Progesterone for the prevention of preterm birth in women with multiple pregnancies: the AMPHIA trial

Background

Adequate vitamin D concentrations during pregnancy are necessary to neonatal calcium homeostasis, bone maturation and mineralization. The aim of study is to evaluate serum vitamin D concentrations in mothers and their newborns and effect of vitamin D deficiency on pregnancy outcomes.

Methods

552 pregnant women were recruited from Tehran University educating hospitals in the winter of 2002. Maternal and cord blood samples were taken at delivery. The serum was assayed for 25-hydroxyvitamin D3, calcium, phosphorus and parathyroid hormone.

Results

The prevalence of vitamin D deficiency in maternal and cord blood samples were 66.8% and 93.3%, respectively (<35 nmol/l). There was significant correlation between maternal and cord blood serum concentrations of vitamin D. In mothers with vitamin D deficiency, cord blood vitamin D concentrations was lower than those from normal mothers (P = .001). Also, a significant direct correlation was seen between maternal vitamin D intake and weight gain during pregnancy.

Conclusion

Consideration to adequate calcium and vitamin D intake during pregnancy is essential. Furthermore, we think it is necessary to reconsider the recommendation for vitamin D supplementation for women during pregnancy.     

Campylobacter enteritis in Portugal: Epidemiological features and biological markers

From 1984 to 1989, stool samples from 2811 gastroenteritis cases were examined for the presence ofCampylobacter jejuni andC. Coli, Salmonella, Shigella andYersinia species. Isolation rates were:Campylobacter jejuni andC. Coli, 5.3%,Salmonella spp., 14.8%,Shigella spp., 4.6% andYersinia enterocolitica, 1.1%. Age group distribution analysis shows a higherCampylobacter isolation rate in children under one year of age. Seasonal distribution revealed a peak incidence in winter as in other Meditteranean countries. Predominant biotypes wereC. jejuni I (51%),C. jejuni II (21.5%) andC. coli I (18.8%). Antimicrobial susceptibility testing did not reveal resistance to erythromycin. Thirty of the strains harboured plasmids with 7 different profiles.     

Structural insights into the conformational selectivity of STI-571 and related kinase inhibitors

STI-571 (Gleevec) is a highly successful cancer drug due to its activity as an inhibitor of the Abelson cytoplasmic tyrosine kinase (Abl), which is constitutively active in a majority of patients with chronic myelogenous leukemia. STI-571 also inhibits two type III receptor tyrosine kinases, c-Kit and platelet-derived growth factor receptor, and functions by targeting inactive conformations of these kinases. This review focuses on recent developments in X-ray co-crystal structure analyses of STI-571 bound to Abl and the c-Kit receptor tyrosine kinase domain, and also three other relevant kinase inhibitor co-crystal structures. The similar structural features of these inactive kinases suggest they will be useful for the successful drug discovery and development of specific and targeted gene-based cancer drugs.     

Seroepidemiological study on sexually transmitted diseases and hepatitis B in African promiscuous heterosexuals in relation to HTLV-III infection

A seroepidemiological study was performed on HTLV-III, T. pallidum, C. trachomatis and Hepatitis B virus (HBV), in Butare, Rwanda, among 33 female prostitutes, 25 male customers of prostitutes, and 60 male and female controls. As compared with female controls the prostitutes had a higher prevalence of antibodies to HTLV-III (29/33 versus 4/33, p<0.001), T. pallidunz (TPHA: 27/33 versus 6/33, p<0.001; RPR: 19/33 versus 233, p<0.001; FTA-Abs: 27/33 versus 5/33, p<0:001) and C. trachomatis (IgG IF: 31/33 versus 13/33, p<0.001). HBV serological markers were more often detected in the prostitutes than in the female controls (31/33 versus 18/33, p<0.001) although HBs antigen carriage rate was similar in both groups. As compared with male controls, the male customers of prostitutes had more frequently detectable antibodies to HTLV-III (7/25 versus 2/27, p = 0.05), and a positive RPR (10/25 versus 1/27, p<0.01). Among the 118 individuals studied, odds ratios and trend analysis disclosed a significant association between HTLV-III seropositivity and a positive TPHA, RPR, FTA-Abs, Chlamvdia IgG IF test and serological markers to HBV. No association was found between HTLV-III seropositivity and IIBs Ag carriage. This study suggests that HTLV-III has to be considered as an infectious agent transmitted among promiscuous Central African heterosexuals by sexual contact and/or parenteral contact with unsterile needles used for STD treatments.     

Evaluation of biomarkers for treatment selection using individual participant data from multiple clinical trials

Biomarkers that predict treatment effects may be used to guide treatment decisions, thus improving patient outcomes. A meta‐analysis of individual participant data (IPD) is potentially more powerful than a single‐study data analysis in evaluating markers for treatment selection. Our study was motivated by the IPD that were collected from 2 randomized controlled trials of hypertension and preeclampsia among pregnant women to evaluate the effect of labor induction over expectant management of the pregnancy in preventing progression to severe maternal disease. The existing literature on statistical methods for biomarker evaluation in IPD meta‐analysis have evaluated a marker's performance in terms of its ability to predict risk of disease outcome, which do not directly apply to the treatment selection problem. In this study, we propose a statistical framework for evaluating a marker for treatment selection given IPD from a small number of individual clinical trials. We derive marker‐based treatment rules by minimizing the average expected outcome across studies. The application of the proposed methods to the IPD from 2 studies in women with hypertension in pregnancy is presented.     

The M-OVIN study: does switching treatment to FSH and / or IUI lead to higher pregnancy rates in a subset of women with world health organization type II anovulation not conceiving after six ovulatory cycles with clomiphene citrate – a randomised controlled trial

Background

Clomiphene citrate (CC) is first line treatment in women with World Health Organization (WHO) type II anovulation and polycystic ovary syndrome (PCOS). Whereas 60% to 85% of these women will ovulate on CC, only about one half will have conceived after six cycles. If women do not conceive, treatment can be continued with gonadotropins or intra-uterine insemination (IUI). At present, it is unclear for how many cycles ovulation induction with CC should be repeated, and when to switch to ovulation induction with gonadotropins and/or IUI.

Methods/Design

We started a multicenter randomised controlled trial in the Netherlands comparing six cycles of CC plus intercourse or six cycles of gonadotrophins plus intercourse or six cycles of CC plus IUI or six cycles of gonadotrophins plus IUI.Women with WHO type II anovulation who ovulate but did not conceive after six ovulatory cycles of CC with a maximum of 150 mg daily for five days will be included.Our primary outcome is birth of a healthy child resulting from a pregnancy that was established in the first eight months after randomisation. Secondary outcomes are clinical pregnancy, miscarriage, multiple pregnancy and treatment costs. The analysis will be performed according to the intention to treat principle. Two comparisons will be made, one in which CC is compared to gonadotrophins and one in which the addition of IUI is compared to ovulation induction only. Assuming a live birth rate of 40% after CC, 55% after addition of IUI and 55% after ovulation induction with gonadotrophins, with an alpha of 5% and a power of 80%, we need to recruit 200 women per arm (800 women in total).An independent Data and Safety Monitoring Committee has criticized the data of the first 150 women and concluded that a sample size re-estimation should be performed after including 320 patients (i.e. 80 per arm).

Discussion

The trial will provide evidence on the most effective, safest and most cost effective treatment in women with WHO type II anovulation who do not conceive after six ovulatory cycles with CC with a maximum of 150 mg daily for five days. This evidence could imply the need for changing our guidelines, which may cause a shift in large practice variation to evidence based primary treatment for these women.

Trial registration number

Netherlands Trial register NTR1449

     

Clinical pharmacokinetics,pharmacodynamics, safety and tolerability of darexaban,an oral direct factor Xa inhibitor,in healthy Caucasian and Japanese subjects

Background. Darexaban (YM150) is a potent direct factor Xa (FXa) inhibitor developed for the prophylaxis of venous and arterial thromboembolic disease. This drug is rapidly and extensively metabolized to darexaban glucuronide (YM‐222714), which is a pharmacologically active metabolite. The objective of the present study was to evaluate the clinical pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of ascending multiple oral doses of darexaban in healthy non‐elderly Caucasian and Japanese subjects. Methods. A randomized, double‐blind, placebo‐controlled, single and multiple dose‐escalating study of healthy Caucasian and Japanese male and female subjects was performed. The tested doses were 20, 60, 120 and 240 mg of darexaban. Results. Plasma concentrations of darexaban glucuronide increased with dose, and C_max and AUC increased dose‐dependently after both single and repeated doses in both Caucasians and Japanese. C_max was about 17%–19% lower in Caucasians than in Japanese, although AUC appeared to be similar. The time‐profiles of prothrombin time reported as the international normalized ratio (PT‐INR), activated partial thromboplastin time (aPTT) and FXa activity closely followed the time–concentration profile of darexaban glucuronide, and no clear differences were observed in ethnicity. Overall, 38 of the 82 enrolled subjects reported a total of 57 treatment‐emergent adverse events (TEAEs). Fifty‐five TEAEs were of mild intensity and two were of moderate intensity. Conclusion. It is concluded that single and multiple doses of darexaban are safe and well tolerated up to 240 mg with predictable PK and PD profiles in both Caucasians and Japanese, and that ethnicity does not affect its PK, PD or tolerability. Copyright © 2013 John Wiley & Sons, Ltd.     

Traumatic events in a general practice population: the patient's perspective

OBJECTIVES: The aim of the present study was to describe the patient's perspective on the GP's care after violent events: which role is the GP assigned; and how is the care appreciated. Events studied were serious accidents, burglary, robbery, physical and sexual abuse, disasters and war. METHOD: A postal questionnaire was sent to a random sample of 2997 patients (> or =20 years) from the practice population of 32 GPs (67 500 patients). RESULTS: The response was 50%. Forty-two per cent of the respondents had experienced one or more events. Twenty-eight per cent of the victims desired some kind of professional help; more than half of them desired that care from their GP, three-quarters actually seeking it. Most frequently sought care was sympathy, "a number of good talks", and care for physical complaints. Overall, contentment with the GP's contribution was high; patients especially appreciate sympathy and support, as well as initiative on the GP's part in commencing and pursuing care. Of those who felt no need for professional help, 88% found that they could cope with the traumatic event well enough, with or without the help of family and friends. For those who did not seek help, although they did desire it, the main reasons were that they considered their problems insufficiently medical or felt that their GP lacked the time. In the case of physical and sexual abuse, feelings of guilt and issues of patient confidentiality played a role for some patients. CONCLUSIONS: The number of events experienced by our respondents is lower than in previous studies for burglary, robbery, physical and sexual abuse (adults and children); the occurrence of accidents is similar. The majority of the people who experience traumatic events cope with them well enough without professional help. For those seeking help, the GP plays an important role. Care could be improved as follows: the GP should make it clear to patients that he/she can play a role in caring for them in the aftermath of a traumatic event and stress the confidential nature of the consultation. On the whole, GPs should be more supportive and attentive when being consulted about this topic; also patients would like their doctors to be more active in raising the subject, as well as in initiating follow-up.