Efficacy of a Carrageenan gel Against Transmission of Cervical HPV (CATCH): interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial.

OBJECTIVES: To evaluate the efficacy of a carrageenan-based lubricant gel in reducing the risk of genital human papillomavirus (HPV) infections in women. METHODS: We conducted a planned interim analysis of a randomized, double-blind, placebo-controlled, phase 2B trial. Women aged 18 years and older were randomly assigned (1:1) to a carrageenan-based gel or a placebo gel to be self-applied every other day for the first month and before and after each intercourse during follow-up. Assessments were performed at 0.5, 1, 3, 6, 9 and 12 months. The primary outcome was incidence of a new infection by an HPV type that was not present at baseline. Intention-to-treat analyses were performed. RESULTS: Between January 2013 and June 2017, a total of 280 participants were randomly assigned to the carrageenan (n = 141) or the placebo (n = 139) arm. All participants were included in safety analyses, but three (1%) were excluded from efficacy analyses (HPV results unavailable for two participants in the carrageenan and one participant in the placebo arm). The median follow-up time was 9.2 months (interquartile range, 1.9-13.2 months). A total of 59 (42%) of 139 participants in the carrageenan arm and 78 (57%) of 138 participants in the placebo arm became infected by at least one new HPV type (hazard ratio = 0.64, 95% confidence interval = 0.45-0.89, p 0.009). A total of 62 (44%) of 141 participants in the carrageenan arm versus 43 (31%) of 139 participants in the placebo arm reported an adverse event (p 0.02), none of which was deemed related to the gels. CONCLUSIONS: Our trial's interim analysis suggests that using a carrageenan-based lubricant gel can reduce the risk of genital HPV infections in women.

Sexual behaviours and head and neck cancer: A systematic review and meta-analysis.

Human papillomaviruses (HPV) are associated with head and neck cancers (H&NC). Transmission of HPV to the upper aerodigestive tract occurs plausibly through sexual contact, although epidemiologic evidence on the role of sexual behaviours in H&NC aetiology is inconsistent. We conducted a meta-analysis of studies examining the association between four indicators of sexual behaviours (number of sexual partners and oral sex partners, oral sex practice, and age at first intercourse) and H&NC. Summary odds ratios (OR) and 95% confidence intervals (CI) were estimated using fixed and random effects models for each indicator, contrasting 'highest' to 'lowest', 'ever' to 'never', or 'youngest' to 'oldest' categories. Twenty case-control studies were included out of 3838 identified publications. Using random effects models, summary ORs suggested an increased risk of H&NC for number of sexual partners [OR=1.29, 95% CI: 1.02-1.63] (19 studies) and number of oral sex partners [OR=1.69, 95% CI: 1.00-2.84] (5 studies), whereas no effect was observed with oral sex practice [OR=1.09, 95% CI: 0.88-1.35] (17 studies) and age at first intercourse [OR=1.40, 95% CI: 0.71-2.79] (6 studies). For number of sexual partners and oral sex practice, which were assessed in more studies, we further excluded studies contributing to heterogeneity and those not adjusted for age, sex, smoking, and alcohol consumption. The summary ORs were 0.95 (95% CI: 0.75-1.20) for number of sexual partners and 1.03 (95% CI: 0.84-1.26) for oral sex practice. Our findings highlight that observed associations might be partly attributed to confounding effects of sociodemographic and behavioural factors.

Is metal fume fever a determinant of welding related respiratory symptoms and/or increased bronchial responsiveness? A longitudinal study.

BACKGROUND: The current prospective study investigated the hypothesis of metal fume fever (MFF) being a predictor for the development of respiratory symptoms and functional abnormalities. METHODS: The study consisted of a pre-exposure and two follow up assessments of 286 welding apprentices during an average period of 15 months. A respiratory and a systemic symptom questionnaire, skin prick tests to common allergens and metal salts, spirometry, and methacholine challenge tests were administered. RESULTS: Developing at least one positive skin prick test to a metallic salt solution was found in 11.8% of apprentices. Possible MFF (at least one of fever, feelings of flu, general malaise, chills, dry cough, metallic taste, or shortness of breath) was reported by 39.2% of apprentices. The presence of at least one welding related respiratory symptom (cough, wheezing, or chest tightness) suggestive of welding related asthma was reported by 13.8%. MFF was significantly associated with these respiratory symptoms (OR = 4.92, 95% CI 2.10 to 11.52), after adjusting for age, atopy, smoking, physician diagnosed asthma, and symptoms of non-welding related asthma. Apprentices with possible MFF, and no welding related respiratory symptoms suggestive of welding related asthma at the first follow up, had an increased risk of developing the latter symptoms by the second follow up visit (OR = 7.4, 95% CI 1.97 to 27.45) compared with those not having MFF. MFF was not significantly associated with an increase in bronchial responsiveness. CONCLUSION: MFF could be a predictor for the development of respiratory symptoms but not for functional abnormalities in welders.

Prevalence and association of welding related systemic and respiratory symptoms in welders.

BACKGROUND: The prevalence of welding related respiratory symptoms coexisting with welding related systemic symptoms in welders is unknown. AIMS: To determine in a sample of welders the prevalence of coexisting welding related systemic symptoms indicative of metal fume fever (MFF) and welding related respiratory symptoms suggestive of occupational asthma (OA), and the strength and significance of any association between these two groups of symptoms. METHODS: A respiratory symptoms questionnaire, a systemic symptoms questionnaire, and a questionnaire on occupational history were administered by telephone to 351 of a sample of 441 welders (79.6%) from two cities in Québec, Canada. RESULTS: The co-occurrence of possible MFF (defined as having at least two symptoms of fever, feelings of flu, general malaise, chills, dry cough, metallic taste, and shortness of breath, occurring at the beginning of the working week, 3-10 hours after exposure to welding fumes) together with welding related respiratory symptoms suggestive of OA (defined as having at least two welding related symptoms of cough, wheezing, and chest tightness) was 5.8%. These two groups of symptoms were significantly associated (chi(2) = 18.9, p < 0.001). CONCLUSION: There is a strong association between welding related MFF and welding related respiratory symptoms suggestive of OA. As such, MFF could be viewed as a pre-marker of welding related OA, a hypothesis that requires further investigation.

Clinical evaluation of serum aminoterminal propeptide of type III procollagen as tumor marker in gynecologic malignancies.

AIMS: The aim of this study was to determine the possible usefulness of the assay of the aminoterminal propeptide of type III procollagen and fibronectin in detecting connective tissue changes associated with gynecologic malignancies. STUDY DESIGN: Serum aminoterminal propeptide of type III procollagen and plasma fibronectin were measured in 36 women with gynecologic malignancies, 20 women with benign gynecologic tumors and 10 healthy women serving as controls. RESULTS: A significant serum propeptide was significantly high in the group with gynecologic malignancies and normal in the benign tumor group. The serum propeptide levels were related to of disease stage and presence of ascites in patients with ovarian carcinoma but not in those with cervical or endometrial carcinoma. In the follow-up study, a favorable clinical response was associated with normalizing propeptide levels whereas in rapidly progressive disease the levels fell initially but rose again. In partial response with ultimate progression, the propeptide concentration decreased but remained clearly above the normal range. No difference in plasma fibronectin was found among the malignant tumor, benign tumor and control groups. CONCLUSIONS: The present study indicates that the aminoterminal propeptide of type III procollagen could serve as an additional, non specific marker to follow the clinical behavior of gynecologic malignancies and consequently of connective tissue metabolism reflecting tumor matrix interaction.

Correlation of renal organic anion and cation transport with blood pressure in SHR.

In 1974, we found that sera from SHR suppressed renal PAH transport (PSEBM 145:97, 1974). Since a "natriuretic factor" depresses PAH as well as Na transport, we proposed that "natriuretic factor" was elevated in SHR. Our current investigation amplifies the previous study. On a given day, one spontaneously hypertensive rat (SHR) and one rat from a normotensive strain [Wistar Kyoto (WKY) or Sprague-Dawley (SD]) were examined together. SHR sera compared to WKY/SD sera significantly depress PAH (organic anion) and TEA (organic cation) uptake by rat renal slices. The ability of SHR sera to depress uptake correlated significantly with the BP: the sera with the greatest depressive influence on renal PAH and TEA uptake came from the SHR with the highest BP (PAH r = 0.89, p less than 0.0001; TEA = r = 0.76, p less than 0.01). Subsequent separation of serum on Sephadex 25 localized the factor to the same fraction as "natriuretic hormone". A similar correlation was found between the ability of the fraction to depress the 2 transports and the height of the BP. The serum factor did not inhibit ATPase activity. In contrast to the serum effects, renal slices removed from SHR showed increased rather than decreased PAH and TEA transport which significantly correlated with the BP. The slices with the highest uptakes came from the SHR with the highest BP. The high uptake of organic ions by the SHR renal slices could be an adaptive response to the serum factor or vice versa. We postulate that a serum factor which depresses PAH and TEA transport and is not "ouabain-like" may play a role in the BP elevation of SHR.