An all-atom protein generative model.

Proteins mediate their functions through chemical interactions; modeling these interactions, which are typically through sidechains, is an important need in protein design. However, constructing an all-atom generative model requires an appropriate scheme for managing the jointly continuous and discrete nature of proteins encoded in the structure and sequence. We describe an all-atom diffusion model of protein structure, Protpardelle, which represents all sidechain states at once as a "superposition" state; superpositions defining a protein are collapsed into individual residue types and conformations during sample generation. When combined with sequence design methods, our model is able to codesign all-atom protein structure and sequence. Generated proteins are of good quality under the typical quality, diversity, and novelty metrics, and sidechains reproduce the chemical features and behavior of natural proteins. Finally, we explore the potential of our model to conduct all-atom protein design and scaffold functional motifs in a backbone- and rotamer-free way.

Impact of income-based public drug coverage deductibles on adherence to asthma medications.

BACKGROUND: Cost-related nonadherence to medications can be a barrier to asthma management. OBJECTIVE: To quantify the impact of public drug plan deductibles on adherence to asthma medications. METHODS: We used a quasi-experimental regression discontinuity analysis to determine whether thresholds in deductibles for public drug coverage, determined on the basis of annual household income, decreased medication use among lower-income children and adults with asthma in British Columbia from 2013 to 2018. Using dispensed medication records, we evaluated deductible thresholds at annual household incomes of $15,000 (a deductible increase from 0% to 2% of annual household income), and $30,000 (a deductible increase from 2% to 3% annual household income). We evaluated medication costs, use, the ratio of inhaled corticosteroids-containing controller medications to total medications, excessive use of short-acting ß-agonists, and the proportion of days covered by controller therapies. All costs are reported in 2020 Canadian dollars. RESULTS: Overall, 88,935 individuals contributed 443,847 person-years of follow-up (57% of female sex, mean age 31 years). Public drug subsidy decreased by -$41.74 (95% CI, -$28.34 to -$55.13) at the $15,000-deductible threshold, a 28% reduction, and patient costs increased by $48.45 (95% CI, $35.37-$61.53). The $30,000 deductible threshold did not affect public drug costs (P = .31), but patient costs increased by $27.65 (95% CI, $15.22-$40.09), which is an 11% increase. Asthma-related medication use, inhaled corticosteroids-to-total medication ratio, excessive use of short-acting ß-agonists, and proportion of days covered by controller therapies were not impacted by deductible thresholds. CONCLUSION: Income-based deductibles reduced public drug costs with no effect on asthma-related medication use, adherence to controller therapies, or excessive reliever therapy use in lower-income individuals with asthma.

Prevalence and predictors of primary nonadherence to medications prescribed in primary care.

BACKGROUND: Most research on medication adherence has focused on secondary nonadherence and persistence to therapy. Medication prescriptions that are never filled by patients (primary nonadherence) remain understudied in the general population. METHODS: We linked prescribing data from primary care electronic medical records to comprehensive pharmacy dispensing claims between January 2013 and April 2019 in British Columbia (BC) to estimate primary nonadherence, defined as failure to dispense a new medication or its equivalent within 6 months of the prescription date. We used hierarchical multivariable logistic regression to determine prescriber, patient and medication factors associated with primary nonadherence among community-dwelling patients in primary care. RESULTS: Among 150 565 new prescriptions to 34 243 patients, 17% of prescriptions were never filled. Primary nonadherence was highest for drugs prescribed mostly on an as-needed basis, including topical corticosteroids (35.1%) and antihistamines (23.4%). In multivariable analysis, primary nonadherence was lower for prescriptions issued by male prescribers (odds ratio [OR] 0.66, 95% confidence interval [CI] 0.50-0.88). Primary nonadherence decreased with patient age (OR 0.91, 95% CI 0.90-0.92 for each additional 10 years) but increased with polypharmacy among patients aged 65 years or older. Patients filled more than 82% of their medication prescriptions within 2 weeks after their primary care provider visit. INTERPRETATION: The prevalence of primary nonadherence to new prescriptions was 17%. Interventions to address primary nonadherence could target older patients with multiple medication use and within the first 2 weeks of the prescription issue date.

The impact of introducing multidisciplinary care assessments on access to rheumatology care in British Columbia: an interrupted time series analysis.

BACKGROUND: In 2011 the British Columbia (BC) Ministry of Health introduced a new fee-for-service billing code that allowed "Multidisciplinary Care Assessment" (MCA). This change has the potential to change access to and quality of care for patients. This study aimed to explore the impact on access to rheumatology services in the province. METHODS: Fee-for-service rheumatology billings were evaluated for each rheumatologist 2 years before and after use of the MCA code. Numbers of 1) unique patients and 2) services provided per month were used as proxy measures of access to care. A multiple-baseline interrupted time series model assessed the impact of the MCA on levels and trends of the access outcomes. RESULTS: Our analysis consisted of 82,360 patients cared for by 26 rheumatologists who billed for an MCA. In our primary analysis we observed a sustained increase in the mean number of unique patients of 4.9% (95% CI: 0.0% to 9.9%, p = 0.049) and the mean number of services of 7.1% (95% CI: 1.0% to 13.6%, (p = 0.021), per month provided by a rheumatologist, corresponding to the initial use of MCA. CONCLUSION: The introduction of the MCA code was associated with an initial increase in the measures of access, which was maintained but did not increase over time. Our study suggests that the use of Multidisciplinary Care Assessment can contribute to expanding and/or sustaining access to care for people with complex chronic conditions, like rheumatic diseases.

How long does it take patients to find a new primary care physician when theirs retires: a population-based, longitudinal study.

BACKGROUND: The retirement of a family physician can represent a challenge in accessibility and continuity of care for patients. In this population-based, longitudinal cohort study, we assess whether and how long it takes for patients to find a new majority source of primary care (MSOC) when theirs retires, and we investigate the effect of demographic and clinical characteristics on this process. METHODS: We used provincial health insurance records to identify the complete cohort of patients whose majority source of care left clinical practice in either 2007/2008 or 2008/2009 and then calculated the number of days between their last visit with their original MSOC and their first visit with their new one. We compared the clinical and sociodemographic characteristics of patients who did and did not find a new MSOC in the three years following their original physician's retirement using Chi-square and Fisher's exact test. We also used Cox proportional hazards models to determine the adjusted association between patient age, sex, socioeconomic status, location and morbidity level (measured using Johns Hopkins' Aggregated Diagnostic Groupings), and time to finding a new primary care physician. We produce survival curves stratified by patient age, sex, income and morbidity. RESULTS: Fifty-four percent of patients found a new MSOC within the first 12 months following their physician's retirement. Six percent of patients still had not found a new physician after 36 months. Patients who were older and had higher levels of morbidity were more likely to find a new MSOC and found one faster than younger, healthier patients. Patients located in more urban regional health authorities also took longer to find a new MSOC compared to those in rural areas. CONCLUSIONS: Primary care physician retirements represent a potential threat to accessibility; patients followed in this study took more than a year on average to find a new MSOC after their physician retired. Providing programmatic support to retiring physicians and their patients, as well as addressing shortages of longitudinal primary care more broadly could help to ensure smoother retirement transitions.

Complete genomic sequences of Propionibacterium freudenreichii phages from Swiss cheese reveal greater diversity than Cutibacterium (formerly Propionibacterium) acnes phages.

BACKGROUND: A remarkable exception to the large genetic diversity often observed for bacteriophages infecting a specific bacterial host was found for the Cutibacterium acnes (formerly Propionibacterium acnes) phages, which are highly homogeneous. Phages infecting the related species, which is also a member of the Propionibacteriaceae family, Propionibacterium freudenreichii, a bacterium used in production of Swiss-type cheeses, have also been described and are common contaminants of the cheese manufacturing process. However, little is known about their genetic composition and diversity. RESULTS: We obtained seven independently isolated bacteriophages that infect P. freudenreichii from Swiss-type cheese samples, and determined their complete genome sequences. These data revealed that all seven phage isolates are of similar genomic length and GC% content, but their genomes are highly diverse, including genes encoding the capsid, tape measure, and tail proteins. In contrast to C. acnes phages, all P. freudenreichii phage genomes encode a putative integrase protein, suggesting they are capable of lysogenic growth. This is supported by the finding of related prophages in some P. freudenreichii strains. The seven phages could further be distinguished as belonging to two distinct genomic types, or 'clusters', based on nucleotide sequences, and host range analyses conducted on a collection of P. freudenreichii strains show a higher degree of host specificity than is observed for the C. acnes phages. CONCLUSIONS: Overall, our data demonstrate P. freudenreichii bacteriophages are distinct from C. acnes phages, as evidenced by their higher genetic diversity, potential for lysogenic growth, and more restricted host ranges. This suggests substantial differences in the evolution of these related species from the Propionibacteriaceae family and their phages, which is potentially related to their distinct environmental niches.

Piperacillin-Tazobactam versus Other Antibacterial Agents for Treatment of Bloodstream Infections Due to AmpC ß-Lactamase-Producing Enterobacteriaceae.

In vivo induction of AmpC beta-lactamases produces high-level resistance to many beta-lactam antibiotics in Enterobacteriaceae, often resulting in the need to use carbapenems or cefepime (FEP). The clinical effectiveness of piperacillin-tazobactam (TZP), a weak inducer of AmpC beta-lactamases, is poorly understood. Here, we conducted a case-control study of adult inpatients with bloodstream infections (BSIs) due to Enterobacter, Serratia, or Citrobacter species from 2009 to 2015 to assess outcomes following treatment with TZP compared to FEP or meropenem (MEM). We collected clinical data and screened all isolates for the presence of ampC alleles by PCR. Primary study outcomes were 30-day mortality and persistent bacteremia at ≥72 h from the time of treatment initiation. Of 493 patients with bacteremia, 165 patients met the inclusion criteria, of which 88 were treated with TZP and 77 with FEP or MEM. To minimize differences between covariates, we carried out propensity score matching, which yielded 41 matched pairs. Groups only differed by age, with patients in the TZP group significantly older (P = 0.012). There were no significant differences in 30-day mortality, persistent bacteremia, 7-day mortality, or treatment escalation between the two treatment groups, including in the propensity score-matched cohort. PCR amplification and sequencing of ampC genes revealed the presence of ampC in isolates with cefoxitin MICs below 16 µg/ml, in particular in Serratia spp., and demonstrated that these alleles were highly genetically diverse. Taken together, TZP may be a valuable treatment option for BSIs due to AmpC beta-lactamase-producing Enterobacteriaceae, diminishing the need for broader-spectrum agents. Future studies are needed to validate these findings.

Erectile Dysfunction Medications and Treatment for Cardiometabolic Risk Factors: A Pharmacoepidemiologic Study.

BACKGROUND: Erectile dysfunction (ED) can be a sentinel marker for future cardiovascular disease and has been described as providing a "window of curability" for men to receive targeted cardiovascular risk assessment. AIM: To determine whether the prescription of phosphodiesterase type 5 inhibitors (PDE5is) for ED leads to the detection and treatment of previously undiagnosed cardiometabolic risk factors. METHODS: We performed a retrospective population-based cohort study of residents of British Columbia, Canada using linked health care databases from 2004 to 2011. An individual-level time series analysis with switching replications was used to determine changes in drug use for hypertension, hypercholesterolemia, and diabetes in men 40 to 59 years old. The observation window for each patient was 720 days before and 360 days after the index date. OUTCOMES: The primary outcome was changes in prescriptions for antihypertensive, statin, and oral antidiabetic drugs, with secondary outcomes being laboratory tests for plasma cholesterol and glucose. RESULTS: 5,858 men 40 to 59 years old newly prescribed a PDE5i were included in the analysis. We found a sudden increase in prescriptions for antihypertensive drugs (40 per 1,000; P < .001), statins (10 per 1,000; P = .001), and antidiabetic drugs (17 per 1,000; P = .002) in the 90 days after a new prescription for a PDE5i. For hypercholesterolemia and diabetes, most of this change was observed in men with relevant screening tests performed in the 30 days after their PDE5i prescription. Only 15% and 17% of men who did not have a screening test for cholesterol and glucose, respectively, in the year before their PDE5i prescription went on to have one in the subsequent 30 days. CLINICAL IMPLICATIONS: The paucity of screening tests observed in our study after PDE5i prescriptions suggests that physicians should be educated on the recommended screening guidelines for men newly diagnosed with ED. STRENGTHS AND LIMITATIONS: The number of men who were ordered a laboratory test or written a prescription but chose not to complete or fill it, respectively, is unknown. CONCLUSION: Treatment for ED with PDE5is can be a trigger or "gateway drug" for the early detection and treatment of cardiometabolic risk factors provided physicians perform the requisite screening investigations. Skeldon SC, Cheng L, Morgan SG, et al. Erectile Dysfunction Medications and Treatment for Cardiometabolic Risk Factors: A Pharmacoepidemiologic Study. J Sex Med 2017;14:1597-1605.

Impact of income-based deductibles on drug use and health care utilization among older adults.

BACKGROUND: Income-based deductibles are present in several provincial public drug plans in Canada and have been the subject of extensive debate. We studied the impact of such deductibles in British Columbia's Fair PharmaCare plan on drug and health care utilization among older adults. METHODS: We used a quasi-experimental regression discontinuity design to compare the impact of deductibles in BC's PharmaCare plan between older community-dwelling adults registered for the plan who were born in 1928 through 1939 (no deductible) and those born in 1940 through 1951 (deductible equivalent to 2% of household income). We used 1.2 million person-years of data between 2003 and 2015 to study public drug plan expenditures, overall drug use, and physician and hospital resource utilization in these 2 groups. RESULTS: The income-based deductible led to a 28.6% decrease in person-years in which public drug plan benefits were received (95% confidence interval [CI] -29.7% to -27.5%) and to a reduction in the per capita extent of annual benefits by $205.59 (95% CI -$247.81 to -$163.37). Despite this difference in public subsidy, we found no difference in the number of drugs received or in total drug spending once privately paid amounts were accounted for (p = 0.4 and 0.8, respectively). Further, we found only small or nonexistent changes in health care resource utilization at the 1939 threshold. INTERPRETATION: A modest income-based deductible had a considerable impact on the extent of public subsidy for prescription drugs. However, it had only a trivial impact on overall access to medicines and use of other health services. Unlike copayments, modest income-based deductibles may safely reduce public spending on drugs for some population groups.

Patterns of physician retirement and pre-retirement activity: a population-based cohort study.

BACKGROUND: Knowing when physicians retire and how they practise in the pre-retirement years is important information for health human resource planning. We identified patterns of retirement for physicians in British Columbia and the determinants of when and how physicians retire. METHODS: For this population-based retrospective cohort study, we used administrative data to examine activity levels and to identify retirements among BC's practising physicians. We included all physicians who were at least 50 years of age as of March 2006 and who had received payments for clinical services in at least 1 year between 2005/06 and 2011/12. We defined retirement as a permanent drop in monthly payments to less than $1667/month ($20 000/yr). We examined the patterns and timing of retirement by age, sex, specialty and location using linear and logistic regression models. RESULTS: Of the 4572 physicians who met the inclusion criteria, 1717 (37.6%) retired during the study period. The average age at retirement was 65.1 (standard deviation 7.8) years. Controlling for other demographic and practice characteristics, we found that women and physicians working in rural areas retired earlier, by 4.1 (95% confidence interval [CI] -4.9 to -3.2) years and 2.3 (95% CI -3.4 to -1.1) years, respectively. We found no difference in retirement age by specialty. We identified 4 patterns of pre-retirement activity: slow decline, rapid decline, maintenance and increasing activity. About 40% of physicians (440/1107) reduced their activity levels by at least 10% in the 3 years preceding retirement. INTERPRETATION: During the study period, physicians in BC - particularly women and those in rural areas - retired earlier than indicated by licensure and survey data. Many physicians reduced their practice activity in the pre-retirement years. These trends indicate that forecasts relying on licensure "head counts" are likely overestimating current and future physician supply.

Patient Compliance in the Setting of BI-RADS Category 3: What Factors Impact Compliance With Short-Term Follow-Up Recommendations?

The study aims to define how imaging findings, patient demographics, patient-provider interactions, and health care practices may affect a woman's decision to follow-up in the setting of a BI-RADS Category 3. A total of 398 women from the University of Arizona Breast Imaging Center with a BI-RADS Category 3 assessment for mammography and/or ultrasound findings were evaluated between February 2012 and June 2014. Demographic information was analyzed for all patients, regardless of follow-up. Women who returned for follow-up within the recommended time period were given one survey at the time of their follow-up appointment, and women who returned for follow-up, but later than recommended, were given a separate survey to complete. Age, palpability of a lesion, and menopause status were related to follow-up. Self-rated general health was the only factor found to be associated with the decision to follow-up on time. The majority of patients who followed up on time reported that mailed reminder cards were the primary practice that prompted follow-up. Of patients who followed up later than recommended, the major reason was "no time." The findings suggest that additional counseling regarding the benefits of short-interval imaging follow-up might be advantageous for patients.

A population-based analysis of incentive payments to primary care physicians for the care of patients with complex disease.

BACKGROUND: In 2007, the province of British Columbia implemented incentive payments to primary care physicians for the provision of comprehensive, continuous, guideline-informed care for patients with 2 or more chronic conditions. We examined the impact of this program on primary care access and continuity, rates of hospital admission and costs. METHODS: We analyzed all BC patients who qualified for the incentive based on their diagnostic profile. We tracked primary care contacts and continuity, hospital admissions (total, via the emergency department and for targeted conditions), and cost of physician services, hospital care and pharmaceuticals, for 24 months before and 24 months after the intervention. RESULTS: Of 155 754 eligible patients, 63.7% had at least 1 incentive payment billed. Incentive payments had no impact on primary care contacts (change in contacts per patient per month: 0.016, 95% confidence interval [CI] -0.047 to 0.078) or continuity of care (mean monthly change: 0.012, 95% CI -0.001 to 0.024) and were associated with increased total rates of hospital admission (change in hospital admissions per 1000 patients per month: 1.46, 95% CI 0.04 to 2.89), relative to preintervention trends. Annual costs per patient did not decline (mean change: $455.81, 95% CI -$2.44 to $914.08). INTERPRETATION: British Columbia's $240-million investment in this program improved compensation for physicians doing the important work of caring for complex patients, but did not appear to improve primary care access or continuity, or constrain resource use elsewhere in the health care system. Policymakers should consider other strategies to improve care for this patient population.

The impact of medication reviews by community pharmacists.

OBJECTIVES: Many Canadians use prescription medicines that are unnecessary or that can lead to adverse events. In response, many provinces have introduced programs in which pharmacists are paid to perform medication reviews with patients. As the evidence on such programs is equivocal, we investigated the impact of British Columbia's program. DESIGN: Interrupted time series. SETTING: British Columbia, Canada. PARTICIPANTS: All residents of British Columbia who received a medication review between May 1, 2012, and June 30, 2013 (163,776 individuals). INTERVENTION: Using British Columbia's population-based PharmaNet drug utilization system, we collected data on community pharmacist-led medication reviews. The PharmaNet database contains a record of all medication reviews conducted in an ambulatory setting. MAIN OUTCOME MEASURES: We studied the impact of first medication reviews conducted between May 2012 and June 2013. We used interrupted time series analysis to assess longitudinal changes in patients receiving a standard review (n = 147,770) and a more intensive pharmacist consultation (n = 16,006). Our outcomes included drug utilization, costs, potentially inappropriate prescriptions, and medication persistence measured through the proportion of commonly used chronic medications that were eventually refilled. RESULTS: Overall, we observed few changes in the level or trend of any of the outcomes we studied. Both review types were followed by significant increases in both the number of prescriptions per month and expenditures. The continuation of long-term medications did not change for 3 of 4 classes, and increased very slightly for the final class. We found no evidence of deprescribing, either for classes that are potentially problematic for long-term use (benzodiazepines and proton pump inhibitors) or for potentially inappropriate prescriptions in seniors. CONCLUSIONS: Our results suggest that medication reviews did not significantly modify prescription drug use by recipients. Future iterations of such programs might be modified to be better targeted and to encourage closer collaboration between pharmacists and prescribing health care professionals.

Impact of allowing pharmacists to independently renew prescriptions: A population-based study.

OBJECTIVES: To study the impact of a 2009 policy change in British Columbia (BC) that allowed pharmacists to independently renew certain prescriptions for chronic conditions. DESIGN: Population-based analysis. SETTING: BC, Canada. PARTICIPANTS: All residents of BC (more than 3.9 million). INTERVENTION: Prescription drug use data were collected from the PharmaNet database. This database contains a record of all ambulatory prescription drug dispensations in BC including a variable indicating whether a pharmacist renewed the prescription. MAIN OUTCOME MEASURES: We studied pharmaceutical and physician insurance claims datasets for all BC residents for 2 years following the 2009 policy change. We assessed the number and types of drugs renewed by pharmacists, and whether these complied with the policy. Further, we matched pharmacist-renewed prescriptions to equivalent potentially renewable prescriptions and assessed the impact on ambulatory physician visits. RESULTS: Over the first 2 years, pharmacists renewed 150,950 prescriptions in BC. Almost one-half of these renewals did not appear to match the conditions set out in the new regulatory policy (n = 69,970, 47%). Those that did match the conditions (n = 80,980, 53%) represented a very small proportion of the 47 million prescriptions that pharmacists could have renewed (0.17%). The most frequently renewed medications were treatments for dyslipidemias, hypertension, diabetes, and gastroesophageal reflux disease. Pharmacist-renewed prescriptions were preceded by a 30% relative decrease in ambulatory physician visits in the week before dispensing, but there was also a 17% relative increase in visits in the week following the pharmacist-renewed prescription. CONCLUSION: Overall, the use of pharmacist renewals was very low and one-half of the renewals were not policy-concordant. Pharmacist renewals were associated with the intended reductions in physician visits before dispensing, but there was also an unintended increase in visits after dispensing. These findings suggest that future policies such as this one need to be differently designed and closely monitored.

Effect of a Billing Code to Reimburse Nurse-Supported Rheumatology Care on Health Care Costs and Access: An Interrupted Time Series Analysis.

OBJECTIVE: This study was undertaken to evaluate the impact of a Multidisciplinary Care Assessment (MCA) billing code on health system costs and access to care in British Columbia (BC). METHODS: Data on all people treated by rheumatologists in BC were obtained from five linked health administrative databases held by Population Data BC from April 1, 2006, to March 31, 2020. Rheumatologists were allocated to either the intervention (ever-billers) or control groups (never-billers). For the intervention group, the index date was the month of the first MCA code billing. For the control group the index dates were imputed from intervention index dates. Our analysis focused on a 48-month period (24 months before and after the index date). We evaluated the impact on two cost (costs related to rheumatoid arthritis [RA]; total health care costs) and access outcomes (rheumatology-related visits per rheumatologist; days between rheumatology visits for patients with RA) using an interrupted time series analysis. RESULTS: A total of 46 rheumatologists (31 intervention and 15 control) met our inclusion criteria. Introduction of the MCA was associated with a small but significant increase in RA-related costs that, at 2 years, translates to a net absolute change of $9.66 per patient per month, but no statistically significant changes in total health care costs. There was no statistically significant change in the number of rheumatology-related visits, but at 2 years there was a net absolute reduction in the median days between rheumatologist visits for patients with RA (6.3 days). CONCLUSION: The introduction of the MCA code was associated with a negligible increase in the RA-related costs and an improvement in access to ongoing care for patients.

The Impact of reference pricing on prescribing patterns, costs, and health services utilization of proton pump inhibitors: A quasi-experimental study in British Columbia, Canada.

INTRODUCTION: The Reference Drug Program (RDP) was established to steer patients toward equally safe and cost-effective medication under British Columbia's public drug coverage. Each RDP class covers at least one reference drug, and non-reference drugs are reimbursed up to the cost of the reference drug. In 2016, the RDP updated to include proton pump inhibitors (PPIs). This study evaluated the impact on drug expenditures, prescription patterns, and health services utilization. METHODS: We identified a cohort of individuals covered by Fair Pharmacare who used PPIs, and a control group of H2 Blockers users. We used interrupted time series analysis on administrative data from June 2014 to December 2019 on the following outcomes: new users, day supply, expenditures, drug costs, reference drug use, and physician visits and costs. RESULTS: The RDP had little impact on overall PPI use patterns. We did not observe any changes in reference drug uptake, new users, physician visits, cost-savings, or significant changes to days supplied post-policy. Cost expenditure results were likely biased due to co-occurring changes to drug prices. CONCLUSION: Inclusion of PPIs to the RDP saw no cost-savings for the provincial drug program and had little impact on prescribing patterns. Overall, our findings are consistent with existing evidence that the RDP is safe for similar therapeutic alternatives, but the impact on PPI costs remains unclear.

The Impact of Blood Glucose Test Strips Reimbursement Limits on Utilization, Costs, and Health-care Utilization in British Columbia.

OBJECTIVE: People living with diabetes and not using insulin may not derive clinically significant benefit from routine glucose self-monitoring. As a result, in 2015, British Columbia (BC) introduced quantity restrictions for blood glucose test strips (BGTS) coverage in public plans. We studied the impact of this policy on utilization, costs, and health-care utilization. METHODS: We identified a cohort of adults (≥18 years old) with diabetes between 2013 and 2019. Using BC's administrative data, we studied utilization and costs among individuals with at least one PharmaCare-eligible BGTS claim. Using interrupted time-series analysis, we studied cost savings and determined the level of policy adherence. In addition, we investigated longitudinal changes in all-cause and diabetes-specific physician visits, all-cause hospitalizations, and health-care spending in the 3 to 5 years after policy implementation. RESULTS: Over the study period, 279.7 million BGTS were eligible for PharmaCare coverage, on which the government spent $124.3 million. After policy implementation, we observed an immediate decline in average utilization and PharmaCare expenditure on BGTS, leading to an estimated $44.6 million in savings between 2015 and 2019 (95% confidence interval $16.9 to $72.3 million). We found no association between the policy's implementation and health services utilization or overall health-care spending over the long term. CONCLUSIONS: Restricting reimbursement for BGTS in BC resulted in significant cost savings without any attendant increase in health services utilization over the subsequent 5 years. This disinvestment freed up resources that could be channeled toward other interventions.

Impact of the COVID-19 pandemic on prescription drug use and costs in British Columbia: a retrospective interrupted time series study.

OBJECTIVES: To assess the impact of the COVID-19 pandemic on prescription drug use and costs. DESIGN: Interrupted time series analysis of comprehensive administrative health data linkages in British Columbia, Canada, from 1 January 2018 to 28 March 2021. SETTING: Retrospective population-based analysis of all prescription drugs dispensed in community pharmacies and outpatient hospital pharmacies and irrespective of the drug insurance payer. PARTICIPANTS: Between 4.30 and 4.37 million individuals (52% women) actively registered with the publicly funded medical services plan. INTERVENTION: COVID-19 pandemic and associated mitigation measures. MAIN OUTCOME MEASURES: Weekly dispensing rates and costs, both overall and stratified by therapeutic groups and pharmacological subgroups, before and after the declaration of the public health emergency related to the COVID-19 pandemic. Relative changes in post-COVID-19 outcomes were expressed as ratios of observed to expected rates. RESULTS: After the onset of the pandemic and subsequent COVID-19 mitigation measures, overall medication dispensing rates dropped by 2.4% (p<0.01), followed by a sustained weekly increase to return to predicted levels by the end of January 2021. We observed abrupt level decreases in antibacterials (30.3%, p<0.01) and antivirals (22.4%, p<0.01) that remained below counterfactuals over the first year of the pandemic. In contrast, there was a week-to-week trend increase in nervous system drugs, yielding an overall increase of 7.3% (p<0.01). No trend changes in the dispensing of respiratory system agents, ACE inhibitors, antidiabetic drugs and antidepressants were detected. CONCLUSION: The COVID-19 pandemic impact on prescription drug dispensing was heterogeneous across medication subgroups. As data become available, dispensing trends in nervous system agents, antibiotics and antivirals warrant further monitoring and investigation.

Uptake and Spending on Biosimilar Infliximab and Etanercept After New Start and Switching Policies in Canada: An Interrupted Time Series Analysis.

OBJECTIVE: Uptake of biosimilars has been suboptimal in North America. This study was undertaken to quantify the impact of various policy interventions (namely, new start and switching policies) on uptake and spending on biosimilar infliximab and etanercept in British Columbia (BC), Canada. METHODS: We used administrative claims data to identify BC residents ≥18 years of age with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and/or plaque psoriasis who qualified for public drug coverage from January 2013 to November 2020. Using interrupted time series analysis, we studied the change in proportion spent on and prescriptions dispensed of biosimilar infliximab and etanercept out of the total amount per agent after new start and biosimilar switching policies were implemented. RESULTS: Our study included 208,984 individuals living with rheumatoid arthritis, ankylosing spondylitis, plaque psoriasis, and/or psoriatic arthritis, corresponding to 5,884 patients taking infliximab and etanercept. After the new start policy, we detected a small gradual increase in the proportion of dispensed biosimilar etanercept prescriptions of 0.65% per month (95% confidence interval [95% CI] 0.44, 0.85). The trend related to the proportion of total spending on biosimilar etanercept also increased (0.51% [95% CI 0.28, 0.73]). After the switching policy, there was a sustained increase in the proportion of dispensed biosimilar etanercept and infliximab prescriptions of 76.98% (95% CI 75.56, 78.41) and 58.43% (95% CI 52.11, 64.75), respectively. Similarly, there was a persistent increase in monthly spending on biosimilar etanercept and infliximab of 78.22% (95% CI 76.65, 79.79) and 71.23% (95% CI 66.82, 75.65), respectively. CONCLUSION: We found that mandatory switching policies were much more effective than new starting policies for increasing the use of biosimilar medications.