 post-first and remained lower throughout all post-MDA weeks; and the RDT test positivity rate (TPR) declined by 35 % (32–38 %) at week 2 and stayed low throughout all post-MDA weeks. The total malaria (clinical + confirmed) cases decreased significantly by 45 % (39–52 %) at week 1 and were lower at week 2 and 3 post-first MDA; and week 1 post-second MDA. The proportion of confirmed malaria cases (out of all-outpatients) fell by 33 % (29–38 %) at week 1 post-first MDA and were lower during all post-MDA weeks. On the contrary, the non-malaria outpatient cases (cases due to other health conditions) either remained unchanged or fluctuated insignificantly. The Ebola alerts decreased by 30 % (13–46 %) at week 1 post-first MDA and much lower during all the weeks post–second MDA.ConclusionsThe MDA achieved its goals of reducing malaria morbidity and febrile cases that would have been potentially diagnosed as suspected Ebola cases with increased risk of nosocomial infections. The intervention also helped reduce patient case-load to the severely strained health services at the peak of the Ebola outbreak and malaria transmission. As expected, the effect of the MDA waned in a matter of few weeks and malaria intensity returned to the pre-MDA levels. Nevertheless, the approach was an appropriate public health intervention in the context of the Ebola epidemic even in high malaria transmission areas of Sierra Leone.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-016-1493-1) contains supplementary material, which is available to authorized users.

Impact of pneumococcal conjugate vaccine in children morbidity and mortality in Peru: Time series analyses

Streptococcus pneumoniae is the leading cause of bacterial pneumonia, meningitis and sepsis in children worldwide. Despite available evidence on pneumococcal conjugate vaccine (PCV) impact on pneumonia hospitalizations in children, studies demonstrating PCV impact in morbidity and mortality in middle-income countries are still scarce. Given the disease burden, PCV7 was introduced in Peru in 2009, and then switched to PCV10 in late 2011. National public healthcare system provides care for 60% of the population, and national hospitalization, outpatient and mortality data are available.We thus aimed to assess the effects of routine PCV vaccination on pneumonia hospitalization and mortality, and acute otitis media (AOM) and all cause pneumonia outpatient visits in children under one year of age in Peru.We conducted a segmented time-series analysis using outcome-specific regression models. Study period was from January 2006 to December 2012. Data sources included the National information systems for hospitalization, mortality, outpatient visits, and RENACE, the national database of aggregated weekly notifications of pneumonia and other acute respiratory diseases (both hospitalized and non-hospitalized). Study outcomes included community acquired pneumonia outpatient visits, hospitalizations and deaths (ICD10 codes J12-J18); and AOM outpatient visits (H65-H67). Monthly age- and sex-specific admission, outpatient visit, and mortality rates per 100,000 children aged <1year, as well as weekly rates for pneumonia and AOM recorded in RENACE were estimated.After PCV introduction, we observed significant vaccine impact in morbidity and mortality in children aged <1year. Vaccine effectiveness was 26.2% (95% CI 16.9–34.4) for AOM visits, 35% (95% CI 8.6–53.8) for mortality due to pneumonia, and 20.6% (95% CI 10.6–29.5) for weekly cases of pneumonia hospitalization and outpatient visits notified to RENACE. We used secondary data sources which are usually developed for other non-epidemiologic purposes. Despite some data limitations, our results clearly demonstrate the overall benefit of PCV vaccination in Peru.

Did FDA Decisionmaking Affect Anti-Psychotic Drug Prescribing in Children?: A Time-Trend Analysis.

BackgroundFollowing Food and Drug Administration (FDA) approval, many drugs are prescribed for non-FDA-approved (“off-label”) uses. If substantial evidence supports the efficacy and safety of off-label indications, manufacturers can pursue formal FDA approval through supplemental new drug applications (sNDAs). We evaluated the effect of FDA determinations on pediatric sNDAs for antipsychotic drugs on prescribing of these products in children.MethodsRetrospective, segmented time-series analysis using new prescription claims during 2003–2012 for three atypical antipsychotics (olanzapine, quetiapine, ziprasidone). FDA approved the sNDAs for pediatric use of olanzapine and quetiapine in December 2009, but did not approve the sNDA for pediatric use of ziprasidone.ResultsDuring the months before FDA approval of its pediatric sNDA, new prescriptions of olanzapine decreased for both children and adults. After FDA approval, the increase in prescribing trends was similar for both age groups (P = 0.47 for schizophrenia and bipolar disorder; P = 0.37 for other indications). Comparable decreases in use of quetiapine were observed between pediatrics and adults following FDA approval of its pediatric sNDA (P = 0.88; P = 0.63). Prescribing of ziprasidone decreased similarly for pediatric and adult patients after FDA non-approval of its pediatric sNDA (P = 0.61; P = 0.79).ConclusionsThe FDA’s sNDA determinations relating to use of antipsychotics in children did not result in changes in use that favored the approved sNDAs and disfavored the unapproved sNDA. Improved communication may help translate the agency’s expert judgments to clinical practice.

Impact of Policies on the Rise in Sepsis Incidence, 2000-2010.

Sepsis hospitalizations have increased dramatically in the last decade. It is unclear whether this represents an actual rise in sepsis illness or improved capture by coding. We evaluated the impact of Centers of Medicare and Medicaid Services (CMS) guidance after newly introduced sepsis codes and medical severity diagnosis-related group (MS-DRG) systems on sepsis trends. In this retrospective cohort study of California hospitalizations from January 2000 to December 2010, sepsis was identified by International Classification of Diseases, Ninth Revision (ICD-9) coding (Dombrovskiy method). Sepsis-associated mortality rates were calculated. Logistic regression models evaluated variables associated with sepsis and mortality. Segmented regression time series analysis assessed changes in sepsis frequency for (1) baseline (January 2000 to September 2003); (2) post-CMS guidelines on sepsis coding (October 2003 to September 2007); and (3) after the introduction of MS-DRG (October 2007 to December 2010). Annual hospitalizations with sepsis diagnoses tripled within a decade, from 21.1 to 59.9 cases per 1000 admissions, with a 2.8- and 2.0-fold increase in severe and nonsevere sepsis, respectively, whereas annual admissions remained unchanged and sepsis-associated mortality decreased. Greatest increases were seen for severe sepsis present on admission (3.8-fold increase). Increases in sepsis were temporally correlated with CMS coding guidance and MS-DRG introduction after adjustment for comorbidity and other factors. Sepsis rate increases were associated with introduction of CMS-issued guidance for new sepsis ICD-9 coding and MS-DRGs. Coding artifact ("up-capture" of less severely ill septic patients) may be contributing to the apparent rise in sepsis incidence and decline in mortality. Epidemiologic trends based on administrative data should account for policy-related effects.

The impact of the 'Better Care Better Value' prescribing policy on the utilisation of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for treating hypertension in the UK primary care setting: longitudinal quasi-experimental design.

BackgroundIn April/2009, the UK National Health Service initiated four Better Care Better Value (BCBV) prescribing indicators, one of which encouraged the prescribing of cheaper angiotensin-converting enzyme inhibitors (ACEIs) instead of expensive angiotensin receptor blockers (ARBs), with 80 % ACEIs/20 % ARBs as a proposed, and achievable target. The policy was intended to save costs without affecting patient outcomes. However, little is known about the actual impact of the BCBV indicator on ACEIs/ARBs utilisation and cost-savings. Therefore, this study aimed to evaluate the impact of BCBV policy on ACEIs/ARBs utilisation and cost-savings, including exploration of regional variations of the policy’s impact.MethodsThis cross-sectional study used data from the UK Clinical Practice Research Datalink. Segmented time-series analysis was applied to monthly ACEIs prescription proportion, adjusted number of ACEIs/ARBs prescriptions and costs.ResultsOverall, the proportion of ACEIs prescription decreased during the study period from 71.2 % in April/2006 to 70.7 % in March/2012, with a small but a statistically significant pre-policy reduction in its monthly trend of 0.02 % (p < 0.001). Instantly after its initiation, the policy was associated with a sudden reduction in the proportion of ACEIs prescription; however, it resulted in a statistically significant increase in the post-policy monthly trend of ACEIs prescription proportion of 0.013 % (p < 0.001), resulting in an overall post-policy slope of −0.007 %. Despite this post-policy induced increment, the policy failed to achieve the 80 % target, which resulted in missing a potential cost-saving opportunity. The pre-policy trend of the adjusted number of ACEIs/ARBs prescriptions was increasing; however, their trends declined after the policy implementation. The policy affected neither total ACEIs/ARBs cost nor individual ACEIs or ARBs costs.ConclusionsACEIs/ARBs utilisation was not affected by the BCBV policy. The small increase in post-policy ACEIs prescription proportion was not associated with any savings. This study represents a case study of a failed or ineffective policy and thus provides key learning lessons for other healthcare authorities. Given the existing opportunity of potential cost-savings from achieving the 80 % target, specific measures would be needed to enhance the policy implementation and uptake; however, this must be balanced against other cost-saving policies in other high-priority areas.Electronic supplementary materialThe online version of this article (doi:10.1186/s12913-015-1013-y) contains supplementary material, which is available to authorized users.

Alcopops, taxation and harm: a segmented time series analysis of emergency department presentations.

BackgroundIn Australia, a Goods and Services Tax (GST) introduced in 2000 led to a decline in the price of ready-to-drink (RTD) beverages relative to other alcohol products. The 2008 RTD (“alcopops”) tax increased RTD prices. The objective of this study was to estimate the change in incidence of Emergency Department (ED) presentations for acute alcohol problems associated with each tax.MethodsSegmented regression analyses were performed on age and sex-specific time series of monthly presentation rates for acute alcohol problems to 39 hospital emergency departments across New South Wales, Australia over 15 years, 1997 to 2011. Indicator variables represented the introduction of each tax. Retail liquor turnover controlled for large-scale economic factors such as the global financial crisis that may have influenced demand. Under-age (15–17 years) and legal age (18 years and over) drinkers were included.ResultsThe GST was associated with a statistically significant increase in ED presentations for acute alcohol problems among 18–24 year old females (0 · 14/100 000/month, 95% CI 0 · 05-0 · 22). The subsequent alcopops tax was associated with a statistically significant decrease in males 15–50 years, and females 15–65 years, particularly in 18–24 year old females (−0 · 37/100 000/month, 95% CI −0 · 45 to −0 · 29). An increase in retail turnover of liquor was positively and statistically significantly associated with ED presentations for acute alcohol problems across all age and sex strata.ConclusionsReduced tax on RTDs was associated with increasing ED presentations for acute alcohol problems among young women. The alcopops tax was associated with declining presentations in young to middle-aged persons of both sexes, including under-age drinkers.

Impact of abuse-deterrent OxyContin on prescription opioid utilization.

We quantified the degree to which the August 2010 reformulation of abuse-deterrent OxyContin affected its use, as well as the use of alternative extended-release and immediate-release opioids. We used the IMS Health National Prescription Audit, a nationally representative source of prescription activity in the USA, to conduct a segmented time-series analysis of the use of OxyContin and other prescription opioids. Our primary time period of interest was 12 months prior to and following August 2010. We performed model checks and sensitivity analyses, such as adjusting for marketing and promotion, using alternative lag periods, and adding extra observation points. OxyContin sales were similar before and after the August 2010 reformulation, with approximately 550 000 monthly prescriptions. After adjusting for declines in the generic extended-release oxycodone market, the formulation change was associated with a reduction of approximately 18 000 OxyContin prescription sales per month (p = 0.02). This decline corresponded to a change in the annual growth rate of OxyContin use, from 4.9% prior to the reformulation to -23.8% during the year after the reformulation. There were no statistically significant changes associated with the sales of alternative extended-release (p = 0.42) or immediate-release (p = 0.70) opioids. Multiple sensitivity analyses supported these findings and their substantive interpretation. The market debut of abuse-deterrent OxyContin was associated with declines in its use after accounting for the simultaneous contraction of the generic extended-release oxycodone market. Further scrutiny into the effect of abuse-deterrent formulations on medication use and health outcomes is vital given their popularity in opioid drug development.