Self-reported calcium use in a cohort of postmenopausal women receiving osteoporosis therapy: results from POSSIBLE US™.

UNLABELLED: Calcium use was common and remained high among women on osteoporosis therapy. Use of calcium-supplemented pharmacologic therapy increased from 65.1 to 76.0% in these women (mean follow-up, 27.5 months). Over 12 months, calcium discontinuation was fairly similar among women using calcium only (23.7%) and women supplementing pharmacologic therapy with calcium (22.5%). INTRODUCTION: Calcium has an important role in bone health. This study describes calcium use and persistence in a postmenopausal osteoporosis treatment cohort. METHODS: Subject-reported calcium use was analyzed for 3,722 participants of the Prospective Observational Scientific Study Investigating Bone Loss Experience (POSSIBLE US(TM)) who used calcium either as their sole osteoporosis treatment (calcium only) or to supplement pharmacologic osteoporosis therapy (supplementers). Descriptive analyses were conducted. Kaplan-Meier methods were used to estimate the probability of discontinuing calcium therapy, and logistic regression was used to assess associations (age-adjusted odds ratios) between healthy behaviors and calcium use. RESULTS: At entry, there were 711 calcium-only subjects and 1,960 of 3,011 subjects on pharmacologic osteoporosis therapy also supplementing with calcium (supplementers). The percentage of supplementers increased from 65.1 to 76.0% during follow-up (mean, 27.5 months). During the first 12 months on study, the probability of calcium discontinuation was 23.7% (95 % confidence interval [CI], 20.7 - 27.0) among calcium-only subjects and 22.5% (95% CI, 20.7-24.5) among supplementers. Supplementers who discontinued pharmacologic therapy were more likely to discontinue calcium than supplementers who continued pharmacologic therapy (34.9 versus 14.8%). Overall 54.2% of calcium-only subjects who discontinued calcium and 42.3% of supplementers who discontinued calcium resumed calcium use during follow-up. Regular exercise was positively correlated with calcium use at study entry. CONCLUSIONS: Calcium supplementation in pharmacologically treated subjects increased over time. Persistence with calcium was high. Discontinuation of pharmacologic osteoporosis therapy was associated with an increased likelihood of discontinuing calcium use.

Fear of falling, fracture history, and comorbidities are associated with health-related quality of life among European and US women with osteoporosis in a large international study.

UNLABELLED: We studied 7,897 women with postmenopausal osteoporosis to assess factors that influence health-related quality of life (HRQoL). An increased number of comorbidities, fear of falling, and previous vertebral fracture were associated with significant reductions in HRQoL. Understanding the factors that affect HRQoL may improve management of these patients. INTRODUCTION: HRQoL is impaired in women treated for postmenopausal osteoporosis (PMO). The objective of this study was to examine the relationship between clinical characteristics, comorbidities, medical history, patient demographics, and HRQoL in women with PMO. METHODS: Baseline data were obtained and combined from two large and similar multinational observational studies: Prospective Observational Scientific Study Investigating Bone Loss Experience in Europe (POSSIBLE EU®) and in the US (POSSIBLE US™) including postmenopausal women in primary care settings initiating or switching bone loss treatment, or who had been on bone loss treatment for some time. HRQoL measured by health utility scores (EQ-5D™) were available for 7,897 women (94 % of study participants). The relationship between HRQoL and baseline clinical characteristics, medical history and patient demographics was assessed using parsimonious, multivariable, mixed-model analyses. RESULTS: Median health utility score was 0.80 (interquartile range 0.69-1.00). In multivariable analyses, young age, low body mass index, previous vertebral fracture, increased number of comorbidities, high fear of falling, and depression were associated with reduced HRQoL. Regression-based model estimates showed that previous vertebral fracture was associated with lower health utility scores by 0.08 (10.3 %) and demonstrated the impact of multiple comorbidities and of fear of falling on HRQoL. CONCLUSIONS: In this large observational study of women with PMO, there was substantial interindividual variability in HRQoL. An increased number of comorbidities, fear of falling, and previous vertebral fracture were associated with significant reductions in HRQoL.

Lack of efficacy of polysorbate 60 in the treatment of male pattern baldness.

Anecdotal reports have indicated that the nonionic detergent polysorbate 60 may be of some value in male pattern baldness. In this double-blind placebo-controlled trial, a photographic and objective scalp measurement system was developed to assess new hair growth. No significant difference was detected between subjects treated for 16 weeks with polysorbate 60 and control subjects treated with glycerin, indicating that polysorbate 60 is ineffective. Of the 141 subjects who completed the trial, 25% perceived that they grew new hair, 67% said they did not, and 8% were uncertain. Subject-reported new hair growth did not correlate with measurements, indicating that the placebo effect may be a major factor in reports of baldness "cures".

Phenotypic and genotypic diversity in a multinational sample of drug-resistant Mycobacterium tuberculosis isolates.

OBJECTIVE: To develop and evaluate rapid, molecular-based drug susceptibility testing (DST) for extensively drug-resistant tuberculosis (XDR-TB), we assembled a phenotypically and genotypically diverse collection of Mycobacterium tuberculosis isolates from patients evaluated for drug resistance in four high-burden countries. METHODS: M. tuberculosis isolates from India (n = 111), Moldova (n = 90), the Philippines (n = 96), and South Africa (n = 103) were selected from existing regional and national repositories to maximize phenotypic diversity for resistance to isoniazid, rifampin (RMP), moxifloxacin, ofloxacin, amikacin, kanamycin, and capreomycin. MGIT™ 960 was performed on viable isolates in one laboratory using standardized procedures and drug concentrations. Genetic diversity within drug resistance phenotypes was assessed. RESULTS: Nineteen distinct phenotypes were observed among 400 isolates with complete DST results. Diversity was greatest in the Philippines (14 phenotypes), and least in South Africa (9 phenotypes). Nearly all phenotypes included multiple genotypes. All sites provided isolates resistant to injectables but susceptible to fluoroquinolones. Many patients were taking drugs to which their disease was resistant. DISCUSSION: Diverse phenotypes for XDR-TB-defining drugs, including resistance to fluoroquinolones and/or injectable drugs in RMP-susceptible isolates, indicate that RMP susceptibility does not ensure effectiveness of a standard four-drug regimen. Rapid, low-cost DST assays for first- and second-line drugs are thus needed.

Blood pressure change and survival after age 75.

Higher diastolic pressure predicted better survival in men 75 years or older in two prior analyses in the Rancho Bernardo population. Diastolic change was implicated as a possible explanation. We studied this by assessing survival according to blood pressure change in 795 men and women aged 75 years and older at the time of a second measurement taken an average of 11 years after the first, who were then followed for 5 years. Sex-specific analyses compared participants with a diastolic decrease of 5 mm Hg or greater and participants with a systolic decrease of 10 mm Hg or greater with those whose blood pressure levels did not change or increased. In men, after adjustment for baseline pressure, a decrease in diastolic pressure of 5 mm Hg or greater was associated with higher all-cause mortality (relative risk, 2.33; 95% confidence interval, 1.39 to 3.91) and cardiovascular mortality (3.13, 1.47 to 6.66). The mortality risk was strongest in men who took antihypertensive medication and had a fall in diastolic pressure (12.33, 2.73 to 55.72) compared with treated men whose pressures did not decrease. Among men with isolated systolic hypertension, those treated whose diastolic pressure remained stable had the best survival. A systolic fall in men and a decrease in either diastolic or systolic in women was not associated with poorer survival after adjustment for baseline pressure. We conclude that a fall in diastolic pressure of 5 mm Hg was associated with poor survival in men after age 75. This risk was strongest in men who took antihypertensive medication.

Incremental cost-effectiveness analysis: the optimal strategy depends on the strategy set.

Evaluating the incremental cost-effectiveness of a technology is critical to understanding the impact of its adoption. The purpose of this study was to evaluate, using a particular example, how the specific alternatives selected for a cost-effectiveness analysis may influence the results of the analysis. In this example, we analyzed the incremental cost-effectiveness of estriol screening for Down syndrome. Model assumptions of expected costs and effectiveness were based on previously published work involving four clinical strategies, including a "do nothing" (no screening) strategy. When the analysis started with all four strategies, two of the strategies could not be considered cost-effective because of extended dominance. However, when we eliminated the "do nothing" from the strategy set because of its clinical irrelevance, all three remaining strategies might be considered cost-effective from a policy perspective. We concluded that the incremental cost-effectiveness of clinical strategies could be strongly affected by the starting point for the analysis.

Effect of normal MSAFP screening on maternal age for genetic amniocentesis.

Routine maternal serum alpha-fetoprotein (MSAFP) screening for neural tube defects is considered by many to be standard obstetrical care, and recently many have encouraged this test to screen for Trisomy-21 (Down's syndrome). We questioned whether, after a normal MSAFP screen, the risk of Trisomy-21 decreases enough to warrant modifying the recommended age for genetic amniocentesis for Down's syndrome. A logistic regression was developed which, using reported values for sensitivity and specificity for MSAFP detection of Trisomy-21 and assuming a constant threshold risk in opting for amniocentesis, indicates that genetic amniocentesis for Trisomy-21 may be deferred in some women who have a normal MSAFP screening. Sensitivity analysis of varying thresholds for a normal MSAFP demonstrates that a 37 year old woman with a median MSAFP level has the same risk for Trisomy-21 as an unscreened women who is 4.5 years younger. An abnormal MSAFP is useful in screening for neural tube defects and possibly for Trisomy-21. A normal MSAFP may allow for delaying the potentially risky amniocentesis in otherwise low-risk pregnancies.

Prevention, policy, and paradox: what is the value of future health?

Cost-effectiveness is an integral part of health care policy, influencing both medical and administrative decisions. However, current research methodology for evaluating cost-effectiveness produces several paradoxes, perhaps because it incorrectly represents the general populations's view of future health states. Recent work introduces clinical and demographic factors to the traditional cost-benefit model for discounting health outcomes. It suggests a revised model that provides a more accurate basis for health policy decision-making. This revised model will likely improve the apparent cost-effectiveness of prevention programs, which are at a distinct disadvantage in present models. This article presents examples of current paradoxes resulting from the standard discounting methodology, findings on the variability of health outcomes discount rates in patients, and preliminary thoughts on developing a revised model for discounting future health outcomes. This revised model should present the value of health promotion programs more accurately.

Primary care and health promotion: a model for preventive medicine.

This paper examines the potential role of the primary care physician in health promotion, specifically the use of behavioral change technologies to modify risk behavior. The primary care physician's strategic position to help people modify risk behavior is discussed, and the available data on the health promotion attitudes and services of these physicians are reviewed. The principles and procedures of behavior modification underlie not only the model proposed for risk assessment and reduction, but are applied to the task of changing and maintaining physician behavior as well. Cost-effectiveness research and the role of reimbursement for primary care prevention services are discussed. Recommendations are made for future health policies, practices, training, and research that might encourage preventive behavioral services in primary care.

Justifying prenatal screening and genetic amniocentesis programs by cost-effectiveness analyses: a re-evaluation.

A strength of cost-effectiveness analysis is the presentation of all relevant clinical options, variables, and outcomes and the placement of values on the outcomes. Despite success in many fields of health policy, cost-effectiveness analysts have failed to provide a complete evaluation of prenatal screening and genetic amniocentesis programs. Specifically, all published cost-effectiveness analyses of these programs at best only partially acknowledge the potential life of the aborted fetus. These incomplete evaluations not only violate some basic principles of cost-effectiveness analysis, they also produce conclusions that may be misleading. Ultimately, society must answer two basic questions regarding the use of cost-effectiveness to justify prenatal screening programs: Is cost-effectiveness analysis an appropriate tool for the evaluation of these programs? If so, then what are the outcomes of interest? This paper first shows that the current literature does not present a complete evaluation of these programs. The ramifications of this incomplete evaluation are presented from several perspectives. Finally, given the problems associated with the use of cost-effectiveness analysis, the article suggests that cost-effectiveness analysis is not yet an appropriate tool to justify prenatal screening or genetic amniocentesis programs.

Routine neonatal circumcision: a cost-utility analysis.

A cost-utility analysis was performed to evaluate the relative importance of each of the various elements in the current circumcision debate. Elements used in the analysis included the cost of the procedure, the pain associated with the procedure, the risk of urinary tract infections, and the risk of penile cancer. The net, discounted lifetime dollar cost of routine circumcision is $102 per person, while the net, discounted lifetime health cost is 14 hours of healthy life. These results suggest that the financial and medical advantages and disadvantages of routine neonatal circumcision cancel each other and that factors other than cost or health outcomes must be used in decision making.

Population-based time preferences for future health outcomes.

CONTEXT: Time preference (how preference for an outcome changes depending on when the outcome occurs) affects clinical decisions, but little is known about determinants of time preferences in clinical settings. OBJECTIVES: To determine whether information about mean population time preferences for specific health states can be easily assessed, whether mean time preferences are constant across different diseases, and whether under certain circumstances substantial fractions of the patient population make choices that are consistent with a negative time preference. DESIGN: Self-administered survey. SETTING: Family physician waiting rooms in four states. PATIENTS: A convenience sample of 169 adults. INTERVENTION: Subjects were presented five clinical vignettes. For each vignette the subject chose between interventions maximizing a present and a future health outcome. The options for individual vignettes varied among the patients so that a distribution of responses was obtained across the population of patients. MAIN OUTCOME MEASURE: Logistic regression was used to estimate the mean preference for each vignette, which was translated into an implicit discount rate for this group of patients. RESULTS: There were marked differences in time preferences for future health outcomes based on the five vignettes, ranging from a negative to a high positive (116%) discount rate. CONCLUSIONS: The study provides empirical evidence that time preferences for future health outcomes may vary substantially among disease conditions. This is likely because the vignettes evoked different rationales for time preferences. Time preference is a critical element in patient decision making and cost-effectiveness research, and more work is necessary to improve our understanding of patient preferences for future health outcomes.

Evaluation of cost-effectiveness research: a survey of recent publications.

Because of interest in cost containment, a series of basic guidelines for performing cost-effectiveness research has evolved in the past decade. These guidelines advise that the perspective of the cost study be clarified, that all applicable costs, benefits, and health outcomes be included, and that discounting and sensitivity analyses be performed where appropriate. A survey of 47 recent cost-effectiveness publications selected via MEDLINE and manual searches confirms our hypothesis that many studies do not adhere to these guidelines. Since such short-comings can lead to misleading or ill-founded conclusions, attention must be paid to the principles of cost-effectiveness research to avoid making major, inappropriate health policy decisions.

Cost-effectiveness analysis.

Cost-effectiveness analysis is increasingly recognized as an important element for health policy formation. Family physicians will be affected by these analyses because they will influence the manner and type of care that physicians offer. The principles of cost-effectiveness research are straightforward and offer primary care clinicians the opportunity to become more involved in the policies that affect their practice.

A glossary of medical decision-making terms.

Many of the terms used in medical decision making are foreign to clinicians. This problem creates a barrier that can prevent physicians from acquiring these new clinical tools. This glossary contains definitions of the most common terms as well as examples of their usage by using Down syndrome as the illustrative condition.

A spectrum of health policy methods: lessons from the British.

Two vignettes about two health care systems (actually, one system and one non-system). Two different cancer screening programs. Two different approaches to developing a national health policy. This is not an issue of money; either approach could be used inside any budget. One approach looks at the entire health care delivery system, trying to maximize gain while assuring appropriate care is provided. The other approach tries to get votes. Is there any doubt which is the better method?

What to do until the POEMs arrive. An endothelial example.

There is a growing trend toward evidence-based medicine, in which patient-oriented data are valued more highly than disease-oriented evidence (DOEs). In the vernacular of evidence-based medicine, the old DOEs are slowly being replaced by POEMs (patient-oriented evidence that matters). Unfortunately, POEMs do not yet exist to meet every family-practice need. When there are no POEMs to determine an appropriate therapeutic choice, another decision-making method must be used. This method includes liberal use of DOEs combined with thoughtful use of causal pathways to provide preliminary direction. This article applies that method to an example from the growing basic science surrounding endothelial functioning.

Principles of cost-effectiveness research.

Recent advances in the theoretical concepts behind cost-effectiveness evaluation have led to a marked improvement of the techniques used in cost-effectiveness research. Any effective program will have not only dollar costs and dollar benefits but also nondollar costs and benefits. Cost studies evaluate the relative weights of these costs and benefits to determine whether the program's value is worth the expense. Key elements to consider include direct costs of the program, costs of future workup of treatment, costs of evaluating and treating complications resulting from the program, future medical costs averted, discounting of future costs and health effects, and a sensitivity analysis. Despite the recent theoretical advances, cost-effectiveness research raises multiple controversies, including some key ethical issues.

Patient preferences for colorectal cancer screening.

BACKGROUND: New guidelines include several options for colorectal cancer screening. The goal of this study was to assess patient preferences for five approaches: no screening, fecal occult blood testing (FOBT), flexible sigmoidoscopy, barium enema, and colonoscopy. METHODS: Patients from offices of primary care providers listened to a scripted oral presentation while viewing a table describing five screening methods and their outcomes. Immediately following the presentation, the subjects completed a questionnaire assessing their most preferred screening option and their likelihood of undergoing each option. RESULTS: One hundred subjects aged 50 to 75 years participated. The average age was 64 years; 54 of the subjects were women, and 87 were white. Ninety-six percent of patients preferred to be screened by some method. When asked which test they would choose as their primary method of screening, 38% preferred colonoscopy, 31% preferred FOBT, 14% preferred barium enema, and 13% preferred flexible sigmoidoscopy. When asked how likely they would be to undergo each procedure on a 5-point scale, patients rated FOBT highest with an average score of 4.4, followed by colonoscopy (3.4), barium enema (3.4), flexible sigmoidoscopy (3.4), and no screening (1.5). Acceptance rates for these tests when recommended by their physician were 96% (FOBT), 82% (flexible sigmoidoscopy), 92% (barium enema), and 86% (colonoscopy). CONCLUSIONS: Patients indicated a strong preference for colorectal cancer screening, but they did not indicate a dominant preference for any single screening test. Physicians need to take into account individual patient preferences when making recommendations regarding colorectal cancer screening.

Does Beano prevent gas? A double-blind crossover study of oral alpha-galactosidase to treat dietary oligosaccharide intolerance.

BACKGROUND: Beano, an over-the-counter oral solution of alpha-galactosidase, is used to prevent flatus and other gastrointestinal symptoms resulting from a high-fiber diet. The efficacy of this product, however, has not yet been adequately evaluated. METHODS: Nineteen subjects were randomized into two groups and fed test meals of meatless chili. At the first test meal, group 1 received eight drops of alpha-galactosidase solution and group 2 received eight drops of placebo. After the meal, subjects were asked to keep a careful record of gastrointestinal symptoms, including occurrences of intestinal gas passage, for the next 6 hours. One week later, an identical test meal was served to each study subject and the solutions were reversed. Again subjects recorded their symptoms for the next 6 hours. Data were analyzed by means of paired t tests. RESULTS: The number of flatulence events per hour was significantly less in the group treated with alpha-galactosidase than placebo over the 6-hour follow-up period (F = 2.87, P = .016). When the two groups were compared at each follow-up interval, this difference was statistically significant only for the 5th hour after ingesting the test meal (t = 2.19, P = .04). No differences between the two groups were found in the extent of bloating or pain following the meal. CONCLUSIONS: Oral alpha-galactosidase solution is efficacious, at least in some patients, for the prophylaxis of gastrointestinal intolerance of oligosaccharides.