Childhood vaccines and antibiotic use in low- and middle-income countries.

Vaccines may reduce the burden of antimicrobial resistance, in part by preventing infections for which treatment often includes the use of antibiotics1-4. However, the effects of vaccination on antibiotic consumption remain poorly understood-especially in low- and middle-income countries (LMICs), where the burden of antimicrobial resistance is greatest5. Here we show that vaccines that have recently been implemented in the World Health Organization's Expanded Programme on Immunization reduce antibiotic consumption substantially among children under five years of age in LMICs. By analysing data from large-scale studies of households, we estimate that pneumococcal conjugate vaccines and live attenuated rotavirus vaccines confer 19.7% (95% confidence interval, 3.4-43.4%) and 11.4% (4.0-18.6%) protection against antibiotic-treated episodes of acute respiratory infection and diarrhoea, respectively, in age groups that experience the greatest disease burden attributable to the vaccine-targeted pathogens6,7. Under current coverage levels, pneumococcal and rotavirus vaccines prevent 23.8 million and 13.6 million episodes of antibiotic-treated illness, respectively, among children under five years of age in LMICs each year. Direct protection resulting from the achievement of universal coverage targets for these vaccines could prevent an additional 40.0 million episodes of antibiotic-treated illness. This evidence supports the prioritization of vaccines within the global strategy to combat antimicrobial resistance8.

Daratumumab utilization and cost analysis among patients with multiple myeloma in a US community oncology setting.

Background: The introduction of daratumumab into the treatment of multiple myeloma has improved outcomes in patients; however, community oncologists often dose more frequently than the US FDA-approved label. Materials and methods: Integra analyzed its database to elucidate daratumumab treatment patterns and the impact of increased utilization on the cost of care for multiple myeloma. Results: Following week 24, 671 (65%) of 1037 patients remained on daratumumab-containing regimens, with 330 patients continuing more frequent treatments than the expected once-every-4-weeks dosing described in the standard dosing schedule. Patients received an average of 14% more daratumumab doses than the FDA-approved label indicates, increasing the 1-year daratumumab costs by an estimated US$31,353. Conclusion: Daratumumab is utilized more frequently than the FDA-recommended dosing, leading to higher multiple myeloma treatment costs.

Lay abstract Since its first approval in 2015, daratumumab has become the backbone of many multiple myeloma treatment regimens. While its approval has improved outcomes in many patients who undergo treatment, it is expensive and has largely contributed to the increasing costs of care in multiple myeloma. In its most common treatment schedule, patients should transition from weekly and biweekly dosing to treatment once every 4 weeks. However, many providers maintain their patients on a more frequent dosing schedule, which increases Medicare 1-year costs by an estimated US$31,353 and may have unforeseen impacts on adverse events and patient outcomes.

Association Between Changes in Postoperative Opioid Utilization and Long-Term Health Care Spending Among Surgical Patients With Chronic Opioid Utilization.

BACKGROUND: There is growing interest in identifying and developing interventions aimed at reducing the risk of increased, long-term opioid use among surgical patients. While understanding how these interventions impact health care spending has important policy implications and may facilitate the widespread adoption of these interventions, the extent to which they may impact health care spending among surgical patients who utilize opioids chronically is unknown. METHODS: This study was a retrospective analysis of administrative health care claims data for privately insured patients. We identified 53,847 patients undergoing 1 of 10 procedures between January 1, 2004, and September 30, 2018 (total knee arthroplasty, total hip arthroplasty, laparoscopic cholecystectomy, open cholecystectomy, laparoscopic appendectomy, open appendectomy, cesarean delivery, functional endoscopic sinus surgery, transurethral resection of the prostate, or simple mastectomy) who had chronic opioid utilization (≥10 prescriptions or ≥120-day supply in the year before surgery). Patients were classified into 3 groups based on differences in opioid utilization, measured in average daily oral morphine milligram equivalents (MMEs), between the first postoperative year and the year before surgery: "stable" (<20% change), "increasing" (≥20% increase), or "decreasing" (≥20% decrease). We then examined the association between these 3 groups and health care spending during the first postoperative year, using a multivariable regression to adjust for observable confounders, such as patient demographics, medical comorbidities, and preoperative health care utilization. RESULTS: The average age of the sample was 62.0 (standard deviation [SD] 13.1) years, and there were 35,715 (66.3%) women. Based on the change in average daily MME between the first postoperative year and the year before surgery, 16,961 (31.5%) patients were classified as "stable," 15,463 (28.7%) were classified as "increasing," and 21,423 (39.8%) patients were classified as "decreasing." After adjusting for potential confounders, "increasing" patients had higher health care spending ($37,437) than "stable" patients ($31,061), a difference that was statistically significant ($6377; 95% confidence interval [CI], $5669-$7084; P < .001), while "decreasing" patients had lower health care spending ($29,990), a difference (-$1070) that was also statistically significant (95% CI, -$1679 to -$462; P = .001). These results were generally consistent across an array of subgroup and sensitivity analyses. CONCLUSIONS: Among patients with chronic opioid utilization before surgery, subsequent increases in opioid utilization during the first postoperative year were associated with increased health care spending during that timeframe, while subsequent decreases in opioid utilization were associated with decreased health care spending.

Association between industry payments and prescriptions of long-acting insulin: An observational study with propensity score matching.

BACKGROUND: The rapidly increased spending on insulin is a major public health issue in the United States. Industry marketing might be one of the upstream determinants of physicians' prescription of long-acting insulin-the most commonly used and costly type of insulin, but the evidence is lacking. We therefore aimed to investigate the association between industry payments to physicians and subsequent prescriptions of long-acting insulin. METHODS AND FINDINGS: Using the databases of Open Payments and Medicare Part D, we examined the association between the receipt of industry payments for long-acting insulin in 2016 and (1) the number of claims; (2) the costs paid for all claims; and (3) the costs per claim of long-acting insulin in 2017. We also examined the association between the receipt of payments and the change in these outcomes from 2016 to 2017. We employed propensity score matching to adjust for the physician-level characteristics (sex, years in practice, specialty, and medical school attended). Among 145,587 eligible physicians treating Medicare beneficiaries, 51,851 physicians received industry payments for long-acting insulin worth $22.3 million. In the propensity score-matched analysis including 102,590 physicians, we found that physicians who received the payments prescribed a higher number of claims (adjusted difference, 57.8; 95% CI, 55.8 to 59.7), higher costs for total claims (adjusted difference, +$22,111; 95% CI, $21,387 to $22,836), and higher costs per claim (adjusted difference, +$71.1; 95% CI, $69.0 to $73.2) of long-acting insulin, compared with physicians who did not receive the payments. The association was also found for changes in these outcomes from 2016 to 2017. Limitations to our study include limited generalizability, confounding, and possible reverse causation. CONCLUSIONS: Industry marketing payments to physicians for long-acting insulin were associated with the physicians' prescriptions and costs of long-acting insulin in the subsequent year. Future research is needed to assess whether policy interventions on physician-industry financial relationships will help to ensure appropriate prescriptions and limit overall costs of this essential drug for diabetes care.

Sales of antibiotics and hydroxychloroquine in India during the COVID-19 epidemic: An interrupted time series analysis.

BACKGROUND: We assessed the impact of the coronavirus disease 2019 (COVID-19) epidemic in India on the consumption of antibiotics and hydroxychloroquine (HCQ) in the private sector in 2020 compared to the expected level of use had the epidemic not occurred. METHODS AND FINDINGS: We performed interrupted time series (ITS) analyses of sales volumes reported in standard units (i.e., doses), collected at regular monthly intervals from January 2018 to December 2020 and obtained from IQVIA, India. As children are less prone to develop symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we hypothesized a predominant increase in non-child-appropriate formulation (non-CAF) sales. COVID-19-attributable changes in the level and trend of monthly sales of total antibiotics, azithromycin, and HCQ were estimated, accounting for seasonality and lockdown period where appropriate. A total of 16,290 million doses of antibiotics were sold in India in 2020, which is slightly less than the amount in 2018 and 2019. However, the proportion of non-CAF antibiotics increased from 72.5% (95% CI: 71.8% to 73.1%) in 2019 to 76.8% (95% CI: 76.2% to 77.5%) in 2020. Our ITS analyses estimated that COVID-19 likely contributed to 216.4 million (95% CI: 68.0 to 364.8 million; P = 0.008) excess doses of non-CAF antibiotics and 38.0 million (95% CI: 26.4 to 49.2 million; P < 0.001) excess doses of non-CAF azithromycin (equivalent to a minimum of 6.2 million azithromycin treatment courses) between June and September 2020, i.e., until the peak of the first epidemic wave, after which a negative change in trend was identified. In March 2020, we estimated a COVID-19-attributable change in level of +11.1 million doses (95% CI: 9.2 to 13.0 million; P < 0.001) for HCQ sales, whereas a weak negative change in monthly trend was found for this drug. Study limitations include the lack of coverage of the public healthcare sector, the inability to distinguish antibiotic and HCQ sales in inpatient versus outpatient care, and the suboptimal number of pre- and post-epidemic data points, which could have prevented an accurate adjustment for seasonal trends despite the robustness of our statistical approaches. CONCLUSIONS: A significant increase in non-CAF antibiotic sales, and particularly azithromycin, occurred during the peak phase of the first COVID-19 epidemic wave in India, indicating the need for urgent antibiotic stewardship measures.

Clinical Pharmacist-Led Impact on Inappropriate Albumin Utilization and Associated Costs in General Ward Patients.

BACKGROUND: Inappropriate albumin use in clinical practice remains problematic. Health-systems face continued challenges in promoting cost-appropriate use. OBJECTIVE: To evaluate the clinical and economic impact of a clinical pharmacist-led intervention strategy targeting inappropriate albumin use in general ward patients. METHODS: A retrospective cohort study evaluated all adult (≥18 years) general ward patients administered ≥1 dose of albumin at a university medical center over a 2-year period. The intervention consisted of a clinical pharmacist-led strategy intervening on all albumin orders not in accordance with institutional guidelines. The primary end point was to compare inappropriate albumin utilization before and after implementation. Secondary end points compared the rates of inappropriate albumin use adjusted for hospital admission and patient-days as well as associated costs by appropriateness between study periods. RESULTS: A total of 4420 patients were screened, with 1971 (44.6%) patients meeting inclusion criteria. The clinical pharmacist strategy significantly reduced inappropriate albumin (grams) utilization by 86.0% (P < 0.001). A 7-fold reduction of inappropriate albumin administered adjusted for the number of patient admissions was found from the preimplementation period following clinical pharmacist intervention strategy implementation (415.3 ± 83.2 vs 57.5 ± 34.2 g per 100 general ward hospital admissions, respectively; P < 0.001). Also, the adjusted inappropriate albumin rate was reduced from 62.2 ± 12.3 to 8.6 ± 5.2 g per 100 patient-days in the preimplementation and postimplementation periods, respectively (P < 0.001). Annual cost savings were $421 455 overall, with $341 930 resulting from mitigation of inappropriate use. CONCLUSION AND RELEVANCE: Clinical pharmacist-led interventions significantly reduced inappropriate albumin use and costs in hospitalized patients.

Evaluation of Drug Wastage in the Operating Rooms and Intensive Care Units of a Regional Health Service.

BACKGROUND: Pharmacological treatments for critical processes in patients need to be initiated as rapidly as possible; for this reason, it is a standard of care to prepare the main anesthesia and emergency drugs in advance. As a result, 20%-50% of the prepared drugs remain unused and are then discarded. Decreasing waste by optimizing drug use is an attractive strategy for meeting both cost containment and environmental sustainability. The primary end point of this study was to measure the actual amount of drug wastage in the operating rooms (ORs) and intensive care units (ICUs) of a Regional Health Service (RHS). The secondary end point was to analyze and estimate the economic implications of this waste for the Health Service and to suggest possible measures to reduce it. METHODS: This prospective observational multicenter study was conducted across 12 hospitals, all of which belong to the same RHS in the north-east of Italy. Data collection took place in March 2018 and included patients admitted to ICUs, emergency areas, and ORs of the participating hospitals. Data concerning drug preparation and administration were collected for all consecutive patients, independent of case types and of whether operations were scheduled or unscheduled. Drug wastage was defined as follows: drugs prepared in ready-to-use syringes but not administered at all and discarded untouched. We then estimated the costs of wasted drugs for a 1-year period using the data from this study and the yearly regional pharmacy orders of drugs provided to the ORs and ICUs. We also performed a sensitivity analysis to validate the robustness of our assumptions and qualitative conclusions. RESULTS: We collected data for a total of 13,078 prepared drug syringes. Drug wastage varied from 7.8% (Urapidil, an alpha-1 antagonist antihypertensive) to 85.7% (epinephrine) of prepared syringes, with an overall mean wastage rate of 38%. The estimated yearly waste was 139,531 syringes, for a total estimated financial cost of €78,060 ($92,569), and an additional quantity of medical waste amounting to 4968 kg per year. The total provider time dedicated to the preparation of unused drugs was predicted to be 1512 working hours per year. CONCLUSIONS: The overall extent of drug wastage in ORs and ICUs is concerning. Interventions aimed at minimizing waste-related costs and improving the environmental sustainability of our practice are paramount. Effort should be put into designing a more efficient workflow that reduces this waste while providing for the emergency availability of these medications in the OR and ICU.

Incorporating Prescription Drugs Into Affordable Care Act Risk Adjustment.

BACKGROUND: The 2010 Patient Protection and Affordable Care Act reformed the individual and small group health insurance markets and established a risk adjustment program to create a level playing field for competition. A new set of predictive models for measuring enrollee risk across plans was developed for the Patient Protection and Affordable Care Act-reformed markets, referred to as the Department of Health and Human Services Hierarchical Condition Category (HHS-HCC) models. Beginning in 2018, selected prescription drug classes were added to the models as risk markers. OBJECTIVE: We describe the motivations, concerns, methodology, and results of adding prescription drug utilization to the HHS-HCC models. METHODS: Separate HHS-HCC models are estimated by enrollee age and plan actuarial value. We defined and added 10 prescription drug classes, called RXCs, to the HHS-HCC adult models. RESULTS: Using selected RXCs alongside demographic and diagnostic indicators yielded modest overall improvement in HHS-HCC models' predictive power. Also, adding RXCs captures the higher costs of enrollees taking certain expensive pharmaceuticals and allows imputation of diagnoses for enrollees utilizing a drug but lacking the associated diagnosis. CONCLUSIONS: Including selected drugs in risk adjustment improved the models' predictive power. In addition, inclusion of selected drugs may discourage insurers from using formulary and drug benefit design to avoid enrollment of patients taking high-cost drugs, such as for HIV, multiple sclerosis, and rheumatoid arthritis, and improve access for enrollees taking these drugs. Adding RXCs also may improve plan risk measurement for plans with less complete diagnosis reporting.

Sales of anti-cancer medicines; China, Indonesia, Kazakhstan, Malaysia, Philippines and Thailand.

OBJECTIVE: To assess sales of anti-cancer medicines in the 2017 World Health Organization's WHO Model list of essential medicines in China, Indonesia, Kazakhstan, Malaysia, Philippines and Thailand from 2007 (2008 for Kazakhstan and Malaysia) to 2017. METHODS: We extracted sales volume data for 39 anti-cancer medicines from the IQVIA database. We divided the total quantity sold by the reference defined daily dose to estimate the total number of defined daily doses sold, per country per year, for three types of anti-cancer therapies (traditional chemotherapy, targeted therapy and endocrine therapy). We adjusted these data by the number of new cancer cases in each country for each year. FINDINGS: We observed an increase in sales across all types of anti-cancer therapies in all countries. The largest number of defined daily doses of traditional chemotherapy per new cancer case was sold in Thailand; however, the largest relative increase per new cancer case occurred in Indonesia (9.48-fold). The largest absolute and relative increases in sales of defined daily doses of targeted therapies per new cancer case occurred in Kazakhstan. Malaysia sold the largest number of adjusted defined daily doses of endocrine therapies in 2017, while China and Indonesia more than doubled their adjusted sales volumes between 2007 and 2017. CONCLUSION: The use of sales data can fill an important knowledge gap in the use of anti-cancer medicines, particularly during periods of insurance coverage expansion. Combined with other data, sales volume data can help to monitor efforts to improve equitable access to essential medicines.

Clinical Pharmacist-Led Impact on Inappropriate Albumin Use and Costs in the Critically Ill.

Background:Optimal albumin use in the intensive care unit (ICU) remains challenging with inappropriate use approaching 50%. No published reports have described clinical pharmacist impact aimed at mitigating inappropriate albumin use in the ICU. Objective: To evaluate the clinical and economic impact of a clinical pharmacist-led intervention strategy targeting inappropriate albumin in the ICU. Methods: A retrospective cohort study evaluated all adult (≥18 years) ICU patients administered albumin at an academic medical center over a 2-year period. Institutional guidelines were developed with clinical pharmacists targeting inappropriate albumin use. The primary end point was to compare inappropriate use of albumin administered before and after pharmacist intervention implementation. Secondary analyses compared the overall albumin use between study periods. In-hospital mortality, length of stay, and albumin-related costs between study periods were also compared. Results: A total of 4419 patients were identified, with 2448 (55.4%) critically ill patients included. The pharmacist-led strategy resulted in a 50.9% reduction of inappropriate albumin use (P < 0.001). The rate of inappropriate albumin use was 44.3 ± 10.5 and 5.5 ± 2.9 g per patient-day in the preimplementation and postimplementation periods, respectively (P < 0.001). Costs associated with overall and inappropriate albumin use in the ICU decreased by 34.8% and 87.1%, respectively. Total annual cost-savings was $355 393 in the ICUs. No differences in clinical outcomes were found. Conclusion and Relevance: Clinical pharmacist-led interventions reduced overall and inappropriate albumin use and costs without negatively affecting clinical outcomes.

Consumption of medicines used for gastric acid-related disorders in Australia and South Korea: a cross-country comparison.

PURPOSE: The study's aim was to compare the use of proton pump inhibitors (PPIs), histamine 2-receptor antagonists (H2RAs) and mucoprotective medicines (MPs) used for gastric acid-related disorders (GARD) in Australia and South Korea (Korea) from 2004 to 2017. METHODS: Prescription data for PPIs, H2RAs and MPs for Australian outpatients were extracted from the Australian Statistics on Medicines annual reports, with dose-specific and expenditure data obtained from Medicare. Similar data were obtained from Korean National Health Insurance Service claims data. We analysed the volume and expenditure of medicines use annually using the defined daily dose per 1,000 population per day. We calculated which medicines accounted for 90% of use and estimated the proportions of use for low- and high-dose PPIs. RESULTS: While total utilisation for GARD medicines increased over time in both countries, patterns of use differed. Overall, use was somewhat higher in Australia but increased more rapidly in Korea. PPIs were used more extensively in Australia, while more MPs and H2RAs were used in Korea. Expenditure and use of low-dose PPIs is escalating in Korea. CONCLUSION: There were substantial differences in the use of GARD medicines in Australia and Korea over 14 years. Both countries face similar challenges to promote rational medicines use and contain medical care costs. The discrepant prescribing patterns can be attributed to differences in healthcare systems, pharmaceutical policies and demographics. This study provides a baseline to influence more rational use of these medicines. It provides insight into medicines policies for other countries that face similar challenges.

The Trend for Antibiotic Use for Clostridioides (Clostridium) difficile Infection in Japan.

In Japan, there is no national surveillance study of Clostridioides (Clostridium) difficile infection (CDI), and details about the epidemiology and treatment status of CDI are unknown. Additionally, clinical practice guidelines (CPGs) for CDI are published by four different institutions. All CPGs recommend that the antimicrobials, vancomycin (VCM) and metronidazole (MNZ), should be selected according to disease severity. However, the trends for VCM and MNZ use in Japan remain unclear. Therefore, this study was aimed at clarifying the secular trends for VCM and MNZ use based on sales data from 2006 to 2015 and discussing its impact on CDI status and drug costs. This is the first study to clarify the antibiotic use trends for CDI treatment. We found that the total use increased over time (r = 0.0013, Pfor trend < 0.0001). While VCM use significantly decreased (r = -0.0003, Pfor trend = 0.0002), MNZ use increased (r = 0.0017, Pfor trend < 0.0001). These results show that although treatment for CDI was in line with CPGs, CDI incidence might be on an increasing trend. Additionally, despite the increased total use, the total drug costs decreased by 55% ($ 25 million) from 2006 to 2015. It was also surmised that CDI treatment in compliance with CPGs would lead to a reduction in drug costs. Hence, to understand the epidemiology of CDI, it is important to continuously investigate the use of drugs used for CDI therapy.

Superficial mycoses in Belgium: Burden, costs and antifungal drugs consumption.

BACKGROUND: Monitoring of superficial mycoses requires more attention due to their important incidence, health costs and antifungal drugs consumption. OBJECTIVES: The objectives were to estimate the burden of superficial mycoses in Belgium and to assess trends in associated antifungal consumption. METHODS: The burden of dermatophytoses (including onychomycosis), as well as skin and genital candidiasis, was estimated using disability-adjusted life years (DALY). Moreover, trends in systemic and topical antifungal consumption in ambulatory care were examined for the period 2010-2017, together with their associated costs. RESULTS: Due to their high incidence and long treatment duration, dermatophytoses represented the bulk of the burden, accounting for 92.2% of the total DALYs of superficial mycoses. Terbinafine was the most prescribed antifungal in terms of doses (35.4% of the total doses) while fluconazole was the most delivered drug in terms of packages (29.1% of the total packages). More than 70% of the prescriptions were made by general practitioners while consumption varied according to age and gender of the patients. A global 12% decrease in antifungal prescriptions was observed between 2011 and 2017. However, this reduction would result mainly from packaging changes and increased self-medication. A significant decrease in itraconazole treatments was notably compensated by an increased prescription of fluconazole packages. CONCLUSION: This study emphasises that dermatological presentations of superficial mycoses are the most important in terms of both burden and antifungal consumption in Belgium. Further reduction in antifungals use can be achieved by applying the adequate treatment after identification of the causative agent.

Economics of reducing antibiotic usage for clinical mastitis and metritis through genomic selection.

Antibiotics use (ABU) in animal agriculture has been implicated in the emergence of antibiotic resistance, a global public health threat. Economically justifiable antibiotic reduction strategies can motivate farmers to reduce ABU for clinical mastitis (CM) and metritis, the most common reasons for ABU on dairy farms. Our objective was to quantify the reduction in incidence of CM, metritis, and ABU, and the herd performance of a representative US herd that uses genomic selection for Lifetime Net Merit 2018 (NM$) selection index, compared with genetic selection based only on the mastitis (MAST) or metritis resistance (METR) trait or a health trait subindex (HTH$). A stochastic dynamic simulation model of a 1,000-cow herd with multi-trait genetics for 19 correlated traits included in the NM$ affected the performance of animals. The incidence of CM and metritis for each animal was affected by the genetic and environmental components of the MAST or METR, along with a standard phenotypic function that calculated the daily underlying herd probability to contract CM or metritis. Selection decisions were made based on genomic estimated breeding values of the traits of interest. A strategy named AI-NM$ based decisions on the NM$ trait so that the correlated genetic trends in MAST and METR are improved. Three other strategies named AI-MAST, AI-METR, and AI-HTH$ maximized respectively MAST, METR, and HTH$ genetic merit, but with a tradeoff in NM$ genetic merit. The cumulative true breeding values (TBV) of NM$ for 15 yr showed a difference of $4,947 per cow between the AI-NM$ (best strategy for NM$) and AI-METR (worst strategy for NM$). However, the 15-yr cumulative TBV of MAST was 26.50 percentage points (PP) higher in AI-MAST, and 18.5 PP higher for METR in AI-METR, compared with AI-NM$. As a result, the 15-yr cumulative phenotypic CM and metritis incidence was respectively 94.03 PP and 58 PP lower in AI-MAST and AI-METR compared with AI-NM$. Therefore the corresponding 15-yr cumulative ABU decreased by 42% in AI-MAST and by 53% in AI-METR. We found that AI-MAST had the lowest CM incidence across the 15 yr, whereas AI-METR had the lowest incidence of metritis and the smallest total ABU for 15 yr. To achieve the lowest incidence of CM, metritis, and ABU strategies AI-MAST, AI-METR, and AI-HTH$ had to incur 15-yr discounted cumulative losses per cow of $1,486, $1,434, and $1,130, respectively, compared with AI-NM$. Hence, AI-NM$ had the best financial performance, despite having slightly higher incidence of CM, metritis, and ABU.

Real-World Experience With Apremilast in the Treatment of Adults With Moderate to Severe Plaque Psoriasis in Québec: A Claims-Based Analysis of Drug Utilization and Healthcare Resource Utilization.

BACKGROUND: In Québec, targeted biologic therapies for moderate to severe plaque psoriasis are restricted to patients who have not responded to phototherapy or conventional systemic treatment, primarily due to high drug costs. Apremilast, an oral treatment for plaque psoriasis, was added to the Québec provincial health insurance plan (Régie de l'assurance maladie du Québec; RAMQ) formulary in 2015, making this the only province in Canada with public drug plan reimbursement for apremilast. OBJECTIVES: The aim of this study is to describe patients' characteristics, treatment patterns, healthcare resource utilization (HCRU), and associated costs and to measure real-world budget impact of using apremilast before biologics in plaque psoriasis. METHODS: This study was performed using RAMQ drug claims and medical services data. Patients diagnosed with psoriasis between January 2015 and December 2017 were identified. Medical services and prescription claims were categorized as all-cause and psoriasis-related. Using RAMQ database estimates, a 3-year budget impact analysis was developed comparing treatment cost with and without the addition of apremilast to the formulary. RESULTS: In all, 540 patients were identified (apremilast: n = 92; biologics: n = 448). Comorbidity burden and treatment persistence and adherence were comparable between apremilast and biologic users. The year following the index date, all-cause HCRU was lower for apremilast versus biologic users (CAN$19 763 vs CAN$28 025; P < .01), mainly driven by drug cost. Using apremilast before biologics resulted in an estimated RAMQ net savings of CAN$49 290 (2015), CAN$746 856 (2016), and CAN$1 216 512 (2017), and a total savings of CAN$2 012 658 since apremilast's addition to the formulary. CONCLUSION: Adding apremilast to the drug formulary of other Canadian provinces could result in significant healthcare savings.

Oral Anticoagulants - Utilisation and Expenditure under the Community Drugs Schemes.

Aims This study determined the impact of the direct oral anticoagulants (DOACs) on the utilisation and expenditure on oral anticoagulants (OACs) in the Irish Community healthcare setting. We also investigated aspects of DOAC prescribing. Methods Using anonymised prescription data from the HSE pharmacy claims database we investigated anticoagulant prescribing over the study period (1/1/2014 - 31/12/2018). Results Some 74,748 patients were being treated with OACs by the year end 2018 an increase of 30,319 over 5 years. Warfarin prescribing fell from 32,751 patients in 2014 to 16,166 by the year end 2018. Apixaban is the most frequently prescribed OAC and annual expenditure on DOACs now exceeds € 51 million. Patients treated with DOACs are older than participants in the pivotal clinical trials and are frequently co-administered interacting drugs. Conclusion The introduction of DOACs has resulted in an overall increase in anticoagulant prescribing, a significant reduction in warfarin usage and a large increase in expenditure.

Effectiveness of an antifungal stewardship programme at a London teaching hospital 2010-16.

Background: The need for antifungal stewardship is gaining recognition with increasing incidence of invasive fungal infection (IFI) and antifungal resistance alongside the high cost of antifungal drugs. Following an audit showing suboptimal practice we initiated an antifungal stewardship programme and prospectively evaluated its impact on clinical and financial outcomes. Patients and methods: From October 2010 to September 2016, adult inpatients receiving amphotericin B, echinocandins, intravenous fluconazole, flucytosine or voriconazole were reviewed weekly by an infectious diseases consultant and antimicrobial pharmacist. Demographics, diagnosis by European Organization for Research and Treatment of Cancer (EORTC) criteria, drug, indication, advice, acceptance and in-hospital mortality were recorded. Antifungal consumption and expenditure, and candidaemia species and susceptibility data were extracted from pharmacy and microbiology databases. Results: A total of 432 patients were reviewed, most commonly receiving AmBisome® (35%) or intravenous fluconazole (29%). Empirical treatment was often unnecessary, with 82% having no evidence of IFI. Advice was given in 64% of reviews (most commonly de-escalating or stopping treatment) and was followed in 84%. Annual antifungal expenditure initially reduced by 30% (£0.98 million to £0.73 million), then increased to 20% above baseline over a 5 year period; this was a significantly lower rise compared with national figures, which showed a doubling of expenditure over the same period. Inpatient mortality, Candida species distribution and rates of resistance were not adversely affected by the intervention. Conclusions: Provision of specialist input to optimize antifungal prescribing resulted in significant cost savings without compromising on microbiological or clinical outcomes. Our model is readily implementable by hospitals with high numbers of at-risk patients and antifungal expenditure.

Pharmaceutical policies: effects of educational or regulatory policies targeting prescribers.

BACKGROUND: Pharmaceuticals make an important contribution to people's health. Medicines, however, are frequently not used appropriately. Improving the use of medicines can improve health outcomes and save resources. On the other hand, regulatory and educational policies may have unintended effects on health and costs. OBJECTIVES: To assess the effects of pharmaceutical educational and regulatory policies targeting prescribers on medicine use, healthcare utilisation, health outcomes and costs (expenditures). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registries in March 2018 and several other databases between 2014 and 2018. We reviewed the reference lists of included studies and other relevant reviews, contacted authors of relevant reviews and studies to identify additional studies, and did a citation search for all included studies using ISI Web of Science (searched 05 January 2016). SELECTION CRITERIA: Randomised trials, non-randomised trials, interrupted time series studies, repeated measures studies and controlled before‒after studies of policies regulating who can prescribe medicines and other policies targeted at prescribers. We included in this category monitoring and enforcement of restrictions, generic prescribing, programmes to implement treatment guidelines, system-wide policies regarding monitoring medicine safety, and legislated or mandatory continuing education or quality improvement specifically targeted at prescribing. We defined 'policies' in this review as laws, rules, financial and administrative orders made by governments, non-governmental organisations or private insurers. We excluded interventions applied at the level of a single facility. For us to include a study, it had to include an objective measure of at least one of the following outcomes: medicine use, healthcare utilization, health outcomes, or costs. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed abstracts and reference lists of relevant reports, assessed full-text studies for inclusion, extracted data, and assessed risk of bias and certainty of the evidence (GRADE). For all the steps in the above process we resolved disagreements by discussion. MAIN RESULTS: We identified two studies that met our selection criteria: a controlled interrupted time series study evaluating a regulatory policy involving the monitoring of prescribing of benzodiazepines; and a controlled before‒after study of an educational policing involving mailed educational materials on prescribing for physicians and Health Maintenance Organization (HMO) members as well as an intervention to regulate drug reimbursement. We are uncertain about the effects on medicine use of a regulatory policy involving the monitoring of prescribing with triplicate prescriptions, compared with no regulatory intervention (very low certainty evidence). We are also uncertain about the effects on medicine use, assessed through doctors' prescribing, and costs of an educational policy involving mailed educational materials on prescribing for physicians and HMO members, compared to no educational intervention or an intervention to regulate drug reimbursement (very low certainty evidence). Neither of the included studies measured healthcare utilization, health outcomes, or additional costs, if any, to patients. AUTHORS' CONCLUSIONS: We are uncertain of the effects of educational or regulatory policies targeting prescribers due to very limited evidence of very low certainty. The impacts of these policies therefore need to be evaluated rigorously using appropriate study designs. Evaluations are needed across a range of settings, including low- and middle-income countries, and across different types of prescribers and medicines.

Does an Antimicrobial Time-Out Impact the Duration of Therapy of Antimicrobials in the PICU?

OBJECTIVES: Our aim was to perform an antimicrobial time-out 48-72 hours after commencing therapy in order to achieve a decrease in days of therapy per 1,000 patient days for vancomycin, meropenem, and piperacillin/tazobactam in all PICU patients during an 8-month period. DESIGN: This is a pre- and postimplementation quality improvement study. SETTINGS: A 30-bed PICU at a tertiary children's hospital. PATIENTS: Patients less than 21 years old admitted to the PICU from July 1, 2015, until March 31, 2016, or from July 1, 2016, until March 31, 2017, who received antibiotics for greater than 48 hours were eligible for inclusion. INTERVENTION: An antimicrobial time-out was performed after 48-72 hours of antimicrobials for all patients in the PICU during postimplementation. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was days of therapy per 1,000 patient-days for three target antibiotics: vancomycin, meropenem, and piperacillin/tazobactam. Ninety-five patients meeting inclusion criteria were admitted to the PICU during the pre-time-out period and 95 patients during the post-time-out period. The cohort that underwent time-outs had lower days of therapy for vancomycin (81.3 vs 138.1; p = 0.037) and meropenem (34.7 vs 67.1; p = 0.045). Total acquisition cost was 31 % lower for piperacillin/tazobactam and vancomycin and 46% for meropenem post implementation. Time-outs led to antimicrobial duration being defined 63% of the time and deescalation or discontinuation of antimicrobials 29% of the time. CONCLUSIONS: A 48-72-hour time-out process in rounds is associated with a reduction in days of therapy for antibiotics commonly used in the PICU and may lead to more appropriate usage. The time-outs are associated with discontinuation, deescalation, or duration being defined, which are key elements of Centers for Disease Control and Prevention-recommended antimicrobial stewardship programs.

Effect of Roux-en-Y gastric bypass on pharmacologic dependence in obese patients with type 2 diabetes

Background: More than half the diabetes-related health care costs in Canada relate to drug costs. We aimed to determine the effect of Roux-en-Y gastric bypass (RYGB) on the use of insulin and orally administered hypoglycemic medications in patients with diabetes. We also looked to determine overall cost savings with the procedure. Methods: We reviewed the bariatric clinic records of all patients with a confirmed diagnosis of type 2 diabetes mellitus who underwent RYGB between 2010/11 and 2014/15. Percentage estimated weight loss was recorded at 1 year, along with reductions in glycated hemoglobin (HbA1c) level and use of oral hypoglycemic therapy and insulin. We estimated medication costs using Manitoba-specific pricing data. Results: Fifty-two patients with at least 12 months of complete follow-up data were identified. The mean percentage estimated weight loss was 50.2%. The mean HbA1c level decreased from 7.6% to 6.0%, the mean number of orally administered hypoglycemics declined from 1.6 to 0.2, and the number of patients receiving insulin decreased from 18 (35%) to 3 (6%) (all p < 0.001). The rate of resolution of type 2 diabetes was 71%. Estimated mean annual per-patient medication costs decreased from $508.56 to $79.17 (p < 0.001). Potential overall health care savings could total $3769 per patient in the first year, decreasing to $1734 at 10 years. Conclusion: Roux-en-Y gastric bypass resulted in significant improvement in diabetic control, with a reduction in hypoglycemic medication use and associated costs in the early postoperative period. Potentially, large indirect and direct cost savings can be realized in the longer term.

Contexte: Plus de la moitié des coûts des soins de santé liés au diabète au Canada sont générés par les médicaments. Nous avons voulu déterminer l'effet de la dérivation gastrique de Roux-en-Y sur l'utilisation des agents hypoglycémiants oraux et de l'insuline chez les patients diabétiques. Nous avons aussi cherché à déterminer l'ensemble des économies associées à cette intervention. Méthodes: Nous avons passé en revue les dossiers cliniques bariatriques de tous les patients ayant un diagnostic confirmé de diabète de type 2 qui ont subi une dérivation gastrique de Roux-en-Y entre 2010­2011 et 2014­2015. La perte de poids ­ estimée en pourcentage ­ a été notée après un an, ainsi que les réductions des taux d'hémoglobine glyquée (HbA1c) et du recours aux hypoglycémiants oraux et à l'insuline. Nous avons estimé les coûts des médicaments à partir des données de tarification du Manitoba. Résultats: Cinquante-deux patients pour lesquels on disposait d'au moins 12 mois de données de suivi complètes ont été retenus. La perte de poids moyenne estimée en pourcentage était de 50,2 %. Le taux moyen d'HbA1c a diminué de 7,6 % à 6,0 %, le nombre moyen de comprimés d'hypoglycémiants oraux est passé de 1,6 à 0,2, et le nombre de patients sous insuline a diminué de 18 (35 %) à 3 (6 %) (tous p < 0,001). Le taux de résolution du diabète de type 2 était de 71 %. Le coût annuel moyen estimé des médicaments par patient est passé de 508,56 $ à 79,17 $ (p < 0,001). Les économies potentielles globales pour le système de santé pourraient totaliser 3769 $ par patient au cours de la première année, puis passer graduellement à 1734 $ au cours des 10 années suivantes. Conclusion: La dérivation gastrique de Roux-en-Y a permis d'améliorer significativement le contrôle du diabète, ainsi que de réduire le recours aux hypoglycémiants et les coûts associés au début de la période postopératoire. À plus long terme, d'importantes économies sur le plan des coûts indirects et directs pourraient potentiellement être réalisées.