The appropriate timing of hip fracture surgery remains a matter of debate. We sought to estimate the effect of changes in timing policy and the proportion of deaths attributable to surgical delay.

2c. Laryngoscope, 128:852-858, 2018.

Investigations of teriparatide (rPTH) as a potential treatment for critical defects have demonstrated the predicted anabolic effects on bone formation, and significant non-anabolic effects on healing via undefined mechanisms. Specifically, studies in murine models of structural allograft healing demonstrated that rPTH treatment increased angiogenesis (vessels <30μm), and decreased arteriogenesis (>30 μm) and mast cell numbers, which lead to decreased fibrosis and accelerated healing. To better understand these non-anabolic effects, we interrogated osteogenesis, vasculogenesis and mast cell accumulation in mice randomized to placebo (saline), rPTH (20μg/kg/2days), or the mast cell inhibitor sodium cromolyn (SC) (24μg/kg/2days), via longitudinal micro-CT and multiphoton laser scanning microscopy (MPLSM), in a critical calvaria defect model. Micro-CT demonstrated that SC significantly increased defect window closure and new bone volume versus placebo (p<0.05), although these effects were not as great as rPTH. Interestingly, both rPTH and SC has similar inhibitory effects on arteriogenesis versus placebo (p<0.05) without affecting total vascular volume. MPLSM time course studies in untreated mice revealed that large numbers of mast cells were detected 1 day post-op (43 +/− 17), peaked at 6 days (76 +/− 6), and were still present in the critical defect at the end of the experiment on day 30 (20 +/− 12). In contrast, angiogenesis was not observed until day 4, and functional vessels were first observed on 6 days, demonstrating that mast cell accumulation precedes vasculogenesis. To confirm a direct role of mast cells on osteogenesis and vasculogenesis, we demonstrated that specific diphtheria toxin-α deletion in Mcpt5-Cre-iDTR mice results in similar affects as SC treatment in WT mice. Collectively, these findings demonstrate that mast cells inhibit bone defect healing by stimulating arteriogenesis associated with fibrotic scaring, and that an efficacious non-anabolic effect of rPTH therapy on bone repair is suppression of arteriogenesis and fibrosis secondary to mast cell inhibition.

IntroductionSeveral new oral drug classes for type 2 diabetes (T2DM) have been introduced in the last 20 years accompanied by developments in clinical evidence and guidelines. The uptake of new therapies and contemporary use of blood glucose-lowering drugs has not been closely examined in Canada. The objective of this project was to describe these treatment patterns and relate them to changes in provincial practice guidelines.Research design and methodsWe conducted a longitudinal drug utilization study among persons with T2DM aged ≥18 years from 2001 to 2020 in British Columbia (BC), Canada. We used dispensing data from community pharmacies with linkable physician billing and hospital admission records. Laboratory results were available from 2011 onwards. We identified incident users of blood glucose-lowering drugs, then determined sequence patterns of medications dispensed, with stratification by age group, and subgroup analysis for patients with a history of cardiovascular disease.ResultsAmong a cohort of 362 391 patients (mean age 57.7 years old, 53.5% male) treated for non-insulin-dependent diabetes, the proportion who received metformin monotherapy as first-line treatment reached a maximum of 90% in 2009, decreasing to 73% in 2020. The proportion of patients starting two-drug combinations nearly doubled from 3.3% to 6.4%. Sulfonylureas were the preferred class of second-line agents over the course of the study period. In 2020, sodium-glucose cotransporter type 2 inhibitors and glucagon-like peptide-1 receptor agonists accounted for 21% and 10% of second-line prescribing, respectively. For patients with baseline glycated hemoglobin (A1C) results prior to initiating diabetic treatment, 41% had a value ≤7.0% and 27% had a value over 8.5%.ConclusionsOral diabetic medication patterns have changed significantly over the last 20 years in BC, primarily in terms of medications used as second-line therapy. Over 40% of patients with available laboratory results initiated T2DM treatment with an A1C value ≤7.0%, with the average A1C value trending lower over the last decade.

Purpose: We explored changes in health services utilization associated with the Biosimilars Initiative introduced in British Columbia on May 27, 2019. To maintain drug coverage, the policy requires users of originator infliximab or etanercept to transition to biosimilar versions. We present a three-month interim analysis of this initiative. Methods: We conducted a rapid monitoring analysis to evaluate changes in health services utilization three months after the policy was introduced compared with a threeyear period before the policy's introduction. Using the administrative claims data of the British Columbia Ministry of Health, we assembled three historical cohorts and one policy cohort of users of each originator drug (8 cohorts in total). Cumulative incidences of medication refills, switching, and visits to physicians were the outcome measures used to compare policy and historical cohorts. Likelihood ratios were used to quantify statistical differences between each policy cohort and its respective historical controls. Likelihood ratios above 7.1 were considered statistically significant. Results: The four infliximab cohorts included 436 patients on average, mean age 56 to 59, 53% to 55% females. The four etanercept cohorts included 1826 patients on average, mean age 57 to 58, 60% to 63% females. Three months after the policy's introduction, 21% of patients treated in the policy cohorts transitioned to the biosimilar versions. Health services utilization in the policy cohorts were consistent with the historical cohorts. Conclusions: An increase in visits to physicians was expected but not detected in the first three months of the Biosimilars Initiative. The impacts of the policy will continue to be monitored.

Background Drug coverage policies that incentivize switching patients from originator to biosimilar products may result in significant health care savings. Our study aimed to detect early impacts on health services utilization following a mandated switch from originator to biosimilar etanercept in British Columbia (BC), Canada. Methods We conducted a prospective, population-based cohort study using linked administrative health data from BC (2010–2020). The policy cohort consisted of patients with inflammatory arthritis who used originator etanercept in 2019, prior to BC’s Biosimilars Initiative switching policy. Three historical cohorts included patients with inflammatory arthritis who used originator etanercept in the years 2016, 2017, and 2018. We compared the daily cumulative incidences of drug refills and outpatient and inpatient services between the policy and historical cohorts. A likelihood ratio sustained (≥ 31 days) at 7.1 or higher compared with the null hypothesis was chosen a priori as a threshold for a potential impact of the policy. Results Each cohort contained between 1694 and 1963 patients. We detected several potential impacts: 1) a transient increase in etanercept refills between months three and eight (cumulative incidence difference of + 3.0%); 2) an anticipated increase in visits to physicians of any specialty between months three and eight (+ 2.6%); and 3) an anticipated increase in visits to a rheumatologist from the end of month three onwards (+ 12.8%). The policy had no impact on incidences of switching to a different biologic antirheumatic drug, visits to emergency departments, or admissions to hospitals. Conclusions Only transient and/or anticipated increases in drug refills and physician visits were observed during the study period. Additional research on clinical outcomes is recommended to strengthen the evidence that no long-term unintended negative health impacts are associated with BC’s Biosimilars Initiative [switching policy].

W orldwide spending on biologic medications is high and increasing, [1][2][3] and governments face the challenge of providing these medications and other treatments within limited budgets. The use of biosimilar medications has the potential to reduce costs 4-6 while providing clinical benefits similar to those of the originator medications. [7][8][9] To encourage switching from originator biologics to biosimilar medications, some governments are implementing voluntary 10 or mandatory 11-14 nonmedical switching policies. Despite evidence that switching is not associated with negative health impacts, 15,16 many patients and physicians are concerned that switching will reduce the effectiveness of treatment or cause adverse effects (or both). 17,18 Unintended negative effects may be a particular concern when switching is mandatory, regardless of a patient's clinical presentation or medical history. 19,20 Close monitoring of the impacts of mandatory switching policies is needed to provide early data on the safety of these policies.On May 27, 2019, British Columbia was the first Canadian province to implement a mandatory nonmedical switch policy from an originator to a biosimilar medication. 21 Phase 1 of the BC Biosimilars Initiative targeted patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis or plaque psor iasis who were treated with the originator infliximab and reimbursed by the provincial drug plan, PharmaCare. In BC, the costs for infliximab are covered under a PharmaCare Special Authority process. 22 Since May 27, 2019, only the biosimilar in fliximab has been approved in response to new or renewal Special Authority requests for patients with inflammatory arthritis or psoriasis. Patients with existing approval were required to switch to the biosimilar infliximab during a 6-month transition period, and after Nov. 25, 2019, PharmaCare no longer covered the costs of originator infliximab.

2c. Laryngoscope, 127:2528-2533, 2017.