Publications

BACKGROUND

Loratadine, a second-generation antihistamine, is commonly used to treat seasonal allergies. Some studies have suggested that use of loratadine by pregnant women increases the risk of hypospadias in male offspring.

OBJECTIVE

This meta-analysis was designed to assess the strength of the association between loratadine and hypospadias.

METHODS

To locate pertinent articles published in any language from January 1989 until August 2007, we searched electronic databases (MEDLINE, OVID, EMBASE, SCOPUS, TOXLINE Special, ReproTox, TERIS, CINAHL and others), conference proceedings and bibliographies. Studies were eligible for this analysis if they were cohort, case-control or case series studies that reported the incidence of hypospadias in the offspring of women who were or were not exposed to loratadine during pregnancy. Two authors independently extracted information on study design, participant characteristics, measures of outcome, control for potential confounding factors and risk estimates using a standardized data collection form. The Newcastle-Ottawa Scale was then used to assess the quality of each study. We used a random-effects meta-analysis model to combine the risk data.

RESULTS

In 1402 potentially relevant titles, we found three case-control studies and seven cohort studies that reported the incidence of hypospadias or other congenital malformations in offspring of women who did or did not use loratadine during pregnancy. Together the studies in our meta-analysis provided information about 453 053 male births in Brazil, Canada, Denmark, Israel, Italy, Sweden, the UK and the US.Of 2694 male infants born to women using loratadine, 39 (1.4%) had hypospadias. Of 450 413 male infants born to women not using loratadine, 4231 (0.9%) had hypospadias. Women who used loratadine during pregnancy were not significantly more likely to have a son with hypospadias (unadjusted odds ratio [OR] 1.27, 95% CI 0.73, 2.23; adjusted OR 1.28, 95% CI 0.69, 2.39).

CONCLUSION

The results of our systematic review and meta-analysis of controlled observational studies indicate that the use of loratadine during pregnancy does not significantly increase the risk of hypospadias in male offspring.

The purpose of this study was to determine how closely certified nurse-midwives in the United States follow contemporary cervical cancer screening guidelines. A survey was sent to 264 randomly selected certified nurse-midwives. Survey questions included demographics and clinical scenarios addressing initiation, frequency, and cessation of screening. Responses were received from 60% of the sampled certified nurse-midwives who had valid mailing addresses; 127 were eligible for the analytic sample. Many nurse-midwives initiate cervical cancer screening earlier than guidelines recommend; 72% would initiate screening in an 18-year-old within 1 month of coitarche, while 36% would begin screening virginal girls at age 18, and many continue cervical cancer screening after guidelines recommend cessation. More than 60% of the respondents would continue screening a woman who had undergone total hysterectomy for symptomatic fibroids who had no history of dysplasia, and half would continue to screen a 70-year-old woman with a 30-year history of previous normal Pap tests. In addition, despite guidelines which recommend less frequent screening, more than one-quarter (28%) would continue annual screening in a 35-year-old woman with three or more normal tests. Certified nurse-midwives are performing cervical cancer screening more frequently than current guidelines recommend. Comparisons to the practice of other providers are offered. Education to limit unnecessary testing is needed.

Smoking cessation is the only available intervention proven to halt progression of chronic obstructive pulmonary disease (COPD). The authors discuss the current existing treatment modalities and the role of a newly approved agent, varenicline, in promotion of smoking cessation. Varenicline is a novel agent that is a centrally acting partial nicotinic acetylcholine receptor agonist. It has both agonistic and antagonistic properties that together are believed to account for reduction of craving and withdrawal as well as blocking the rewarding effects of smoking. Its targeted mechanism of action, better efficacy and tolerability makes varenicline a useful therapeutic option for smoking cessation. In this article, we discuss presently available options for smoking cessation and review the literature on efficacy of varenicline.

UNLABELLED

Using data from a randomized placebo-controlled trial of 10,101 postmenopausal women not selected on the basis of osteoporosis, we examined whether the effect of raloxifene treatment on fractures was consistent across categories of fracture risk. Treatment with raloxifene for 5 yr reduced the risk of clinical vertebral fractures, but not nonvertebral fractures, irrespective of the presence or absence of risk factors for fracture.

INTRODUCTION

In The Raloxifene Use for The Heart (RUTH) trial, women assigned to raloxifene had a lower risk of clinical vertebral fractures but not nonvertebral fractures. However, it is uncertain whether the effect of raloxifene on fractures in this population not selected for low BMD differs according to risk factors for fractures.

MATERIALS AND METHODS

We randomly assigned 10,101 postmenopausal women >or=55 yr of age with documented coronary heart disease or at high risk for coronary events to 60 mg raloxifene daily or placebo and followed them for a median of 5.6 yr. Fractures (nonvertebral and clinical vertebral) were prespecified secondary endpoints that were reported at semiannual visits. Fractures were adjudicated and confirmed using X-ray reports or medical records.

RESULTS

There was no difference between raloxifene and placebo groups in risk of nonvertebral fractures (428 versus 438 events; hazard ratio [HR], 0.96; 95% CI, 0.84-1.10), including hip/femur (89 versus 103 events; HR, 0.85; 95% CI, 0.64-1.13) and wrist (107 versus 111 events; HR, 0.95; 95% CI, 0.73-1.24) fractures. Women treated with raloxifene had a lower risk of clinical vertebral fractures (64 versus 97 events; HR, 0.65; 95% CI, 0.47-0.89). The effect of treatment with raloxifene on risk of nonvertebral and clinical vertebral fractures was consistent across fracture risk categories defined at baseline by age, smoking status, physical activity level, prior history of fracture, family history of hip fracture, diabetes mellitus, previous use of hormone therapy, thyroid hormone use, statin use, weight loss, body mass index, or fracture specific summary risk score.

CONCLUSIONS

In older women with or at high risk of coronary heart disease not selected on the basis of osteoporosis or increased fracture risk, treatment with raloxifene for 5 yr reduced the risk of clinical vertebral fractures, but not nonvertebral fractures, irrespective of presence or absence of risk factors for fracture.

BACKGROUND

Transplantation of cells derived through the manipulation of pluripotent stem cells may involve great uncertainty and the possibility of serious risks.

PURPOSE

To develop guidelines for the ethical conduct of clinical trials using such stem cells.

METHODS

Review of literature on clinical trials ethics and clinical applications of stem cells; critical deliberation on potential guidelines.

RESULTS

Such transplantation should be allowed in clinical practice only after clinical trials demonstrate efficacy and safety. These clinical trials should follow ethical principles that guide all clinical research. Additional requirements to strengthen trial design, coordinate scientific and ethics review, verify that participants understand key features of the trial, and ensure publication of findings are also warranted because of the highly innovative nature of the intervention, limited experience in humans, and the high hopes of patients who have no alternative effective treatments.

LIMITATIONS

These recommendations will need to be modified in light of actual experience with stem cell clinical trials.

CONCLUSIONS

These recommendations will help guarantee that the efficacy and safety of innovative stem cell interventions will be rigorously established, while also protecting study participants.

OBJECTIVE

Tympanostomy tube insertion is the most common procedure that requires general anesthesia for children in the United States. We report on the clinical characteristics of a cohort of New York City children who received tympanostomy tubes in 2002.

METHODS

This retrospective cohort study included all 1046 children who received tubes in 2002 in any of 5 New York City area hospitals. We analyzed clinical data for all 682 (65%) children for whom we were able to abstract data for the preceding year from all of 3 sources: hospital, pediatrician, and otolaryngologist medical charts.

RESULTS

Mean age was 3.8 years, 57% were male, and 74% had private insurance. More than 25% of children had received tubes previously. The stated reason for surgery was otitis media with effusion for 60.4% of children, recurrent acute otitis media for 20.7%, and eustachian tube dysfunction for 10.6%. Children with recurrent acute otitis media averaged 3.1 +/- 0.2 episodes (median: 3.0) in the previous year; those with otitis media with effusion averaged effusions that were 29 +/- 1.7 days long (median: 16 days) at surgery. Twenty-five percent of children had bilateral effusions of >42 days' duration at surgery. Despite a clinical practice guideline for otitis media with effusion that recommends withholding tympanostomy tubes for otherwise healthy children until a bilateral effusion is at least 3 to 4 months old, 50% of children had surgery without having had 3 months of effusion cumulatively during the year before surgery.

CONCLUSIONS

The clinical characteristics of children who received tympanostomy tubes varied widely. Many children with otitis media with effusion had shorter durations of effusions than are generally recommended before surgery. The extent of variation in treating this familiar condition with limited treatment options suggests both the importance and the difficulty of managing common practice in accordance with clinical practice guidelines.