Indirect impact of childhood 13-valent pneumococcal conjugate vaccine (PCV13) in Canadian older adults: a Canadian Immunization Research Network (CIRN) retrospective observational study.

BACKGROUND: 13-valent pneumococcal conjugate vaccine (PCV13) has been part of publicly funded childhood immunisation programmes in Ontario and British Columbia (BC) since 2010. We assessed the indirect impact of infant PCV13 programmes on invasive pneumococcal disease (IPD) and all-cause pneumonia hospitalisation in older adults (aged ≥65 years) using a retrospective observational study. METHODS: We extracted monthly IPD and all-cause pneumonia cases from laboratory and health administrative databases between January 2005 and December 2018. Using a quasi-experimental difference-in-differences design, we calculated the ratio of risk ratios (RRRs) using incidence rates of IPD or all-cause pneumonia cases before (pre-PCV13 period) and after (PCV13 period) 2010 with rates of fractures as controls. RESULTS: The rates of all IPD or PCV serotype-specific IPD for older adults in both Ontario and BC did not change in 8 years after childhood PCV13 programme implementation. All-cause pneumonia increased in Ontario (RRR 1.38, 95% CI 1.11 to 1.71) but remained unchanged in BC. CONCLUSIONS: Indirect community protection of older adults from hospitalisation with pneumococcal disease stalled despite maturation of childhood PCV13 vaccination programmes in two Canadian provinces.

Quality of antibiotic prescribing for pediatric community-acquired Pneumonia in outpatient care.

BACKGROUND: Antibiotics remain the primary treatment for community acquired pneumonia (CAP), however rising rates of antimicrobial resistance may jeopardize their future efficacy. With higher rates of disease reported in the youngest populations, effective treatment courses for pediatric pneumonia are of paramount importance. This study is the first to examine the quality of pediatric antibiotic use by agent, dose and duration. METHODS: A retrospective cohort study included all outpatient/primary care physician visits for pediatric CAP (aged < 19 years) between January 1 2014 to December 31 2018. Relevant practice guidelines were identified, and treatment recommendations extracted. Amoxicillin was the primary first-line agent for pediatric CAP. Categories of prescribing included: guideline adherent, effective but unnecessary (excess dose and/or duration), under treatment (insufficient dose and/or duration), and not recommended. Proportions of attributable-antibiotic use were examined by prescribing category, and then stratified by age and sex. RESULT(S): A total of 42,452 episodes of pediatric CAP were identified. Of those, 31,347 (76%) resulted in an antibiotic prescription. Amoxicillin accounted for 51% of all prescriptions. Overall, 27% of prescribing was fully guideline adherent, 19% effective but unnecessary, 10% under treatment, and 44% not recommended by agent. Excessive duration was the hallmark of effective but unnecessary prescribing (97%) Macrolides accounted for the majority on non-first line agent use, with only 32% of not recommended prescribing preceded by a previous course of antibiotics. CONCLUSION(S): This study is the first in Canada to examine prescribing quality for pediatric CAP by agent, dose and duration. Utilizing first-line agents, and shorter-course treatments are targets for stewardship.

Retrospective Cohort Analysis of Outpatient Antibiotic Use for Clostridioides difficile-Indicated Agents in British Columbia, from 2000 to 2018.

Background: Clostridioides difficile (CDI) is the most common cause of nosocomial diarrheal infections. Historically, metronidazole was the first-line treatment, but guidelines now indicate oral vancomycin and fidaxomicin as primary antibiotics for initial episodes. A provincial stewardship program has operated in British Columbia (BC), since 2005. Since the program's inception, surveillance of antibiotic use has been ongoing. However, this is the first study to review community-acquired CDI-indicated antibiotic use. Moreover, this study offers the first interpretation of fidaxomicin use in BC since its addition to the provincial formulary. Methods: A retrospective cohort analysis included all outpatient dispensations for CDI-related antibiotics from January 1, 2000, to December 31, 2018. Antibiotic dispensations were extracted for metronidazole, vancomycin, and fidaxomicin. Consumption rates were calculated as prescriptions per 1000 population. Rates were examined overall and then stratified by medication, age, and sex. Secondary outcomes of interest included an examination of adherence to provincial special authority criteria; and proportions of outpatient antibiotic use attributable to administrative health records for CDI. Results: The average annual rate of prescribing was 18.5 per 1000 population for all CDI-indicated antibiotics. The rate of prescribing increased (15%) over the 19-year study period, from 17.2 to 19.8 dispensations per 1000 population. Metronidazole accounted for the most antibiotics dispensed in every study year; however, by 2018 it demonstrated the most modest increase in use (15%). In comparison, fidaxomicin increased by 226% by 2018. Vancomycin had the highest percentage increase (621%), with the greatest change occurring from 2014 to 2015, correlating to the dissemination of new clinical practice guidelines. Conclusion: This is the first study to evaluate outpatient prescribing for CDI-indicated antibiotics, and one of the few studies to examine fidaxomicin since its introduction to Canadian formularies. Although causation cannot be inferred from study results, oral vancomycin, and fidaxomicin use has increased in line with, or in advance-of guidelines.

Healthcare Costs for Pneumococcal Disease in the Era of Infant Immunization With 13-Valent Pneumococcal Conjugate Vaccine: A Population-Based Study.

OBJECTIVES: Invasive pneumococcal disease (IPD) and a variety of clinical syndromes caused by pneumococci, such as acute otitis media (AOM), acute sinusitis (AS), and community-acquired pneumonia (CAP), cause a substantial burden on healthcare systems. Few studies have explored the short-term financial burden of pneumococcal disease after the 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the infant immunization programs. This population-based study evaluated changes in costs associated with healthcare utilization for pneumococcal disease after the PCV13 introduction in the infant immunization program in British Columbia, Canada. METHODS: Individuals with pneumococcal disease were identified using provincial administrative data for the 2000 to 2018 period. Total direct healthcare costs were determined using case-mix methodology for hospitalization and fee-for-service codes for outpatient visits and medications dispensed. Costs were adjusted to 2018 Canadian dollars. Changes in the annual healthcare costs were evaluated across vaccine eras (pre-PCV13, 2000-2010; PCV13, 2011-2018) using generalized linear models, adjusting for the 7-valent pneumococcal conjugate vaccine program (2004-2010). RESULTS: During the 19-year study period, pneumococcal disease resulted in 6.3 million cases among 85 million total patient-years, resulting in total healthcare costs of $7.9 billion. More than 6.2 million cases were treated in outpatient setting, costing $0.65 billion (8% of total costs associated with pneumococcal disease treatment), whereas 370 000 hospitalized cases were 3% of all cases, which accrued $7.25 billion (92% of total costs) in costs. Healthcare costs for all studied infections nearly doubled over the study period from $248 million in 2000 to $476 million in 2018 (P = .003). In contrast, there were large declines in total annual costs in the PCV13 era for IPD (adjusted relative rate (aRR) 0.73; 95% confidence interval [CI] 0.56-0.95; P = .032), AOM (aRR 0.70; 95% CI 0.59-0.83; P = .001), and AS (aRR 0.68; 95% CI 0.54-0.85; P = .004) compared with the pre-PCV13 era. Total costs increased marginally in the PCV13 era for all-cause CAP (aRR 1.04; 95% CI 0.94-1.15; P = .484). CONCLUSIONS: This study confirms a temporal association in declining economic burden for IPD, AOM, and AS after the PCV13 introduction. Nevertheless, the total economic burden continues to be high in the PCV13 era, mainly driven by increasing CAP costs.

Impact of the 13-valent pneumococcal conjugate vaccine on acute otitis media and acute sinusitis epidemiology in British Columbia, Canada.

BACKGROUND: Numerous studies have characterized the 13-valent pneumococcal conjugate vaccine (PCV13) programme's beneficial effects on acute otitis media (AOM) and acute sinusitis (AS) rates in children; however, few studies have examined the impact on adults. OBJECTIVES: This retrospective cohort study evaluates the overall effect of the PCV13 immunization programme on the incidence of AOM and AS at the population level. METHODS: Health administrative databases were linked to assess outpatient visits, hospitalizations and antibiotic utilization from 2000 to 2018. Multivariable Poisson regression was used to evaluate the impact of the PCV13 vaccine programme (2011-18) compared with the pre-PCV13 era (2000-10), overall and by age. RESULTS: From 2000 to 2018, the incidence of AOM decreased by 50% (62 to 31 per 1000 population) while sinusitis decreased by 18% (33 to 27 per 1000 population). In the PCV13 era, the incidence of AOM declined [incidence rate ratio (IRR): 0.70; 95% CI: 0.70-0.70], in parallel with decreased incidence of antibiotic utilization (IRR: 0.65; 95% CI: 0.64-0.65). A reduction was also observed in the incidence of AS during the PCV13 era compared with the pre-PCV13 era (IRR: 0.88; 95% CI: 0.88-0.88), mainly driven by declines among those younger than 65 years of age. In contrast, an increase in AS incidence was noted in individuals aged ≥65 years (IRR: 1.03; 95% CI: 1.02-1.03). A decrease in antibiotic prescription rates for sinusitis was observed for those under 65 years of age. CONCLUSIONS: The PCV13 immunization programme is associated with a reduction in the incidence of AOM and AS. Moreover, the associated use of antibiotics for these diagnoses has comparably decreased across paediatric, as well as adult populations.

Regional variation in the potentially inappropriate first-line use of fluoroquinolones in Canada as a key to antibiotic stewardship? A drug utilization review study.

BACKGROUND: Serious adverse effects of fluoroquinolone antibiotics have been described for more than decade. Recently, several drug regulatory agencies have advised restricting their use in milder infections for which other treatments are available, given the potential for disabling and possibly persistent side effects. We aimed to describe variations in fluoroquinolone use for initial treatment of urinary tract infection (UTI), acute bacterial sinusitis (ABS), and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the outpatient setting across Canada. METHODS: Using administrative health data from six provinces, we identified ambulatory visits with a diagnosis of uncomplicated UTI, uncomplicated AECOPD or ABS. Antibiotic exposure was determined by the first antibiotic dispensed within 5 days of the visit. RESULTS: We identified 4,303,144 uncomplicated UTI events among 2,170,027 women; the proportion of events treated with fluoroquinolones, mostly ciprofloxacin, varied across provinces, ranging from 18.6% (Saskatchewan) to 51.6% (Alberta). Among 3,467,678 ABS events (2,087,934 patients), between 2.2% (Nova Scotia) and 11.2% (Ontario) were dispensed a fluoroquinolone. For 1,319,128 AECOPD events among 598,347 patients, fluoroquinolones, mostly levofloxacin and moxifloxacin, ranged from 5.8% (Nova Scotia) to 35.6% (Ontario). The proportion of uncomplicated UTI and ABS events treated with fluoroquinolones declined over time, whereas it remained relatively stable for AECOPD. CONCLUSIONS: Fluoroquinolones were commonly used as first-line therapies for uncomplicated UTI and AECOPD. However, their use varied widely across provinces. Drug insurance formulary criteria and enforcement may be a key to facilitating better antibiotic stewardship and limiting potentially inappropriate first-line use of fluoroquinolones.

Impacts of Human Papillomavirus Immunization Programs on Rates of Anogenital Warts in British Columbia, Canada, 2000 to 2017.

BACKGROUND: In 2008, British Columbia (BC) implemented a school-based quadrivalent human papillomavirus (HPV-4) immunization program for girls born in 1994 or later. In 2015, an expanded clinic-based program included men who report sex with men (MSM) born in 1989 or later. To evaluate the impacts of HPV-4 programs on anogenital warts (AGWs), diagnosis rates were measured among women who report sex with men (WSM), men who report sex with women (MSW), and MSM. METHODS: Diagnoses of AGW were ascertained from 16 sexually transmitted infection clinics. Rates were calculated as new AGW diagnoses over person-years (py) at risk and stratified by age group, calendar period, and birth cohort. Adjusted relative rates (aRR) were estimated using multivariable Poisson regression. RESULTS: There were 204,832 clinic visits by 85,158 individuals: 28,366 (33%) WSM, 35,688 (42%) MSW, and 14,534 (17%) MSM. After adjusting for age and period, AGW rates in the 1994-1996 birth cohort decreased by 56% overall (1.21 vs. 2.72 cases/100 py; aRR, 0.44; 95% confidence interval [CI], 0.34-0.59), 65% among WSM (0.97 vs. 2.77 cases/100 py; aRR, 0.35; 95% CI, 0.22-0.57), 58% among MSW (1.60 vs. 3.78 cases/100 py; aRR, 0.42; 95% CI, 0.28-0.65), and 41% among MSM (1.14 vs. 1.19 cases/100 py; aRR, 0.59; 95% CI, 0.38-0.91) versus the 1991-1993 birth cohort. CONCLUSIONS: The HPV-4 programs had significant impacts on lowering AGW rates in BC. The greatest decrease was among WSM eligible for the school-based program, followed by birth cohorts of men who likely have sex with HPV-4 eligible women. The smallest decrease among MSM may reflect the later introduction of the clinic-based program.

Impact of the 13-Valent Pneumococcal Conjugate Vaccine Among Adults: A Systematic Review and Meta-analysis.

BACKGROUND: A notable reduction of the pneumococcal disease burden among adults was observed after the introduction of a 7-valent pneumococcal conjugate vaccine (PCV7) in childhood immunization programs. In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in many jurisdictions; a comparative assessment of PCV13's impact was missing. Our objective was to summarize the available data and assess the change in the incidence of invasive pneumococcal disease (IPD) in adults after the introduction of PCV13 in childhood immunization programs. METHODS: We conducted a systematic literature search from January 1946 to May 2017 of randomized, controlled trials and observational studies OBS reporting the incidence of IPD, non-invasive pneumococcal disease, hospitalizations, and mortality in adults for the periods before and after the introduction of PCV13. Incidence rate ratios (IRRs) were pooled across studies using restricted, maximum-likelihood, random-effects models. RESULTS: From 3306 records,we included 29 OBS studies and 2033961 cases. Significantly lower IPD rates were seen after PCV13 introduction in adults aged <65 years (IRR 0.78, 95% confidence interval [CI] 0.72-0.85) and those aged ≥65 years (IRR 0.86, 95% CI 0.81-0.91). Lower rates of IPD were seen with PCV7 (IRR 0.45, 95% CI 0.38-0.54) and PCV13 serotypes (IRR 0.60, 95% CI 0.54-0.68). A significantly higher IRR of 1.10 (95% CI 1.04-1.17) for non-vaccine serotypes was observed, especially among those aged 65 years and older (IRR 1.20, 95% CI 1.11-1.29). CONCLUSIONS: PCV13 use in children had a moderate impact on reducing the overall and vaccine-type IPDs, but there was a significant increase in non-vaccine type IPDs among adults, especially in those over 65 years.

Estimated Impact of World Health Organization Latent Tuberculosis Screening Guidelines in a Region With a Low Tuberculosis Incidence: Retrospective Cohort Study.

BACKGROUND: Latent tuberculosis infection (LTBI) screening and treatment is a key component of the World Health Organization (WHO) EndTB Strategy, but the impact of LTBI screening and treatment at a population level is unclear. We aimed to estimate the impact of LTBI screening and treatment in a population of migrants to British Columbia (BC), Canada. METHODS: This retrospective cohort included all individuals (N = 1 080 908) who immigrated to Canada as permanent residents between 1985 and 2012 and were residents in BC at any time up to 2013. Multiple administrative databases were linked to identify people with risk factors who met the WHO strong recommendations for screening: people with tuberculosis (TB) contact, with human immunodeficiency virus, on dialysis, with tumor necrosis factor-alpha inhibitors, who had an organ/haematological transplant, or with silicosis. Additional TB risk factors included immunosuppressive medications, cancer, diabetes, and migration from a country with a high TB burden. We defined active TB as preventable if diagnosed ≥6 months after a risk factor diagnosis. We estimated the number of preventable TB cases, given optimal LTBI screening and treatment, based on these risk factors. RESULTS: There were 16 085 people (1.5%) identified with WHO strong risk factors. Of the 2814 people with active TB, 118 (4.2%) were considered preventable through screening with WHO risk factors. Less than half (49.4%) were considered preventable with expanded screening to include people migrating from countries with high TB burdens, people who had been prescribed immunosuppressive medications, or people with diabetes or cancer. CONCLUSIONS: The application of WHO LTBI strong recommendations for screening would have minimally impacted the TB incidence in this population. Further high-risk groups must be identified to develop an effective LTBI screening and treatment strategy for low-incidence regions.

Cost-effectiveness of Latent Tuberculosis Infection Screening before Immigration to Low-Incidence Countries.

Prospective migrants to countries where the incidence of tuberculosis (TB) is low (low-incidence countries) receive TB screening; however, screening for latent TB infection (LTBI) before immigration is rare. We evaluated the cost-effectiveness of mandated and sponsored preimmigration LTBI screening for migrants to low-incidence countries. We used discrete event simulation to model preimmigration LTBI screening coupled with postarrival follow-up and treatment for those who test positive. Preimmigration interferon-gamma release assay screening and postarrival rifampin treatment was preferred in deterministic analysis. We calculated cost per quality-adjusted life-year gained for migrants from countries with different TB incidences. Our analysis provides evidence of the cost-effectiveness of preimmigration LTBI screening for migrants to low-incidence countries. Coupled with research on sustainability, acceptability, and program implementation, these results can inform policy decisions.

Screening for Latent Tuberculosis Infection in Migrants With CKD: A Cost-effectiveness Analysis.

RATIONALE & OBJECTIVE: In countries with a low tuberculosis (TB) incidence, TB disproportionately affects populations born abroad. TB persists in these populations through reactivation of latent TB infection (LTBI) acquired before immigration. Those with chronic kidney disease (CKD) are at increased risk for reactivation and may benefit from LTBI screening and treatment. STUDY DESIGN: Health administrative data from British Columbia, Canada, were used to inform a cost-effectiveness analysis evaluating LTBI screening in those diagnosed with stage 4 or 5 CKD not requiring dialysis (late-stage CKD) and those who began dialysis therapy. SETTING & POPULATION: Permanent residents establishing residency in British Columbia, Canada, between 1985 and 2012 who had late-stage CKD diagnosed or began dialysis therapy. INTERVENTIONS: Screening with the tuberculin skin test or interferon-gamma release assay (IGRA) compared to no LTBI screening at the time of late-stage CKD diagnosis and time of dialysis therapy initiation. Treatment for those who tested positive was isoniazid for 9 months. OUTCOMES: Costs (2016 Can $), TB cases, and quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio for QALYs gained was calculated. MODEL, PERSPECTIVE, & TIMEFRAME: Discrete event simulation model using a health care system perspective, 1.5% discount rate, and 5-year time horizon. RESULTS: Screening with IGRA was superior to the tuberculin skin test in all situations. Screening with IGRA was less expensive and resulted in better outcomes compared to no screening in those initiating dialysis therapy from countries with an elevated TB incidence. In individuals with late-stage CKD, screening with IGRA was only cost-effective in those 60 years or older (cost per QALY gained, <$48,000) from countries with an elevated TB incidence. LIMITATIONS: This study has limitations in generalizability to different epidemiologic settings and in modeling complicated clinical decisions. CONCLUSIONS: LTBI screening should be considered in non-Canadian-born residents initiating dialysis therapy and those with late stage CKD who are older.

The effect of text messaging on latent tuberculosis treatment adherence: a randomised controlled trial.

There is limited high-quality evidence available to inform the use of text messaging to improve latent tuberculosis infection (LTBI) treatment adherence.We performed a parallel, randomised controlled trial at two sites to assess the effect of a two-way short message service on LTBI adherence. We enrolled adults initiating LTBI therapy from June 2012 to September 2015 in British Columbia, Canada. Participants were randomised in a 1:1 ratio to standard LTBI treatment (control) or standard LTBI treatment plus two-way weekly text messaging (intervention). The primary outcome was treatment completion, defined as taking ≥80% prescribed doses within 12 months (isoniazid) or 6 months (rifampin) of enrolment. The trial was unblinded except for the data analyst.A total of 358 participants were assigned to the intervention (n=170) and control (n=188) arms. In intention-to-treat analysis, the proportion of participants completing LTBI therapy in the intervention and control arms was 79.4% and 81.9%, respectively (RR 0.97, 95% CI 0.88-1.07; p=0.550). Results were similar for pre-specified secondary end-points, including time-to-completion of LTBI therapy, completion of >90% of prescribed LTBI doses and health-related quality of life.Weekly two-way text messaging did not improve LTBI completion rates compared to standard LTBI care; however, completion rates were high in both treatment arms.

Demographic predictors of active tuberculosis in people migrating to British Columbia, Canada: a retrospective cohort study.

BACKGROUND: Canadian tuberculosis (TB) guidelines recommend targeting postlanding screening for and treatment of latent tuberculosis infection (LTBI) in people migrating to Canada who are at increased risk for TB reactivation. Our objectives were to calculate robust longitudinal estimates of TB incidence in a cohort of people migrating to British Columbia, Canada, over a 29-year period, and to identify groups at highest risk of developing TB based on demographic characteristics at time of landing. METHODS: We included all individuals (n = 1 080 908) who became permanent residents of Canada between Jan. 1, 1985, and Dec. 31, 2012, and were resident in BC at any time between 1985 and 2013. Multiple administrative databases were linked to the provincial TB registry. We used recursive partitioning models to identify populations with high TB yield. RESULTS: Active TB was diagnosed in 2814 individuals (incidence rate 24.2/100 000 person-years). Demographic factors (live-in caregiver, family, refugee immigration classes; higher TB incidence in country of birth; and older age) were strong predictors of TB incidence in BC, with elevated rates continuing many years after entry into the cohort. Recursive partitioning identified refugees 18-64 years of age from countries with a TB incidence greater than 224/100 000 population as a high-yield group, with 1% developing TB within the first 10 years. INTERPRETATION: These findings support recommendations in Canadian guidelines to target postlanding screening for and treatment of LTBI in adult refugees from high-incidence countries. Because high-yield populations can be identified at entry via demographic data, screening at this point may be practical and high-impact, particularly if the LTBI care cascade can be optimized.

Testing the External Validity of a Discrete Choice Experiment Method: An Application to Latent Tuberculosis Infection Treatment.

OBJECTIVES: To explore the external validity and predictive power of stated preferences obtained from a discrete choice experiment (DCE) by comparing the predicted behavior of respondents to their actual choices at an individual level. METHODS: A DCE was performed in patients before being offered treatment for latent tuberculosis infection. A mixed logit model was estimated using hierarchical Bayes. The individual-specific preference coefficients were used to calculate the expected probability of choosing the treatment by each patient. The predicted choice using this probability was compared with their actual decision. We used a receiver-operating characteristic curve and different thresholds to convert probabilities into the predicted choices. The comparability of different distributions for the random parameters was also examined. RESULTS: Our results identified significant heterogeneity in preferences for all attributes among respondents. The best model correctly predicted actual treatment decisions for 83% of the participants. The results from using different thresholds and a receiver-operating characteristic curve also confirmed the compatibility between predicted and actual choices. We showed that individual-specific coefficients reflected respondents' actual choices more closely compared with the aggregate-level estimates. CONCLUSIONS: The results of this study provided support for the external validity of DCEs on the basis of their power to predict actual behavior in this setting. Future investigations are, however, required to establish the external validity of DCEs in different settings.

Impact of pharmacist administration of influenza vaccines on uptake in Canada.

BACKGROUND: Uptake of influenza vaccination in Canada remains suboptimal despite widespread public funding. To increase access, several provinces have implemented policies permitting pharmacists to administer influenza vaccines in community pharmacies. We examined the impact of such policies on the uptake of seasonal influenza vaccination in Canada. METHODS: We pooled data from the 2007-2014 cycles of the Canadian Community Health Survey (n = 481 526). To determine the impact of influenza vaccine administration by pharmacists, we estimated the prevalence ratio for the association between the presence of a pharmacist policy and individual-level vaccine uptake using a modified Poisson regression model (dependent variable: vaccine uptake) with normalized weights while controlling for numerous health and sociodemographic factors. RESULTS: Across all survey cycles combined, 28.8% of respondents reported receiving a seasonal influenza vaccine during the 12 months before survey participation. Introduction of a policy for pharmacist administration of influenza vaccine was associated with a modest increase in coverage (2.2%) and an individual's likelihood of uptake (adjusted prevalence ratio 1.05, 95% confidence interval 1.02-1.08). INTERPRETATION: Uptake of influenza immunization was modestly increased in Canadian jurisdictions that allowed pharmacists to administer influenza vaccines.

A meta-analysis of stroke risk following herpes zoster infection.

BACKGROUND: The incidence of herpes zoster (HZ) is increasing and poses a significant health concern to aging populations. Several studies suggest an increased risk of stroke following zoster infection, but the results are conflicting. We conducted a systematic review and meta-analysis to determine if stroke risk is increased following HZ infection. METHODS: A search of MEDLINE, EMBASE, Google scholar, Web of Science, CAB Direct, Cumulative Index to Nursing and Allied Health Literature, and Evidence Based Medicine Reviews was conducted for observational studies of adults with HZ infection that examined stroke and TIA risk from January 1, 1966 to May 31, 2016. Adjusted relative risks reported for similar follow-up durations were pooled across studies separately using random-effects inverse variance models. RESULTS: Data were pooled from nine studies. Relative risk for stroke after zoster was 1.78 (95% CI 1.70-1.88) for the first month following herpes zoster, dropping progressively to 1.43 (95% CI 1.38-1.47) after 3 months, to 1.20 (95% CI 1.14-1.26) after 1 year. We found that stroke risk increases by a larger margin during the first month after a herpes zoster ophthalmicus episode: relative risk 2.05 (95% CI 1.82-2.31). The risk remains elevated one year after the acute episode. CONCLUSIONS: Herpes zoster is an established risk factor for increasing the risk of stroke, especially shortly after infection. Vaccination should be encouraged in patients at high risk of cardiovascular disease.

Increasing incidence associated with herpes zoster infection in British Columbia, Canada.

BACKGROUND: Recent studies have shown an increasing incidence of herpes zoster (HZ) infection, which may be related to the introduction of varicella vaccination programs in children. We examined the epidemiology and treatment costs of HZ and post-herpetic neuralgia (PHN) over time in British Columbia, Canada. METHODS: The cohort consisted of all cases with HZ infection from January 1, 1997 and December 31, 2012. Incident zoster was defined as a case (ICD-9 053 or ICD-10 B02) without a previous episode of HZ or PHN in the previous 12 months. We determined the incidence for HZ and PHN and the age-sex standardized rate for the overall population. We determined the association between the varicella vaccination program and increased HZ rates by evaluating the rate ratios in the publicly-funded varicella vaccine period compared to the non-publicly funded period in a regression model. We evaluated the hospitalization rates, treatment by GPs and their associated yearly costs for HZ and PHN. RESULTS: HZ incidence increased for the entire study period from 3.2 per 1000 population in 1997 to 4.5 in 2012. HZ rates were higher for females than males and all age groups had an increased incidence rate, except the 0-9 year olds, where the rate decreased. Crude and age-sex standardized incidence rates of PHN demonstrated very similar patterns to HZ incidence. Based on the regression model, rates of HZ were higher in the older individuals. No significant increase with HZ incidence was seen during the publically funded varicella vaccination program compared to the non-publicly funded period. From 1997 to 2012, the annual HZ-related costs associated with hospitalizations and GP visits were over $CDN4.9 million and $CDN537,286, respectively; treatment costs for hospitalizations have increased significantly over time. Majority of PHN-related cases are managed by GPs, with a steady increase over time in number of cases and associated annual costs. CONCLUSIONS: The incidence of zoster and PHN is increasing with time, particularly in the elderly population and the risk is greater in the over 65 year olds. Treatment costs for both HZ and PHN represent a significant burden on the Canadian healthcare system.

Characterization of Clostridium difficile Strains in British Columbia, Canada: A Shift from NAP1 Majority (2008) to Novel Strain Types (2013) in One Region.

Background. Clostridium difficile is a major cause of gastrointestinal illness. Epidemic NAP1 strains contain toxins A and B, a deletion in repressor tcdC, and a binary toxin. Objectives. To determine the molecular epidemiology of C. difficile in British Columbia and compare between two time points in one region. Methods. C. difficile isolates from hospital and community laboratories (2008) and one Island Health hospital laboratory (2013) were characterized by pulsed-field gel electrophoresis, PCR-ribotyping, toxin possession, tcdC genotype, and antimicrobial susceptibility. Results. In 2008, 42.7% of isolates had NAP1 designation. Hospital-collected isolates were associated with older patients and more NAP1 types. Unlike other isolates, most NAP1 isolates possessed binary toxin and a 19 bp loss in tcdC. All isolates were susceptible to metronidazole and vancomycin. A 2013 follow-up revealed a 28.9% decrease in NAP1 isolates and 20.0% increase in isolates without NAP designation in one region. Then, community-associated cases were seen in younger patients, while NAP types were evenly distributed. Isolates without NAP designation did not cluster with a PFGE pattern or ribotype. Conclusions. Evaluation of C. difficile infections within British Columbia revealed demographic associations, epidemiological shifts, and characteristics of strain types. Continuous surveillance of C. difficile will enable detection of emerging strains.

Value of an aggregate index in describing the impact of trends in antimicrobial resistance for Escherichia coli.

BACKGROUND: Drug resistance indexes (DRIs) quantify the cumulative impact of antimicrobial resistance on the likelihood that a given pathogen will be susceptible to antimicrobial therapy. OBJECTIVE: To derive a DRI for community urinary tract infections caused by Escherichia coli in British Columbia for the years 2007 to 2010, and to examine trends over time and across patient characteristics. METHODS: Indication-specific utilization data were obtained from BC PharmaNet for outpatient antimicrobial prescriptions linked to diagnostic information from physician payment files. Resistance data for E coli urinary isolates were obtained from BC Biomedical Laboratories (now part of LifeLabs Medical Laboratory Services). DRIs were derived by multiplying the rate of resistance to a specific antimicrobial by the proportional rate of utilization for that drug class and aggregating across drug classes. Higher index values indicate more resistance. RESULTS: Adaptive-use DRIs remained stable over time at approximately 18% (95% CI 17% to 18%) among adults ≥15 years of age and approximately 28% (95% CI 26% to 31%) among children <15 years of age. Similar results were observed when proportional drug use was restricted to the baseline year (ie, a static-use model). Trends according to age group suggest a U-shaped distribution, with the highest DRIs occurring among children <10 years of age and adults ≥65 years of age. Males had consistently higher DRIs than females for all age groups. CONCLUSIONS: The stable trend in adaptive-use DRIs over time suggests that clinicians are adapting their prescribing practices for urinary tract infections to local resistance patterns. Results according to age group reveal a higher probability of resistance to initial therapy among young children and elderly individuals.

HISTORIQUE: Les indices de pharmacorésistance (IPR) quantifient l'effet cumulatif de la résistance antimicrobienne sur la probabilité qu'un pathogène donné soit susceptible à un traitement antimicrobien. OBJECTIF: Dériver l'IPR des infections urinaires d'origine non nosocomiale causées par l'Escherichia coli en Colombie-Britannique entre 2007 et 2010 et examiner les tendances au fil du temps et selon les caractéristiques des patients. MÉTHODOLOGIE: Les données sur les indications d'utilisation, tirées du système PharmaNet de la Colombie-Britannique relativement aux prescriptions d'antimicrobiens, étaient liées à l'information diagnostique prélevée dans les dossiers d'honoraires des médecins. Les données de résistance reliées aux isolats urinaires d'E coli provenaient des BC Biomedical Laboratories (qui font désormais partie des LifeLabs Medical Laboratory Services). Les IPR étaient dérivés en multipliant le taux de résistance à un antimicrobien précis au taux proportionnel d'utilisation de cette classe de médicament et en les regroupant entre les classes de médicaments. Des indices de valeur plus élevés indiquaient une plus forte résistance. RÉSULTATS: Les IPR à utilisation adaptée demeuraient stables au fil du temps, à environ 18 % (95 % IC 17 % à 18 %) chez les adultes de 15 ans et plus, et à environ 28 % (95 % IC 26 % à 31 %) chez les enfants de moins de 15 ans. Les chercheurs ont observé des résultats similaires lorsque l'utilisation proportionnelle des médicaments était restreinte à l'année de référence (modèle à utilisation statique). Les tendances en fonction des groupes d'âge laissent supposer une répartition en U, les IPR les plus élevés se produisant chez les enfants de moins de dix ans et les adultes de 65 ans et plus. Dans tous les groupes d'âge, les hommes présentaient un IPR plus élevé que les femmes. CONCLUSIONS: D'après la tendance stable des IPR à utilisation adaptée au fil du temps, les cliniciens adaptent leurs pratiques de prescription pour le traitement des infections urinaires aux profils de résistance locaux. Les résultats en fonction des groupes d'âge révèlent une plus forte probabilité de résistance à la thérapie initiale chez les jeunes enfants et les personnes âgées.

Effectiveness of neuraminidase inhibitors in preventing hospitalization during the H1N1 influenza pandemic in British Columbia, Canada.

OBJECTIVES: In British Columbia (BC), Canada, neuraminidase inhibitors (NIs) were publicly funded during the 2009 A(H1N1)pdm09 pandemic for treatment of high-risk patients and/or anyone with moderate-to-severe illness. We assessed antiviral effectiveness (AVE) against hospitalization in that context. METHODS: A population-based cohort study was conducted using linked administrative data. The cohort included all individuals living in BC during the study period (1 September to 31 December 2009) with a diagnostic code consistent with influenza or pandemic H1N1. The main study period pertained to the second-wave A(H1N1)pdm09 circulation (1 October to 31 December 2009), with sensitivity analyses around the more specific pandemic peak (18 October to 7 November). Exposure was defined by same-day NI prescription. The main outcome was all-cause hospitalization within 14 days of the outpatient influenza diagnosis. Cox proportional hazards models assessed AVE with 1 : 1 propensity-score matching and covariate adjustment. RESULTS: After matching, there were 304/58,061 NI-exposed and 345/58,061 unexposed patients hospitalized during the main study period. The very young [<6 months (35.0; 95% CI 16.7-73.4)], the old [65-79 years (13.7; 95% CI 10.1-18.6)] and the very old [≥80 years (38.7; 95% CI 26.6-56.5)] had the highest hospitalization rate per 1000 patients overall. Fully adjusted AVE against all-cause hospitalization during the main study period was 16% (95% CI 2%-28%), similar to the pandemic peak (15%; 95% CI -4%-30%). CONCLUSIONS: The use of NIs was associated with modest protection against hospitalization during the 2009 pandemic, but appeared underutilized in affected age groups with the highest hospitalization risk.