Publications

BACKGROUND

Low bone mineral density (BMD) is common in dialysis patients. Low BMD predicts the fracture risk in the general population. Bisphosphonate therapy improves BMD and lowers the fracture risk in many populations, but has not been tested in dialysis patients because of concerns about toxicity. In this investigation, the effect of a short course of alendronate on BMD in haemodialysis (HD) patients is evaluated.

METHODS

Thirty-one healthy HD patients were randomized to placebo versus 40 mg alendronate, taken once a week for 6 weeks. Hip and lumbar spine BMD were measured by dual energy X-ray absorptiometry at baseline and at 6 months. Osteocalcin, parathyroid hormone, calcium, phosphorous and alkaline phosphatase levels were assayed at baseline and at 1, 3 and 6 months.

RESULTS

The BMD and T-scores in specific regions of the hip were stable in the treatment group and decreased in the placebo group (P=0.05). The lumbar spine density increased minimally in both groups. In the treatment group, osteocalcin levels declined significantly at 1 month (P<0.05) and remained low. The main side-effect in the alendronate group was occurrence of gastroesophageal reflux symptoms in three subjects.

CONCLUSIONS

Low-dose alendronate, administered for a limited duration, appears to be well tolerated in dialysis patients. The BMD and T-scores declined at certain hip regions in the placebo group over 6 months, while remaining stable in the treatment group, suggesting a bone-preserving effect of alendronate. Further studies of longer duration, and including examination of bone histology, are needed to assess whether bisphosphonates can be used to preserve BMD in dialysis patients.

BACKGROUND

Many women experience a breast lump. Clinical guidelines suggest that a normal mammogram result alone is not adequate to exclude a diagnosis of cancer.

OBJECTIVE

To examine the characteristics of women with a breast lump and a normal mammogram that were associated with receiving further evaluation, and to examine cancer outcomes.

DESIGN

Observational cohort.

PARTICIPANTS

Women aged 35 to 70 years who participated in a population-based mammography registry and who did not have a history of breast cancer noted at the time of their mammogram that they had a breast lump, and had a "normal" (Breast Imaging Reporting and Data System 1 or 2) mammogram result (n=771).

MEASUREMENTS

Telephone survey performed 6 months after the mammogram to ascertain information about evaluation. Cancer outcomes within 12 months of the index mammogram were confirmed through linkage with a cancer registry.

RESULTS

Only 56.9% of women reported receiving an adequate evaluation for their breast lump, including a subsequent clinical breast exam, a visit to a breast specialist, an ultrasound, a biopsy, or aspiration. Latinas were less likely than white women to have received adequate evaluation, as were obese women compared with normal-weight women, and uninsured women compared with women with insurance. Among women with at least 12 months of follow-up, 1.4% were diagnosed with cancer.

CONCLUSIONS

Many women do not receive adequate evaluation for a recent breast lump. Interventions should be designed to improve the follow-up of women with this common clinical problem.

BACKGROUND

With advances in antiretroviral therapy, many human immunodeficiency virus (HIV)-infected individuals are living longer and developing end-stage renal or hepatic disease requiring transplantation. Maintaining the viability of the transplant and suppressing HIV replication requires concomitant use of immunosuppressants (e.g., cyclosporine) and antiretrovirals (e.g., protease inhibitors or nonnucleoside reverse transcriptase inhibitors), which leads to drug interactions. To assist in appropriate clinical management of HIV-infected transplant recipients, the authors describe the pharmacokinetic interactions between cyclosporine and the antiretroviral medications, and required modifications of cyclosporine dosing.

METHODS

Eighteen HIV-infected subjects with end-stage kidney or liver disease underwent transplantation. Subjects had pharmacokinetic studies before transplantation and for up to 2 years posttransplantation (at weeks 2-4, 12, 28, 52, and 104). Protease inhibitors, nonnucleoside reverse transcriptase inhibitors, and cyclosporine concentrations were measured by liquid chromatography-mass spectrometry in plasma and whole blood, respectively.

RESULTS

Subjects using protease inhibitors and cyclosporine had a threefold increase in cyclosporine area under the curve (4,190+/-2,180-11,900+/-1,600 ng*hr/mL, P<0.01), necessitating an 85% reduction in cyclosporine dose over a 2-year period (1.3+/-1.5-0.2+/-0.0 mg/kg/dose), leading to a progressive increase in oral cyclosporine bioavailability (R=0.92, P<0.02). Subjects on nonnucleoside reverse-transcriptase inhibitors showed minimal interactions with cyclosporine, and subjects on both HIV treatments had intermediate responses.

CONCLUSIONS

HIV-infected transplant recipients on protease inhibitors require markedly lower doses of cyclosporine, with continued lowering of the cyclosporine dose over time and ongoing cyclosporine trough monitoring because of progressively increasing cyclosporine bioavailability. Medication changes must be carefully managed to avoid insufficient immunosuppression or toxicity resulting from drug interactions.