Folic Acid Supplementation to Prevent Neural Tube Defects: US Preventive Services Task Force Reaffirmation Recommendation Statement.

Importance: Neural tube defects are among the most common congenital malformations in the US, with an estimated 3000 pregnancies affected each year. Many of these neural tube defects are caused by low folate levels in the body. Objective: The US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update on the benefits and harms of folic acid supplementation. Population: Persons who are planning to or could become pregnant. Evidence Assessment: The USPSTF concludes that, for persons who are planning to or could become pregnant, there is high certainty that folic acid supplementation has a substantial net benefit to prevent neural tube defects in their offspring. Recommendation: The USPSTF recommends that all persons planning to or who could become pregnant take a daily supplement containing 0.4 to 0.8 mg (400 to 800 µg) of folic acid. (A recommendation).

Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and Cancer: US Preventive Services Task Force Recommendation Statement.

Importance: According to National Health and Nutrition Examination Survey data, 52% of surveyed US adults reported using at least 1 dietary supplement in the prior 30 days and 31% reported using a multivitamin-mineral supplement. The most commonly cited reason for using supplements is for overall health and wellness and to fill nutrient gaps in the diet. Cardiovascular disease and cancer are the 2 leading causes of death and combined account for approximately half of all deaths in the US annually. Inflammation and oxidative stress have been shown to have a role in both cardiovascular disease and cancer, and dietary supplements may have anti-inflammatory and antioxidative effects. Objective: To update its 2014 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on the efficacy of supplementation with single nutrients, functionally related nutrient pairs, or multivitamins for reducing the risk of cardiovascular disease, cancer, and mortality in the general adult population, as well as the harms of supplementation. Population: Community-dwelling, nonpregnant adults. Evidence Assessment: The USPSTF concludes with moderate certainty that the harms of beta carotene supplementation outweigh the benefits for the prevention of cardiovascular disease or cancer. The USPSTF also concludes with moderate certainty that there is no net benefit of supplementation with vitamin E for the prevention of cardiovascular disease or cancer. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of supplementation with multivitamins for the prevention of cardiovascular disease or cancer. Evidence is lacking and the balance of benefits and harms cannot be determined. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of supplementation with single or paired nutrients (other than beta carotene and vitamin E) for the prevention of cardiovascular disease or cancer. Evidence is lacking and the balance of benefits and harms cannot be determined. Recommendation: The USPSTF recommends against the use of beta carotene or vitamin E supplements for the prevention of cardiovascular disease or cancer. (D recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the use of multivitamin supplements for the prevention of cardiovascular disease or cancer. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the use of single- or paired-nutrient supplements (other than beta carotene and vitamin E) for the prevention of cardiovascular disease or cancer. (I statement).

Advance Care Planning in Older Adults with CKD: Patient, Care Partner, and Clinician Perspectives.

BACKGROUND: Older patients with advanced CKD are at high risk for serious complications and death, yet few discuss advance care planning (ACP) with their kidney clinicians. Examining barriers and facilitators to ACP among such patients might help identify patient-centered opportunities for improvement. METHODS: In semistructured interviews in March through August 2019 with purposively sampled patients (aged ≥70 years, CKD stages 4-5, nondialysis), care partners, and clinicians at clinics in across the United States, participants described discussions, factors contributing to ACP completion or avoidance, and perceived value of ACP. We used thematic analysis to analyze data. RESULTS: We conducted 68 semistructured interviews with 23 patients, 19 care partners, and 26 clinicians. Only seven of 26 (27%) clinicians routinely discussed ACP. About half of the patients had documented ACP, mostly outside the health care system. We found divergent ACP definitions and perspectives; kidney clinicians largely defined ACP as completion of formal documentation, whereas patients viewed it more holistically, wanting discussions about goals, prognosis, and disease trajectory. Clinicians avoided ACP with patients from minority groups, perceiving cultural or religious barriers. Four themes and subthemes informing variation in decisions to discuss ACP and approaches emerged: (1) role ambiguity and responsibility for ACP, (2) questioning the value of ACP, (3) confronting institutional barriers (time, training, reimbursement, and the electronic medical record, EMR), and (4) consequences of avoiding ACP (disparities in ACP access and overconfidence that patients' wishes are known). CONCLUSIONS: Patients, care partners, and clinicians hold discordant views about the responsibility for discussing ACP and the scope for it. This presents critical barriers to the process, leaving ACP insufficiently discussed with older adults with advanced CKD.

Interventions to Prevent Perinatal Depression: US Preventive Services Task Force Recommendation Statement.

Importance: Perinatal depression, which is the occurrence of a depressive disorder during pregnancy or following childbirth, affects as many as 1 in 7 women and is one of the most common complications of pregnancy and the postpartum period. It is well established that perinatal depression can result in adverse short- and long-term effects on both the woman and child. Objective: To issue a new US Preventive Services Task Force (USPSTF) recommendation on interventions to prevent perinatal depression. Evidence Review: The USPSTF reviewed the evidence on the benefits and harms of preventive interventions for perinatal depression in pregnant or postpartum women or their children. The USPSTF reviewed contextual information on the accuracy of tools used to identify women at increased risk of perinatal depression and the most effective timing for preventive interventions. Interventions reviewed included counseling, health system interventions, physical activity, education, supportive interventions, and other behavioral interventions, such as infant sleep training and expressive writing. Pharmacological approaches included the use of nortriptyline, sertraline, and omega-3 fatty acids. Findings: The USPSTF found convincing evidence that counseling interventions, such as cognitive behavioral therapy and interpersonal therapy, are effective in preventing perinatal depression. Women with a history of depression, current depressive symptoms, or certain socioeconomic risk factors (eg, low income or young or single parenthood) would benefit from counseling interventions and could be considered at increased risk. The USPSTF found adequate evidence to bound the potential harms of counseling interventions as no greater than small, based on the nature of the intervention and the low likelihood of serious harms. The USPSTF found inadequate evidence to assess the benefits and harms of other noncounseling interventions. The USPSTF concludes with moderate certainty that providing or referring pregnant or postpartum women at increased risk to counseling interventions has a moderate net benefit in preventing perinatal depression. Conclusions and Recommendation: The USPSTF recommends that clinicians provide or refer pregnant and postpartum persons who are at increased risk of perinatal depression to counseling interventions. (B recommendation).

Effects of Tai Chi versus Physical Therapy on Mindfulness in Knee Osteoarthritis.

Tai Chi mind-body exercise is widely believed to improve mindfulness through incorporating meditative states into physical movements. A growing number of studies indicate that Tai Chi may improve health in knee osteoarthritis (OA), a chronic pain disease and a primary cause of global disability. However, little is known about the contribution of mindfulness to treatment effect of Tai Chi practice. Therefore, our purpose was to investigate the effect of Tai Chi mind-body practice compared to physical therapy (PT) on mindfulness in knee OA. Adults with radiographic-confirmed, symptomatic knee OA were randomized to either 12 weeks (twice weekly) of Tai Chi or PT. Participants completed the Five Facet Mindfulness Questionnaire (FFMQ) before and after intervention along with commonly-used patient-reported outcomes for pain, physical function, and other health-related outcomes. Among 86 participants (74% female, 48% white, mean age 60 years, 85% at least college educated), mean total FFMQ was 142±17. Despite substantial improvements in pain, function, and other health-related outcomes, each treatment group's total FFMQ did not significantly change from baseline (Tai Chi= 0.76, 95% CI: -2.93, 4.45; PT= 1.80, 95% CI: -2.33, 5.93). The difference in total FFMQ between Tai Chi and PT was not significant (-1.04 points, 95% CI: -6.48, 4.39). Mindfulness did not change after Tai Chi or PT intervention in knee OA, which suggests that Tai Chi may not improve health in knee OA through cultivating mindfulness. Further study is needed to identify underlying mechanisms of effective mind-body interventions among people with knee OA.

Mindfulness Is Associated With Treatment Response From Nonpharmacologic Exercise Interventions in Knee Osteoarthritis.

OBJECTIVE: To examine the association between baseline mindfulness and response from exercise interventions in knee osteoarthritis (OA). DESIGN: Cohort study; responder analysis of a clinical trial subset. SETTING: Urban tertiary care academic hospital. PARTICIPANTS: Participants with symptomatic, radiographic knee OA (N=86; mean age, 60y; 74% female; 48% white). INTERVENTIONS: Twelve weeks (twice per week) of Tai Chi or physical therapy exercise. MAIN OUTCOME MEASURES: Treatment response was defined using Osteoarthritis Research Society International criteria indicating meaningful improvements in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, WOMAC function, or Patient Global Assessment scores. At baseline, participants completed the Five Facet Mindfulness Questionnaire (mean total score, 142±17) and were grouped into 3 categories of total mindfulness: higher, medium, or lower. Relative risk (RR) ratios were used to compare treatment response across groups. RESULTS: Participants with higher total mindfulness were 38% (95% confidence interval [CI], 1.05-1.83) more likely to meet responder criteria than those with lower mindfulness. We found no significant difference between medium and lower mindfulness groups (RR=1.0; 95% CI, 0.69-1.44). Among the 5 mindfulness facets, medium acting-with-awareness was 46% (95% CI, 1.09-1.96) more likely to respond than lower acting-with-awareness, and higher acting-with-awareness was 34% more likely to respond, but this did not reach significance (95% CI, 0.97-1.86). CONCLUSIONS: In this study, higher mindfulness, primarily driven by its acting-with-awareness facet, was significantly associated with a greater likelihood of response to nonpharmacologic exercise interventions in knee OA. This suggests that mindfulness-cultivating interventions may increase the likelihood of response from exercise.

Comparative Effectiveness of Tai Chi Versus Physical Therapy for Knee Osteoarthritis: A Randomized Trial.

BACKGROUND: Few remedies effectively treat long-term pain and disability from knee osteoarthritis. Studies suggest that Tai Chi alleviates symptoms, but no trials have directly compared Tai Chi with standard therapies for osteoarthritis. OBJECTIVE: To compare Tai Chi with standard physical therapy for patients with knee osteoarthritis. DESIGN: Randomized, 52-week, single-blind comparative effectiveness trial. (ClinicalTrials.gov: NCT01258985). SETTING: An urban tertiary care academic hospital. PATIENTS: 204 participants with symptomatic knee osteoarthritis (mean age, 60 years; 70% women; 53% white). INTERVENTION: Tai Chi (2 times per week for 12 weeks) or standard physical therapy (2 times per week for 6 weeks, followed by 6 weeks of monitored home exercise). MEASUREMENTS: The primary outcome was Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 12 weeks. Secondary outcomes included physical function, depression, medication use, and quality of life. RESULTS: At 12 weeks, the WOMAC score was substantially reduced in both groups (Tai Chi, 167 points [95% CI, 145 to 190 points]; physical therapy, 143 points [CI, 119 to 167 points]). The between-group difference was not significant (24 points [CI, -10 to 58 points]). Both groups also showed similar clinically significant improvement in most secondary outcomes, and the benefits were maintained up to 52 weeks. Of note, the Tai Chi group had significantly greater improvements in depression and the physical component of quality of life. The benefit of Tai Chi was consistent across instructors. No serious adverse events occurred. LIMITATION: Patients were aware of their treatment group assignment, and the generalizability of the findings to other settings remains undetermined. CONCLUSION: Tai Chi produced beneficial effects similar to those of a standard course of physical therapy in the treatment of knee osteoarthritis. PRIMARY FUNDING SOURCE: National Center for Complementary and Integrative Health of the National Institutes of Health.

Comparative effectiveness of pharmacologic interventions for knee osteoarthritis: a systematic review and network meta-analysis.

BACKGROUND: The relative efficacy of available treatments of knee osteoarthritis (OA) must be determined for rational treatment algorithms to be formulated. PURPOSE: To examine the efficacy of treatments of primary knee OA using a network meta-analysis design, which estimates relative effects of all treatments against each other. DATA SOURCES: MEDLINE, EMBASE, Web of Science, Google Scholar, Cochrane Central Register of Controlled Trials from inception through 15 August 2014, and unpublished data. STUDY SELECTION: Randomized trials of adults with knee OA comparing 2 or more of the following: acetaminophen, diclofenac, ibuprofen, naproxen, celecoxib, intra-articular (IA) corticosteroids, IA hyaluronic acid, oral placebo, and IA placebo. DATA EXTRACTION: Two reviewers independently abstracted study data and assessed study quality. Standardized mean differences were calculated for pain, function, and stiffness at 3-month follow-up. DATA SYNTHESIS: Network meta-analysis was performed using a Bayesian random-effects model; 137 studies comprising 33,243 participants were identified. For pain, all interventions significantly outperformed oral placebo, with effect sizes from 0.63 (95% credible interval [CrI], 0.39 to 0.88) for the most efficacious treatment (hyaluronic acid) to 0.18 (CrI, 0.04 to 0.33) for the least efficacious treatment (acetaminophen). For function, all interventions except IA corticosteroids were significantly superior to oral placebo. For stiffness, most of the treatments did not significantly differ from one another. LIMITATION: Lack of long-term data, inadequate reporting of safety data, possible publication bias, and few head-to-head comparisons. CONCLUSION: This method allowed comparison of common treatments of knee OA according to their relative efficacy. Intra-articular treatments were superior to nonsteroidal anti-inflammatory drugs, possibly because of the integrated IA placebo effect. Small but robust differences were observed between active treatments. All treatments except acetaminophen showed clinically significant improvement from baseline pain. This information, along with the safety profiles and relative costs of included treatments, will be helpful for individualized patient care decisions. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Assessing the comparative effectiveness of Tai Chi versus physical therapy for knee osteoarthritis: design and rationale for a randomized trial.

BACKGROUND: Knee osteoarthritis (OA) causes pain and long-term disability with annual healthcare costs exceeding $185 billion in the United States. Few medical remedies effectively influence the course of the disease. Finding effective treatments to maintain function and quality of life in patients with knee OA is one of the national priorities identified by the Institute of Medicine. We are currently conducting the first comparative effectiveness and cost-effectiveness randomized trial of Tai Chi versus a physical-therapy regimen in a sample of patients with symptomatic and radiographically confirmed knee OA. This article describes the design and conduct of this trial. METHODS/DESIGN: A single-center, 52-week, comparative effectiveness randomized controlled trial of Tai Chi versus a standardized physical-therapy regimen is being conducted at an urban tertiary medical center in Boston, Massachusetts. The study population consists of adults ≥ 40 years of age with symptomatic and radiographic knee OA (American College of Rheumatology criteria). Participants are randomly allocated to either 12 weeks of Tai Chi (2x/week) or Physical Therapy (2x/week for 6 weeks, followed by 6 weeks of rigorously monitored home exercise). The primary outcome measure is pain (Western Ontario and McMaster Universities WOMAC) subscale at 12 weeks. Secondary outcomes include WOMAC stkiffness and function domain scores, lower extremity strength and power, functional balance, physical performance tests, psychological and psychosocial functioning, durability effects, health related quality of life, and healthcare utilization at 12, 24 and 52 weeks. DISCUSSION: This study will be the first randomized comparative-effectiveness and cost-effectiveness trial of Tai Chi versus Physical Therapy in a large symptomatic knee OA population with long-term follow up. We present here a robust and well-designed randomized comparative-effectiveness trial that also explores multiple outcomes to elucidate the potential mechanisms of mind-body effect for a major disabling disease with substantial health burdens and economic costs. Results of this study are expected to have important public health implications for the large and growing population with knee OA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01258985.

Economic analysis of nutrition interventions for chronic disease prevention: methods, research, and policy.

Increased interest in the potential societal benefit of incorporating health economics as a part of clinical translational science, particularly nutrition interventions, led the Office of Dietary Supplements at the National Institutes of Health to sponsor a conference to address key questions about the economic analysis of nutrition interventions to enhance communication among health economic methodologists, researchers, reimbursement policy makers, and regulators. Issues discussed included the state of the science, such as what health economic methods are currently used to judge the burden of illness, interventions, or healthcare policies, and what new research methodologies are available or needed to address knowledge and methodological gaps or barriers. Research applications included existing evidence-based health economic research activities in nutrition that are ongoing or planned at federal agencies. International and US regulatory, policy, and clinical practice perspectives included a discussion of how research results can help regulators and policy makers within government make nutrition policy decisions, and how economics affects clinical guideline development.

Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials.

BACKGROUND: Antifracture efficacy with supplemental vitamin D has been questioned by recent trials. METHODS: We performed a meta-analysis on the efficacy of oral supplemental vitamin D in preventing nonvertebral and hip fractures among older individuals (> or =65 years). We included 12 double-blind randomized controlled trials (RCTs) for nonvertebral fractures (n = 42 279) and 8 RCTs for hip fractures (n = 40 886) comparing oral vitamin D, with or without calcium, with calcium or placebo. To incorporate adherence to treatment, we multiplied the dose by the percentage of adherence to estimate the mean received dose (dose x adherence) for each trial. RESULTS: The pooled relative risk (RR) was 0.86 (95% confidence interval [CI], 0.77-0.96) for prevention of nonvertebral fractures and 0.91 (95% CI, 0.78-1.05) for the prevention of hip fractures, but with significant heterogeneity for both end points. Including all trials, antifracture efficacy increased significantly with a higher dose and higher achieved blood 25-hydroxyvitamin D levels for both end points. Consistently, pooling trials with a higher received dose of more than 400 IU/d resolved heterogeneity. For the higher dose, the pooled RR was 0.80 (95% CI, 0.72-0.89; n = 33 265 subjects from 9 trials) for nonvertebral fractures and 0.82 (95% CI, 0.69-0.97; n = 31 872 subjects from 5 trials) for hip fractures. The higher dose reduced nonvertebral fractures in community-dwelling individuals (-29%) and institutionalized older individuals (-15%), and its effect was independent of additional calcium supplementation. CONCLUSION: Nonvertebral fracture prevention with vitamin D is dose dependent, and a higher dose should reduce fractures by at least 20% for individuals aged 65 years or older.

Calcium intake and hip fracture risk in men and women: a meta-analysis of prospective cohort studies and randomized controlled trials.

BACKGROUND: The role of total calcium intake in the prevention of hip fracture risk has not been well established. OBJECTIVE: The objective of the study was to assess the relation of calcium intake to the risk of hip fracture on the basis of meta-analyses of cohort studies and clinical trials. RESULTS: In women (7 prospective cohort studies, 170,991 women, 2,954 hip fractures), there was no association between total calcium intake and hip fracture risk [pooled risk ratio (RR) per 300 mg total Ca/d = 1.01; 95% CI: 0.97, 1.05]. In men (5 prospective cohort studies, 68,606 men, 214 hip fractures), the pooled RR per 300 mg total Ca/d was 0.92 (95% CI: 0.82, 1.03). On the basis of 5 clinical trials (n = 5666 women, primarily postmenopausal, plus 1074 men) with 814 nonvertebral fractures, the pooled RR for nonvertebral fractures between calcium supplementation (800-1600 mg/d) and placebo was 0.92 (95% CI: 0.81, 1.05). On the basis of 4 clinical trials with separate results for hip fracture (6,504 subjects with 139 hip fractures), the pooled RR between calcium and placebo was 1.64 (95% CI:1.02, 2.64). Sensitivity analyses including 2 additional small trials with <100 participants or per-protocol results did not substantially alter results. CONCLUSIONS: Pooled results from prospective cohort studies suggest that calcium intake is not significantly associated with hip fracture risk in women or men. Pooled results from randomized controlled trials show no reduction in hip fracture risk with calcium supplementation, and an increased risk is possible. For any nonvertebral fractures, there was a neutral effect in the randomized trials.

Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials.

CONTEXT: The role and dose of oral vitamin D supplementation in nonvertebral fracture prevention have not been well established. OBJECTIVE: To estimate the effectiveness of vitamin D supplementation in preventing hip and nonvertebral fractures in older persons. DATA SOURCES: A systematic review of English and non-English articles using MEDLINE and the Cochrane Controlled Trials Register (1960-2005), and EMBASE (1991-2005). Additional studies were identified by contacting clinical experts and searching bibliographies and abstracts presented at the American Society for Bone and Mineral Research (1995-2004). Search terms included randomized controlled trial (RCT), controlled clinical trial, random allocation, double-blind method, cholecalciferol, ergocalciferol, 25-hydroxyvitamin D, fractures, humans, elderly, falls, and bone density. STUDY SELECTION: Only double-blind RCTs of oral vitamin D supplementation (cholecalciferol, ergocalciferol) with or without calcium supplementation vs calcium supplementation or placebo in older persons (> or =60 years) that examined hip or nonvertebral fractures were included. DATA EXTRACTION: Independent extraction of articles by 2 authors using predefined data fields, including study quality indicators. DATA SYNTHESIS: All pooled analyses were based on random-effects models. Five RCTs for hip fracture (n = 9294) and 7 RCTs for nonvertebral fracture risk (n = 9820) met our inclusion criteria. All trials used cholecalciferol. Heterogeneity among studies for both hip and nonvertebral fracture prevention was observed, which disappeared after pooling RCTs with low-dose (400 IU/d) and higher-dose vitamin D (700-800 IU/d), separately. A vitamin D dose of 700 to 800 IU/d reduced the relative risk (RR) of hip fracture by 26% (3 RCTs with 5572 persons; pooled RR, 0.74; 95% confidence interval [CI], 0.61-0.88) and any nonvertebral fracture by 23% (5 RCTs with 6098 persons; pooled RR, 0.77; 95% CI, 0.68-0.87) vs calcium or placebo. No significant benefit was observed for RCTs with 400 IU/d vitamin D (2 RCTs with 3722 persons; pooled RR for hip fracture, 1.15; 95% CI, 0.88-1.50; and pooled RR for any nonvertebral fracture, 1.03; 95% CI, 0.86-1.24). CONCLUSIONS: Oral vitamin D supplementation between 700 to 800 IU/d appears to reduce the risk of hip and any nonvertebral fractures in ambulatory or institutionalized elderly persons. An oral vitamin D dose of 400 IU/d is not sufficient for fracture prevention.

Effect of Vitamin D on falls: a meta-analysis.

CONTEXT: Falls among elderly individuals occur frequently, increase with age, and lead to substantial morbidity and mortality. The role of vitamin D in preventing falls among elderly people has not been well established. OBJECTIVE: To assess the effectiveness of vitamin D in preventing an older person from falling. DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Register from January 1960 to February 2004, EMBASE from January 1991 to February 2004, clinical experts, bibliographies, and abstracts. Search terms included trial terms: randomized-controlled trial or controlled-clinical trial or random-allocation or double-blind method, or single-blind method or uncontrolled-trials with vitamin D terms: cholecalciferol or hydroxycholecalciferols or calcifediol or dihydroxycholecalciferols or calcitriol or vitamin D/aa[analogs & derivates] or ergocalciferol or vitamin D/bl[blood]; and with accidental falls or falls, and humans. STUDY SELECTION: We included only double-blind randomized, controlled trials (RCTs) of vitamin D in elderly populations (mean age, 60 years) that examined falls resulting from low trauma for which the method of fall ascertainment and definition of falls were defined explicitly. Studies including patients in unstable health states were excluded. Five of 38 identified studies were included in the primary analysis and 5 other studies were included in a sensitivity analysis. DATA EXTRACTION: Independent extraction by 3 authors using predefined data fields including study quality indicators. DATA SYNTHESIS: Based on 5 RCTs involving 1237 participants, vitamin D reduced the corrected odds ratio (OR) of falling by 22% (corrected OR, 0.78; 95% confidence interval [CI], 0.64-0.92) compared with patients receiving calcium or placebo. From the pooled risk difference, the number needed to treat (NNT) was 15 (95% CI, 8-53), or equivalently 15 patients would need to be treated with vitamin D to prevent 1 person from falling. The inclusion of 5 additional studies, involving 10 001 participants, in a sensitivity analysis resulted in a smaller but still significant effect size (corrected RR, 0.87; 95% CI, 0.80-0.96). Subgroup analyses suggested that the effect size was independent of calcium supplementation, type of vitamin D, duration of therapy, and sex, but reduced sample sizes made the results statistically nonsignificant for calcium supplementation, cholecalciferol, and among men. CONCLUSIONS: Vitamin D supplementation appears to reduce the risk of falls among ambulatory or institutionalized older individuals with stable health by more than 20%. Further studies examining the effect of alternative types of vitamin D and their doses, the role of calcium supplementation, and effects in men should be considered.

Is it influenza or anthrax? A decision analytic approach to the treatment of patients with influenza-like illnesses.

STUDY OBJECTIVE: We analyze the risks and benefits of alternative treatment strategies for non-septic-appearing febrile patients with influenza-like illnesses and possible exposure to anthrax. METHODS: We used a decision analytic model to evaluate 6 testing and treatment strategies in an emergency department. Patients were non-septic-appearing and had influenza-like illnesses but low likelihood of exposure to anthrax. The following interventions were used: (1) no empiric antibiotics; (2) blood culture and treatment only if the result was positive; (3) rapid testing for influenza and, for those who tested negative, treatment with 60 days of ciprofloxacin; (4) a two-test strategy in which all patients were first tested for influenza; those who tested negative had a blood culture test and were treated empirically with ciprofloxacin for 3 days while waiting for blood culture results; (5) culture test for all patients and treatment with ciprofloxacin for up to 3 days while waiting for blood culture results; and (6) treatment of all patients with ciprofloxacin empirically for 60 days. Main outcome measures were deaths, complications from anthrax, adverse events from ciprofloxacin, and ciprofloxacin patient-days. RESULTS: For nonzero probabilities of anthrax, patient mortality was always lowest in the strategies in which all patients were treated empirically for anthrax either for 60 days or for 3 days pending blood culture results. These strategies, however, were associated with more morbidity (more ciprofloxacin patient-days and more antibiotic adverse events) than were strategies without empiric treatment. The numbers of adverse events and antibiotic patient-days were reduced substantially with the two-test strategy, in which patients with influenza were identified early and not treated. In general, for probabilities of anthrax equaling or exceeding 2%, treating all patients empirically for 60 days was best, but for probabilities between 0.1% and 2%, the sensitivity of blood culture for anthrax determined the optimal strategy: when the sensitivity exceeded 95%, a short course of empiric ciprofloxacin until blood culture results became available was best, but for sensitivities below 95%, more aggressive empiric antibiotics use was warranted. The proportion of patients with influenza in the community affected the choice of strategy, so that seasonal variation exists. CONCLUSION: During influenza season, our findings support rapid testing for influenza, followed by empiric treatment for anthrax pending blood culture results for those who test negative for influenza. Our results help to highlight the importance of developing rapid and sensitive tests for anthrax and of developing improved surveillance and methods to calculate the previous probability of attacks.

Intermittent claudication: cost-effectiveness of revascularization versus exercise therapy.

PURPOSE: To compare the costs, effectiveness, and cost-effectiveness of alternative treatment strategies for intermittent claudication. MATERIALS AND METHODS: By combining data from the literature and original patient data, a Markov decision model was developed to evaluate the societal cost-effectiveness. Patients presented with previously untreated intermittent claudication, and treatment options were exercise, percutaneous transluminal angioplasty (with stent placement, if necessary), and/or bypass surgery. Treatment strategies were defined as the initial therapy in combination with secondary treatment options should the initial therapy fail. The main outcome measures were quality-adjusted life days, expected lifetime costs (in 1995 U.S. dollars), and incremental cost-effectiveness ratios. RESULTS: Compared with an exercise program, revascularization (either angioplasty or bypass surgery) improved effectiveness by 33-61 quality-adjusted life days among patients with no history of coronary artery disease. The incremental cost-effectiveness ratio was $38,000 per quality-adjusted life year gained when angioplasty was performed whenever feasible, as compared with exercise alone, and $311,000 with additional bypass surgery. The incremental cost-effectiveness ratios were sensitive to age, history of coronary artery disease, estimated health values for no or mild claudication versus severe claudication, and revascularization costs. CONCLUSION: The results suggest that, on average, the expected gain in effectiveness achieved with bypass surgery for intermittent claudication is small compared with the costs. Angioplasty performed whenever feasible was more effective than was exercise alone, and the cost-effectiveness ratio was within the generally accepted range.