Mélanie Drolet

Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis.

BACKGROUND Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations. METHODS We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I(2) and χ(2) statistics and we did trends analysis to examine the dose-response association between HPV vaccination coverage and each study effect measure. FINDINGS We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19-0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22-0·71) in girls 13-19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54-0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0·66 [95% CI 0·47-0·91]) and in women 20-39 years of age (0·68 [95% CI 0·51-0·89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34-0·74]) and in anogenital warts (0·86 [95% CI 0·79-0·94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects. INTERPRETATION Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement. FUNDING The Canadian Institutes of Health Research.

Secondary impairments after spinal cord injury: a population-based study.

ObjectiveTo determine the prevalence of secondary impairments among individuals with long-standing spinal cord injury in Quebec and the potential relationships between these impairments and several variables. DesignA review of 2200 medical files was conducted to determine the target population; 976 patients were selected randomly and mailed questionnaires. The results were based on 482 individuals with spinal cord injury who returned the completed questionnaire. The questionnaire included 14 subsections, such as sociodemographic, medical, psychosocial, and environmental information. The medical section, including the type and level of lesion and the presence of secondary impairments, was analyzed. ResultsUrinary tract infection, spasticity, and hypotension were the most frequently reported secondary impairments, regardless of the severity of injury. Relationships between the prevalence of secondary impairments and the duration of injury, as well as perceived health status, were observed. ConclusionsThis is the first study to describe secondary impairments after long-standing spinal cord injury in Quebec. Patients with spinal cord injury still present a high prevalence of secondary impairments many years after their rehabilitation, despite preventive education or medical follow-up visits. Further studies are required to determine the specific impact that these impairments have on the patients’ social role and their quality-of-life.

The impact of herpes zoster and postherpetic neuralgia on health-related quality of life: a prospective study

Background: Vaccination against herpes zoster is being considered in many countries. We conducted a multicentre prospective study to describe the impact of herpes zoster and postherpetic neuralgia on health-related quality of life. Methods: From October 2005 to July 2006, 261 outpatients aged 50 years or older with herpes zoster were recruited from the clinical practices of 83 physicians within 14 days after rash onset. The Zoster Brief Pain Inventory was used to measure severity of pain and interference with activities of daily living because of pain. The EuroQol EQ-5D assessment tool was used to measure quality of life. These outcomes were assessed at recruitment and on days 7, 14, 21, 30, 60, 90, 120, 150 and 180 following recruitment. Results: Acute herpes zoster interfered in all health domains, especially sleep (64% of participants), enjoyment of life (58%) and general activities (53%). The median duration of pain was 32.5 days. The median duration of interference with activities of daily living because of pain varied between 27 and 30 days. Overall, 24% of the participants had postherpetic neuralgia (pain for more than 90 days after rash onset). Anxiety and depression, enjoyment of life, mood and sleep were most frequently affected during the postherpetic neuralgia period. The mean EQ-5D score was 0.59 at enrolment and remained at 0.67 at all follow-up points among participants who reported clinically significant pain. Interpretation: These data support the need for preventive strategies and additional early intervention to reduce the burden of herpes zoster and postherpetic neuralgia.

Dietary Change After Breast Cancer: Extent, Predictors, and Relation With Psychological Distress

PURPOSE Some women may try to cope with breast cancer by making lifestyle modifications, possibly in the hope of improving disease outcome. We assessed extent, predictors, and effect on psychological distress of dietary changes in the year after diagnosis among 250 women with newly diagnosed, nonmetastatic breast cancer. PATIENTS AND METHODS Data came from medical records, and from interviews 3 days and 12 months after initial treatment. RESULTS At 12 months, 41% (n = 103) reported dietary changes at some time since diagnosis, with decreases in meat (77%) and increases in fruit and vegetable intake (72%) being the most frequent. Women reporting changes were more likely to be younger, to have positive nodes, to be receiving adjuvant therapy, and to be more distressed initially. The mean 0 to 12 month decrease in psychological distress was greater in women who reported changes (9 points) than those who did not (4.7 points) (P =.03), although regression toward the mean cannot be excluded. CONCLUSION A sizable proportion of women made dietary changes on their own initiative. Most changes reported were generally consistent with current scientific hypotheses about dietary changes that might favorably affect prognosis. The profile of women reporting changes suggests a group with more concerns about recurrence, who may have initiated dietary change to help cope with and gain a sense of control over the disease, and possibly to improve prognosis. Our results suggest that newly diagnosed women could be receptive to explicit attention to diet as part of psychosocial care. However, this interest in dietary change may not, as yet, have been maximally channeled into trying to improve the care and quality of life of women facing diagnosis, treatments, and fears about recurrence.

Wage Losses in the Year After Breast Cancer: Extent and Determinants Among Canadian Women

BACKGROUND Wage losses after breast cancer may result in considerable financial burden. Their assessment is made more urgent because more women now participate in the workforce and because breast cancer is managed using multiple treatment modalities that could lead to long work absences. We evaluated wage losses, their determinants, and the associations between wage losses and changes for the worse in the familys financial situation among Canadian women over the first 12 months after diagnosis of early breast cancer. METHODS We conducted a prospective cohort study among women with breast cancer from eight hospitals throughout the province of Quebec. Information that permitted the calculation of wage losses and information on potential determinants of wage losses were collected by three pretested telephone interviews conducted over the year following the start of treatment. Information on medical characteristics was obtained from medical records. The main outcome was the proportion of annual wages lost because of breast cancer. Multivariable analysis of variance using the general linear model was used to identify personal, medical, and employment characteristics associated with the proportion of wages lost. All statistical tests were two-sided. RESULTS Among 962 eligible breast cancer patients, 800 completed all three interviews. Of these, 459 had a paying job during the month before diagnosis. On average, these working women lost 27% of their projected usual annual wages (median = 19%) after compensation received had been taken into account. Multivariable analysis showed that a higher percentage of lost wages was statistically significantly associated with a lower level of education (P(trend) = .0018), living 50 km or more from the hospital where surgery was performed (P = .070), lower social support (P = .012), having invasive disease (P = .086), receipt of chemotherapy (P < .001), self-employment (P < .001), shorter tenure in the job (P(trend) < .001), and part-time work (P < .001). CONCLUSION Wage losses and their effects on financial situation constitute an important adverse consequence of breast cancer in Canada.

Work absence after breast cancer diagnosis: a population-based study

Background: Absence from work after breast cancer diagnosis may be part of the burden of disease for women with cancer, but little research has addressed this. We examined work absences of 4 weeks or more among women who had had breast cancer during the 3 years after diagnosis and compared their absences with those of women who had never had cancer. Methods: Our 2 target study groups were women in Quebec 18–59 years of age who were working when they first received therapy for breast cancer between November 1996 and August 1997 and similarly aged women randomly selected from provincial health care files who had never had cancer and were working at the time of diagnosis in women who had cancer. We interviewed 646 women who had had breast cancer (73% of those eligible) and 890 women in the comparison group (51% of those eligible) by telephone 3 years after first diagnosis. Results: One year after diagnosis, 85% (459/541) of breast cancer survivors who remained free of disease during the 3-year study period were absent from work for 4 weeks or more compared with 18% (156/881) of healthy women (geometric mean total duration 5.6 v. 1.7 months, p < 0.001). By the third year, disease-free women were not absent more than women in the comparison group; however, more women who had experienced any new cancer event continued to be absent from work and to be absent from work for longer periods of time. Receiving adjuvant chemotherapy prolonged absence duration (9.5 v. 5.4 months among women not receiving chemotherapy). Compared with survivors belonging to a union, those who did not belong to a union (multivariate relative risk [RR] 7.54, 95% confidence interval [CI] 3.02–18.83) and those who were self-employed (RR 13.95, 95% CI 5.53–35.21) were more likely to report no work absence. Interpretation: Most of the women with breast cancer took time off work (almost 6 months on average) after receiving the diagnosis. Three years after diagnosis, breast cancer survivors who remained disease-free — a large proportion of women with nonmetastatic breast cancer — were not absent from work more often or for longer periods of time than other working women.

Incremental Impact of Adding Boys to Current Human Papillomavirus Vaccination Programs: Role of Herd Immunity

Our aim was to examine the potential incremental impact of vaccinating boys against human papillomavirus (HPV) on vaccine-type infection in females and males, using an individual-based HPV transmission-dynamic model. Under base assumptions (vaccine efficacy = 99%, duration of protection = 20 years, coverage = 70%), vaccinating 12-year-old boys, in addition to girls, resulted in an incremental reduction in HPV-16/18 (HPV-6/11) incidence over 70 years of 16% (3%) in females and 23% (4%) in males. The benefit of vaccinating boys decreased with improved vaccination coverage in girls. Given the important predicted herd immunity impact of vaccinating girls under moderate to high vaccine coverage, the potential incremental gains of vaccinating boys are limited.

Population-Level Impact of the Bivalent, Quadrivalent, and Nonavalent Human Papillomavirus Vaccines: A Model–Based Analysis

BACKGROUND Bivalent and quadrivalent human papillomavirus (HPV) vaccines are now licensed in several countries. Furthermore, clinical trials examining the efficacy of a nonavalent vaccine are underway. We aimed to compare the potential population-level effectiveness of the bivalent, quadrivalent, and candidate nonavalent HPV vaccines. METHODS We developed an individual-based, transmission-dynamic model of HPV infection and disease in a population stratified by age, gender, sexual activity, and screening behavior. The model was calibrated to highly stratified sexual behavior, HPV epidemiology, and cervical screening data from Canada. RESULTS Under base case assumptions, vaccinating 12-year-old girls (70% coverage) with the bivalent (quadrivalent) vaccine is predicted to reduce the cumulative incidence of anogenital warts (AGWs) by 0.0% (72.1%), diagnosed cervical intraepithelial neoplasia lesions 2 and 3 (CIN2 and -3) by 51.0% (46.1%), and cervical squamous cell carcinoma (SCC) by 31.9% (30.5%), over 70 years. Changing from a bivalent (quadrivalent) to a nonavalent vaccine is predicted to reduce the cumulative number of AGW episodes by an additional 66.7% (0.0%), CIN2 and -3 episodes by an additional 9.3% (12.5%), and SCC cases by an additional 4.8% (6.6%) over 70 years. Differences in predicted population-level effectiveness between the vaccines were most sensitive to duration of protection and the time horizon of analysis. The vaccines produced similar effectiveness at preventing noncervical HPV-related cancers. CONCLUSIONS The bivalent vaccine is expected to be slightly more effective at preventing CIN2 and -3 and SCC in the longer term, whereas the quadrivalent vaccine is expected to substantially reduce AGW cases shortly after the start of vaccination programs. Switching to a nonavalent vaccine has the potential to further reduce precancerous lesions and cervical cancer.

Predictors of Postherpetic Neuralgia Among Patients With Herpes Zoster: A Prospective Study

UNLABELLED Postherpetic neuralgia (PHN) is the most common complication of herpes zoster (HZ). The main objectives of this study were to: 1) estimate the severity and duration of PHN; and 2) identify the predictors of PHN. From October, 2005 to July, 2006, 261 outpatients with HZ, aged ≥ 50, were recruited within 14 days of rash onset during the routine clinical practice of 83 physicians across Canada. Physicians documented HZ characteristics, treatments, general health, functional, and immune status. HZ pain was measured at recruitment and on days 7, 14, 21, 30, 60, 90, 120, 150, and 180 following recruitment. PHN was defined as a worst pain ≥ 3 persisting or appearing more than 90 days after rash onset. Predictors of PHN were obtained by hierarchical log-binomial regression. Twenty-two percent of 249 immunocompetent subjects with HZ developed PHN. Median duration of PHN was 77 days. Independent predictors of PHN included: older age, limitation in performing usual activities prior to HZ, and pain severity at recruitment. This study confirms that older age and greater acute pain severity are predictors of PHN, while functional status emerges as a novel independent predictor of PHN that deserves further exploration. These findings will contribute to optimal use of the HZ vaccine and testing of new therapies that might prevent PHN. PERSPECTIVE This study confirmed that older age and greater acute pain severity are robust predictors of PHN, whereas functional status emerged as a novel predictor. Despite the high proportion of subjects treated with antivirals, the burden of PHN remains considerable, suggesting that prevention and additional early interventions are needed to reduce the burden of HZ.

Modeling the impact of one- and two-dose varicella vaccination on the epidemiology of varicella and zoster.

In many countries, policymakers are being asked to make recommendations regarding the introduction of a 2-dose varicella vaccination program. The objective of this study was to examine the potential impact of 1-dose versus 2-dose varicella vaccination programs on varicella and zoster incidence, using Canada as an example. We developed a deterministic realistic age-structured model that fits 1- and 2-dose vaccine efficacy, varicella force of infection and zoster incidence. Assuming 90% coverage, the base case model (range: min; max) predicts that 1-dose vaccination will reduce varicella and zoster cases by 64% (14%; 96%) and 5% (-2%; 22%), respectively, over 80-years. Adding a second dose is predicted to reduce varicella and zoster by an additional 22% (0%; 82%) and 6% (0%; 14%), respectively. Most varicella cases prevented by the second dose are breakthrough infections. Although the incremental effectiveness of adding the second dose is highly sensitive to vaccine efficacy and mixing, predictions of the overall benefit of a 2-dose program is relatively robust to model assumptions. Adding a 2-dose program may help guarantee high population-level effectiveness against varicella. However, the incremental benefit of a second dose is highly dependant on the effectiveness of the first dose and its impact on zoster.