Effects of three years of low-dose thiazides on mineral metabolism in healthy elderly persons.

UNLABELLED: In this clinical trial of 12.5 or 25 mg/day of hydrochlorothiazide, the urine calcium showed significant decreases from placebo in men at one year, but the effects had waned by 3 years. Serum bicarbonate was consistently greater in the thiazide than in the placebo groups throughout the three years. These effects could be beneficial to the skeleton. INTRODUCTION: Previous studies have shown increased bone density and reduced risk of fracture in patients taking thiazide diuretics. The long-term effects of low-dose thiazides on mineral metabolism have not been reported in normal subjects. METHODS: We conducted a randomized, double-blinded trial in normals aged 60-79 years, using hydrochlorothiazide 12.5 or 25 mg/d or placebo for three years. Subjects were encouraged to maintain calcium intake of 1,000 to 1,500 mg/day. Measurements of serum and urine calcium metabolism were done at baseline, six months, and yearly. Data were analyzed in 88 men and 177 women who had taken study medication. Adjusted change in the measurements from baseline to one and three years were compared among groups. RESULTS: The calcium intake increased in all groups. Urine calcium per day was significantly lower in thiazide than placebo groups in men at one year but not at three years; in women the changes were not significantly different. Serum bicarbonate was higher in thiazide compared to placebo groups at one and three years. No changes were seen in serum calcium, phosphate, parathyroid hormone, sodium or magnesium. CONCLUSIONS: The results suggest that both increased calcium availability from a hypocalciuric effect and reduction in acid-induced bone buffering could be mechanisms for the beneficial skeletal effects.

Association between caffeine intake and bone mass among young women: potential effect modification by depot medroxyprogesterone acetate use.

UNLABELLED: This study assessed associations between habitual caffeine intake and bone mass among young women. Analyses of the entire study population revealed no significant associations, while analyses restricted to women using depot medroxyprogesterone acetate (DMPA) showed modest inverse associations between caffeine intake and bone mineral content (BMC). INTRODUCTION: Some previous investigations among postmenopausal women suggest an inverse relationship between caffeine intake and bone mass, yet studies of this association among young women are few. METHODS: The association between habitual caffeine intake and bone mass was evaluated prospectively in a population-based cohort of 625 females, aged 14 to 40 years, adjusting for relevant biological and lifestyle factors. Caffeinated beverage intake was self-reported, and bone mineral content (BMC) and bone mineral density (BMD) were measured at baseline and every 6 months throughout a 24-month follow-up period using dual-energy x-ray absorptiometry. RESULTS: Cross-sectional analyses revealed no significant differences in mean BMC or BMD at baseline. Mean percentage and absolute changes in BMC and BMD were not associated with caffeine use. Repeated measures analyses similarly showed no significant association between caffeine intake at baseline and mean BMC or BMD measured during follow-up. However, among women using depot medroxyprogesterone acetate (DMPA), modest inverse associations between caffeine and BMC (but not BMD) were detected. CONCLUSIONS: Our data suggest that heavy habitual consumption of caffeinated beverages does not adversely impact bone mass among young women in general. Greater caffeine intake may be associated with lower BMC among DMPA users.

Ineffective use of condoms among young women in managed care.

Condoms must be used effectively in order to prevent pregnancy and the spread of HIV/STD. This study investigated two types of ineffective condom use, delayed condom use (initiated after penetration has occurred) and condom slippage and/or breakage. We estimated prevalence and identified predictors of ineffective condom use among young women at risk of STDs. The study used baseline survey data from a randomized trial of women 18-24 years old at two managed care sites; 779 participants who were recent condom users were included in this analysis. Forty-four per cent of the sample reported delayed condom use in the past three months and 19% reported condom slippage and/or breakage. In multivariate logistic regression, younger age, primary partner, lack of partner support, multiple recent sexual partners and using condoms for contraception were positively associated with delayed condom use. Correlates of condom slippage and/or breakage were non-white race/ethnicity and history of any STD. Greater frequency of condom use independently predicted both outcomes. Ineffective condom use was common in this sample of experienced condom users and predictors were different for each outcome. HIV/STD prevention interventions must address more specific aspects of condom use than have previously been their focus, especially when condom use is already high.

Effects of contraceptive use on bone biochemical markers in young women.

The purpose of this study was to compare biochemical markers of bone resorption and formation in young women using different hormonal contraceptive methods. Women aged 18-39 yr who were using depot medroxyprogesterone acetate (DMPA) contraception were recruited for the study; comparison women were matched by age and clinic location. There were 116 women using DMPA, 39 using oral contraceptives containing estrogen and progestin, and 72 not currently using hormonal contraceptives. Biochemical measurements were serum calcium, PTH and osteocalcin, and urine N-telopeptide. Bone density was measured using dual-energy x-ray absorptiometry. The N-telopeptide levels, adjusted for age and other risk factors, were 42.4 +/- 2.3 nmol/mmol creatinine in the DMPA group, 26.2 +/- 3.3 nmol/mmol in the oral contraceptive group, and 35.4 +/- 2.9 nmol/mmol in the nonusers; significant differences were seen in all pairwise comparisons. Osteocalcin levels showed the same pattern, although the difference between the DMPA users and nonusers was not statistically significant. There were no differences among groups in the PTH levels. The bone density at the spine was 1.086 +/- 0.085 g/cm(2) in the DMPA group, 1.103 +/- 0.095 g/cm(2) in the oral contraceptive group, and 1.093 +/- 0.090 g/cm(2) in nonusers (P = 0.051). The results suggest that in women using DMPA bone resorption exceeded bone formation.

Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Thiazide may have beneficial effects on bone mineral density and may reduce risk for hip fracture. However, the existence of a causal role remains uncertain because experimental evidence is limited. OBJECTIVE: To determine the effect of hydrochlorothiazide on rates of bone loss in older adults. DESIGN: Randomized, double-blind, placebo-controlled trial with 3-year follow-up. SETTING: A large health maintenance organization in western Washington State. PARTICIPANTS: 320 healthy, normotensive adults (205 women, 115 men) 60 to 79 years of age. INTERVENTION: Random assignment to one of three study groups: 12.5 mg of hydrochlorothiazide per day, 25 mg of hydrochlorothiazide per day, or placebo. MEASUREMENTS: Bone mineral density using dual-energy x-ray absorptiometry at the total hip, posterior-anterior spine, and total body; blood and urine markers of bone metabolism; incident falls, clinical fractures, and radiographic vertebral fractures. RESULTS: 309 of 320 participants completed the 36-month visit (97%). Adherence to study medication throughout follow-up was high in all participants (81.6% to 89.7%) except men in the high-dose hydrochlorothiazide group (60.5%). According to intention-to-treat analysis, the 36-month differences in percentage change in total hip bone mineral density were 0.79 percentage point (95% CI, -0.12 to 1.71) for the 12.5-mg hydrochlorothiazide group and 0.92 percentage point (CI, -0.001 to 1.85) for the 25-mg group compared with placebo (P = 0.03). Percentage change at the posterior-anterior spine was significantly greater for the 25-mg hydrochlorothiazide group at 6 months (intergroup difference, 1.04 percentage points [CI, 0.22 to 1.86]) compared with placebo (P = 0.005); at 36 months, this difference was 0.82 percentage point (CI, -0.36 to 2.01; P = 0.12). No significant differences were seen in total-body bone mineral density between the treatment groups. Treatment effects were stronger in women than in men. CONCLUSIONS: In healthy older adults, low-dose hydrochlorothiazide preserves bone mineral density at the hip and spine. The modest effects observed over 3 years, if accumulated over 10 to 20 years, may explain the one-third reduction in risk for hip fracture associated with thiazide in many epidemiologic studies.

Depressive symptoms in users and non-users of depot medroxyprogesterone acetate.

To evaluate the possible effects of depot medroxyprogesterone acetate (DMPA) injectable contraception on depressive symptoms, we conducted a population-based prospective study with women aged 18-39 years old enrolled at a health maintenance organization. At baseline, 183 women used DMPA and 274 were non-users. Data on depressive symptoms and on factors potentially related to DMPA use and depression were collected by questionnaire at 6-month intervals for up to 3 years. In multivariate longitudinal analysis, we found an increased likelihood of reporting depressive symptoms among continuous DMPA users (OR = 1.44; 95% CI = 1.00-2.07) and discontinuers (OR = 1.60; 95% CI = 1.03-2.48) when compared to non-users. Women who discontinued DMPA use had elevated depressive symptoms prior to discontinuation (OR = 2.30; 95% CI = 1.42-3.70) and immediately following discontinuation (OR = 2.46; 95% CI = 1. 46-4.14), and depressive symptoms subsided at subsequent visits relative to non-users. Our prospective analyses found an association between DMPA use and depressive symptoms but further research is needed to determine whether the relationship is causal.

Analysis of case-cohort designs.

The case-cohort design is most useful in analyzing time to failure in a large cohort in which failure is rare. Covariate information is collected from all failures and a representative sample of censored observations. Sampling is done without respect to time or disease status, and, therefore, the design is more flexible than a nested case-control design. Despite the efficiency of the methods, case-cohort designs are not often used because of perceived analytic complexity. In this article, we illustrate computation of a simple variance estimator and discuss model fitting techniques in SAS. Three different weighting methods are considered. Model fitting is demonstrated in an occupational exposure study of nickel refinery workers. The design is compared to a nested case-control design with respect to analysis and efficiency in a small simulation. In this example, case-cohort sampling from the full cohort was more efficient than using a comparable nested case-control design.

Bone mineral density in women using depot medroxyprogesterone acetate for contraception.

OBJECTIVE: To evaluate the possible effects of depot medroxyprogesterone acetate injectable contraception on bone mineral density in reproductive-age women. METHODS: We conducted a population-based cross-sectional comparison of bone mineral density levels in women using depot medroxyprogesterone acetate contraception and in women of similar age not using this method. The study recruited 457 nonpregnant women aged 18-39 years who were enrollees of a Washington state health maintenance organization. One hundred eighty-three women were receiving injections and 274 were not. Bone mineral density at several anatomic sites (spine, femoral neck, greater trochanter, and whole body) was measured using dual-energy x-ray absorptiometry. Data on other factors potentially related to bone density were collected through questionnaire and examination. RESULTS: Overall, age-adjusted mean bone density levels were lower for users of this method than for nonusers at all anatomic sites: The mean difference was 2.5% for the spine (P = .03) and 2.2% for the femoral neck (P = .12). Exposure to depot medroxyprogesterone acetate continued to be significantly (P < .01) associated with decreased bone density at the femoral neck, spine, and trochanter after multivariate adjustment for other risk factors related to bone density. Age-specific comparisons indicated that the major differences in bone density between users and nonusers occurred in the youngest age group (women 18-21 years); the mean femoral neck bone density was 10.5% lower (P < .01) for the exposed women, and differences were consistent (P < .01) across all anatomic sites. We also noted a significant dose-response relation between longer use of depot medroxyprogesterone acetate and decreased bone density levels in this age group (P < .01 for all sites). CONCLUSION: These results provide evidence that contraception with depot medroxyprogesterone acetate, particularly long-term use, may adversely affect bone mineral density levels in young women aged 18-21 years. The implications for future bone health need further study.

Does stent placement improve the results of ineffective or complicated iliac artery angioplasty?

OBJECTIVE: This study was undertaken to determine the results and complications of stents placed for initially unsuccessful or complicated iliac percutaneous transluminal angioplasty (PTA), the effect of location (external iliac or common iliac) on outcome, and the influence of superficial femoral artery patency on benefit. DESIGN: From 1992 through 1997, 350 patients underwent iliac artery PTA at the authors' institutions. Of this group, 88 patients (88 arteries) had one or more stents placed after PTA (140 stents in total) for residual stenosis or pressure gradient (63 patients), iliac dissection (12 patients), long-segment occlusion (10 patients), or recurrent stenosis (3 patients). Thirty patients required the placement of more than one stent. The indications for PTA in these 88 patients were claudication (48 patients) and limb-threatening ischemia (40 patients). Forty-seven patients had stents placed in the common iliac, 29 patients had stents placed in the external iliac, and 12 patients had stents placed in both. Seventy-one arteries (81%) were stenotic, and 17 (19%) were occluded before PTA. Sixty-six arteries were treated by interventional radiologists, 15 by a vascular surgeon, and 7 jointly. MAIN OUTCOME MEASURE: Criteria for success included (1) increase of at least one clinical category of chronic limb ischemia from baseline or satisfactory wound healing, (2) maintenance of an ankle/brachial index increase of more than 0.10 above the preprocedure index, and (3) residual angiographic stenosis less than 25% and, for patients with pressure gradient measurements, a residual gradient less than 10 mm Hg. RESULTS: Stent placement was accomplished in all 88 patients with 16 (18%) major complications. Mean follow-up was 17 months (range, 3 to 48 months). By life-table analysis, success was 75% at 1 year, 62% at 2 years, and 57% at 3 years. No cardiovascular risk factor or independent variable was statistically significant in predicting success. There was no difference in success rates for common iliac or external iliac lesions. Superficial femoral artery patency did not correlate with outcome. CONCLUSIONS: Although stents can eliminate residual lesions and arterial dissection, these patients are likely to require adjuvant or subsequent procedures to attain clinical success. By controlling the PTA complication and treating the emergent problem, stents may allow for subsequent elective intervention.

Vaginal douching as a risk factor for cervical Chlamydia trachomatis infection.

OBJECTIVE: To evaluate the association between vaginal douching and cervical Chlamydia trachomatis infection. METHODS: We analyzed cross-sectional data from a study conducted at Group Health Cooperative of Puget Sound, a nonprofit health maintenance organization in western Washington state. Participants were nonpregnant women Group Health enrollees between the ages of 18 and 34 years who were attending two primary care clinics either for nonurgent visits, primarily routine preventive health visits, or in response to an invitation from the study. Before the clinical examination, all completed a self-administered survey assessing demographic and behavioral characteristics, including the timing, frequency, products used, and reasons for douching. Chlamydial infection was ascertained via cell culture isolation of C trachomatis from endocervical specimens obtained at the same visit. RESULTS: Chlamydia trachomatis was isolated from cervical cultures in 58 (3.4%) of 1692 study participants. Women who reported douching in the 12 months before their clinic visit had an increased likelihood of chlamydial infection compared with women who did not douche (prevalence odds ratio [OR] 2.29, 95% confidence interval [CI] 1.22, 4.30, after adjusting for confounding factors). The likelihood was higher for women who reported douching more often: OR 2.60 (95% CI 1.29, 5.24) for women who douched one to three times per month, and OR 3.84 (95% CI 1.26, 11.70) for those douching four times or more per month. These associations were slightly stronger when women who reported douching because of an infection were excluded from the analysis. CONCLUSION: These results support the hypothesis that vaginal douching predisposes to acquisition of cervical chlamydial infection and are compatible with previous studies that report associations between douching and sequelae of chlamydial infection, including pelvic inflammatory disease, ectopic pregnancy, and infertility.

A prospective study of contact lens complications in a managed care setting.

BACKGROUND: Understanding the rate of contact lensrelated complications and the factors that affect their occurrence can facilitate better prescribing decisions. METHODS: In a managed care setting, 1496 patient visits were evaluated using a common protocol by 11 optometrists to determine the prevalence of all contact lens-related complications. RESULTS: Over one-half (61%) of the visits were normal, with the remainder showing some type of complication. The more prevalent complications included superficial punctate staining (17.3%) and neovascularization (11.4%). Total complications were less prevalent with rigid gas permeable (RGP) and disposable lens types. Planned replacement soft lenses, used on a daily wear schedule, had the lowest prevalence of more serious complications when compared to conventional soft and disposable lenses. Patients on an extended wear schedule greater than 3 days were more likely to experience complications. The use of nonapproved care systems showed more complications, with serious complications reduced when a one-step care system was used. CONCLUSION: Choice of lens type, wearing schedule, and care system does affect the prevalence of complications, which underlines the importance of the recommendations of the prescriber.

Should percutaneous transluminal angioplasty be recommended for treatment of infrageniculate popliteal artery or tibioperoneal trunk stenosis?

PURPOSE: The purpose of this study was to determine the effectiveness of percutaneous transluminal angioplasty (PTA) for treatment of patients with localized stenosis of the infrageniculate popliteal artery and tibio-peroneal trunk (IGPA). METHODS: The records of 25 patients undergoing IGPA PTA from 1983 to 1993 were reviewed. Patients underwent follow-up with clinical examinations, ankle-brachial indexes, Duplex scanning, and arteriography. Demographic variables and cardiovascular risk factors were analyzed and correlated with outcome. RESULTS: Mean follow-up was 44 months. With life-table analysis, clinical and hemodynamic success was 59%, 32%, and 20% at 1, 2, and 3 years, respectively. Average time to recurrence was 17 months. Sixteen patients required a subsequent procedure; two had only repeat PTA, six had repeat PTA followed by arterial bypass, and eight had bypass alone. The mean additional benefit of repeat PTA was 8 months. Eleven of the 14 patients treated with bypass became symptom-free with patent grafts at a mean follow-up of 52 months. No risk factor was statistically significant in predicting success of IGPA PTA. CONCLUSIONS: IGPA PTA is an expensive temporizing measure with a high rate of recurrence requiring subsequent intervention. The procedure should be restricted to patients with limited life expectancy or contraindications to operation.

Stage, age, comorbidity, and direct costs of colon, prostate, and breast cancer care.

PURPOSE: This study was conducted to evaluate the effect of stage at diagnosis, age, and level of comorbidity (presence of other illness) on the costs of treating three types of cancer among members of a health maintenance organization. METHODS: Among 388,000 members enrolled anytime during 1990 and 1991 in Group Health Cooperative (GHC) of Puget Sound (Washington State), we estimated the total and net direct costs of medical care for colon, prostate, and breast cancers, including both incident (290, 554, and 645 patients, respectively) and prevalent (1046, 1295, and 2299 patients, respectively) cases. We summarized costs for initial, continuing, and terminal phases of care. Net costs were the difference between the costs of the care of each case subject and the average costs of the care for all enrollees without the cancer of interest who were of the same sex and in the same 5-year age group. Differences in estimated total and net costs by stage at diagnosis, age, and comorbidity were separately evaluated using multivariate regression modeling. All P values were two-sided. Comorbidity was based on a score calculated from 1988 pharmacy data. RESULTS: Total costs of initial care increased with stage at diagnosis for colon (P = .0013) and breast (P < .0001) cancer cases, but not for prostate cancer cases. Total initial costs decreased with age for prostate (P = .0225) and breast (P = .0002) cancers but did not change with degree of comorbidity for any of the three cancers. Total continuing medical care costs increased with stage at diagnosis for colon (P < .0001) and breast (P < .0001) cancer cases but not for prostate cancer cases. Total terminal care costs were similar by stage for all three cancers. Net initial costs differed with stage for all three cancers (P < .05). Net continuing care costs increased with stage (P < .0001) and decreased with age (P < .001) for colon and breast cancers but not for prostate cancer. Net continuing care costs decreased with comorbidity for all three cancers (P = .004, P = .011, and P < .0001 for colon, prostate, and breast cancers, respectively). Among regional stage cancers, continuing care costs decreased with age for colon (P < .0017) and breast (P = .033) cancers but not for prostate cancers. CONCLUSIONS: The results show that total costs vary by stage at diagnosis and age, but the patterns of variation differ for each cancer. Costs of cancer are not simply additive to costs of other conditions. IMPLICATIONS: More needs to be done to explore the reasons and implications of age-related cost differences. Cost-effectiveness analyses of cancer control interventions that shift cancer stage distributions may need to consider both the age and comorbidity of the target populations.

Treatment of recurrent femoral or popliteal artery stenosis after percutaneous transluminal angioplasty.

PURPOSE: This study was undertaken to compare repeat percutaneous transluminal angioplasty (rPTA), arterial reconstruction, and noninvasive therapy for treatment of patients with recurrent stenosis after PTA of the superficial femoral or popliteal artery. METHODS: From 1983 to 1993, 93 patients were treated for recurrent femoropopliteal stenosis. Indication for treatment was claudication in 72 patients, rest pain in 9, and ischemic ulcer in 12. Thirty-six patients (38%) were treated with arterial bypass, 35 (38%) with rPTA, and 22 (24%) with exercise and medication. Patients were monitored with clinical examination, ankle-brachial indexes, and duplex scanning. Follow-up ranged from 6 to 110 months (mean 42 months). RESULTS: With life-table analysis, the clinical and hemodynamic success of patients treated with rPTA was 41% at 1 year, 20% at 2 years, and 11% at 3 years. For patients treated with arterial bypass, the primary graft patency rate was 84%, 72%, and 72% at 1, 2, and 3 years, respectively. The secondary graft patency rate was 94%, 88%, and 88% at the same intervals. All patients with patent grafts were symptom free. All 22 patients treated with noninvasive therapy continued to have symptoms, but none required amputation during follow-up (range 6 to 108 months). Overall, patients with claudication did better than those treated for rest pain or an ischemic lesion after either rPTA or arterial bypass, but no other variable was statistically significant in predicting outcome. CONCLUSIONS: This study finds that arterial bypass is safe and more effective than rPTA in treating patients with recurrent stenosis. Preoperative evaluation is unable to select patients likely to benefit from rPTA. Repeat PTA should be reserved for patients with limited life expectancy or contraindications to operation.