Extended interval dosing of natalizumab in multiple sclerosis.

BACKGROUND: Natalizumab (NTZ), a monoclonal antibody to human α4ß1/ß7 integrin, is an effective therapy for multiple sclerosis (MS), albeit associated with progressive multifocal leukoencephalopathy (PML). Clinicians have been extending the dose of infusions with a hypothesis of reducing PML risk. The aim of the study is to evaluate the clinical consequences of reducing NTZ frequency of infusion up to 8 weeks 5 days. METHODS: A retrospective chart review in 9 MS centres was performed in order to identify patients treated with extended interval dosing (EID) regimens of NTZ. Patients were stratified into 3 groups based on EID NTZ treatment schedule in individual centres: early extended dosing (EED; n=249) every 4 weeks 3 days to 6 weeks 6 days; late extended dosing (LED; n=274) every 7 weeks to 8 weeks 5 days; variable extended dosing (n=382) alternating between EED and LED. These groups were compared with patients on standard interval dosing (SID; n=1093) every 4 weeks. RESULTS: 17% of patients on SID had new T2 lesions compared with 14% in EID (p=0.02); 7% of patients had enhancing T1 lesions in SID compared with 9% in EID (p=0.08); annualised relapse rate was 0.14 in the SID group, and 0.09 in the EID group. No evidence of clinical or radiographic disease activity was observed in 62% of SID and 61% of EID patients (p=0.83). No cases of PML were observed in EID group compared with 4 cases in SID cohort. CONCLUSIONS: Dosing intervals up to 8 weeks 5 days did not diminish effectiveness of NTZ therapy. Further monitoring is ongoing to evaluate if the risk of PML is reduced in patients on EID.

Prevalence and correlates of cervico-vaginal clinical syndromes among women attending a health camp in Lalitpur district of Nepal.

BACKGROUND: Sexual and reproductive health of women is a major public health problem in Nepal. Screening of cervico-vaginal clinical syndromes could potentially provide insights to the prevalence of sexually transmitted infections (STIs), which is not known. OBJECTIVE: To investigate the prevalence and factors associated with cervico-vaginal clinical syndromes in the socio-behavioral, medical, and public health context of Nepal. METHODS: Married women attending a clinical health camp held by the Nepal Fertility Care Centerin Khokana of Lalitpur district were recruited to the study. Seventy-three participants completed face-to-face questionnaires on basic socio-demographic, behavioral and reproductive health factors and underwent pelvic screening including clinical diagnosis of cervicitis and vaginitis. An univariate analysis was performed to determine if any of the self-reported variables were associated with abnormal pelvic examination (cervicitis and/or vaginitis). RESULTS: Vaginitis was diagnosed in three (4.4%) participants, while cervicitis was detected in 16 (23.5%) women. None of the participants reported any high risk sexual behavior. However, 28% of the participants reported having had STI diagnosis in the past and was associated (P<0.008) with abnormal pelvic results. Additionally, women with lower education were associated (p<0.02) with abnormal pelvic results. CONCLUSIONS: The high occurrence of cervicitis in our exploratory could indicate the high prevalence of STIs. However, while there could potentially be an unknown epidemic of STIs related to the clinical syndromes, point of care testing practice might help to understand the true prevalence of STIs in Nepali women and also reduce the health burden and consequences of over treatment based on the current symptomatic diagnosis.

Prevalence and predictors of HIV infection amongst Malian students.

The objectives of this cross-sectional study were to assess the prevalence and identify predictors of HIV-1 and HIV-2 infection among students in three cities of Mali. Between January and June 2005, we assessed HIV knowledge, attitudes, associated sexual behaviors and tested HIV serostatus among 950 high school and university students in Sikasso, Bamako, and Koulikoro cities, using a combination of enzyme-linked immunosorbent assay (ELISA) and Western blot testing. Univariate and logistic regression analyses were used to determine predictors of infection among students. Mean HIV prevalence was 3.1%, ranging from 1.8% in Sikasso to 3.6% in Bamako. The results showed the presence of all three HIV subtypes in Bamako, though HIV-1 predominated in all cities. Infection rates were slightly higher among males (3.6%) than among females (2.8%), but the difference was not significant. The single significant predictor of HIV infection was knowledge of HIV routes of transmission (p=0.01). HIV prevalence rates observed in this population were higher than general adult prevalence rates previously reported for Mali. HIV/AIDS education and prevention campaigns should be targeted to students at both the secondary and university levels. Students may represent an informative HIV sentinel population for Mali.

Variability in women's desire for information about mammography screening: implications for informed consent.

This study aimed to explore women's desire for information about mammography screening in a population where overly optimistic perceptions of mammography screening were common. A self-administered questionnaire was completed by 2305 women aged 50-69 years, residents of Geneva, Switzerland. The questionnaire assessed the respondents' wish to receive information (detailed, general or none) about seven aspects of mammography screening: personal risk of breast cancer, prevention of breast cancer, benefits of mammography screening, limitations, minor inconveniences, more important problems, why some people oppose screening. The seven items formed a unidimensional scale (Cronbach's alpha=0.91). Women differed considerably in their stated desire for detailed or general information. For instance, whereas 14% wanted detailed information on all items and 36% general information on all items, 39% were not interested in detailed information on the limits and adverse consequences of screening. In multivariate analysis, some women's characteristics were associated with higher scores of desire for information, but little variance was explained (adjusted R=0.05). In conclusion, many women currently decline information about mammography screening that is deemed relevant by public health authorities. This may lead to poorly informed choices in an important area of prevention.

Gonorrhea incidence and HIV testing and counseling among adolescents and young adults seen at a clinic for sexually transmitted diseases.

OBJECTIVE: To determine whether HIV testing and posttest counseling may be associated with an increase in gonorrhea incidence among adolescents and young adults seen at a clinic for sexually transmitted diseases (STD). DESIGN: A historical cohort study with the collection of longitudinal data on the patients' HIV testing and counseling experience. SETTING: Delgado STD clinic of New Orleans, Louisiana, a public ambulatory primary care center that serves mainly the economically disadvantaged Black population. PATIENTS: A record-based inception cohort of 4031 patients aged 15-25 years diagnosed at the clinic between June 1989 and May 1991 with a first lifetime gonorrhea infection. INTERVENTION: Routine confidential HIV tests and posttest counseling sessions experienced at the clinic during follow-up. OUTCOME MEASURE: Incidence rate of reported gonorrhea reinfection. RESULTS: Of the patients, 51.5% were tested once for HIV antibodies and 25.9% twice or more. Formal posttest counseling occurred after 8.5% of the 4665 HIV-negative and 44.0% of the 49 HIV-positive tests. In the most pessimistic of several models controlling for history of gonorrhea, HIV testing and counseling history, and other potential confounding factors, a significantly lower rate of gonorrhea reinfection was observed after a first HIV-negative test than before [adjusted relative risk (RR), 0.66; 95% confidence interval (CI), 0.59-0.74; P < 0.00011. As compared with the pretest period, significantly higher rates of gonorrhea were observed after respectively a second (RR, 1.18; 95% CI, 1.01-1.37; P = 0.03) and a third (RR, 1.52; 95% CI, 1.22-1.88; P = 0.0001) HIV-negative test. No significant association was found between HIV-positive testing and any variation in gonorrhea rate (RR, 0.95; 95% CI, 0.56-1.62; P = 0.85). Posttest counseling for HIV-negative and HIV-positive results were followed respectively by a significantly higher rate of gonorrhea (RR; 1.27; 95% CI, 1.09-1.48; P = 0.002) and a non-significantly lower rate of gonorrhea (RR, 0.53; 95% CI, 0.17-1.60; P = 0.85). CONCLUSION: Our results do not exclude the possibility of a modest increase in gonorrhea incidence after routine HIV testing and counseling in an STD clinic. Nevertheless, this conclusion holds only under the least favorable assumptions and applies solely to a minority of patients.

Loss of antibodies against hepatitis C virus in HIV-seropositive intravenous drug users.

A time-point survey of 262 ex-intravenous drug users (IVDUs) on methadone treatment showed serological evidence of hepatitis C virus (HCV) in 64%, hepatitis B virus in 74% and HIV in 36%. Analysis of previously collected frozen stored sera of the same patients showed that 31 further IVDUs had had anti-HCV antibodies in the past and had lost them in a time-dependent fashion. Most HCV seroreversion was detected in HIV-positive people: 20 out of 85 in the HIV-positive group versus 11 out of 18 in the HIV-negative group.

Influence of previous exposure to antibiotic therapy on the susceptibility pattern of Pseudomonas aeruginosa bacteremic isolates.

Many patients who present with Pseudomonas aeruginosa bacteremia have been previously exposed to antibiotics. To assess whether resistance of bacteremic strains to antipseudomonal antibiotics (piperacillin, ceftazidime, imipenem, ciprofloxacin, or aminoglycosides) is associated with previous exposure to these drugs, a case-control study including 267 cases of P. aeruginosa bacteremia was conducted. Twenty-five percent of the episodes had been preceded by the exposure to an antipseudomonal antibiotic. Eighty-one strains were resistant to at least 1 antibiotic; 186 were susceptible to all drugs. Via univariate analysis, the risks of resistance to ceftazidime and imipenem were found to be significantly associated with previous receipt of these agents. Using multivariate analysis, exposure to any antipseudomonal antibiotic as a monotherapy was found to be associated with an increased risk of subsequent resistance to itself (odds ratio, 2.5; P=.006). Therefore, clinicians should avoid readministering previously prescribed antibiotics when initiating empiric therapies for possible P. aeruginosa bacteremia, especially when they have been given as monotherapies.

Predicting stages of adoption of mammography screening in a general population.

This study assessed predictions of the Transtheoretical Model (TTM) of behaviour change applied to mammography screening in a random sample of 909 Swiss women aged 40-80 years. We examined stages of mammography adoption, positive and negative attitudes toward screening (pros, cons and decisional balance), and additional predisposing, enabling and reinforcing characteristics. The stage of mammography adoption was defined for 827 women, of whom 46.9% reported on-schedule screening (action 10.2%, maintenance 29.7%, relapse risk 7.0%) and 53% did not (precontemplation 23.1%, contemplation 13.5%, relapse 16.4%). Independent factors associated with more advanced stages (from precontemplation to maintenance) were high pros, low cons, belief that mammography screening is recommended every 2 years, high objective risk of breast cancer, being married and higher income. Independent correlates of stage regression (from action/maintenance to relapse) were high cons, belief that mammography screening is recommended every 4 years or not at all and not being married. Perceived utility of an organised screening programme and reluctance to pay for a mammogram were independently associated with only certain transitions between stages of adoption. Our results confirm the applicability of the TTM to mammography screening in a European context. They also suggest that constructs other than pros and cons may be useful in predicting mammography use.

Misconceptions about efficacy of mammography screening: a public health dilemma.

OBJECTIVE: This study assessed accuracy of women's opinions about reduction in mortality from breast cancer attributable to mammography screening. DESIGN: Cross sectional survey. SETTING: General population of Geneva, Switzerland. PARTICIPANTS: 895 randomly selected women aged 40 to 80 years, free of breast cancer. RESULTS: Women estimated the proportion of deaths from breast cancer that regular mammography screening prevents in women over age 50. Only 19.3% of the respondents assessed screening efficacy realistically (that is, reduction by about one fourth); 52.0% overestimated efficacy; 26.0% "didn't know", and 2.6% stated that screening prevents no death. Women who believed mammography screening to be effective had more positive attitudes toward screening (higher scores of pros and lower scores of cons) and were more likely to plan to have a mammogram (both p<0.001). Lack of opinion about the benefit of mammography screening was more common among women who had not consulted a gynaecologist recently (p=0.02) nor had had a mammogram during the past two years (p=0.009), who had no opinion about their risk of breast cancer (p<0.001), and who were 70 to 80 years old (p=0.04). Compared with women who provided realistic estimates of screening efficacy, those who overestimated efficacy believed to be at higher risk of breast cancer than other women (p=0.04) and were more likely to be Swiss nationals (p=0.001). CONCLUSIONS: Most women overestimated and many were uninformed about the efficacy of mammography screening. Therefore, few women were able to take truly informed decisions about screening mammography.

Patterns of use of ambulatory mental health services in a universal care setting.

OBJECTIVE: As health care expenditures grow, it is important to understand whether mental health services are being used appropriately. This study examined participants' reasons for seeking the services of a psychiatrist or psychologist to determine the extent to which factors other than an existing clinical disorder, such as culture, stress, or lack of social support, played a role. METHODS: A total of 1,257 randomly selected students who were enrolled at the University of Geneva in 1997 and who had unrestricted access to psychiatric services were asked how many times in the past 12 months they had consulted a psychiatrist or a psychologist. The respondents' mental health, perceived stress, self-esteem, sense of mastery, and social support were measured with validated instruments. RESULTS: A total of 131 respondents (10 percent) reported an encounter with a mental health provider in the past year. In adjusted analyses, female sex, Swiss citizenship, a higher level of stress, and a lower level of mental health were significantly associated with a greater number of visits to a mental health specialist, and self-esteem, sense of mastery, and social support were not. CONCLUSIONS: The respondents' use of mental health services was determined by a lower level of mental health, indicating appropriate use of services based on clinical need. However, service use was also determined by consumer-related variables such as perceived stress and sociocultural characteristics.

[Estimation of the efficacy of three strains of mumps vaccines during an epidemic of mumps in the Geneva canton (Switzerland)]. / Estimation de l'efficacité de trois souches vaccinales ourliennes au cours d'une épidémie d'oreillons dans le canton de Genève (Suisse).

BACKGROUND: The number of mumps cases reported in Switzerland markedly increased from 1993 to 1995 although vaccination coverage against mumps had risen steadily since the national MMR immunization program was launched in 1987. In 1991, an estimated 80% of children 27 to 36 month-old were immunized against mumps. The purpose of the present study was to assess the hypothesis that the epidemic was the consequence of a low vaccine efficacy of the Rubini strain--a mumps vaccine strain that has been widely used in Switzerland. METHODS: Vaccine efficacy was assessed by measuring secondary attack rates among immunized and nonimmunized children 16 year-old or younger who wre family contacts of cases. RESULTS: From February 1993 to April 1996, Geneva pediatricians reported 283 primary cases of mumps and 63 secondary cases. Estimate of vaccine efficacy was equal to 6.3% (95% CI: -45.9; 39.8) for the Rubini strain, as compared to 73.1% (95% CI: 41.8; 87.6) for the Urabe Am 9 strain, and 61.6% (95% CI: 0.0; 85.4) for the Jeryl Lynn strain, two vaccine strains of mumps that had also been used in Geneva. CONCLUSION: Our study supports the hypothesis that the Rubini vaccine strain of mumps does not confer sufficient long-lasting protection against mumps.

Derivation of a tuberculosis screening rule for sub-Saharan African prisons.

SETTING: Lusaka Central Prison, Zambia. OBJECTIVE: To derive screening rules for tuberculosis (TB) using data collected during a prison-wide TB and human immunodeficiency virus (HIV) screening program. DESIGN: We derived rules with two methodologies: logistic regression and classification and regression trees (C&RT). We evaluated the performance of the derived rules as well as existing World Health Organization (WHO) screening recommendations in our cohort of inmates, as measured by sensitivity, specificity, and positive and negative predictive values. RESULTS: The C&RT-derived rule recommended diagnostic testing of all inmates who were underweight (defined as body mass index [BMI] < 18.5 kg/m(2)] or HIV-infected; the C&RT-derived rule had 60% sensitivity and 71% specificity. The logistic regression-derived rule recommended diagnostic testing of inmates who were underweight, HIV-infected or had chest pain; the logistic regression-derived rule had 74% sensitivity and 57% specificity. Two of the WHO recommendations had sensitivities that were similar to our logistic regression rule but had poorer specificities, resulting in a greater testing burden. CONCLUSION: Low BMI and HIV infection were the most robust predictors of TB in our inmates; chest pain was additionally retained in one model. BMI and HIV should be further evaluated as the basis for TB screening rules for inmates, with modification as needed to improve the performance of the rules.

Serum protein electrophoresis: any role in monitoring for antiretroviral therapy?

BACKGROUND: Developing world are always looking for monitoring tools during reagent shortage and equipments troubles which are very frequent. The aim of this study was to evaluate Serum Protein Electrophoresis (SPE) as a marker for assessing HIV treatment response. METHODS: A cross-sectional study was conducted with 220 participants in four distinct groups: Symptomatic HIV positive patients [specifically those on antiretroviral treatment (ART) versus those not on ART] asymptomatic HIV positive patients, and healthy blood donors. Five serum protein fractions (Albumin, Alpha-1, Alpha-2, Beta, and Gamma) were compared between these groups after measuring the density of the fractions. RESULTS: Concentration of gamma globulin was lowest among healthy blood donors, intermediate and comparable among asymptomatic HIV positive and symptomatic HIV positive on ART and highest among untreated symptomatic HIV positive. Concentration of gamma globulin was inversely correlated with the disease stage (p < 0.001). CONCLUSION: In this study, conducted in a setting where the burden of infectious diseases is high, the density of gamma globulin and albumin fractions were significantly associated with HIV status, and among HIV positive patients, with stage of HIV disease and ART. These results suggest that the feasibility of using SPE for monitoring the response of ART in low resource settings should be further explored.

Rapid disease course in African Americans with multiple sclerosis.

OBJECTIVE: To investigate utility of a Multiple Sclerosis Severity Scale (MSSS)-based classification system for comparing African American (AA) and white American (WA) multiple sclerosis (MS) subpopulations in the New York State Multiple Sclerosis Consortium (NYSMSC) database. MSSS is a frequency-rank algorithm relating MS disability to disease duration in a large, untreated reference population. Design/ METHODS: Distributions of patients in 6 MSSS-based severity grades were calculated for AA and WA registrants. RESULTS: There were 419 AA and 5,809 WA patients in the NYSMSC, who had EDSS recorded during years 1-30 since symptom onset. Median EDSS was not different in AA and WA (3.5 vs 3.0, p = 0.60), whereas median MSSS in AA was higher than in WA (6.0 vs 4.8, p = 0.001). AA patients were overrepresented in the 2 most severe grades (41.5% vs 29.3% for WA) and underrepresented in the 2 lowest grades (23.4% vs 35.4%; p < 0.001). In multivariable analysis (ordered logistic and median regression), MSSS for AA remained significantly higher than in WA after adjusting for age, gender, disease duration, disease type distribution, and treatment with disease-modifying therapies. CONCLUSIONS: The 6-tiered MSSS grading system is a powerful tool for comparing rate of disease progression in subpopulations of interest. MSSS-based analysis demonstrates that African ancestry is a risk factor for a more rapidly disabling disease course.

Association of misconceptions about HIV transmission and discriminatory attitudes in rural China.

This study examined HIV-related knowledge and attitudes among 524 randomly selected adult residents from 12 rural Chinese communities where HIV infection among plasma donors has been reported. Most participants were familiar with the main routes of HIV transmission but had substantial misconceptions about risk of HIV transmission through casual social contacts. Higher score of misconception and being older and married independently predicted stronger discriminatory attitude. Intervention programs with focus on eliminating misconceptions about HIV transmission may reduce stigma.

Public health importance and risk factors for cercarial dermatitis associated with swimming in Lake Leman at Geneva, Switzerland.

Fifteen cohorts of healthy bathers were recruited at four Lake Leman beaches between 3 July and 23 August 1996 to assess the public health importance of cercarial dermatitis in Geneva, Switzerland. Telephone follow-up interviews were carried out after 2-7 days. Overall, 153 bathers out of 555 reported probable cercarial dermatitis at follow-up. Median daily attack rate was 27.7% (2.2-57.7%). Of the cases, 11.1% noticed more than 30 skin lesions, 19.6% described severe itching, 50.3% used a drug treatment, 3.9% visited a doctor and 15% claimed they would reduce their bathing activities. History of cercarial dermatitis, time spent in the water, hour of the day, barometric pressure and maximum daily atmospheric temperature predicted disease occurrence in multivariate analysis. While a benign disease, cercarial dermatitis may have a negative impact on the local water recreation industry. The identification of risk factors for the disease may help produce better preventive recommendations for the bathers.

Quantitation of human immunodeficiency virus provirus and circulating virus: relationship with immunologic parameters.

Virologic and seroimmunologic parameters were determined in 56 persons infected with human immunodeficiency virus (HIV). The provirus level varied from 10 to 100,000/10(6) CD4+ lymphocytes, and genomic HIV RNA was detectable in 39 of 56 patients at a relative concentration varying from 10 to greater than 250 copies/mL of serum. Provirus expressed as copies per 10(6) CD4+ lymphocytes and as circulating virus per milliliter of serum increased with disease progression and decrease of CD4+ cell concentration. The mean provirus concentration expressed per milliliter of blood varied little among categories of patients with various levels of CD4+ cells, but there was a progressive increase of circulating HIV genomic RNA. These virologic data suggest that during the course of HIV infection, an increasing proportion of the remaining CD4+ lymphocytes harbor the HIV genome and produce infectious virus. Finally, there was a marked correlation between increased provirus and genomic RNA concentration and three seroimmunologic markers: decrease in CD4+ cell count, p24 antigenemia, and disappearance of antibodies to HIV core antigen.

Importance of patients' perceptions and general practitioners' recommendations in understanding missed opportunities for immunisations in Swiss adults.

Over the last decades, tremendous efforts have been made to strengthen childhood immunisation programs. However, the burden of influenza and pneumococcal infections remains disturbingly high in adults and elderly. We conducted a cross-sectional self-administered mail survey to identify characteristics associated with low use of recommended vaccines in adult patients attending routine primary care appointments in Switzerland. Tetanus vaccination was reported by 84% of respondents aged 16-34, and by only 42% of respondents aged 65 or more. For influenza and pneumococcal vaccination, of high-risk patients (age > or =65 or history of diabetes, kidney, heart, or chronic pulmonary disease), only 41% were on schedule for influenza and 6% for pneumococcal vaccination. Compared with patients from the German- and Italian-speaking areas of the country, patients from the French-speaking region were more likely to report past immunisation against influenza and pneumococcal disease or a recent physician's recommendation for immunisation against influenza, but equally likely to have ever refused influenza vaccination. For all three diseases, area of residence, physician's recommendation for immunisation, and patient's perceived usefulness of vaccination were independently and significantly associated with vaccination status. Although patient's opinion is an important determinant of vaccination coverage in adults, lack of physician's encouragement accounted for most missed vaccination opportunities in this study. The higher vaccination coverage among patients from the French-speaking area suggests that the promotion campaigns carried out in this region effectively improved influenza vaccine use. Interventions designed to increase vaccination coverage in adults must help providers incorporate immunisation in routine health care.