Prescription ranitidine use and population exposure in 6 Canadian provinces, 1996 to 2019: a serial cross-sectional analysis.

BACKGROUND: Ranitidine was the most prescribed histamine-2 receptor antagonist (H2RA) in Canada when recalled in 2019 because of potential carcinogenicity. We sought to compare geographic and temporal patterns in use of prescription ranitidine and 3 other HRAs and estimated population exposure to ranitidine in 6 provinces between 1996 and 2019. METHODS: This population-based serial cross-sectional study used prescription claims for H2RAs dispensed from community pharmacies in Nova Scotia, Ontario, Manitoba, Saskatchewan, Alberta and British Columbia. We estimated the period prevalence of ranitidine use per 100 population by province, age category and sex. We estimated exposure to ranitidine between 2015 and 2019 using defined daily doses (DDDs). RESULTS: Overall, 2.4 million ranitidine prescriptions were dispensed to patients aged 65 years and older, and 1.7 million were dispensed to younger adults. Among older adults, the median period prevalence of ranitidine use among females was 16% (interquartile range [IQR] 13%-27%) higher than among males. Among younger adults, the median prevalence was 50% (IQR 37%-70%) higher among females. Among older adults, between 1996 and 1999, use was highest in Nova Scotia (33%) and Ontario (30%), lower in the prairies (Manitoba [18%], Saskatchewan [26%], Alberta [17%]) and lowest in BC (11%). By 2015-2019, use of ranitidine among older adults dropped by at least 50% in all provinces except BC. We estimate that at least 142 million DDDs of prescribed ranitidine were consumed annually in 6 provinces (2015-2019). INTERPRETATION: Over the 24-year period in 6 provinces, patients aged 65 years and older were dispensed 2.4 million prescriptions of ranitidine and younger adults were dispensed 1.7 million prescriptions of ranitidine. These estimates of ranitidine exposure can be used for planning studies of cancer risk and identifying target populations for cancer surveillance.

Quantifying the economic effects of ravulizumab versus eculizumab treatment in patients with atypical hemolytic uremic syndrome.

AIMS: This study compared the aggregate duration of treatment administration of approved eculizumab and ravulizumab treatment regimens and resultant productivity implications for patients with atypical hemolytic uremic syndrome (aHUS) and their caregivers. METHODS: The aggregate duration of treatment administration (which includes waiting time for medication preparation and time for infusion, recovery, and travel to and from the clinic) was determined for a hypothetical population of patients with aHUS treated with eculizumab (10 mg/mL) or ravulizumab (10 or 100 mg/mL), in the clinic or at home, for 1 year, in Germany, Italy, the UK, and the US. The data for US patients treated in the clinic was used to extend a previously published cost-minimization model (CMM) to estimate the annual lost productivity associated with treatment administration and to compare the overall annual treatment costs for hypothetical adult and pediatric patients in the US. RESULTS: The aggregate duration of treatment administration associated with ravulizumab 10 mg/mL and 100 mg/mL was reduced by 44-52% and 69-74%, respectively, compared with eculizumab 10 mg/mL, across all four countries. Using the CMM, the adult and pediatric US patient lost productivity costs due to treatment were reduced by 56-60% and 73-76% with ravulizumab 10 mg/mL and 100 mg/mL, respectively, compared with eculizumab 10 mg/mL, and overall discounted annual treatment costs (direct and lost productivity costs owing to treatment) were reduced for ravulizumab (10 mg/mL and 100 mg/mL) vs eculizumab 10 mg/mL for adult and pediatric patients. LIMITATIONS: This study was based on hypothetical patients, and assumptions were made regarding caregiver involvement, patient characteristics, and treatment patterns. CONCLUSIONS: Compared with eculizumab, ravulizumab reduces the lost productivity costs associated with treatment. This reduction in costs is greater with the ravulizumab 100 mg/mL formulation, compared with ravulizumab 10 mg/mL, owing to shorter infusion times with this more concentrated formulation.

PLAIN LANGUAGE SUMMARY[Figure: see text][Figure: see text].

Factors affecting access to administrative health data for research in Canada: a study protocol.

INTRODUCTION: In Canada, most provinces have established administrative health data repositories to facilitate access to these data for research. Anecdotally, researchers have described delays and substantial inter-provincial variations in the timeliness of data access approvals and receipt of data. Currently, the reasons for these delays and variations in timeliness are not well understood. This paper provides a study protocol for (1) identifying the factors affecting access to administrative health data for research within select Canadian provinces, and (2) comparing factors across provinces to assess whether and how they contribute to inter-provincial variations in access to administrative health data for research. METHODS: A qualitative, multiple-case study research design will be used. Three cases will be included, representing three different provinces. For each case, data will be collected from documents and interviews. Specifically, interviews will be carried out with (1) research stakeholders, and (2) regulatory stakeholders (10 individuals/group * 2 groups/province * 3 provinces = 60). During within-case analysis, interview data for each stakeholder group will be analyzed separately using constant comparative analysis. Document analysis will occur iteratively, and will inform interview guide adaptation, and supplement interview data. Cross-case analysis will involve systematic comparison of findings across cases. DISCUSSION: This study represents the first in-depth examination of access to administrative health data in Canada. The main outcome will be an overarching mid-range theory explaining inter-provincial variations in access to administrative health data in Canada. This theory will be strengthened by the inclusion of the perspectives of both researchers and those involved in the regulation of data access. The findings from this study may be used to improve equitable and timely access to administrative health data across provinces, and may be transferable to other jurisdictions where barriers to access to administrative health data have been reported.

Health expenditures after first hospital admission for heart failure in Nova Scotia, Canada: a retrospective cohort study.

BACKGROUND: Although the frequency of heart failure makes it among the costliest of illnesses, there are scant Canadian data on annual costs of treatment or the costs as the condition advances. Our objective was to estimate mean prevalence- and incidence-based direct medical costs among older adults discharged alive after a first hospital admission for heart failure. METHODS: We conducted a retrospective cohort study using population-based administrative health databases for Nova Scotia. The cohort comprised persons 50 years of age or older with an incident hospital admission for heart failure between 2009 and 2012. We considered the costs (expressed as 2020 Canadian dollars) of hospital admissions, physician visits and, for patients 65 years of age or older, outpatient cardiac medications. We estimated costs for calendar years, longitudinally and in the last 2 years of life. We analyzed costs from the perspective of a third-party public payer. RESULTS: The cohort consisted of 3327 patients (mean age 77.6 yr; 1605 [48.2%] women). Median survival was 2.5 and 2.2 years among men and women, respectively. Annual prevalence-based costs were about $7100. Mean incidence-based costs ranged between $65 000 and $164 000 in the year after diagnosis and decreased by 90% subsequently. Costs were 4 to 7 times higher in the year before death than in the period from 1 to 2 years before death. INTERPRETATION: The direct medical costs of treating patients with heart failure in Nova Scotia displayed a reverse J shape, with costs highest after diagnosis, declining subsequently and then increasing during the final year of life. Strategies designed to improve the quality of care immediately after diagnosis and during more advanced stages of disease might reduce these costs.

Variation in surgical demand and time to hip fracture repair: a Canadian database study.

BACKGROUND: Competing demands for operative resources may affect time to hip fracture surgery. We sought to determine the time to hip fracture surgery by variation in demand in Canadian hospitals. METHODS: We obtained discharge abstracts of 151,952 patients aged 65 years or older who underwent surgery for a hip fracture between January, 2004 and December, 2012 in nine Canadian provinces. We compared median time to surgery (in days) when demand could be met within a two-day benchmark and when demand required more days, i.e. clearance time, to provide surgery, overall and stratified by presence of medical reasons for delay. RESULTS: For persons admitted when demand corresponded to a 2-day clearance time, 68% of patients underwent surgery within the 2-day benchmark. When demand corresponded to a clearance time of one week, 51% of patients underwent surgery within 2 days. Compared to demand that could be served within the two-day benchmark, adjusted median time to surgery was 5.1% (95% confidence interval [CI] 4.1-6.1), 12.2% (95% CI 10.3-14.2), and 22.0% (95% CI 17.7-26.2) longer, when demand required 4, 6, and 7 or more days to clear the backlog, respectively. After adjustment, delays in median time to surgery were similar for those with and without medical reasons for delay. CONCLUSION: Increases in demand for operative resources were associated with dose-response increases in the time needed for half of hip fracture patients to undergo surgery. Such delays may be mitigated through better anticipation of day-to-day supply and demand and increased response capability.

Symptoms of Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis: A Prospective Cohort Study.

RATIONALE & OBJECTIVE: Although multiple lines of evidence suggest a negative impact of secondary hyperparathyroidism on patients with kidney failure treated by hemodialysis, it is uncertain whether patients can detect associated symptoms. The objective was to determine whether changes in parathyroid hormone (PTH) levels are associated with changes in symptoms within this patient population. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: 165 adults with hyperparathyroidism secondary to kidney failure diagnosed, a range of dialysis vintages, and receiving regular hemodialysis from a US single-provider organization. EXPOSURE: Change in PTH levels over 24 weeks. OUTCOMES: 19 putative symptoms of secondary hyperparathyroidism measured up to 4 times using a self-administered questionnaire that assessed severity on a 5-level ordinal scale. ANALYTICAL APPROACH: Longitudinal associations between changes in PTH levels and symptom severity were assessed using generalized additive models. RESULTS: The 165 participants studied represented 81% of enrollees (N=204) who had sufficiently complete data for analysis. Mean age was 56 years and 54% were women. Increases in PTH levels over time were associated (P<0.1) with worsening of bone aches and stiffness, joint aches, muscle soreness, overall pain, itchy skin, and tiredness, and the effects were more pronounced with larger changes in PTH levels. LIMITATIONS: Findings may have been influenced by confounding by unmeasured comorbid conditions, concomitant medications, and multiple testing coupled with a P value threshold of 0.10. CONCLUSIONS: In this exploratory study, we observed that among patients with secondary hyperparathyroidism, increases in PTH levels over time were associated with worsening of 1 or more cluster of symptoms. Replication of these findings in other populations is needed before concluding about the magnitude and shape of these associations. If replicated, these findings could inform clinically useful approaches for measuring patient-reported outcomes related to secondary hyperparathyroidism.

A contemporary description of patients' estimated blood losses from diagnostic phlebotomy in a census of hospital episodes from a Canadian tertiary care center.

BACKGROUND: Phlebotomy for diagnostic testing is among the commonest hospital procedures, but hospital-wide surveys of all inpatients characterizing blood draw volumes have not been published. The objectives were to characterize the daily blood volumes drawn for diagnostic testing from patients discharged from a Canadian tertiary care center, describe the daily distributions of phlebotomy volumes across service locations, and describe changes in hemoglobin (Hb) and transfusion across service locations. STUDY DESIGN AND METHODS: Data were obtained on all patients discharged between 2012 and 2014 using linked discharge abstract and laboratory data. Cumulative daily blood volume and draw frequency were reported by service and days since admission. Changes in Hb and red blood cell (RBC) transfusion rates were reported for nontransfused and transfused patients. RESULTS: Data were included on 59,715 subjects. Mean daily estimated blood loss varied from 8.5 ± 6.5 mL/day onward to 27.2 ± 20.0 mL/day in the intensive care unit (ICU; p < 0.001). Phlebotomy volumes were highest on the first day of admission and declined thereafter (p < 0.001). For nontransfused individuals in the first week of admission, Hb levels decreased by the highest percentage in the ICU. The rate of RBC unit transfusion was highest in the ICU (232.4 units/1000 patient-days; 95% confidence interval, 225.8-239.2; p < 0.0001 compared with all other locations). CONCLUSION: Considerable variation was observed in estimated blood loss due to diagnostic phlebotomy across different services within one teaching hospital. Thi information is foundational for planning interventions to minimize estimated blood loss from phlebotomy.

Characteristics of non-randomised studies using comparisons with external controls submitted for regulatory approval in the USA and Europe: a systematic review.

OBJECTIVES: Non-randomised clinical trial designs involving comparisons against external controls or specific standards can be used to support regulatory submissions for indications in diseases that are rare, with high unmet need, without approved therapies and/or where placebo is considered unethical. The objective of this review was to summarise the characteristics of non-randomised trials submitted to the European Medicines Agency (EMA) or Food and Drug Administration (FDA) for indications in haematological cancers, haematological non-malignant conditions, stem cell transplants or rare metabolic diseases. METHODS: We conducted systematic searches of EMA databases of conditional approvals, exceptional circumstances, or orphan drug designations and FDA inventories of orphan drug designations, accelerated approvals, breakthrough therapy, fast-track and priority approvals. Products were included if reviewed by at least one agency between 2005 and 2017, the primary evidence base was non-randomised trial(s) and the indication was for haematological cancers, stem cell transplantation, haematological conditions or rare metabolic conditions. RESULTS: We identified 43 eligible indication-specific products using non-randomised study designs involving comparisons with external controls, submitted to the EMA (n=34) and/or FDA (n=41). Of the 43 indication-specific products, 4 involved matching external controls to the population of a non-randomised interventional study using individual patient-level data (IPD), 12 referred to external controls without IPD and 27 did not explicitly reference external controls. The FDA approved 98% of submissions, with 56% accelerated approvals; most required postapproval confirmatory randomised controlled trials (RCT). The EMA approved 79% of submissions, with a quarter of approvals conditional on completion of a postapproval RCT or additional non-randomised trials. CONCLUSIONS: There has been a large increase in submissions to the EMA and FDA using non-randomised study designs involving comparisons with external controls in recent years. This study demonstrated that regulators may be willing to approve such submissions, although approvals are often conditional on further confirmatory evidence from postapproval studies.

Determining proton pump inhibitor prescription dispensing patterns and adherence to STOPP criteria for Nova Scotia Seniors Pharmacare Program beneficiaries.

BACKGROUND: Proton pump inhibitors (PPIs) are often prescribed potentially inappropriately. The screening tool of older person's potentially inappropriate prescriptions (STOPP) for therapeutic dose PPIs has been adapted to examine PPI discontinuation, dose reduction, or switching to Histamine-2 Receptor Antagonist (H2RA) after 60 days. OBJECTIVES: The objectives of the present study were to (1) describe the use of acid suppression therapy (PPIs and H2RAs) 60 and 90 days after a new PPI dispensing, (2) assess predictors of lack of adherence to adapted STOPP criteria for PPI use, and (3) assess PPI dispensing over time. METHODS: This was a retrospective cohort study of beneficiaries of the Nova Scotia Seniors Pharmacare (NSSP) aged 66 years or older who were newly dispensed a PPI between January 1, 1997 and March 31, 2011. The main outcome measure was adherence to the adapted STOPP criteria, which was analyzed using logistic regression. RESULTS: A total of 14,453 participants were included: 89.8% beginning on standard dose and 10.2% beginning on high-dose PPI. Of those beginning on high-dose PPI, 26.4% were dispensed high-dose PPI at day 60 and 30.2% were dispensed high-dose PPI at day 90. Predictors of lack of adherence to our adapted STOPP criteria included age ≥86 years, rural residence, and hospitalization within 1 year prior to cohort entry. CONCLUSIONS: Many PPI prescriptions dispensed for NSSP beneficiaries fail to adhere to the STOPP criteria. Predictors of lack of adherence to the adapted STOPP criteria were identified.

Operationalising a conceptual framework for a contiguous hospitalisation episode to study associations between surgical timing and death after first hip fracture: a Canadian observational study.

OBJECTIVE: We describe steps to operationalise a published conceptual framework for a contiguous hospitalisation episode using acute care hospital discharge abstracts. We then quantified the degree of bias induced by a first abstract episode, which does not account for hospital transfers. DESIGN: Retrospective observational study. SETTING: All acute care hospitals in nine Canadian provinces. PARTICIPANTS: We retrieved acute hospitalisation discharge abstracts for 189 448 patients aged 65 years and older admitted to acute care with hip fracture between 2003 and 2013. PRIMARY AND SECONDARY OUTCOME MEASURES: The percentage of patients treated surgically, delayed to surgery (defined as two or more days after admission) and dying, between contiguous hospitalisation episodes and the first abstract episodes of care. RESULTS: Using contiguous hospitalisation episodes, 91.6% underwent surgery, 35.7% were delayed two or more days after admission and 6.7% died postoperatively, whereas, using the first abstract only, these percentages were 83.7%, 32.5% and 6.5%, respectively. CONCLUSION: We demonstrate that not accounting for hospital transfers when evaluating the association between surgical timing and death underestimates reporting of the percentage of patients treated surgically and delayed to surgery by 9%, and the percentage who die after surgery by 3%. Researchers must be aware of this potential and avoidable bias as, depending on the purpose of the study, erroneous inferences may be drawn.

Uptake of elective laparoscopic colectomy for colon cancer in Canada from 2004/05 to 2014/15: a descriptive analysis.

BACKGROUND: Evidence from randomized controlled trials published since 2004 shows that elective laparoscopic colectomy for colon cancer improves short-term postoperative outcomes with equivalent oncologic outcomes compared to open colectomy. The objective of this study was to examine the uptake of elective laparoscopic colectomy in Canada and compare its use among Canadian provinces. METHODS: In this descriptive analysis, we identified from hospital discharge abstracts all patients in the Canadian provinces (except Quebec) who underwent elective colectomy for colon cancer between 2004/05 and 2014/15. We compared temporal changes in the proportion of patients who underwent laparoscopic colectomy or open colectomy among provinces using logistic regression. RESULTS: Of 63 504 patients who underwent elective colectomy between 2004/05 and 2014/15, 19 691 (31.0%) underwent laparoscopic colectomy. The annual proportion of patients who underwent laparoscopic colectomy increased from 9.2% in 2004/05 to 51.5% in 2014/15 (mean annual percent increase 4.2%). There were significant differences between provinces in the overall proportion of patients who underwent laparoscopic colectomy (p < 0.001), ranging from 7.6% in Newfoundland and Labrador to 36.9% in Ontario. By 2014/15, most colectomy procedures were performed laparoscopically in 3 provinces; British Columbia (60.2%), Ontario (59.4%) and Alberta (53.1%). In addition to year and province, urban residence, younger age, female sex, fewer medical comorbidities, high surgeon volume, high hospital volume and right-sided tumours were significantly associated with increased likelihood of laparoscopic colectomy. INTERPRETATION: Although the use of laparoscopic colectomy increased rapidly between 2004/05 and 2014/15 in Canada, substantial interprovincial variation exists. Further knowledge-translation strategies are needed to ensure equal access to laparoscopic colectomy for all Canadians.

Mortality effects of timing alternatives for hip fracture surgery.

BACKGROUND: 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. METHODS: We obtained discharge abstracts from the Canadian Institute for Health Information for hip fracture surgery in Canada (excluding Quebec) between 2004 and 2012. We estimated the expected population-average risks of inpatient death within 30 days if patients were surgically treated on day of admission, inpatient day 2, day 3 or after day 3. We weighted observations with the inverse propensity score of surgical timing according to confounders selected from a causal diagram. RESULTS: Of 139 119 medically stable patients with hip fracture who were aged 65 years or older, 32 120 (23.1%) underwent surgery on admission day, 60 505 (43.5%) on inpatient day 2, 29 236 (21.0%) on day 3 and 17 258 (12.4%) after day 3. Cumulative 30-day in-hospital mortality was 4.9% among patients who were surgically treated on admission day, increasing to 6.9% for surgery done after day 3. We projected an additional 10.9 (95% confidence interval [CI] 6.8 to 15.1) deaths per 1000 surgeries if all surgeries were done after inpatient day 3 instead of admission day. The attributable proportion of deaths for delays beyond inpatient day 2 was 16.5% (95% CI 12.0% to 21.0%). INTERPRETATION: Surgery on admission day or the following day was estimated to reduce postoperative mortality among medically stable patients with hip fracture. Hospitals should expedite operating room access for patients whose surgery has already been delayed for nonmedical reasons.

Effects of calcimimetics on long-term outcomes in dialysis patients: literature review and Bayesian meta-analysis.

AIM: Randomized controlled trials (RCTs) with clinical outcomes are considered the gold standard for regulatory approval. However, by design they are only able to answer a small number of clinical questions. Other high-quality studies are required for clinical decision-making. The EVOLVE was the largest RCT, evaluating the effects of cinacalcet on clinical outcomes among adult patients receiving maintenance dialysis suffering from secondary hyperparathyroidism. While the EVOLVE trial did not reach its primary end point, imbalance in subjects' age at randomization and discontinuation rates are two of the reasons that the lack of mortality benefit is in question. We undertook a systematic literature review and Bayesian meta-analysis combining randomized and observational studies on the estimated effects of the oral calcimimetic cinacalcet on clinical outcomes including all-cause mortality, cardiovascular-related mortality, hospitalization for cardiovascular events, fracture and parathyroidectomy among patients on maintenance dialysis. METHODS: Data sources included MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases. RCTs and observational studies were included. Data extraction was completed by two authors independently and in duplicate determined the methodological quality of the studies and extracted data. RESULTS: Of 564 unique citations identified, 16 studies were included: six observational studies and ten RCTs. Four high-quality studies (two observational and two RCTs) were deemed suitable for meta-analysis. Results indicated a statistically significant reduction in the risk of death associated with cinacalcet (hazard ratio: 0.83; 95% credible interval: 0.78-0.89). CONCLUSION: The results of this meta-analysis indicate that treatment of secondary hyperparathyroidism with calcimimetic therapy may in fact reduce mortality among patients receiving maintenance dialysis. This finding provides justification for a well-designed and adequately powered randomized trial to definitively address the question.

Diagnostic Accuracy of Transient Ischemic Attack from Physician Claims.

BACKGROUND: Hospitalization data underestimate the occurrence of transient ischemic attack (TIA). As TIA is frequently diagnosed in primary care, methodologies for the accurate ascertainment of a TIA from physician claims data are required for surveillance and health systems planning in this population. The present study evaluated the diagnostic accuracy of multiple algorithms for TIA from a longitudinal population-based physician billing database. METHODS: Population-based administrative data from the province of British Columbia were used to identify the base population (1992-2007; N=102,492). Using discharge records for hospital admissions for acute ischemic stroke with a recent (<90 days) TIA as the reference standard, we performed receiver-operating characteristic analyses to calculate sensitivity, specificity, positive and negative predictive values and overall accuracy, and to compare area under the curve for each physician billing algorithm. To evaluate the impact of different case definitions on population-based TIA burden, we also estimated the annual TIA occurrence associated with each algorithm. RESULTS: Physician billing algorithms showed low to moderate sensitivity, with the algorithm for two consecutive physician visits within 90 days showing the highest sensitivity at 37.7% (CI 95%=37.4-38.1). All algorithms demonstrated high specificity and moderate to high overall accuracy, resulting in low positive predictive values (≤5%), low discriminability (0.53-0.57) and high false positive rates (1 - specificity). Population-based estimates of TIA occurrence were comparable to prior studies and declined over time. CONCLUSIONS: Physician billing data have insufficient sensitivity to identify TIAs but may be used in combination with hospital discharge data to improve the accuracy of estimating the population-based occurrence of TIAs.

Funding and remuneration of interdisciplinary primary care teams in Canada: a conceptual framework and application.

BACKGROUND: Reliance on interdisciplinary teams in the delivery of primary care is on the rise. Funding bodies strive to design financial environments that support collaboration between providers. At present, the design of financial arrangements has been fragmented and not based on evidence. The root of the problem is a lack of systematic evidence demonstrating the superiority of any particular financial arrangement, or a solid understanding of options. In this study we develop a framework for the conceptualization and analysis of financial arrangements in interdisciplinary primary care teams. METHODS: We use qualitative data from three sources: (i) interviews with 19 primary care decision makers representing 215 clinics in three Canadian provinces, (ii) a research roundtable with 14 primary care decision makers and/or researchers, and (iii) policy documents. Transcripts from interviews and the roundtable were coded thematically and a framework synthesis approach was applied. RESULTS: Our conceptual framework differentiates between team level funding and provider level remuneration, and characterizes the interplay and consonance between them. Particularly the notions of hierarchy, segregation, and dependence of provider incomes, and the link between funding and team activities are introduced as new clarifying concepts, and their implications explored. The framework is applied to the analysis of collaboration incentives, which appear strongest when provider incomes are interdependent, funding is linked to the team as a whole, and accountability does not have multiple lines. Emergent implementation issues discussed by respondents include: (i) centrality of budget negotiations; (ii) approaches to patient rostering; (iii) unclear funding sources for space and equipment; and (iv) challenges with community engagement. The creation of patient rosters is perceived as a surprisingly contentious issue, and the challenges of funding for space and equipment remain unresolved. CONCLUSIONS: The development and application of a conceptual framework is an important step to the systematic study of the best performing financial models in the context of interdisciplinary primary care. The identification of optimal financial arrangements must be contextualized in terms of feasibility and the implementation environment. In general, financial hierarchy, both overt and covert, is considered a barrier to collaboration.

How best to structure interdisciplinary primary care teams: the study protocol for a systematic review with narrative framework synthesis.

BACKGROUND: Western publicly funded health care systems increasingly rely on interdisciplinary teams to support primary care delivery and management of chronic conditions. This knowledge synthesis focuses on what is known in the academic and grey literature about optimal structural characteristics of teams. Its goal is to assess which factors contribute to the effective functioning of interdisciplinary primary care teams and improved health system outcomes, with specific focus on (i) team structure contribution to team process, (ii) team process contribution to primary care goals, and (iii) team structure contribution to primary care goals. METHODS AND DESIGN: The systematic search of academic literature focuses on four chronic conditions and co-morbidities. Within this scope, qualitative and quantitative studies that assess the effects of team characteristics (funding, governance, organization) on care process and patient outcomes will be searched. Electronic databases (Ovid MEDLINE, Embase, CINAHL, PAIS, Web of Science) will be searched systematically. Online web-based searches will be supported by the Grey Matters Tool. Studies will be included, if they report on interdisciplinary primary care in publicly funded Western health systems, and address the relationships between team structure, process, and/or patient outcomes. Studies will be selected in a three-stage screening process (title/abstract/full text) by two independent reviewers in each stage. Study quality will be assessed using the Mixed Methods Assessment Tool. An a priori framework will be applied to data extraction, and a narrative framework approach is used for the synthesis. DISCUSSION: Using an integrated knowledge translation approach, an electronic decision support tool will be developed for decision makers. It will be searchable along two axes of inquiry: (i) what primary care goals are supported by specific team characteristics and (ii) how should teams be structured to support specific primary care goals? The results of this evidence review will contribute directly to the design of interdisciplinary primary care teams. The optimized design will support the goals of primary care, contributing to the improved health of populations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016041884.

Association Between Incretin-Based Drugs and the Risk of Acute Pancreatitis.

IMPORTANCE: The association between incretin-based drugs, such as dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists, and acute pancreatitis is controversial. OBJECTIVE: To determine whether the use of incretin-based drugs, compared with the use of 2 or more other oral antidiabetic drugs, is associated with an increased risk of acute pancreatitis. DESIGN, SETTING, AND PARTICIPANTS: A large, international, multicenter, population-based cohort study was conducted using combined health records from 7 participating sites in Canada, the United States, and the United Kingdom. An overall cohort of 1 532 513 patients with type 2 diabetes initiating the use of antidiabetic drugs between January 1, 2007, and June 30, 2013, was included, with follow-up until June 30, 2014. EXPOSURES: Current use of incretin-based drugs compared with current use of at least 2 oral antidiabetic drugs. MAIN OUTCOMES AND MEASURES: Nested case-control analyses were conducted including hospitalized patients with acute pancreatitis matched with up to 20 controls on sex, age, cohort entry date, duration of treated diabetes, and follow-up duration. Hazard ratios (HRs) and 95% CIs for hospitalized acute pancreatitis were estimated and compared current use of incretin-based drugs with current use of 2 or more oral antidiabetic drugs. Secondary analyses were performed to assess whether the risk varied by class of drug (DPP-4 inhibitors and GLP-1 agonists) or by duration of use. Site-specific HRs were pooled using random-effects models. RESULTS: Of 1 532 513 patients included in the analysis, 781 567 (51.0%) were male; mean age was 56.6 years. During 3 464 659 person-years of follow-up, 5165 patients were hospitalized for acute pancreatitis (incidence rate, 1.49 per 1000 person-years). Compared with current use of 2 or more oral antidiabetic drugs, current use of incretin-based drugs was not associated with an increased risk of acute pancreatitis (pooled adjusted HR, 1.03; 95% CI, 0.87-1.22). Similarly, the risk did not vary by drug class (DPP-4 inhibitors: pooled adjusted HR, 1.09; 95% CI, 0.86-1.22; GLP-1 agonists: pooled adjusted HR, 1.04; 95% CI, 0.81-1.35) and there was no evidence of a duration-response association. CONCLUSIONS AND RELEVANCE: In this large population-based study, use of incretin-based drugs was not associated with an increased risk of acute pancreatitis compared with other oral antidiabetic drugs.

The impact of adverse events on health care costs for older adults undergoing nonelective abdominal surgery.

BACKGROUND: Postoperative complications have been identified as an important and potentially preventable cause of increased hospital costs. While older adults are at increased risk of experiencing complications and other adverse events, very little research has specifically examined how these events impact inpatient costs. We sought to examine the association between postoperative complications, hospital mortality and loss of independence and direct inpatient health care costs in patients 70 years or older who underwent nonelective abdominal surgery. METHODS: We prospectively enrolled consecutive patients 70 years or older who underwent nonelective abdominal surgery between July 1, 2011, and Sept. 30, 2012. Detailed patient-level data were collected regarding demographics, diagnosis, treatment and outcomes. Patient-level resource tracking was used to calculate direct hospital costs (2012 $CDN). We examined the association between complications, hospital mortality and loss of independence cost using multiple linear regression. RESULTS: During the study period 212 patients underwent surgery. Overall, 51.9% of patients experienced a nonfatal complication (32.5% minor and 19.4% major), 6.6% died in hospital and 22.6% experienced a loss of independence. On multivariate analysis nonfatal complications (p < 0.001), hospital mortality (p = 0.021) and loss of independence at discharge (p < 0.001) were independently associated with health care costs. These adverse events respectively accounted for 30%, 4% and 10% of the total costs of hospital care. CONCLUSION: Adverse events were common after abdominal surgery in older adults and accounted for 44% of overall costs. This represents a substantial opportunity for better patient outcomes and cost savings with quality improvement strategies tailored to the needs of this high-risk surgical population.

CONTEXTE: Les complications postopératoires sont une cause évitable qui contribue grandement aux coûts hospitaliers élevés. Malgré le fait que les personnes âgées courent un risque accru de subir des complications ou des événements indésirables, peu de recherches ont étudié l'incidence de ces éléments sur les coûts d'hospitalisation. Nous nous sommes penchés sur la relation entre les coûts des soins de santé assumés par les malades hospitalisés et les complications postopératoires, la mortalité hospitalière et la perte d'autonomie auprès d'une population de patients de 70 ans et plus ayant subi une intervention chirurgicale abdominale non facultative. MÉTHODES: La cohorte prospective a été formée de patients consécutifs âgés de 70 ans et plus ayant subi une intervention chirurgicale abdominale non facultative entre le 1er juillet 2011 et le 30 septembre 2012. Des données détaillées concernant leur profil démographique, leur diagnostic, leur traitement et leurs résultats ont été recueillies. Le calcul des coûts hospitaliers directs est basé sur un suivi des ressources utilisées par les patients (en dollars canadiens, 2012). Au moyen d'une régression linéaire multiple, nous avons analysé la relation entre les complications, la mortalité hospitalière et la perte d'autonomie. RÉSULTATS: Pendant la période à l'étude, 212 patients ont subi une intervention chirurgicale. Parmi eux, 51,9 % ont subi une complication non mortelle (mineure dans 32,5 % des cas; majeure dans 19,4 % des cas), 6,6 % sont décédés à l'hôpital, et 22,6 % ont subi une perte d'autonomie. Une analyse multivariable a permis de conclure que les complications non mortelles (p < 0,001), la mortalité hospitalière (p = 0,021) et la perte d'autonomie à la sortie de l'hôpital (p < 0,001) étaient indépendamment associées aux coûts des soins de santé et qu'elles représentaient respectivement 30 %, 4 % et 10 % des coûts d'hospitalisation totaux. CONCLUSION: Les événements indésirables étaient fréquents dans le contexte des interventions chirurgicales abdominales réalisées sur des personnes âgées et représentaient 44 % des coûts totaux. Nous devons saisir cette occasion et nous doter de stratégies d'amélioration de la qualité adaptées aux besoins de cette population, à risque élevé sur le plan chirurgical, afin d'améliorer les résultats pour les patients et de diminuer les coûts.

Liver-specific case fatality due to chronic hepatitis C virus infection: a systematic review.

Despite reports that mortality is increasing, overall case fatality due to hepatitis C virus (HCV) is thought to be low. Given the variability in published rates, we aimed to synthesize estimates of liver-specific case fatality and all-cause mortality in chronic HCV according to follow-up duration, sustained viral response (SVR) to treatment, and liver disease severity. A systematic review was conducted of studies published in English from 2003 to 2013, reporting liver-specific case fatality estimates from HCV-infected samples. Thirty-five eligible articles were identified; 26 also presented estimates of all-cause mortality. Among community-based samples, liver-specific case fatality ranged from 0.3% over 5.7 years to 9.2% over 8.2 years of follow-up; and of all-cause mortality, from 4.0% over 5.7 years, to 23.0% over 8.2 years of follow-up. Estimates were higher among clinic-based samples and those with more severe liver disease. Among treated patients achieving SVR, liver-specific case fatality was low: up to 1.4% over 11.5 years of follow-up among samples with any severity of liver disease. Estimates were higher among those without SVR: up to 14.0% over 10 years of followup among samples with any severity of liver disease, and higher still among samples with more severe liver disease. The proportion of deaths attributable to liver-specific causes ranged from 55 to 85% among those with severe liver disease. Published estimates of fatality are high among certain populations of chronic HCV patients, with liver-specific causes being an important contributor. Understanding current HCV mortality rates is important for quantifying the total burden of HCV disease.

Incidence and Costs of Clostridium difficile Infections in Canada.

Background. Limited data are available on direct medical costs and lost productivity due to Clostridium difficile infection (CDI) in Canada. Methods. We developed an economic model to estimate the costs of managing hospitalized and community-dwelling patients with CDI in Canada. The number of episodes was projected based on publicly available national rates of hospital-associated CDI and the estimate that 64% of all CDI is hospital-associated. Clostridium difficile infection recurrences were classified as relapses or reinfections. Resource utilization data came from published literature, clinician interviews, and Canadian CDI surveillance programs, and this included the following: hospital length of stay, contact with healthcare providers, pharmacotherapy, laboratory testing, and in-hospital procedures. Lost productivity was considered for those under 65 years of age, and the economic impact was quantified using publicly available labor statistics. Unit costs were obtained from published sources and presented in 2012 Canadian dollars. Results. There were an estimated 37 900 CDI episodes in Canada in 2012; 7980 (21%) of these were relapses, out of a total of 10 900 (27%) episodes of recurrence. The total cost to society of CDI was estimated at $281 million; 92% ($260 million) was in-hospital costs, 4% ($12 million) was direct medical costs in the community, and 4% ($10 million) was due to lost productivity. Management of CDI relapses alone accounted for $65.1 million (23%). Conclusions. The largest proportion of costs due to CDI in Canada arise from extra days of hospitalization. Interventions reducing the severity of infection and/or relapses leading to rehospitalizations are likely to have the largest absolute effect on direct medical costs.