Publications

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.