A randomized study of the effect of mifepristone alone or in conjunction with ethinyl estradiol on ovarian function in women using the etonogestrel-releasing subdermal implant,Implanon®

BackgroundMifepristone alone or in combination with ethinyl estradiol (EE) can effectively stop an episode of uterine bleeding in women using the etonogestrel-releasing contraceptive implant, Implanon® but could impair contraceptive efficacy.AimTo examine the effects of administration of mifepristone alone or with EE on ovarian function and cervical mucus consistency in women using Implanon.Study DesignWomen using Implanon were randomized to mifepristone 25 mg twice daily on day 1 plus placebo 1 daily for 4 days or plus EE 20 mcg daily for days 2–5. Measurements of serum estradiol (E₂), progesterone (P₄), luteinizing hormone (LH), follicle-stimulating hormone (FSH), cervical mucus examination and maximal follicle size (by vaginal ultrasound) were carried out at various times.ResultsFollowing mifepristone intake, there was a dramatic increase in E₂ levels ranging from 543 to 1183 pmol/L (p=.000), which was not correlated with maximal follicle size or preceded by LH or FSH increase. The increase in E₂ triggered an LH increase resulting in development of a luteinized follicle in four women with no evidence of ovulation. One of these women had estradiol and progesterone levels suggestive of ovulation, but no corpus luteum was seen. Almost all women had very low mucus scores, which did not correlate with E₂ levels.DiscussionDespite a transient increase in E₂ levels after mifepristone, there was no evidence of subsequent ovulation irrespective of whether they also received EE. The mechanism by which mifepristone in the presence of etonogestrel results in a rapid increase in E₂ levels remains unclear and could not be related to any significant changes in FSH, LH, ovarian follicle dynamics or subsequent possible ovulation.ConclusionPregnancy is very unlikely to occur if mifepristone and EE are given during use of Implanon to stop an episode of bleeding.     

Zooprophylaxis,artefact or reality? A paired-cohort study of the effect of passive zooprophylaxis on malaria in The Gambia

The World Health Organization has recommended the use of cattle for zooprophylaxis as a protective measure against malaria since 1982. However, concern has been raised about this practice, since some studies have shown that the presence of cattle may instead increase malaria prevalence. This study was designed to investigate the effect of passive zooprophylaxis on malaria in an area of moderate seasonal transmission in The Gambia, West Africa. The study was based on a paired-cohort of 204 children aged < 7 years, sleeping < 20 m or > 50 m from cattle, and surveys were done from 14 October to 2 December 1997. Entomological investigations showed that the presence of cattle did not alter the risk of malaria transmission in nearby houses. There was also no significant difference in the prevalence of Plasmodium falciparum between the 2 groups. Although the presence of cattle appeared to be protective against high parasitaemia, cattle were also associated with greater wealth of the children's families. Conditional logistic regression analysis showed that the decreased risk of high parasitaemia in the group with cattle present was an artefact associated with the higher general wealth of the cattle owners. We concluded that zooprophylaxis is not an effective intervention method against malaria in settings similar to The Gambia.     

Effects of concurrent vaginal miconazole treatment on the absorption and exposure of Nestorone® (segesterone acetate) and ethinyl estradiol delivered from a contraceptive vaginal ring: a randomized,crossover drug–drug interaction study

Objectives

To evaluate the effects of concurrent administration of three vaginal miconazole nitrate formulations on the absorption and exposure of Nestorone® (segesterone acetate) and ethinyl estradiol from a novel contraceptive vaginal ring (NES/EE CVR).

Comparative study on the acceptability of two modern monophasic oral contraceptive preparations: 30 μg ethinyl estradiol combined with 150 μg desogestrel or 75 μg gestodene

Cycle control and tolerability of two monophasic oral contraceptive pills containing 30 g ethinyl estradiol (EE) with either 150 g desogestrel (DSG) or 75 g gestodene (GSD) were compared in women starting oral contraception.A minimum of 200 healthy women at risk for pregnancy were to be treated for a total of 6 cycles per patient in a prospective, randomized open parallel-group multicenter trial.Two hundred and forty-one subjects were randomized, 115 to DSG/EE and 126 to GSD/EE. Compliance to the study preparation was high (around 95%) in both groups and no pregnancies occurred during the study. Cycle control was excellent; there were no differences between the two groups with regard to incidence of spotting and breakthrough bleeding or duration and intensity of withdrawal bleeding. Side-effects were mild and in general comparable in the two groups. Both at baseline and during treatment, a higher proportion of women taking GSD/EE complained about breast tenderness. This resulted in more early withdrawals because of breast tenderness in the GSD/EE group.It was concluded that monophasic DSG/EE and GSD/EE are equally effective, have similar cycle control and both are generally well tolerated.     

Ethinyl estradiol vs estradiol valerate in combined oral contraceptives – Effect on glucose tolerance: A randomized,controlled clinical trial

ObjectiveTo compare the effects of two formulations of combined oral contraceptives (COCs), estradiol valerate (EV) and ethinyl estradiol (EE) combined with dienogest (DNG), and DNG-only, on glucose tolerance.Study DesignWe performed a randomized, controlled 9-week clinical trial. Inclusion criteria were: age 18–35 years, regular menstrual cycle (28 ± 7 days), no polycystic ovaries, non-smoking, no contraindications for COC use and a 2-month wash-out from hormonal contraceptive use. The women were randomized to EV + DNG (n = 20), EE + DNG (n = 20), and DNG-only (n = 19), and evaluated at baseline, at 4–5 weeks and 8–9 weeks of treatment. Study medications were used continuously for 63 days. Primary outcome measure was change in the whole-body insulin sensitivity index (Matsuda index) derived from the oral glucose tolerance test (OGTT) over the treatment period. Secondary outcome measures were area under curves (AUC) of glucose and insulin, homeostatic model assessment – insulin resistance (HOMA-IR) and Insulin Sensitivity Index (ISI).ResultsFifty-nine women enrolled, and 56 women completed the study. The Matsuda index changed from baseline as follows (mean percentage change, mean change [95%CI]): DNG-only ?12%, ?1.45 [95%CI ?3.22–0.325] P = 0.10; EV + DNG + 2.7%, ?0.10 [?1.34 to 1.14] P = 0.86; EE + DNG ?5.5%, ?1.02 [?2.51 to 0.46] P = 0.16, comparing the groups P = 0.27. There were no clinically significant differences in glucose tolerance between the COC groups, but the DNG-only group showed an improvement in the 2-h glucose levels (5.5 [95%CI 5.0–6.0] to 4.7 mmol/l [4.2–5.2], P = 0.001).ConclusionWe found no clinically significant differences between EV and EE combined with DNG and DNG-only on glucose tolerance in healthy, young, normal-weight women, indicating that these preparations appear close to neutral regarding glucose metabolism when used continuously for nine weeks.ImplicationsCombinations of both ethinyl estradiol and natural estradiol (estradiol valerate) with dienogest (DNG), as well as DNG-only, seem metabolically safe in young and healthy women in short-term continuous use.     

Coffee or Tea? A prospective cohort study on the associations of coffee and tea intake with overall and cause-specific mortality in men versus women

Coffee and tea intake have been associated with reduced mortality, but no studies have investigated possible substitution effects. The relationship of mortality with coffee, tea, and substituting coffee with tea was investigated in the Netherlands Cohort Study. In 1986, 120,852 men and women aged 55–69 years provided information on dietary and lifestyle habits. Mortality follow-up until 1996 consisted of linkage to Statistics Netherlands. Multivariate case-cohort analyses were based on 8665 deaths and 3166 subcohort members with complete data on coffee, tea and confounders. Higher coffee intake was significantly, nonlinearly related to lower overall and cause-specific mortality in women. In men, coffee was significantly positively related to cancer and cardiovascular mortality, and inversely to respiratory and other causes of death. Tea intake was significantly, nonlinearly related to lower overall, cancer and cardiovascular mortality in men, but showed no association with mortality in women. In substitution analyses, increasing the proportion tea (replacing coffee with tea) was significantly and nonlinearly related to lower overall, cancer and cardiovascular mortality in men, but in women higher tea proportions were positively associated with overall mortality (and most causes of death). This study suggests that for men, compared to exclusive coffee drinkers, those drinking 30–50% tea showed the lowest mortality; any tea drinking seemed better than only coffee. For women, those who drank exclusively coffee or drinking up to 40% tea had the lowest mortality, but those drinking higher percentages of tea were at increased mortality risk [HR = 1.41 (95% CI 1.01–1.99) for 80–100% tea compared to exclusive coffee drinkers].     

Does size matter in females? An overview of the impact of the high variation in the ovarian reserve on ovarian function and fertility, utility of anti-Müllerian hormone as a diagnostic marker for fertility and causes of variation in the ovarian reserve in cattle

The mechanism whereby the inherently high variation in ovary size and the total number of high-quality oocytes in ovaries (ovarian reserve) impact on ovarian function and fertility, diagnostics to measure the size of the ovarian reserve and the factors that cause variation in the ovarian reserve are unknown. Our results show that cattle can be phenotyped reliably based on the number of antral follicles growing during follicular waves (antral follicle count, AFC). Young adult cattle with a consistently low v. a high AFC have smaller gonads, a markedly diminished ovarian reserve and many other phenotypic characteristics usually associated with ovarian aging and infertility. A powerful new approach based on a single measurement of serum concentration of anti-Müllerian hormone (AMH) is described to test the longstanding hypothesis that the size of the ovarian reserve is positively associated with fertility. Also, new evidence shows that maternal environment has a critical role in regulation of the high variation in the ovarian reserve and perhaps fertility in offspring. These results support the conclusion that the inherently high variation in the ovarian reserve, potentially caused by alterations in the maternal environment, has a negative impact on ovarian function that may result in suboptimal fertility in young adult cattle, and a single AMH measurement can be used reliably in future studies to determine if fertility is suboptimal in young adult cattle with low circulating AMH concentrations and a correspondingly diminished ovarian reserve.     

The effect of various types of patients’ reminders on the uptake of pneumococcal vaccine in adults: A randomized controlled trial

BackgroundInvasive pneumococcal disease is one of the most important vaccine-preventable diseases threatening the adult community due to missed opportunities for vaccination. This study compares the effect of three different types of patient reminder system on adulthood Streptococcus pneumoniae immunization in a primary care setting.MethodsThe study targeted patients aged 40 and older eligible for pneumococcal vaccine, but did not receive it yet (89.5% of 3072 patients) based on their electronic medical records in a family medicine center in Beirut. The sample population was randomized using an automated computer randomization system into six equal groups, receiving short phone calls, short text messaging system (sms-text) or e-mails each with or without patient education. Each group received three identical reminders spaced by a period of four weeks. Documentation of vaccine administration was then added to the longitudinal electronic patient record. The primary outcome was the vaccine administration rate in the clinics.ResultsOf the eligible patients due for the pneumococcal 23-polyvalent vaccine, 1380 who had mobile phone numbers and e-mails were randomized into six equal intervention groups. The various reminders increased vaccination rate to 14.9%: 16.5% of the short phone calls group, 7.2% of the sms-text group and 5.7% of the e-mail group took the vaccine. The vaccination rate was independent of the age, associated education message and the predisposing condition.ConclusionUse of electronic text reminders via e-mails and mobile phones seems to be a feasible and sustainable model to increase pneumococcal vaccination rates in a primary care center.     

Nursing managers, transformed or deformed? A case study in the ideology of competency

Examines the ideological nature of competence-based approaches to the management training of nurse managers. Explores the transition required from a "clinical" identity to a managerial one. Employs Habermas' theory of communicative action to analyse the ideological features and to provide a way of reflecting on the nature of the professional identity they are being encouraged to accept. Indicates some further avenues for research.     

An open-label, randomized, multi-center study of the immunogenicity and safety of DTaP-IPV (Kinrix™) co-administered with MMR vaccine with or without varicella vaccine in healthy pre-school age children

Background

In the US, it is recommended that 4-6 year old children receive diphtheria-tetanus-acellular pertussis (DTaP), inactivated poliovirus (IPV), measles-mumps-rubella (MMR), varicella (V), and influenza vaccines. Data relating to the concomitant administration of combination DTaP-IPV vaccine (Kinrix™; GlaxoSmithKline Biologicals) and influenza or V vaccines are currently limited. This study was undertaken to evaluate the immunogenicity and reactogenicity of Kinrix™ when co-administered with MMR (M-M-RII^®, Merck & Co.) and Varivax™ (Merck & Co.) in 4-6 year old children.

Methods

Phase IIIb, open-label, non-inferiority study (NCT00871117). We randomized (1:1) healthy 4-6 year olds to receive Kinrix™ + MMR + V on day 0 (Group 1), or Kinrix™ + MMR on day 0, followed by V at month 1 (Group 2). We measured DTaP-IPV immunogenicity before and 1 month post-vaccination (prior to V vaccination in Group 2). We collected local and general solicited symptoms within 4 days after vaccination and serious adverse events (SAEs) through 6 months post-vaccination.

Results

We enrolled 478 subjects. One month post-vaccination, >95% of subjects in both groups had booster responses to diphtheria, tetanus and pertussis antigens and all subjects had seroprotective anti-poliovirus antibody titers. Immune responses in Group 1 were non-inferior to Group 2 for responses to DTaP-IPV antigens according to pre-specified criteria. Reporting of solicited local events at the DTaP-IPV site appeared to be similar between the two vaccine groups, as was reporting of solicited general adverse events within 4 days of vaccination; no vaccine related SAEs were reported.

Conclusion

Concomitant administration of varicella vaccine with Kinrix™ and MMR did not impact the immunogenicity of diphtheria, tetanus, pertussis or poliovirus antigens. Both vaccine regimens were well tolerated. These results support the co-administration of DTaP-IPV, MMR, and V vaccines in 4-6-year-old children, providing protection against multiple diseases in a timely and efficient manner.