Feasibility of administering mifepristone as a once a month contraceptive pill

Many women find the idea of a once-a-month contraceptive pill an attractive concept. Mifepristone has been shown to be effective as a contraceptive if administered in the early luteal phase. We tested the contraceptive efficacy of 200 mg of mifepristone on day luteinizing hormone (LH) + 2 in a group of 32 women who used a fertility monitor to identify the LH surge. We also recruited a control group, comprising 20 women who were trying to conceive. In this group, 12 women conceived during a total of 50 control cycles (probability of pregnancy 0.25-0.32). Women in the treatment group contributed to a total of 178 cycles and there were two pregnancies (probability of pregnancy 0.01). An LH surge was not detected in 34 cycles (19.1%). In 20 cycles (11.2%) this was due to imperfect use while 14 were monitor method failures (7.9%). Treatment with mifepristone in the early luteal phase did not disrupt the cycle length but women reported slight vaginal bleeding in 15% of the cycles. The combination of a home-use fertility monitor with once-a-month administration of mifepristone (especially if mifepristone is administered at the early luteal phase) is an acceptable contraceptive option with minimal side effects. Unfortunately, it is difficult to envisage how an easier way of defining the correct timing, which required less compliance, could be devised.     

Potential impact of hormonal male contraception: cross-cultural implications for development of novel preparations

The prospect of a hormonal male contraceptive is no longer distant. Data on the potential impact of this improvement in contraceptive provision, however, is limited, particularly between different cultures. We have therefore carried out a multi-centre study to assess men's attitudes to proposed novel hormonal methods. Questionnaire-based structured interviews were administered to men in Edinburgh, Cape Town, Shanghai and Hong Kong. Approximately 450 men were interviewed in Edinburgh, Shanghai and Hong Kong, and a slightly larger group (n = 493) in Cape Town to give samples (n > 150) of black, coloured and white men. Knowledge of existing male and female methods of contraception was high in all centres and groups. The majority of men welcomed a new hormonal method of contraception, 44-83% stating that they would use a male contraceptive pill. Overall, a pill was more acceptable than an injectable form (most popularly given at 3-6 month intervals); long-acting implants were least so except in Shanghai. Familiarity with comparable female methods appeared to influence acceptability, for both oral and injectable methods. Hong Kong was the only centre where a male method (condom) was currently the most commonly used; men there appeared to rate the convenience of condoms highly while being least likely to think that they provided effective protection against pregnancy compared to other centres, and were least enthusiastic about novel male methods. The acceptability of potential male hormonal methods of contraception was high in some groups but showed wide variability, determining factors including cultural background and current contraceptive usage. These results suggest that the emerging emphasis that men should have greater involvement in family planning will be substantiated when appropriate contraceptive methods become available.     

A comparison of the effects on follicular development between clomiphene citrate, its two separate isomers and spontaneous cycles

An investigation of the effects on follicular development of clomiphene citrate and its two isomers En clomiphene and Zu clomiphene given separately was carried out on 19 normally cycling women being treated with donor insemination. All women received clomiphene citrate in the first cycle and, following a washout control cycle, were treated with either En clomiphene or Zu clomiphene alone. The number of follicles present, follicular phase oestrogen secretion and luteal phase pregnanediol excretion were not significantly different when Zu clomiphene cycles were compared with control cycles, but were significantly increased in En clomiphene and clomiphene citrate cycles. It is concluded that the En isomer, which has largely antioestrogenic properties, is the isomer active in inducing follicular development. The oestrogenic properties of Zu isomer did not appear to protect it from the possibly detrimental effects on sperm-cervical mucus interaction observed in both isomers and in the combined preparation.     

Gastrointestinal haemorrhage due to erosion of the duodenal wall by a biliary stent

Complications from improperly placed biliary stents are not uncommon. Free loose wires from the ends of an uncovered stent can irritate and damage adjacent mucosal surfaces. Effective management can be achieved via percutaneous placement of a second stent to alter the orientation of the original stent.     

Preventing repeat pregnancy in adolescents

PURPOSE OF REVIEW: Teenage pregnancy is on a decline, but there are wide inequalities in those who are still becoming pregnant at an early age. Teenage pregnancy remains a public health concern. Numbers of repeat pregnancy in adolescence are small but contribute to poor health outcomes for young women and their children. RECENT FINDINGS: A number of studies have demonstrated the impact that low levels of educational attainment, lack of aspiration, low socioeconomic status, dislike of school, lack of family connectedness and poor parental monitoring can have on early sexual activity and, in some cases, pregnancy among adolescents. Risks for repeat pregnancy in adolescence would appear to be linked to whether the pregnancy was intended or not, and what incentives or motivations, if any, existed to prevent subsequent early pregnancies. SUMMARY: There would appear to be two options available to those who wish to reduce the negative health outcomes associated with repeat pregnancy in adolescence. First, to increase the life choices available to young women, which improve their social and economic circumstances. Secondly, to develop a clear understanding of pregnancy intentions within this group to ensure the provision of appropriate services which deliver the best possible outcomes for them and their child.     

Advance provision of emergency contraception for pregnancy prevention: a meta-analysis

OBJECTIVE: Advance provision of emergency contraception can circumvent some obstacles to timely use. We performed a meta-analysis to summarize randomized controlled trials evaluating advance provision of emergency contraception to explore effects on pregnancy rates, sexually transmitted infections, and sexual and contraceptive behaviors. DATA SOURCES: In August 2006, we searched CENTRAL, EMBASE, POPLINE, MEDLINE, a specialized emergency contraception article database, and contacted experts to identify published or unpublished trials. METHODS OF STUDY SELECTION: We included randomized controlled trials comparing advance provision to standard access, defined as any of the following: counseling (with or without information about emergency contraception) or provision of emergency contraception on request at a clinic or pharmacy. TABULATION, INTEGRATION AND RESULTS: Two reviewers independently assessed study quality. We performed a meta-analysis using Review Manager software. Eight randomized controlled trials met inclusion criteria, representing 6,389 patients in the United States, China, and India. Advance provision did not decrease pregnancy rates, despite increased use (single use, odds ratio [OR] 2.52, 95% confidence interval [CI] 1.72-3.70; multiple use: OR 4.13, 95% CI 1.77-9.63) and faster use (weighted mean difference -14.6 hours, 95% CI -16.77 to -12.4 hours). Advance provision did not increase rates of sexually transmitted infections (OR 0.99, 95% CI 0.73-1.34), unprotected intercourse, or changes in contraceptive methods. Women who received emergency contraception in advance were as likely to use condoms as other women. CONCLUSION: Advance provision of emergency contraception did not reduce pregnancy rates and did not negatively affect sexual and reproductive health behaviors and outcomes compared with conventional provision. LEVEL OF EVIDENCE: III.     

Informant ratings of cognitive decline of elderly people: relationship to longitudinal change on cognitive tests

Formal assessment of cognitive decline with cognitive tests can be difficult, requiring either two measurement points or a comparison of 'hold' with 'don't hold' tests. Informant-based assessment provides an alternative approach because informants can adopt a longitudinal perspective and directly rate cognitive change. A study was carried out to assess the validity of informant ratings collected by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). A community sample of 500 subjects aged 74 or over underwent four cognitive tests on two occasions 3½ years apart. On the second occasion, informants filled out the IQCODE. Subjects rated as having moderate or severe decline were found to have greater change on the cognitive tests. These findings support the validity of informant ratings of cognitive decline.     

Restriction of cell lysis by homologous complement: II. Protection of erythrocytes against lysis by newly activated complement

Our previous work revealed that homologous complement (C) was ineffective in lysing antibody-sensitized erythrocytes (EA) even at high concentrations. It was also shown that activation of complement on homologous EA resulted in the binding of C9 and the formation of EA bearing complement proteins C1 through C9 (EAC1-9), yet few hemolytic sites were formed. Instead, as shown here, the formation of homologous EAC1-9 caused the cells to become resistant to lysis even by heterologous complement during a second incubation. In contrast, when homologous EAC1-8 were produced by incubating EA with C9-depleted serum, such intermediates were not protected against lysis by heterologous complement during a second incubation. Furthermore, homologous C9 on EAC1-9 was able to reduce the hemolytic efficiency of heterologous complement without blocking C activation and the formation of new C5b-9 complexes. Protection was not modified when homologous EAC1-9 were produced in one step, by incubation of EA with serum, or sequentially by adding C9 to EAC1-8. The minimum number of 9-sites required to confer a protective effect on EAC1-9 was less than 200 per cell. Thus, in addition to its known effect in heterologous cell killing, homologous C9 is capable of protecting homologous cells against inadvertent complement lysis.     

Factors affecting mortality of critical care trauma patients

Background

Critically-ill trauma patients have a high mortality.

Objective

To study the factors affecting the mortality of ICU trauma patients treated at Al-Ain Hospital, United Arab Emirates (UAE).

Methods

All trauma patients who were admitted to the ICU were prospectively collected over three years (2003–2006). Univariate and multivariate analysis were used to compare patients who died and who did not. Gender, age, nationality, mechanism of injury, systolic blood pressure and GCS on arrival, the need for ventilation, presence of head or chest injuries, AIS for the chest and head injuries and the ISS were studied.

Results

There were 202 patients (181 males). The most common mechanism of injury was road traffic collisions (72.3 %). The overall mortality was 13.9%. A direct logistic regression model has shown that factors that affected mortality were decreased GCS (p < 0.0001), mechanism of injury (p = 0.004) with burns having the highest mortality, increased age (p = 0.004), and increased ISS (p = 0.02). The best GCS that predicted mortality was 5.5 while the best ISS that predicted mortality was 13.5.

Conclusion

Road traffic collision is the most common cause of serious trauma in UAE followed by falls. Decreased GCS was the most significant factor that predicted mortality in the ICU trauma patients.     

Effects of Odanacatib on Bone Structure and Quality in Postmenopausal Women With Osteoporosis: 5-Year Data From the Phase 3 Long-Term Odanacatib Fracture Trial (LOFT) and its Extension

Odanacatib (ODN), a selective oral inhibitor of cathepsin K, was an investigational agent previously in development for the treatment of osteoporosis. In this analysis, the effects of ODN on bone remodeling/modeling and structure were examined in the randomized, double-blind, placebo-controlled, event-driven, Phase 3, Long-term Odanacatib Fracture Trial (LOFT; NCT00529373) and planned double-blind extension in postmenopausal women with osteoporosis. A total of 386 transilial bone biopsies, obtained from consenting patients at baseline (ODN n = 17, placebo n = 23), month 24 (ODN n = 112, placebo n = 104), month 36 (ODN n = 42, placebo n = 41), and month 60 (ODN n = 27, placebo n = 20) were assessed by dynamic and static bone histomorphometry. Patient characteristics at baseline and BMD changes over 5 years for this subset were comparable to the overall LOFT population. Qualitative assessment of biopsies revealed no abnormalities. Consistent with the mechanism of ODN, osteoclast number was higher with ODN versus placebo over time. Regarding bone remodeling, dynamic bone formation indices in trabecular, intracortical, and endocortical surfaces were generally similar in ODN-treated versus placebo-treated patients after 2 years of treatment. Regarding periosteal modeling, the proportion of patients with periosteal double labels and the bone formation indices increased over time in the ODN-treated patients compared with placebo. This finding supported the observed numerical increase in cortical thickness at month 60 versus placebo. In conclusion, ODN treatment for 5 years did not reduce bone remodeling and increased the proportion of patients with periosteal bone formation. These results are consistent with the mechanism of action of ODN, and are associated with continued BMD increases and reduced risk of fractures compared with placebo in the LOFT Phase 3 fracture trial. © 2020 American Society for Bone and Mineral Research.