Two-year effects of alendronate on bone mineral density and vertebral fracture in patients receiving glucocorticoids: a randomized, double-blind, placebo-controlled extension trial.

OBJECTIVE: To evaluate the continued efficacy and safety of alendronate (ALN) for up to 2 years in patients receiving glucocorticoids. METHODS: This is a 12-month extension of a previously completed 1-year trial of daily ALN, performed to evaluate the effects of ALN over a total of 2 years in 66 men and 142 women continuing to receive at least 7.5 mg of prednisone or equivalent daily. All patients received supplemental calcium and vitamin D. The primary end point was the mean percentage change in lumbar spine bone mineral density (BMD) from baseline to 24 months. Other outcomes included changes in hip and total body BMD, biochemical markers of bone turnover, radiographic joint damage of the hands, and vertebral fracture incidence. RESULTS: The mean (+/-SEM) lumbar spine BMD increased by 2.8 +/- 0.6%, 3.9 +/- 0.7%, and 3.7 +/- 0.6%, respectively, in the groups that received 5 mg, 10 mg, and 2.5/10 mg of ALN daily (P < or = 0.001) and decreased by -0.8 +/- 0.6% in the placebo group (P not significant) over 24 months. In patients receiving any dose of ALN, BMD was increased at the trochanter (P < or = 0.05) and maintained at the femoral neck. Total body BMD was increased in patients receiving 5 or 10 mg ALN (P < or = 0.01). These 2 dose levels of ALN were more effective than placebo at all sites (P < or = 0.05). Bone turnover markers (N-telopeptides of type I collagen and bone-specific alkaline phosphatase) decreased 60% and 25%, respectively, during treatment with ALN (P < or = 0.05). There were fewer patients with new vertebral fractures in the ALN group versus the placebo group (0.7% versus 6.8%; P = 0.026). The safety profile was similar between treatment groups. CONCLUSION: Alendronate is an effective, well-tolerated therapy for the prevention and treatment of glucocorticoid-induced osteoporosis, with sustained treatment advantages for up to 2 years.

Structured review of neonatal deaths in a managed care organisation.

We sought to quantify neonatal mortality (< 28 days) in a 10-hospital system, determine what proportion was associated with suboptimal neonatal care and make recommendations on how neonatal mortality rates (NMRs) could be used in quality improvement efforts. Deaths were identified using electronic linkage to the State of California Death Certificate Tapes. Individual fatalities were reviewed by a minimum of two physicians who did not care for the infant. Deaths were classified as either being associated with suboptimal care or not. For deaths where suboptimal care was an issue, emphasis was on delineating the process involved in the death. Subjects were all neonatal deaths among 64,469 babies born in 1990-91 in the 10 birth facilities of the Kaiser Permanente Medical Care Program, Northern California Region. A total of 241 neonatal deaths were identified. Adjusting for prematurity by increasing the follow-up period in preterm babies (included as neonatal deaths if they died up to 40 weeks corrected gestational age + 27.9 days) increased overall mortality rates by 5%. Birthweight-specific NMRs in Kaiser Permanente are similar to those of other published reports. Among the 198 deaths in babies weighing > or = 500 g at birth, only 14 (7%) were possibly associated with suboptimal care. In populations with access to health insurance, reporting only aggregate NMRs is of limited use. The number of deaths that could be ascribed to suboptimal neonatal care is very small and measuring variations in rates of such deaths is difficult. Future measurements of quality of care will require more sophisticated measures, database systems, review strategies and dissemination methods.

Identification of neonatal deaths in a large managed care organisation.

The neonatal (< 28 days) mortality rate (NMR) is one of the most commonly employed maternal and child health epidemiological measures. It is also being employed in quality measures ("report cards') used to assess the performance of health care organisations. The objectives were to (1) develop methods for the rapid quantification of the neonatal mortality rate in a multi-hospital system, the Kaiser Permanente Medical Care Program's Northern California Region (KPMCP NCR), (2) develop methods for generating facility-specific rates and case lists, and (3) ascertain the capture rates of the information sources available to us. Potential neonatal deaths were identified in the KPMCP NCR for the 1990 and 1991 calendar years from 3 sources: (1) clerical searches of local facility records, (2) electronic searches of the KPMCP NCR hospitalisation database, and (3) linking KPMCP electronic birth records to death certificate tapes. The medical records of all infants identified through these methods were reviewed. The neonatal mortality rate was calculated in three ways: (1) including all livebirths, (2) excluding births weighing < 500 g, and (3) adjusting for prematurity by increasing the follow-up period in preterm babies (these babies were included as neonatal deaths if they died up to 40 weeks corrected age + 27.9 days). A total of 352 records out of 64 469 birth records in the KPMCP NCR were reviewed. If one includes babies < 500 g, the neonatal mortality rate was 3.72/1000 livebirths; if these babies are excluded, the rate was 3.05/1000. Adjusting for prematurity increased these rates to 3.91/1000 and 3.24/1000, respectively. Accurate quantification of the neonatal mortality rate in a multi-hospital system requires the use of multiple information sources. Use of a single source can lead to varying rates of over- or under-estimation. It is possible to employ our methodology for both research and operational purposes.

Effect of cyclical therapy with phosphorus and etidronate on axial bone mineral density in postmenopausal osteoporotic women.

Forty seven women with postmenopausal osteoporosis and at least one but no more than four vertebral compression fractures received sequential and cyclical therapy with phosphorus and etidronate (p/etid). During the same 2-year period of observation, three other groups of patients received either sodium fluoride (n = 12), estrogen replacement therapy (n = 12), or vitamin D and calcium (Ca++) alone (n = 15). Axial bone mineral density (BMD) was measured by means of dual-photon absorptiometry. Lateral thoracic and lumbar spine radiographs were taken to assess fractures. Bone mineral density increased from baseline during p/etid therapy: Mean 15.7 +/- 1.6% (SD) (P less than 0.001). During the same time, the patients in the sodium fluoride group showed a comparable increase in their BMD from baseline: mean 15.7 +/- 1.1% (P less than 0.001). During the first year of therapy, patients in the estrogen replacement group had an increase in their BMD from baseline: mean: 4.6% +/- 1.1% (P less than 0.05). No change in BMD was seen in the control group that received vitamin D and Ca++ alone. No patient who received p/etid, sodium fluoride, or estrogen replacement therapy had any new vertebral compression fractures or height loss, whereas in the control group that received vitamin D and Ca++ alone 6 out of 15 had height loss and at least one new vertebral fracture (P less than 0.01). p/etid therapy increases BMD in women with postmenopausal osteoporosis comparable to sodium fluoride but without side effects or toxicity and stabilizes vertebral compression fractures.

Intermittent cyclical etidronate treatment of postmenopausal osteoporosis.

BACKGROUND: To determine the effects of etidronate (a bisphosphonate that inhibits osteoclast-mediated bone resorption) in the treatment of postmenopausal osteoporosis, we conducted a prospective, two-year, double-blind, placebo-controlled, multicenter study in 429 women who had one to four vertebral compression fractures plus radiographic evidence of osteopenia. METHODS: The patients were randomly assigned to treatment with phosphate (1.0 g) or placebo twice daily on days 1 through 3, etidronate (400 mg) or placebo daily on days 4 through 17, and supplemental calcium (500 mg) daily on days 18 through 91 (group 1, placebo and placebo; group 2, phosphate and placebo; group 3, placebo and etidronate; and group 4, phosphate and etidronate). The treatment cycles were repeated eight times. The bone density of the spine was measured by dual-photon absorptiometry, and the rates of new vertebral fractures were determined from sequential radiographs. RESULTS: After two years, the patients receiving etidronate (groups 3 and 4) had significant increases in their mean (+/- SE) spinal bone density (4.2 +/- 0.8 percent and 5.2 +/- 0.7 percent, respectively; P less than 0.017). The rate of new vertebral fractures was reduced by half in the etidronate-treated patients (groups 3 and 4 combined) as compared with the patients who did not receive etidronate (groups 1 and 2 combined) (29.5 vs. 62.9 fractures per 1000 patient-years; P = 0.043); the effect of treatment was most striking in the subgroup of patients with the lowest spinal bone mineral density at base line, in whom fracture rates were reduced by two thirds (42.3 vs. 132.7 fractures per 1000 patient-years; P = 0.004). The addition of phosphate provided no apparent benefit. There were no significant adverse effects of treatment. CONCLUSIONS: Intermittent cyclical therapy with etidronate for two years significantly increases spinal bone mass and reduces the incidence of new vertebral fractures in women with postmenopausal osteoporosis.

The role of intensive dialysis in acute renal failure.

The efficacy of vigorous dialysis in the management of acute renal failure remains controversial. In order to examine the beneficial role of vigorous dialysis, a prospective study was carried out in 34 patients paired by acute renal failure etiology and treated with sufficient dialysis to maintain predialysis blood urea nitrogen and serum creatinine below either 60 and 5 mg/dl (intensive) or 100 and 9 mg/dl, respectively (non-intensive). Serum creatinine was at least 8 mg/dl in all patients prior to random assignment to intensive or non-intensive dialysis. Mean predialysis blood urea nitrogen and serum creatinine, respectively, were 60 +/- 23 and 5.3 +/- 1.5 mg/dl in the intensively dialyzed group and 101 +/- 18 and 9.1 +/- 1.4 mg/dl in the non-intensively dialyzed group (both p less than .001). Predialysis serum bicarbonate and blood pH were lower and serum phosphate higher in the non-intensively dialyzed patients. Daily weight changes, increases in blood urea nitrogen, protein and calorie intakes were similar. While hemorrhagic episodes tended to be more frequent in non-intensively dialyzed patients, overall complication rates were not different between the two groups. Mortality rates, which were 58.8% in the intensive and 47.1% in the non-intensive groups, also were not different. On the other hand, urine output prior to dialysis did influence survival. It is concluded that, within the limits of the study, there is no advantage to intensive dialysis in the management of acute renal failure.

Perinatal care of low-risk mothers and infants. Early discharge with home care.

A family-centered perinatal-care program featuring collaboration by nurse practitioners, obstetricians, pediatricians, and paramedical personnel was developed to enhance family participation and achieve a shorter but safe hospital stay. Discharge from the hospital was permitted as early as 12 hours after delivery. A perinatal nurse practitioner made daily home visits. The program's safety, feasibility, and acceptability to patients was studied by comparison of 44 patients so treated (study group) with 44 receiving traditional care (controls). Twenty-one study families, but no controls, went home within 24 hours. The study and control groups had no significant differences or trends in numbers of types of morbidity during hospitalization or the six-week post-partum period. The expense of the program is approximately equaled by hospital costs saved through early discharge. The results indicate that early discharge with home-care follow-up observation as described is safe, economically feasible, and well accepted by patients.