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.

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.

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.

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.

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.

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.

Predictors of interleukin-33 and thymic stromal lymphopoietin levels in cord blood.

BACKGROUND: The fetal immune system is a critical window of development. The epithelial cell-derived cytokines, thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33) have received attention for their role in allergic responses but not been studied during this critical window. The objectives were to assess correlations among IL-33, TSLP, and IgE in umbilical cord blood samples and identify prenatal predictors of these biomarkers. METHODS: This study utilized data and banked cord blood collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2001 pregnant women. Our analytic sample comprised the 1254 women with a singleton, term birth with a cord blood sample. Spearman correlation coefficients (SCC) and logistic regression models were used to examine associations between biomarkers and identify potential predictors of elevated biomarker levels. RESULTS: Thymic stromal lymphopoietin and IL-33 were more strongly correlated with each other (SCC = 0.75, p < 0.0001) than with IgE (IL-33 SCC = 0.14, TSLP SCC = 0.21). Maternal allergy, heavy street traffic, and elevated birth weight were significantly associated with jointly elevated TSLP and IL-33 levels, whereas maternal age and female infant sex were inversely associated with elevated IgE. CONCLUSIONS: In this population of Canadian women and infants, TSLP and IL-33 were detectable in cord blood, more strongly correlated with each other than with IgE, and associated with maternal characteristics indicative of inflammatory responses. This study motivates investigation into the value of cord blood IL-33 and TSLP levels as childhood allergy predictors and raises interesting questions regarding in utero coordinated regulation of these cytokines.

Prenatal exposure to phthalates, bisphenol A and perfluoroalkyl substances and cord blood levels of IgE, TSLP and IL-33.

The fetal time period is a critical window of immune system development and resulting heightened susceptibility to the adverse effects of environmental exposures. Epidemiologists and toxicologists have hypothesized that phthalates, bisphenol A (BPA) and perfluoroalkyl substance have immunotoxic properties. Immunotoxic effects of chemicals may manifest in an altered immune system profile at birth. Immunoglobulin E, thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33) are integral in the etiology of childhood allergy and detectable at birth. The objective of this study was to determine the association between maternal levels of phthalates, bisphenol A (BPA), and perfluoroalkyl substances and elevated umbilical cord blood levels of IgE, TSLP, and IL-33. This study utilized data collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2001 pregnant women. Of these women, 1258 had a singleton, term birth and cord blood sample. A Bayesian hierarchical model was employed to determine associations between log-transformed continuous variables and immune system biomarkers while adjusting for potential confounding from correlated environmental contaminants. Inverse, nonlinear associations were observed between maternal urinary MCPP levels and elevated levels of both IL-33/TSLP and IgE and between maternal urinary BPA levels and elevated levels of IL-33/TSLP. In this primarily urban Canadian population of pregnant women and their newborns, maternal urinary and plasma concentrations of phthalate metabolites, BPA, and perfluoroalkyl substances were not associated with immunotoxic effects that manifest as increased odds of elevated levels of IgE, TSLP or IL-33.

Maternal exposure to metals and persistent pollutants and cord blood immune system biomarkers.

BACKGROUND: The fetal time period is a critical window of immune system development and resulting heightened susceptibility to the adverse effects of environmental exposures. Epidemiologists and toxicologists have hypothesized that persistent organic pollutants, pesticides and metals have immunotoxic properties. Immunotoxic effects may manifest as an altered immune system profile at birth. Immunoglobulin E, thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33) may be implicated in the etiology of childhood allergy and are detectable at birth. The objective of this study was to examine the potential relationship between maternal concentrations of metals, persistent organic pollutants, and pesticides and elevated umbilical cord blood concentrations of IgE, TSLP, and IL-33 in a Canadian birth cohort. METHODS: This study utilized data collected in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada cohort study of 2,001 pregnant women. Of these women, 1258 had a singleton, term birth and cord blood sample. Logistic regression was used to determine associations between log-transformed continuous variables and immune system biomarkers. RESULTS: Inverse relationships were observed between lead, DDE, PCB-118, and a summary index of organophosphorous metabolites and jointly elevated concentrations of IL-33 and TSLP. None of the environmental contaminants were associated with increased odds of a high cord blood immune system biomarker concentration. CONCLUSIONS: In this primarily urban Canadian population of pregnant women and their newborns, maternal blood or urine concentrations of persistent organic pollutants, pesticides, and metals were not associated with immunotoxic effects that manifest as increased odds of elevated concentrations of IgE, TSLP or IL-33.

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.

A population-based study of childhood respiratory morbidity after severe lower respiratory tract infections in early childhood.

OBJECTIVES: To estimate the risk of childhood chronic respiratory morbidity among those hospitalized for severe lower respiratory tract infection (LRTI) in early childhood, and to determine whether severe LRTI is an independent predictor. STUDY DESIGN: The population-based Régie de l'Assurance Maladie du Québec datasets were used to identify LRTI hospitalizations before age 2 years in a birth cohort from 1996-1997 and a comparison cohort of children without an LRTI hospitalization. The incidence rate and incidence rate ratio of chronic respiratory morbidity before age 10 years were calculated, and multivariable logistic regression was performed to estimate the impact of LRTI hospitalization on chronic respiratory morbidity. Population-attributable risks of chronic respiratory morbidity due to severe LRTI were estimated, and similar analyses were performed for respiratory syncytial virus LRTI. RESULTS: Among the birth cohort, 7104 patients (4.9%) were hospitalized for LRTI before age 2 years. By age 10 years, 52.5% of the LRTI cohort and 27.9% of the nonhospitalized cohort had developed chronic respiratory morbidity; the incidence rate ratio was 1.81 (95% CI, 1.76-1.86) for males and 1.91 (95% CI, 1.84-1.99) for females. The OR for chronic respiratory morbidity based on LRTI hospitalization before age 2 years was 2.79 (95% CI, 2.66-2.93). The population-attributable risk of chronic respiratory morbidity due to any LRTI was approximately 25%, and that for respiratory syncytial virus LRTI was similar. CONCLUSIONS: Hospitalization of young children for LRTIs is associated with two-fold increased risk of childhood chronic respiratory morbidity, demonstrating the ongoing impact of LRTI in infancy.

Projecting long-term graft and patient survival after transplantation.

OBJECTIVE: In spite of increases in short-term kidney transplant survival rates and reductions in acute rejection rates, increasing long-term graft survival rates remains a major challenge. The objective here was to project long-term graft- and survival-related outcomes occurring among renal transplant recipients based on short-term outcomes including acute rejection and estimated glomerular filtration rates observed in randomized trials. METHODS: We developed a two-phase decision model including a trial phase and a Markov state transition phase to project long-term outcomes over the lifetimes of hypothetical renal graft recipients who survived the trial period with a functioning graft. Health states included functioning graft stratified by level of renal function, failed graft, functioning regraft, and death. Transitions between health states were predicted using statistical models that accounted for renal function, acute rejection, and new-onset diabetes after transplant and for donor and recipient predictors of long-term graft and patient survival. Models were estimated using data from 38,015 renal transplant recipients from the United States Renal Data System. The model was populated with data from a 3-year, randomized phase III trial comparing belatacept to cyclosporine. RESULTS: The decision model was well calibrated with data from the United States Renal Data System. Long-term extrapolation of Belatacept Evaluation of Nephroprotection and Efficacy as Firstline Immunosuppression Trial was projected to yield a 1.9-year increase in time alive with a functioning graft and a 1.2 life-year increase over a 20-year time horizon. CONCLUSIONS: This is the first long-term follow-up model of renal transplant patients to be based on renal function, acute rejection, and new-onset diabetes. It is a useful tool for undertaking comparative effectiveness and cost-effectiveness studies of immunosuppressive medications.

Decreasing incidence of inflammatory bowel disease in eastern Canada: a population database study.

BACKGROUND: Nova Scotia has one of the highest incidences of inflammatory bowel disease (IBD) in the world. We wished to determine trends of IBD over time. METHODS: All Provincial residents have government provided health insurance and all interactions with the hospital, and physician billing systems, are captured on an administrative database. We used a validated measure to define incident cases of Crohn's (CD), ulcerative colitis (UC) and undifferentiated IBD (IBDU). Incidence rates of these diseases for the years 1996-2009 were calculated. RESULTS: Over the study period, 7,153 new cases of IBD were observed of which 3,046 cases were categorized as CD (42.6%), 2,960 as UC (41.4%) and 1,147 as IBDU (16.0%). Annual age standardized incidence rates were very high but have declined for CD from 27.4 to 17.7/100,000 population and for UC from 21.4 to 16.7/100,000. The decline was seen in all age groups and both genders. The decrease was not explained by a small increase in IBDU. CONCLUSION: The incidence of CD and UC are decreasing in Nova Scotia. If replicated elsewhere this indicates a reversal after a long period of increasing occurrence of IBD. This has implications for both epidemiology and health planning.

Health technology assessment and personalized medicine: are economic evaluation guidelines sufficient to support decision making?

BACKGROUND: Many jurisdictions delivering health care, including Canada, have developed guidance for conducting economic evaluation, often in the service of larger health technology assessment (HTA) and reimbursement processes. Like any health intervention, personalized medical (PM) interventions have costs and consequences that must be considered by reimbursement authorities with limited resources. However, current approaches to economic evaluation to support decision making have been largely developed from population-based approaches to therapy-that is, evaluating the costs and consequences of single interventions across single populations. This raises the issue as to whether these methods, as they are or more refined, are adequate to address more targeted approaches to therapy, or whether a new paradigm for assessing value in PM is required. OBJECTIVES: We describe specific issues relevant to the economic evaluation of diagnostics-based PM and assess whether current guidance for economic evaluation is sufficient to support decision making for PM interventions. METHODS: Issues were identified through literature review and informal interviews with national and international experts (n = 10) in these analyses. This article elaborates on findings and discussion at a workshop held in Ottawa, Canada, in January 2012. RESULTS: Specific issues related to better guiding economic evaluation of personalized medicine interventions include: how study questions are developed, populations are characterized, comparators are defined, effectiveness is evaluated, outcomes are valued and how resources are measured. Diagnostics-based PM also highlights the need for analyses outside of economic evaluation to support decision making. CONCLUSIONS: The consensus of this group of experts is that the economic evaluation of diagnostics-based PM may not require a new paradigm. However, greater complexity means that existing approaches and tools may require improvement to undertake these more analyses.

Elevated risk of asthma after hospitalization for respiratory syncytial virus infection in infancy.

Severe respiratory syncytial virus (RSV) infection in infancy is associated with substantial morbidity worldwide; whether it is a risk factor for childhood asthma is contentious. A systematic review of 28 articles was conducted, summarizing estimates of asthma risk after RSV hospitalization during infancy. Prevalence estimates of asthma, among those hospitalized for RSV in infancy, were from 8% to 63%, 10% to 92%, and 37%, at ages <5, 5 to 11, and ≥ 12 years, respectively. These rates were higher than those among non-hospitalized comparisons. The attributable risk of asthma due to RSV ranged from 13% to 22% and from 11% to 27% among children aged ≤ 5 and aged 5 to 11, respectively, and was 32% among children ≥ 12 years of age. Overall, 59% of asthma prevalence estimates from those previously hospitalized for RSV exceeded 20%, compared to only 6% of non-hospitalized comparison estimates. Despite variability in asthma prevalence estimates after RSV-related hospitalization, available data suggest a link between severe RSV infection in infancy and childhood asthma.

The risk of mortality among young children hospitalized for severe respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is the leading cause of childhood morbidity. Although also an important cause of childhood mortality worldwide, the impact of key risk factors has not been established. A systematic review of 34 articles reporting case fatality rates in young children hospitalized for severe RSV LRTI, according to the presence of underlying RSV risk factors, was conducted. The weighted mean case fatality rate was 1.2% (range, 0-8.3%; median, 0%; n = 10) among preterm infants; 5.2% (range, 2.0-37.0%; median, 5.9%; n = 7) among children with CHD; and 4.1% (range, 0-10.5%; median, 7.0%; n = 6) among children with BPD. Case fatality estimates among children not at high risk (n = 6) ranged from 0% to 1.5% (weighted mean, 0.2%; median, 0.0%). Fatality during hospitalization for severe RSV LRTI is rare among children not at high risk, but occurs more commonly among children at higher risk of RSV LRTI.

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.

Hierarchical priors for bias parameters in Bayesian sensitivity analysis for unmeasured confounding.

Recent years have witnessed new innovation in Bayesian techniques to adjust for unmeasured confounding. A challenge with existing methods is that the user is often required to elicit prior distributions for high-dimensional parameters that model competing bias scenarios. This can render the methods unwieldy. In this paper, we propose a novel methodology to adjust for unmeasured confounding that derives default priors for bias parameters for observational studies with binary covariates. The confounding effects of measured and unmeasured variables are treated as exchangeable within a Bayesian framework. We model the joint distribution of covariates by using a log-linear model with pairwise interaction terms. Hierarchical priors constrain the magnitude and direction of bias parameters. An appealing property of the method is that the conditional distribution of the unmeasured confounder follows a logistic model, giving a simple equivalence with previously proposed methods. We apply the method in a data example from pharmacoepidemiology and explore the impact of different priors for bias parameters on the analysis results.

Increased risk of cardiovascular and cerebrovascular diseases in individuals with ankylosing spondylitis: a population-based study.

OBJECTIVE: To estimate the excess risk of cardiovascular and cerebrovascular diseases among individuals with ankylosing spondylitis (AS) in Quebec compared with the general population of Quebec. METHODS: A retrospective cohort study was conducted using population-based administrative data from Quebec. The cohort included all adult individuals with at least 1 AS diagnosis on physician billing or hospital discharge records between 1996 and 2006. A comparison cohort was generated using a 1% random sample of individuals without AS. Cardiovascular and cerebrovascular diseases, and associated hospitalizations, were classified into 1 of 6 subcategories: congestive heart failure, valvular (aortic or nonaortic) heart disease, ischemic heart disease, cerebrovascular disease, or "other" cardiovascular disease. The age- and sex-stratified prevalence estimates, and standardized prevalence ratios, of cardiovascular or cerebrovascular disease in patients with AS, compared to that in the general population, were calculated. RESULTS: The AS cohort included 8,616 individuals diagnosed over the period 1996-2006. The prevalence of cardiovascular and cerebrovascular diseases increased with increasing age for all cardiovascular disease subgroups, and was similar for individuals of both sexes. Age- and sex-stratified prevalence ratios were highest in younger individuals with AS. The age- and sex-standardized prevalence ratios comparing the risk among those with AS to the risk in the general population were as follows: for aortic valvular heart disease 1.58 (95% confidence interval [95% CI] 1.31-1.91), for nonaortic valvular heart disease 1.58 (95% CI 1.43-1.74), for ischemic heart disease 1.37 (95% CI 1.31-1.44), for congestive heart failure 1.34 (95% CI 1.26-1.42), for "other" cardiovascular disease 1.36 (95% CI 1.29-1.44), for cerebrovascular disease 1.25 (95% CI 1.15-1.35), and for any hospitalization for a cardiovascular or cerebrovascular disease 1.31 (95% CI 1.22-1.41). CONCLUSION: Compared with the general population, patients with AS are at increased risk for many types of cardiovascular and cerebrovascular diseases, and are more likely to be hospitalized for these diseases. The excess risk is greatest in younger patients with AS.