Risque d’acquisition du virus de l’immunodéficience humaine (VIH) chez les femmes utilisant des hormones contraceptives orales et injectables

Objectif : Étudier l'association entre l’utilisation de contraceptifs hormonaux et le risque d'acquisition du VIH-1 chez les femmes au Malawi, en Afrique du Sud, en Zambie et au Zimbabwe. Devis : Analyses secondaires de 2887 femmes âgées de 17-55 ans ayant participé à l’étude HPTN 035, une étude de phase II/IIb sur l’efficacité de deux gels microbicides pour prévenir la transmission du VIH chez les femmes à risque. Méthodes : L'association entre l'utilisation de contraceptifs hormonaux et le risque d'acquisition du VIH-1 a été évaluée en utilisant des modèles de Cox. Des risques relatifs sont estimés où le groupe de référence est celui des femmes qui n’utilisent pas de contraceptifs hormonaux. De plus, un modèle multivarié de Cox est utilisé afin de contrôler pour les facteurs potentiellement confondants. Résultats : Les contraceptifs injectables ont été utilisés par 52,1% des femmes, alors que les contraceptifs oraux ont été utilisés par 20,7% de celles-ci. Pendant l'étude, il y a eu 192 séroconversions. L'incidence observée du VIH était de 2,28; 4,19 et 4,69 pour 100 personne-années pour les contraceptifs oraux, injectables et non hormonaux, respectivement. Lors de l’analyse multivariée, nous n'avons trouvé aucune association significative entre l’usage des contraceptifs hormonaux et l’acquisition du VIH-1. Le risque relatif ajusté (RRa) pour les contraceptifs oraux est de 0,573 (IC de 95% : [0,31-1,06]) et 0,981 (IC de 95% : [0,69 ; 1,39]) pour les contraceptifs injectables. Conclusions : Bien que cette étude ne démontre pas d’association entre l’usage des contraceptifs hormonaux et le VIH-1, nous concluons toutefois que ces méthodes de contraception ne protègent pas contre le VIH-1, et il est ainsi recommandé aux femmes utilisant des hormones contraceptives de toujours utiliser le condom pour prévenir l'infection au VIH-1.

Both a combined oral contraceptive and depot medroxyprogesterone acetate impair endothelial function in young women

Background: The study was conducted to determine whether the use of a combined oral contraceptive (COC) or depot medroxyprogesterone acetate (DMPA) interferes with endothelial function. Study Design: The study was conducted on 100 women between the ages of 18 and 30 years. Fifty women had not used hormonal contraception (control group) for at least 12 months, 25 were current users of a COC (ethinylestradiol 30 mcg+levonorgestrel 150 mcg) and 25 were current users of DMPA (150 mg) for at least a 6-month period. All women were evaluated for brachial flow-mediated dilation (FMD), intima-media thickness, carotid distensibility and stiffness index, arterial pressure, body mass index, waist circumference, heart rate and lipid profile. Results: A significant difference in FMD was observed between the COC and control groups (6.4 +/- 2.2% vs. 8,7 +/- 3.4%, p<.01) and between the DMPA and control groups (6.2 +/- 2.1% vs. 8.7 +/- 3.4%, p<.01). The DMPA group had lower values of total cholesterol (TC) and low-density lipoprotein (LDL-C) than COC users and the control group (TC: DMPA=139.9 +/- 21.5 mg/dL vs. controls=167.1 +/- 29.2 mg/dL vs. COC=168.2 +/- 37.5. p=.001; LDL-C: DMPA-85.3 +/- 20.1 mg/dL vs. controls=102 +/- 24.5 mg/dL vs. COC=106.7 +/- 33.3 mg/dL, p=.01). The control group had higher levels of high-density lipoprotein (HDL-C) than the DMPA and COC groups (controls=52.4 +/- 14.1 mg/dL vs. DMPA=42.2 +/- 7.2 mg/dL vs. COC=45.4 +/- 9.1 mg/dL, p=.001). No significant differences were observed regarding the other variables. Conclusions: FMD was lower among COC and DMPA users, Suggesting that these hormonal contraceptives may promote endothelial dysfunction. (C) 2009 Elsevier Inc. All rights reserved.

Living with Uncertainty: Acting in the Best Interests of Women

A recent multi-country study on hormonal contraceptives (HC) and HIV acquisition and transmission among African HIV-serodiscordant couples reported a statistically significant doubling of risk for HIV acquisition among women as well as transmission from women to men for injectable contraceptives. Together with a prior cohort study on African women seeking health services, these data are the strongest yet to appear on the HC-HIV risk. This paper will briefly review the Heffron study strengths and relevant biological and epidemiologic evidence; address the futility of further trials; and propose instead an alternative framework for next steps. The weight of the evidence calls for a discontinuation of progestin-dominant methods. We propose here five types of productive activities: (1) scaling injectable hormones down and out of the contraceptive mix; (2) strengthening and introducing public health strategies with proven potential to reduce HIV spread; (3) providing maximal choice to reduce unplanned pregnancy, starting with quality sexuality education through to safe abortion access; (4) expanding provider training, end-user counseling and access to male and female barriers, with a special renewed focus on female condom; (5) initiating a serious research agenda to determine anti-STI/HIV potential of the contraceptive cervical cap. Trusting women to make informed choices is critical to achieve real progress in dual protection.

Reasons For Brazilian Women To Switch From Different Contraceptives To Long-acting Reversible Contraceptives.

Long-acting reversible contraceptives (LARCs) include the copper-releasing intrauterine device (IUD), the levonorgestrel-releasing intrauterine system (LNG-IUS) and implants. Despite the high contraceptive efficacy of LARCs, their prevalence of use remains low in many countries. The objective of this study was to assess the main reasons for switching from contraceptive methods requiring daily or monthly compliance to LARC methods within a Brazilian cohort. Women of 18-50 years of age using different contraceptives and wishing to switch to a LARC method answered a questionnaire regarding their motivations for switching from their current contraceptive. Continuation rates were evaluated 1 year after method initiation. Sample size was calculated at 1040 women. Clinical performance was evaluated by life table analysis. The cutoff date for analysis was May 23, 2013. Overall, 1167 women were interviewed; however, after 1 year of use, the medical records of only 1154 women were available for review. The main personal reason for switching, as reported by the women, was fear of becoming pregnant while the main medical reasons were nausea and vomiting and unscheduled bleeding. No pregnancies occurred during LARC use, and the main reasons for discontinuation were expulsion (in the case of the IUD and LNG-IUS) and a decision to undergo surgical sterilization (in the case of the etonogestrel-releasing implant). Continuation rate was ~95.0/100 women/year for the three methods. Most women chose a LARC method for its safety and for practical reasons, and after 1 year of use, most women continued with the method.

Comment On 'practical Advice For Avoidance Of Pain Associated With Insertion Of Intrauterine Contraceptives': Authors' Response.

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Clinical outcomes of long-acting injectable risperidone in patients with schizophrenia: six-month follow-up from the Electronic Schizophrenia Treatment Adherence Registry in Latin America

Background: Risperidone long-acting injection (RLAI) has been shown to be efficacious, improve compliance, and increase long-term retention rate on therapy. The aim of this work was to determine the effect of RLAI on clinical outcome and hospitalization rate in patients with schizophrenia or schizoaffective disorder enrolled in the electronic Schizophrenia Treatment Adherence Registry in Latin America. Methods: Data were collected at baseline, retrospectively for the 12 months prior to baseline, and prospectively every three months for 24 months. Hospitalization prior to therapy was assessed by a retrospective chart review. Efficacy and functioning were evaluated using Clinical Global Impression of Illness Severity (CGI-S), Personal and Social Performance (PSP), and Global Assessment of Functioning (GAF) scores. Relapse and treatment were also registered. Results: Patients were recruited in Mexico (n = 53), Brazil (n = 11), and Colombia (n = 15). Sixty-five percent (n = 52) were male, and mean age was 32.9 years. Patients were classified as having schizophrenia (n = 73) or schizoaffective disorder (n = 6). The mean dose of RLAI at six months was 34.1 mg (standard deviation = 10.2 mg). The percentage of hospitalized patients before treatment was 28.2% and 5.1% at six months after initiating RLAI (P < 0.001). Significant changes were registered on CGI-S, GAF, and PSP scores. Conclusions: RLAI was associated with an improvement in clinical symptoms and functioning, and a greater reduction in hospitalization.

Long-acting injectable risperidone in partially adherent and nonadherent patients with schizophrenia

Background: Long-acting injectable antipsychotics may improve medication adherence, thereby improving overall treatment effectiveness. This study aimed to evaluate the effectiveness, safety, and tolerability of risperidone long-acting injection in schizophrenic patients switched from oral antipsychotic medication. Methods: In a 12-month, multicenter, open-label, noncomparative study, symptomatically stable patients on oral antipsychotic medication with poor treatment adherence during the previous 12 months received intramuscular injections of risperidone long-acting injection (25 mg starting dose) every 2 weeks. The primary endpoint was the change in Positive and Negative Syndrome Scale (PANSS) total score. Results: Of the 60 patients who were screened, 53 received at least one injection (safety population), and 51 provided at least one postbaseline assessment. Mean PANSS total scores improved significantly throughout the study and at endpoint. Significant improvements were also observed in Clinical Global Impression of Severity, Personal and Social Performance, and Drug Attitude Inventory scales. Risperidone long-acting injection was safe and well-tolerated. Severity of movement disorders on the Extrapyramidal Symptom Rating Scale was reduced significantly. The most frequently reported adverse events were insomnia (22.6%), increased prolactin (17.0%), and weight gain (13.2%). Conclusion: Risperidone long-acting injection was associated with significant symptomatic improvements in stable patients with schizophrenia following a switch from previous antipsychotic medications.

Simultaneous Determination of Choline Citrate and Acetylmethionine in Injectable Solutions by High Performance Liquid Chromatography

Choline citrate (CC) and acetylmethionine (AM) are lipotropic drugs used in several pharmaceutical formulations. The objective of this research was to develop and validate a high performance liquid chromatographic (HPLC) method for simultaneous determination of CC and AM in injectable solutions, aiming its application in routine analysis for quality control of these pharmaceutical formulations. The method was validated using a Shim-Pack (R) C18 (250 x 4.6 mm, 5 mu m) column. The mobile phase was constituted of 25 mM potassium phosphate buffer solution, pH 5.7, adjusted with 10 % orthophosphoric acid, acetonitrile and methanol (88:10:2, v/v/v). The flow rate was 1.1 mL.min(-1) and the UV detection was made at 210 nm. The analyses were made at room temperature (25 +/- 1 degrees C). The method is precise, selective, accurate and robust, and was successfully applied for simultaneous quantitative determination of CC and AM in injectables.

Investigation of the antinociceptive efficacy and relative potency of extended duration injectable 3-acylmorphine-6-sulfate prodrugs in rats

This investigation was designed to examine the antinociceptive activity in rats of 3-O-acyl prodrugs of M6S relative to the parent drug, after intravenous and intramuscular injection, using the tail flick latency test of antinociception. M6S, 3-acetylmorphine-6-sulfate (3AcM6S), 3-propionylmorphine-6-sulfate (3PrM6S), 3-butanoylmorphine-6-sulfate (3BuM6S) and 3-heptanoylmorphine-6-sulfate (3HpM6S) were administered by the IV route in a dose of 4.10 mu mol/kg. Relatively high levels of antinociception (>40% Maximum Possible Effect) were achieved following administration of M6S, 3AcM6S and 3PrM6S, whereas insignificant antinociception (<20%MPE) was achieved following administration of 3BuM6S or 3HpM6S. Although the mean duration of action for 3AcM6S (6 h) was longer than for M6S or 3PrM6S (4 h), the mean area (+/- S.E.M.) under the degree of antinociception versus time curve (AUG) for 3AcM6S (151.6 +/- 6.9%MPE h) was not significantly different (p <0.05) from that for M6S (120.8 +/- 32.7%MPE h) or for 3PrM6S (106.0 +/- 21.3%MPE h). The mean ED50 (range) doses for M6S, 3AcM6S and 3PrM6S were calculated to be 4.16 (3.61-4.48), 4.32 (3.55-5.09) and 4.54 (4.21-4.79) mu mol/kg, respectively. Preliminary studies were conducted on potential long-acting formulations containing 8 x ED50 doses of M6S and the 3-acetyl and 3-propionyl esters suspended in soybean oil. These showed that 3PrM6S gave a greater AUC (mean + S.E.M.) (1087.4 +/- 97.4%MPE h) and longer duration of action (20 h) than did M6S (613.1 +/- 155.9%MPE h; 10 h duration) or 3AcM6S (379.3 + 114.2%MPE h: 8 h duration). Further studies are needed to more fully investigate these findings. (C) 1998 Elsevier Science B.V. All rights reserved.

Beyond ovulation: Oral contraceptives and epithelial ovarian cancer

In a case-control study in three Australian states that included 794 women with epithelial ovarian cancer and 853 community controls for whom we had adequate contraceptive and reproductive histories, Re examined the effects of oral contraceptive use after controlling for estimated number of ovulatory cycles. Other covariates included in the multiple logistic regression analysis were parity, smoking, and history of pelvic surgery. The protective effect of duration of oral contraceptive use appeared to be multiplicative, with a 7% decrease in relative risk per year [95% confidence interval (CI) = 4-9%], persisting beyond 15 years of exposure. Use for up to 1 year may have a greater effect than predicted (odds ratio = 0.57; 95% CI = 0.40-0.82), whereas use before the first pregnancy may be additionally beneficial (odds ratio = 0.95; 95% CI = 0.87-1.03, adjusted for overall duration of use). Better control for ovulatory life might attenuate these estimates somewhat. There was little evidence of waning protection with time since last exposure or of extra benefit with early commencement of oral contraceptive use. We found no convincing evidence of effect modification in any factor examined or differences in effect among the three main histologic cancer types or between borderline and malignant tumors. Oral contraceptives may act by both suppressing ovulation and altering the tumor-promoting milieu.

Hormonal Contraceptives and the Length of Their Use Are Not Independent Risk Factors for High-Risk HPV Infections or High-Grade CIN

Aims: To evaluate the role of hormonal contraceptives as a risk factor of high-risk human papillomavirus (HR-HPV), cervical intraepithelial lesions (CIN) and cervical cancer in our multi-center population-based LAMS (Latin American Screening) study. Methods: A cohort study with >12,000 women from Brazil and Argentina using logistic regression to analyze the covariates of hormonal contraception (HOC - oral, injections, patches, implants, vaginal ring and progesterone intrauterine system) use followed by multivariate modeling for predictors of HR-HPV and CIN2+. Results: HR-HPV infection was a consistent risk factor of high-grade CIN in all three groups of women. The length of HOC use was not significantly related to high-grade squamous intraepithelial lesions (HSIL)+ Pap (p = 0.069), LSIL+ Pap (p = 0.781) or ASCUS+ (p = 0.231). The same was true with the length of HOC use and histology CIN3+ (p = 0.115) and CIN2+ (p = 0.515). Frequently, HOC users have previously shown more HPV-related lesions, as well as lower HPV prevalence if they were current smokers. But HOC use and time of usage were not independent risk factors of either HR-HPV infection or high-grade CIN using multiple logistic regressions. Conclusions: No evidence was found for an association between the use of HOC with an increased risk for HR-HPV infection or high-grade CIN in this cohort. Copyright (C) 2010 S. Karger AG, Basel

Influence of third-generation oral contraceptives on the complexity analysis and symbolic dynamics of heart rate variability

Objective To evaluate the influence of oral contraceptives (OCs) containing 20 mu mu g ethinylestradiol (EE) and 150 mu mu g gestodene (GEST) on the autonomic modulation of heart rate (HR) in women. Methods One-hundred and fifty-five women aged 24 +/-+/- 2 years were divided into four groups according to their physical activity and the use or not of an OC: active-OC, active-non-OC (NOC), sedentary-OC, and sedentary-NOC. The heart rate was registered in real time based on the electrocardiogram signal for 15 minutes, in the supine-position. The heart rate variability (HRV) was analysed using Shannon`s entropy (SE), conditional entropy (complexity index [CInd] and normalised CInd [NCI]), and symbolic analysis (0V%, 1V%, 2LV%, and 2ULV%). For statistical analysis the Kruskal-Wallis test with Dunn post hoc and the Wilcoxon test (p < 0.05 was considered significant) were applied. Results Treatment with this COC caused no significant changes in SE, CInd, NCI, or symbolic analysis in either active or sedentary groups. Active groups presented higher values for SE and 2ULV%, and lower values for 0V% when compared to sedentary groups (p < 0.05). Conclusion HRV patterns differed depending on life style; the non-linear method applied was highly reliable for identifying these changes. The use of OCs containing 20 mu mu g EE and 150 mu mu g GEST does not influence HR autonomic modulation.

Breaking the deadlock over an Australian trial of injectable opioid maintenance

INJECTABLE HEROIN MAINTENANCE has been advocated as a form of treatment for opioid dependence that would attract, and retain in treatment, addicts who have either not sought treatment or who have failed at other forms of treatment, including methadone maintenance. Advocates of heroin maintenance argue that it would increase the proportion of addicts in treatment and reduce heroin use, drug related crime, and deaths due to overdose.

Development of an injectable grout for concrete repair and strengthening

This paper deals with the coupled effect of temperature and silica fume addition on rheological, mechanical behaviour and porosity of grouts based on CEMI 42.5R, proportioned with a polycarboxylate-based high range water reducer. Preliminary tests were conducted to focus on the grout best able to fill a fibrous network since the goal of this study was to develop an optimized grout able to be injected in a mat of steel fibers for concrete strengthening. The grout composition was developed based on criteria for fresh state and hardened state properties. For a CEMI 42.5R based grout different high range water reducer dosages (0%, 0.2%, 0.4%, 0.5%, 0.7%) and silica fume (SF) dosages (0%, 2%, 4%) were tested (as replacement of cement by mass). Rheological measurements were used to investigate the effect of polycarboxylates (PCEs) and SF dosage on grout properties, particularly its workability loss, as the mix was to be injected in a matrix of steel fibers for concrete jacketing. The workability behaviour was characterized by the rheological parameters yield stress and plastic viscosity (for different grout temperatures and resting times), as well as the procedures of mini slump cone and funnel flow time. Then, further development focused only on the best grout compositions. The cement substitution by 2% of SF exhibited the best overall behaviour and was considered as the most promising compared to the others compositions tested. Concerning the fresh state analysis, a significant workability loss was detected if grout temperature increased above 35 degrees C. Below this temperature the grout presented a self-levelling behaviour and a life time equal to 45 min. In the hardened state, silica fumes increased not only the grout's porosity but also the grout's compressive strength at later ages, since the pozzolanic contribution to the compressive strength does not occur until 28 d and beyond. (C) 2012 Elsevier Ltd. All rights reserved.

Therapy of the experimental infection by Strongyloides venezuelensis in rats with injectable ivermectin or levamizole

For the therapy of human strongyloidiasis, are necessary effective drugs to eliminate both larvae and adult worm parasitism, which may also be used by parenteral route, to obviate the particular conditions presented by many patients. A study based on the experimental infection by Strongyloides venezuelensis in rats was done, administering injectable ivermectin or levamizole. Both drugs were shown to be active, when used in single doses of 0.2 to 0.5 mg/kg of ivermectin, or 26 mg/kg for levamizole. Ivermectin was slightly more effective as far as larval stage of the infection is concerned, and the same happened for levamisole for the adult worm stage. Promising perspectives are visualized to improve the therapy of patients with serious disseminated infection by Strongyloides stercoralis.