Fawziah Marra

Immunogenicity of 2 Doses of HPV Vaccine in Younger Adolescents vs 3 Doses in Young Women: A Randomized Clinical Trial

IMPORTANCE Global use of human papillomavirus (HPV) vaccines to prevent cervical cancer is impeded by cost. A 2-dose schedule for girls may be possible. OBJECTIVE To determine whether mean antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses was noninferior to women receiving 3 doses. DESIGN, SETTING, AND PATIENTS Randomized, phase 3, postlicensure, multicenter, age-stratified, noninferiority immunogenicity study of 830 Canadian females from August 2007 through February 2011. Follow-up blood samples were provided by 675 participants (81%). INTERVENTION Girls (9-13 years) were randomized 1:1 to receive 3 doses of quadrivalent HPV vaccine at 0, 2, and 6 months (n = 261) or 2 doses at 0 and 6 months (n = 259). Young women (16-26 years) received 3 doses at 0, 2, and 6 months (n = 310). Antibody levels were measured at 0, 7, 18, 24, and 36 months. MAIN OUTCOMES AND MEASURES Primary outcome was noninferiority (95% CI, lower bound >0.5) of geometric mean titer (GMT) ratios for HPV-16 and HPV-18 for girls (2 doses) compared with young women (3 doses) 1 month after last dose. Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 vs 3 doses of vaccine; and durability of noninferiority to 36 months. RESULTS The GMT ratios were noninferior for girls (2 doses) to women (3 doses): 2.07 (95% CI, 1.62-2.65) for HPV-16 and 1.76 (95% CI, 1.41-2.19) for HPV-18. Girls (3 doses) had GMT responses 1 month after last vaccination for HPV-16 of 7736 milli-Merck units per mL (mMU/mL) (95% CI, 6651-8999) and HPV-18 of 1730 mMU/mL (95% CI, 1512-1980). The GMT ratios were noninferior for girls (2 doses) to girls (3 doses): 0.95 (95% CI, 0.73-1.23) for HPV-16 and 0.68 (95% CI, 0.54-0.85) for HPV-18. The GMT ratios for girls (2 doses) to women (3 doses) remained noninferior for all genotypes to 36 months. Antibody responses in girls were noninferior after 2 doses vs 3 doses for all 4 vaccine genotypes at month 7, but not for HPV-18 by month 24 or HPV-6 by month 36. CONCLUSIONS AND RELEVANCE Among girls who received 2 doses of HPV vaccine 6 months apart, responses to HPV-16 and HPV-18 one month after the last dose were noninferior to those among young women who received 3 doses of the vaccine within 6 months. Because of the loss of noninferiority to some genotypes at 24 to 36 months in girls given 2 doses vs 3 doses, more data on the duration of protection are needed before reduced-dose schedules can be recommended. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00501137.

Antibiotic Use in Children Is Associated With Increased Risk of Asthma

BACKGROUND. Antibiotic exposure in early childhood is a possible contributor to the increasing asthma prevalence in industrialized countries. Although a number of published studies have tested this hypothesis, the results have been conflicting. OBJECTIVE. To explore the association between antibiotic exposure before 1 year of age and development of childhood asthma. METHODS. Using administrative data, birth cohorts from 1997 to 2003 were evaluated (N = 251817). Antibiotic exposure was determined for the first year of life. After the first 24 months of life, the incidence of asthma was determined in both those exposed and not exposed to antibiotics in the first 12 months of life. Cox proportional hazards models were used to adjust for potential confounders and determine the hazard ratios associated with antibiotic exposure for the development of asthma. RESULTS. Antibiotic exposure in the first year of life was associated with a small risk of developing asthma in early childhood after adjusting for gender, socioeconomic status at birth, urban or rural address at birth, birth weight, gestational age, delivery method, frequency of physician visits, hospital visit involving surgery, visits to an allergist, respirologist, or immunologist, congenital anomalies, and presence of otitis media, acute, or chronic bronchitis, and upper and lower respiratory tract infections during the first year of life. As the number of courses of antibiotics increased, this was associated with increased asthma risk, with the highest risk being in children who received >4 courses. All antibiotics were associated with an increased risk of developing asthma, with the exception of sulfonamides. CONCLUSIONS. This study provides evidence that the use of antibiotics in the first year of life is associated with a small risk of developing asthma, and this risk increases with the number of courses of antibiotics prescribed.

A Population-Based Evaluation of a Publicly Funded, School-Based HPV Vaccine Program in British Columbia, Canada: Parental Factors Associated with HPV Vaccine Receipt

Analysis of a telephone survey by Gina Ogilvie and colleagues identifies the parental factors associated with HPV vaccine uptake in a school-based program in Canada.

Effectiveness and cost effectiveness of human papillomavirus vaccine: a systematic review.

AbstractThe recent approval of human papillomavirus (HPV) vaccine means that decision makers need information beyond that available from randomized clinical trials to recommend funding for this vaccination programme. Modelling and economic studies have addressed some of those information needs. We conducted a qualitative systematic review to summarize the existing data. Review articles were obtained from an extensive literature search on studies using mathematical modelling (either a Markov or transmission dynamic model) to determine the effectiveness or cost effectiveness of an HPV vaccine compared with the current cytology-based Pap smear screening programme.A total of 21 studies (but 22 models) were included in the review after being assessed for methodological quality. All of the included studies had used a mathematical model to determine the effectiveness of an HPV vaccine, whilst 13 had also conducted a cost-effectiveness analysis. Although the studies used different model structures, baseline parameters and assumptions, all studies showed that vaccination would decrease rates of HPV infection, precancerous lesions and cervical cancer. Studies had a consistent message with respect to cost effectiveness: a female-only vaccination programme is cost effective compared with the current cytology-based Pap smear screening programme, while the cost effectiveness of a male and female vaccination programme is generally not cost effective compared with female-only vaccination.

Fluoroquinolones for the Treatment of Pulmonary Tuberculosis

Tuberculosis (TB) continues to be a significant problem globally. Treatment includes a multiple drug regimen with isoniazid, rifampicin (rifampin), pyrazinamide and ethambutol. Often, one of these medications needs to be replaced as a result of adverse events or because Mycobacterium tuberculosis develops resistance against one these first-line agents. Fluoroquinolones, particularly the newer ones, possess good in vitro (levofloxacin, gatifloxacin, moxifloxacin) and in vivo (gatifloxacin and moxifloxacin) bactericidal activity against M. tuberculosis, making them attractive agents for the treatment of pulmonary TB.All relevant clinical trials, cohort studies and case reports investigating the clinical efficacy and tolerability of fluoroquinolones when used for the treatment of pulmonary TB were evaluated for this review. Specifically, efficacy and safety in the following indications were investigated: (i) first-line treatment of drug-sensitive pulmonary TB; (ii) first-line treatment for multi-drug resistant (MDR) TB; and (iii) treatment of patients with drug intolerance. Twenty-seven articles met our inclusion criteria; nine articles presented data from randomised, controlled or cohort studies. Seven studies used fluoroquinolones as first-line agents in drug-sensitive TB (1469 patients), 15 studies used fluoroquinolones to treat MDR-TB (1025 patients) and six studies (951 patients) investigated the use of fluoroquinolones in patients intolerant to other TB medications.In patients with susceptible M. tuberculosis strains, substitution with a fluoroquinolone did not have an effect on cure or radiological improvement at 8 weeks or failure at 12 months. Substitution of older fluoroquinolones into a regimen, especially ciprofloxacin, resulted in a higher rate of relapse and a longer time to sputum-culture conversions. The use of fluoroquinolones in patients with MDR-TB is supported by some trials where others show a lack of improvement in efficacy of a regimen.Our review of the literature does not support the use of older fluoroquinolones, especially ciprofloxacin, as substitute agents for drug-sensitive or drug-resistant TB. However, newer fluoroquinolones, such as moxifloxacin, may be a reasonable alternative based on results from one large clinical trial. Fluoroquinolones have an important role as substitute agents for those who are intolerant of first-line TB agents.

Epidemiology and costs associated with genital warts in Canada

Background: Genital warts (condyloma acuminatum) remain one of the most commonly reported sexually transmitted infections (STI) worldwide. Most genital warts are caused by non-oncogenic human papilloma virus. Recurrence is common and many patients receive several rounds of treatment. There are limited data in the literature on the burden of illness and costs associated with genital warts at a population level. Methods: Episodes of anogenital warts (AGW) were identified from the physician billing database, hospitalisation records and STI clinics from 1998 to 2006. To be included from the physician billing and STI databases, the person had to have a claim that had a diagnosis of condyloma acuminatum (078.11), viral warts (078.1), viral warts unspecified (078.10) or other unspecified warts (078.19), as well as one of the relevant fee codes associated with the treatment of AGW. To be included from the hospital database, the person could be of any age and have a diagnosis of AGW (A63.0), condyloma acuminatum (078.11), viral warts (078.1 or B07), viral warts unspecified (078.10) or other unspecified warts (078.19) in any of the diagnosis fields, as well as one of the relevant procedure codes associated with the treatment of AGW. Results: A total of 39 493 people was diagnosed with AGW and during this period they had a total of 43 586 episodes. The average cost per episode of AGW was

The Cost Effectiveness of Human Papillomavirus Vaccines A Systematic Review

C190 (

Genetic variations of NAT2 and CYP2E1 and isoniazid hepatotoxicity in a diverse population

C176 for men;

Per Capita Antibiotic Consumption: How Does a North American Jurisdiction Compare with Europe?

C207 for women). The majority of treatment was with ablative therapy alone (98%). Conclusions: AGW are associated with a significant burden of illness and costs to the healthcare system.

Health-Related Quality of Life Trajectories Among Adults With Tuberculosis: Differences Between Latent and Active Infection

AbstractIntroduction: Human papillomavirus (HPV) is one of the world’s most common sexually transmitted infections, and has been associated with a number of cervical and non-cervical diseases, including cancer. HPV vaccines have been licensed for use in females for some time, but the quadrivalent vaccine has only recently become licensed for use in males. Many countries have adopted a vaccination programme for adolescent females based on results of cost-effectiveness analyses. However, given the new indications for use of the vaccine in males, decision makers require information on the cost effectiveness of vaccinating males in order to make policy decisions on whether or not to fund such programmes. Objective: Our objective was to conduct a qualitative systematic review to update a previously conducted review of HPV vaccine studies. Methods: Articles were obtained from an extensive literature search to determine the cost effectiveness of implementing an HPV vaccination programme with routine cervical cancer screening. A total of 29 studies were included in this review. Seventeen of the included articles looked only at cervical disease outcomes, and 12 studies also included non-cervical disease outcomes. Four studies explored the economic impact of vaccinating both boys and girls. One study focused on a population of men who have sex with men (MSM). Results: While different model structures, input parameters and baseline assumptions were used, the consistent message in studies that focused on female-only vaccination programmes was that routine vaccination of females is cost effective compared with cervical cancer screening alone. Discussion: Based on the currently available literature, it appears that the addition of boys to a vaccination programme generally exceeds traditional cost-effectiveness thresholds. The MSM population represents a potential additional target for routine HPV vaccination; however, more cost-effectiveness studies are required before making such a policy change.