Mei Chong

Randomized Controlled Trial of Dose Response to Influenza Vaccine in Children Aged 6 to 23 Months

OBJECTIVES: We assessed whether 2 full versus 2 half-doses of trivalent inactivated influenza vaccine (TIV) could improve immunogenicity without increasing reactogenicity in infants (aged 6–11 months) and toddlers (aged 12–23 months). METHODS: Previously unimmunized infants and toddlers were separately randomly assigned to receive 2 full (0.5-mL) or 2 half (0.25-mL) doses of 2008–2009 split TIV. Sera were collected at enrollment and at 27 to 45 days after the second injection. Parents recorded adverse events after each injection. The primary immunogenicity outcome was superiority (1-sided, α = 0.025) of the full versus the half-dose based on a >10% increase in rates of seroprotection (hemagglutination inhibition titer of ≥40). The primary reactogenicity outcome was fever of ≥38°C within 3 days of either injection. RESULTS: In per-protocol analyses, 252 participants (full dose: n = 124; half-dose: n = 128) were included. In toddlers, postimmunization seroprotection rates exceeded 85% for all 3 vaccine components without significant difference by dose. In infants, the full dose induced higher responses for all 3 vaccine components, meeting the 10% test of superiority for the H3N2 (75.4% vs 47.6%; Δ = 27.8% [95% confidence interval (CI): 11.2–44.5]; P = .02) and B/Yamagata (70.2% vs 41.3%; Δ = 28.9% [95% CI: 11.9–45.9]; P = .02) components but not H1N1 (71.9% vs 54.0%; Δ = 18.0% [95% CI: 1.0–34.9]; P = .2). Rates of fever were not increased among full- versus half-dose recipients in either age group (5.6% vs 12.7% combined). CONCLUSIONS: Administration of 2 full TIV doses may improve immunogenicity without increasing reactogenicity in infants. Current TIV dosing recommendations for young children warrant additional evaluation.

Age-related trends in the timeliness and prediction of medical visits, hospitalizations and deaths due to pneumonia and influenza, British Columbia, Canada, 1998-2004.

The influenza immunization program in North America has been primarily designed to provide direct benefit to vaccinated individuals at highest risk of serious influenza outcomes. Some evidence suggests that immunization of certain age groups may also extend indirect protective benefit to vulnerable populations. Our goal was to identify age groups associated earliest with seasonal influenza activity and who may have the greatest indirect impact at the population level. We examined age-based associations between influenza medical visits and population-wide hospitalization/mortality due to pneumonia & influenza (P&I) using administrative datasets in British Columbia, Canada. A peak week was identified for each age group based on the highest rates observed in a given week for that study year. Mean rates at the peak week were averaged over the study years per age group. Timeliness (T) was defined as the mean difference in days between the first peak in influenza medical visits and population-wide P&I hospitalizations/deaths. Poisson regression was applied to calculate prediction (Pr) as the average proportion of deviance in P&I explained by influenza medical visits. T and Pr were derived by age group, and the product (T x Pr) was used as a summary measure to rank potential indirect effects of influenza by age group. Young children (0-23 months) and the elderly (> or = 65 years) had the highest peak rates of P&I hospitalization. Children < 6m and the elderly had the highest peak rates of P&I mortality. We found no significant differences by age for influenza medical visits in predicting population-wide P&I hospitalizations or deaths. School-aged children (5-19 years) showed the best relative combination of T x Pr, followed by preschool-aged children (2-4 years). We conclude that the very young and old suffer the greatest morbidity due to P&I, and an indirect role for school-aged children in anticipating the risk to others warrants further evaluation.

Long-term effect of sustained virological response on hepatocellular carcinoma in patients with hepatitis C in Canada

BACKGROUND & AIMS Evidence is limited on hepatocellular carcinoma (HCC) risk after sustained virological response (SVR) to interferon-based treatment of hepatitis C virus (HCV) infection. We evaluated the effect of SVR on the risk of HCC and estimated its incidence in post-SVR HCV patients from a large population-based Canadian cohort. METHODS The British Columbia Hepatitis Testers Cohort includes individuals tested for HCV between 1990-2013 linked with data on their medical visits, hospitalizations, cancers, prescription drugs and mortality. Patients receiving interferon-based HCV treatments were followed from the end of treatment to HCC diagnosis, death or December 31, 2012. We examined HCC risk among those who did and did not achieve SVR using multivariable proportional hazard models with the Fine and Gray modification for competing risks. RESULTS Of 8147 individuals who received HCV treatment and were eligible for analysis, 4663 (57%) achieved SVR and 3484 (43%) did not. Each group was followed for a median of 5.6years (range: 0.5-12.9) for an HCC incidence rate of 1.1/1000 person-years (PY) among the SVR and 7.2/1000 PY among the no SVR group. The HCC incidence rate was higher among those with cirrhosis (SVR: 6.4, no SVR: 21.0/1000 PY). In the multivariable model, SVR was associated with a lower HCC risk (subdistribution hazard ratio [SHR]=0.20, 95% CI: 0.13-0.3), while cirrhosis (SHR=2.61, 95% CI: 1.68-4.04), age ⩾50years, being male and genotype 3 infection were associated with a higher HCC risk. Among those who achieved SVR, cirrhosis, age ⩾50years and being male were associated with a higher HCC risk. CONCLUSION SVR after interferon-based treatment substantially reduces but does not eliminate HCC risk, which is markedly higher among those with cirrhosis and age ⩾50years at treatment initiation. Treatment of patients at an advanced fibrosis stage with new highly effective drugs will warrant continued surveillance for HCC post-SVR. LAY SUMMARY We assessed the effect of successful hepatitis C treatment with older interferon-based treatment on the occurrence of liver cancer (hepatocellular carcinoma) and found that successful treatment prevents liver cancer. However, more people with cirrhosis and older age continued to develop liver cancer after successful treatment. Thus, treatment with new drugs among those with cirrhosis will require continued monitoring for liver cancer.

Antibiotic prescribing by dentists has increased: Why?

BACKGROUND Although the overall rate of antibiotic prescribing has been declining in British Columbia, Canada, the authors conducted a study to explain the increased rate of prescribing by dentists. METHODS The authors obtained anonymized, line-listed data on outpatient prescriptions from 1996 to 2013 from a centralized, population-based prescription database, including a variable coding prescriber licensing body. Analyses used Anatomical Therapeutic Classification standard codes and defined daily dose (DDD) values. The authors normalized prescribing rates to the population and expressed the rates in DDDs per 1,000 inhabitants per day (DID). The Canadian Dental Association released a webinar that invited correspondence from dentists about the drivers of the trend. RESULTS From 1996 to 2013, overall antibiotic use declined from 18.24 DID to 15.91 DID, and physician prescribing declined 18.2%, from 17.25 DID to 14.11 DID. However, dental prescribing increased 62.2%, from 0.98 DID to 1.59 DID, and its proportionate contribution increased from 6.7% to 11.3% of antibiotic prescriptions. The rate of prescribing increased the most for dental patients 60 years or older. Communication from dentists in Canada and the United States identified the following explanatory themes: unnecessary prescriptions for periapical abscess and irreversible pulpitis; increased prescribing associated with dental implants and their complications; slow adoption of guidelines calling for less perioperative antibiotic coverage for patients with valvular heart disease and prosthetic joints; emphasis on cosmetic practices reducing the surgical skill set of average dentists; underinsurance practices driving antibiotics to be a substitute for surgery; the aging population; and more dental registrants per capita. CONCLUSIONS Emerging themes for dental prescribing should be explored further in future studies; however, themes already identified may guide priorities in antibiotic stewardship for continuing dental education sessions. PRACTICAL IMPLICATIONS Antibiotic prescribing should be reviewed to make sure that we are compliant with guidelines. Most practitioners will find opportunities to prescribe less often and for shorter durations.

A Comparison of Antibiotic Use in Children Between Canada and Denmark

Background: High rates of antibiotic prescribing in children lead to antibiotic resistance in the community. Surveillance on utilization rates and comparisons with other jurisdictions are methods for benchmarking. Surveillance on antibiotic use is well established in Europe, including Denmark, but until recently, similar data from Canada were lacking. Objective: To compare pediatric antibiotic prescribing rates in British Columbia, Canada, with those in Denmark. Methods: Population-based data on antibiotic prescriptions from British Columbia and Denmark were obtained from 1999 to 2003 for children less than 15 years of age. Annual trends in prescription rates per 1000 children were analyzed by using generalized linear models for all children less than 15 years of age; they were stratified by age group (0–4, 5–9, 10–14 y) for all antibiotics. Class-specific trends were also evaluated for penicillins, cephalosporins, macrolides, sulfonamides and trimethoprim, tetracyclines, and fluoroquinolones. Results: From 1999 to 2003, the overall British Columbia prescription rate was significantly higher than that of Denmark (p < 0.0001) at all age stratifications. In 2003, the British Columbia prescription rate was twice that of Denmark, at 608 versus 385 prescriptions per 1000 children, respectively. In both jurisdictions, the majority of antibiotics used were penicillins (Anatomical Therapeutic Chemical class J01C), However, in British Columbia, most penicillins used were extended-spectrum (83% in 2003); in Denmark, 34% of penicillins used in 2003 were extended-spectrum and 56% were β-lactamase sensitive. In British Columbia, use of penicillins (−4.5%), cephalosporins (−5.5%), trimethoprim/sulfamethoxazole (−36%), and tetracycline (−1.6%) decreased over time, whereas in Denmark, use of penicillins increased by 11% over time and non-penicillin antibiotics remained stable. A significant increase in macrolide consumption was seen in British Columbia due to use of clarithromycin and azithromycin; in contrast, macrolide consumption declined in Denmark. Conclusions: Compared with Denmark, the antibiotic prescription rate for children is substantially higher in British Columbia. In addition, there has been a significant increase in the use of macrolides, especially the second-generation agents, in British Columbia compared with the use in Denmark. Further studies are required to delineate reasons for antibiotic prescribing patterns in these 2 jurisdictions.

Population-Based Study of the Increased Incidence of Skin and Soft Tissue Infections and Associated Antimicrobial Use

ABSTRACT Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has spread rapidly throughout the world in the last decade. We sought to demonstrate the impact of the emergence of CA-MRSA in Western Canada on physician visits, incision-and-drainage procedures, and antibiotic prescribing for skin and soft tissue infections (SSTI). We used the provincial physician billing system to determine the rate of physician visits (per 1,000 population per year) of SSTI and incision-and-drainage procedures. A database capturing all outpatient prescriptions in the province was anonymously linked to associated physician billing codes to quantify prescriptions associated with SSTI. Antibiotic prescriptions (overall and class specific) were expressed as their defined daily dose (DDD) per 1,000 inhabitants per day. Between 1996 and 2008, the rate of visits for all SSTI increased by 15%, and the majority of visits did not include an incision-and-drainage procedure. The rate of antibiotic prescribing for SSTI increased by 49%. The majority of this increase was attributable to the higher rates of use of clindamycin (627%), trimethoprim-sulfamethoxazole (380%), cephalosporins (160%), and amoxicillin-clavulanate (627%). Health care utilization and antibiotic prescribing rates for SSTI, but not incision-and-drainage procedures, have increased in association with the CA-MRSA epidemic. While much of the increase in antibiotic use reflects an appropriate change to trimethoprim-sulfamethoxazole, there is room for education regarding the limitations of cephalosporins and clindamycin, given current susceptibility profiles.

Prevalence and incidence of hepatitis C virus in hemodialysis patients in British Columbia: Follow-up after a possible breach in hemodialysis machines

BACKGROUND A possible breach of the transducer protector in specific dialysis machines was reported in June 2004 in British Columbia (BC), which led to testing of hemodialysis patients for hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV. This testing provided an opportunity to examine HCV incidence, prevalence and coinfection with HBV and HIV, and to compare anti-HCV and HCV polymerase chain reaction (PCR). METHODS The results of hemodialysis patients who were dialyzed on the implicated machines (65% of BC dialysis patients), and tested for HCV, HBV and HIV, between June 1, 2004, and December 31, 2004, were reviewed and compared with available previous results. RESULTS Of 1286 hemodialysis patients with anti-HCV and/or HCV-PCR testing, 69 (5.4%) tested positive. Two HCV genotype 4 seroconversions were identified. HCV incidence rate on dialysis was 78.8 cases per 100,000 person-years. Younger age, history of renal transplant and past HBV infection were associated with HCV infection. No occult infection was identified using HCV-PCR. INTERPRETATION Hemodialysis patients had three times the HCV prevalence rate of the general BC population, and more than 20 times the incident rate of the general Canadian population. One of the two seroconversions occurred before the testing campaign; the patient was likely infected during hemodialysis in South Asia. The other was plausibly a late seroconversion following renal transplant in South Asia. Nosocomial transmission cannot be ruled out because both patients were dialyzed in the same centre. Baseline and annual anti-HCV testing is recommended. HCV-PCR should be considered at baseline for persons with HCV risk factors, and for returning travellers who received dialysis in HCV-endemic countries to identify HCV infection occurring outside the hemodialysis unit.

Assessing Hepatitis C Burden and Treatment Effectiveness through the British Columbia Hepatitis Testers Cohort (BC-HTC): Design and Characteristics of Linked and Unlinked Participants

Background The British Columbia (BC) Hepatitis Testers Cohort (BC-HTC) was established to assess and monitor hepatitis C (HCV) epidemiology, cost of illness and treatment effectiveness in BC, Canada. In this paper, we describe the cohort construction, data linkage process, linkage yields, and comparison of the characteristics of linked and unlinked individuals. Methods The BC-HTC includes all individuals tested for HCV and/or HIV or reported as a case of HCV, hepatitis B (HBV), HIV or active tuberculosis (TB) in BC linked with the provincial health insurance client roster, medical visits, hospitalizations, drug prescriptions, the cancer registry and mortality data using unique personal health numbers. The cohort includes data since inception (1990/1992) of each database until 2012/2013 with plans for annual updates. We computed linkage rates by year and compared the characteristics of linked and unlinked individuals. Results Of 2,656,323 unique individuals available in the laboratory and surveillance data, 1,427,917(54%) were included in the final linked cohort, including about 1.15 million tested for HCV and about 1.02 million tested for HIV. The linkage rate was 86% for HCV tests, 89% for HCV cases, 95% for active TB cases, 48% for HIV tests and 36% for HIV cases. Linkage rates increased from 40% for HCV negatives and 70% for HCV positives in 1992 to ~90% after 2005. Linkage rates were lower for males, younger age at testing, and those with unknown residence location. Linkage rates for HCV testers co-infected with HIV, HBV or TB were very high (90–100%). Conclusion Linkage rates increased over time related to improvements in completeness of identifiers in laboratory, surveillance, and registry databases. Linkage rates were higher for HCV than HIV testers, those testing positive, older individuals, and females. Data from the cohort provide essential information to support the development of prevention, care and treatment initiatives for those infected with HCV.

Evaluation of the Do Bugs Need Drugs? Program in British Columbia: Can We Curb Antibiotic Prescribing?

OBJECTIVE Antibiotic resistance is accelerated by the overuse of antibiotics. Do Bugs Need Drugs? is an educational program adapted in British Columbia to target both the public and health care professionals, with the aim of reducing unnecessary prescribing. The current article presents a descriptive evaluation of the impact of the program over the first four years. METHOD Program implementation was measured by the amount of educational material distributed and the level of participation in educational sessions. The impact of the program was assessed by measuring changes in knowledge and prescribing habits of participating physicians, and by investigating provincial trends in antibiotic use. RESULTS A total of 51,367 children, assisted-living residents and health care professionals have participated in the program since its inception in the fall of 2005. Pre- and postcourse assessments of participating physicians indicated significant improvements in clinical knowledge and appropriate antibiotic treatment of upper respiratory tract infections. Overall rates of antibiotic use in the province have stabilized since 2006. The rates of consumption of fluoroquinolones and macrolides have levelled off since 2005. Utilization rates for acute bronchitis are at the same level as when the program was first implemented, but rates for other acute upper respiratory tract infections of interest have declined. CONCLUSIONS The Do Bugs Need Drugs? program significantly improves physician antibiotic prescription decisions and is ecologically associated with desirable change in population antibiotic consumption patterns.

Characteristics of an Acanthamoeba Keratitis Outbreak in British Columbia between 2003 and 2007

OBJECTIVE Quantify and describe Acanthamoeba keratitis (AK) cases in British Columbia (BC). DESIGN A comparison of annual incidence rates confirms the presence of an outbreak. A case series describes characteristics of the outbreak. PARTICIPANTS All laboratory-confirmed AK cases (persons) in BC (1988-2011; n = 68) were included in the incidence rate comparison. Of the 42 cases (persons) between 2003 and 2007, 32 were selected to interview (laboratory confirmed, 2005-2007), and the 23 who completed interviews form the case series. METHODS A comparison of standardized annual incidence rates in historic to outbreak periods is performed by z-score test. A telephone interview and descriptive analysis detailing demographics, risk factors, and contact lens (CL) wearing habits was completed for 23 cases. MAIN OUTCOME MEASURES We measure number of laboratory confirmed cases in BC. In addition, risk factors and potential exposures of these cases are reported. RESULTS The annual incidence of AK increased significantly from 0.029 to 0.200 per 100 000 population between historic years (1988-2002) and outbreak years (2003-2007; P = 0.022). The annual incidence of AK has since returned to near historic levels (0.056/100 000 population). The case series identified multiple risk factors, including the use of a specific recalled solution (60.9%), daily soft CL wear (95.7%), all-in-one solutions (95.7%), showering while wearing CL (65.2%), and generally poor CL hygiene. CONCLUSIONS A significant increase in annual AK incidence occurred between 2003 and 2007 in BC. After 2007, the incidence of AK returned to near historic levels. The recalled solution was associated with many cases; however, other risk factors were also identified, including being unaware of the recall and poor CL hygiene practices, highlighting the need for improved education about the severity of AK and consequences of improper CL hygiene. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any of the materials discussed in this article.