Biomedical subjects

Dena M Bravata

Publications and source records attributed to Dena M Bravata.

13 recordsLinked to original sources

PubMed2007

Systematic review: the safety and efficacy of growth hormone in the healthy elderly.

BACKGROUND: Human growth hormone (GH) is widely used as an antiaging therapy, although its use for this purpose has not been approved by the U.S. Food and Drug Administration and its distribution as an antiaging agent is illegal in the United States. PURPOSE: To evaluate the safety and efficacy of GH therapy in the healthy elderly. DATA SOURCES: The authors searched MEDLINE and EMBASE databases for English-language studies published through 21 November 2005 by using such terms as growth hormone and aging. STUDY SELECTION: The authors included randomized, controlled trials that compared GH therapy with no GH therapy or GH and lifestyle interventions (exercise with or without diet) with lifestyle interventions alone. Included trials provided GH for 2 weeks or more to community-dwelling participants with a mean age of 50 years or more and a body mass index of 35 kg/m2 or less. The authors excluded studies that evaluated GH as treatment for a specific illness. DATA EXTRACTION: Two authors independently reviewed articles and abstracted data. DATA SYNTHESIS: 31 articles describing 18 unique study populations met the inclusion criteria. A total of 220 participants who received GH (107 person-years) completed their respective studies. Study participants were elderly (mean age, 69 years [SD, 6]) and overweight (mean body mass index, 28 kg/m2 [SD, 2]). Initial daily GH dose (mean, 14 microg per kg of body weight [SD, 7]) and treatment duration (mean, 27 weeks [SD, 16]) varied. In participants treated with GH compared with those not treated with GH, overall fat mass decreased (change in fat mass, -2.1 kg [95% CI, -2.8 to -1.35] and overall lean body mass increased (change in lean body mass, 2.1 kg [CI, 1.3 to 2.9]) (P < 0.001), and their weight did not change significantly (change in weight, 0.1 kg [CI, -0.7 to 0.8]; P = 0.87). Total cholesterol levels decreased (change in cholesterol, -0.29 mmol/L [-11.21 mg/dL]; P = 0.006), although not significantly after adjustment for body composition changes. Other outcomes, including bone density and other serum lipid levels, did not change. Persons treated with GH were significantly more likely to experience soft tissue edema, arthralgias, carpal tunnel syndrome, and gynecomastia and were somewhat more likely to experience the onset of diabetes mellitus and impaired fasting glucose. LIMITATIONS: Some important outcomes were infrequently or heterogeneously measured and could not be synthesized. Most included studies had small sample sizes. CONCLUSIONS: The literature published on randomized, controlled trials evaluating GH therapy in the healthy elderly is limited but suggests that it is associated with small changes in body composition and increased rates of adverse events. On the basis of this evidence, GH cannot be recommended as an antiaging therapy.

Aged↗

PubMed2006

Meta-analysis: accuracy of quantitative ultrasound for identifying patients with osteoporosis.

BACKGROUND: There is increased interest in quantitative ultrasound for osteoporosis screening because it predicts fracture risk, is portable, and is relatively inexpensive. However, there is no consensus regarding its accuracy for identifying patients with osteoporosis. PURPOSE: To determine the sensitivity and specificity of calcaneal quantitative ultrasound for identifying patients who meet the World Health Organization's diagnostic criteria for osteoporosis. Dual-energy x-ray absorptiometry (DXA) was used as the reference standard. DATA SOURCES: MEDLINE (1966 to October 2005), EMBASE (1993 to May 2004), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (1952 to March 2004), and the Science Citation Index (1945 to April 2004). STUDY SELECTION: English-language articles that evaluated the sensitivity and specificity of calcaneal quantitative ultrasound for identifying adults with DXA T-scores of -2.5 or less at the hip or spine. DATA EXTRACTION: Two authors independently reviewed articles and abstracted data. DATA SYNTHESIS: The authors identified 1908 potentially relevant articles, of which 25 met the inclusion criteria, and calculated the sensitivity and specificity of quantitative ultrasound over a range of thresholds. For the quantitative ultrasound index parameter T-score cutoff threshold of -1, sensitivity was 79% (95% CI, 69% to 86%) and specificity was 58% (CI, 44% to 70%) for identifying individuals with DXA T-scores of -2.5 or less at the hip or spine. For a T-score threshold of 0, sensitivity improved to 93% (CI, 87% to 97%) but specificity decreased to 24% (CI, 10% to 47%). At a pretest probability of 22% (for example, a 65-year-old white woman at average risk), the post-test probability of DXA-determined osteoporosis was 34% (CI, 26% to 41%) after a positive result and 10% (CI, 5% to 12%) after a negative result when using a T-score cutoff threshold of -1. Analysis of other quantitative ultrasound parameters (for example, broadband ultrasound attenuation) revealed similar estimates of accuracy. LIMITATIONS: The relatively small number of included studies limited the authors' ability to evaluate the effects of heterogeneous study characteristics on the diagnostic accuracy of quantitative ultrasound. CONCLUSIONS: The currently available literature suggests that results of calcaneal quantitative ultrasound at commonly used cutoff thresholds do not definitively exclude or confirm DXA-determined osteoporosis. Additional research is needed before use of this test can be recommended in evidence-based screening programs for osteoporosis.

Absorptiometry, Photon↗

PubMed2006

Anthrax: a systematic review of atypical presentations.

During the 2001 US anthrax attacks, mortality from inhalational anthrax was significantly lower than had been reported historically, which was attributed in part to early identification and timely treatment. During future attacks, clinicians will rely on published descriptions of the clinical features of inhalational anthrax to rapidly diagnose patients and institute appropriate treatment. Published descriptions of typical inhalation anthrax usually include patients presenting with cough, dyspnea, or chest pain and found to have abnormal lung examination results with pleural effusions or enlarged mediastinum. The purpose of this article is to evaluate whether atypical presentations of inhalational anthrax occur and to describe the features of these presentations. We define atypical presentations as those in patients with confirmed anthrax infection who do not have known cutaneous, gastrointestinal, or inhalational ports of entry. We reviewed the case reports of 42 patients with atypical anthrax (published between 1900 and 2004) that may have had an inhalational source of infection to evaluate whether their clinical presentations differed from the typical findings of inhalational anthrax. Patients with atypical anthrax were less likely to have cough, chest pain, or abnormal lung examination results than patients with typical inhalational anthrax (P<.05 for all comparisons). A previously published screening protocol for patients with suspected anthrax correctly identified 91% of patients with atypical presentations. We conclude that although uncommon, atypical presentations of inhalational anthrax likely occur. Timely diagnosis and treatment of patients with inhalational anthrax require clinical awareness of the full spectrum of signs and symptoms associated with inhalational anthrax.

Algorithms↗

PubMed2006

Systematic review: a century of inhalational anthrax cases from 1900 to 2005.

BACKGROUND: Mortality from inhalational anthrax during the 2001 U.S. attack was substantially lower than that reported historically. PURPOSE: To systematically review all published inhalational anthrax case reports to evaluate the predictors of disease progression and mortality. DATA SOURCES: MEDLINE (1966-2005), 14 selected journal indexes (1900-1966), and bibliographies of all retrieved articles. STUDY SELECTION: Case reports (in any language) between 1900 and 2005 that met predefined criteria. DATA EXTRACTION: Two authors (1 author for non-English-language reports) independently abstracted patient data. DATA SYNTHESIS: The authors found 106 reports of 82 cases of inhalational anthrax. Mortality was statistically significantly lower for patients receiving antibiotics or anthrax antiserum during the prodromal phase of disease, multidrug antibiotic regimens, or pleural fluid drainage. Patients in the 2001 U.S. attack were less likely to die than historical anthrax case-patients (45% vs. 92%; P < 0.001) and were more likely to receive antibiotics during the prodromal phase (64% vs. 13%; P < 0.001), multidrug regimens (91% vs. 50%; P = 0.027), or pleural fluid drainage (73% vs. 11%; P < 0.001). Patients who progressed to the fulminant phase had a mortality rate of 97% (regardless of the treatment they received), and all patients with anthrax meningoencephalitis died. LIMITATIONS: This was a retrospective case review of previously published heterogeneous reports. CONCLUSIONS: Despite advances in supportive care, fulminant-phase inhalational anthrax is usually fatal. Initiation of antibiotic or anthrax antiserum therapy during the prodromal phase is associated with markedly improved survival, although other aspects of care, differences in clinical circumstances, or unreported factors may contribute to this observed reduction in mortality. Efforts to improve early diagnosis and timely initiation of appropriate antibiotics are critical to reducing mortality.

Anthrax↗

PubMed2006

Reducing mortality from anthrax bioterrorism: strategies for stockpiling and dispensing medical and pharmaceutical supplies.

A critical question in planning a response to bioterrorism is how antibiotics and medical supplies should be stockpiled and dispensed. The objective of this work was to evaluate the costs and benefits of alternative strategies for maintaining and dispensing local and regional inventories of antibiotics and medical supplies for responses to anthrax bioterrorism. We modeled the regional and local supply chain for antibiotics and medical supplies as well as local dispensing capacity. We found that mortality was highly dependent on the local dispensing capacity, the number of individuals requiring prophylaxis, adherence to prophylactic antibiotics, and delays in attack detection. For an attack exposing 250,000 people and requiring the prophylaxis of 5 million people, expected mortality fell from 243,000 to 145,000 as the dispensing capacity increased from 14,000 to 420,000 individuals per day. At low dispensing capacities (<14,000 individuals per day), nearly all exposed individuals died, regardless of the rate of adherence to prophylaxis, delays in attack detection, or availability of local inventories. No benefit was achieved by doubling local inventories at low dispensing capacities; however, at higher dispensing capacities, the cost-effectiveness of doubling local inventories fell from 100,000 US dollars to 20,000 US dollars/life year gained as the annual probability of an attack increased from 0.0002 to 0.001. We conclude that because of the reportedly rapid availability of regional inventories, the critical determinant of mortality following anthrax bioterrorism is local dispensing capacity. Bioterrorism preparedness efforts directed at improving local dispensing capacity are required before benefits can be reaped from enhancing local inventories.

Anthrax↗

PubMed2005

Challenges in systematic reviews: synthesis of topics related to the delivery, organization, and financing of health care.

Some important health policy topics, such as those related to the delivery, organization, and financing of health care, present substantial challenges to established methods for evidence synthesis. For example, such reviews may ask: What is the effect of for-profit versus not-for-profit delivery of care on patient outcomes? Or, which strategies are the most effective for promoting preventive care? This paper describes innovative methods for synthesizing evidence related to the delivery, organization, and financing of health care. We found 13 systematic reviews on these topics that described novel methodologic approaches. Several of these syntheses used 3 approaches: conceptual frameworks to inform problem formulation, systematic searches that included nontraditional literature sources, and hybrid synthesis methods that included simulations to address key gaps in the literature. As the primary literature on these topics expands, so will opportunities to develop additional novel methods for performing high-quality comprehensive syntheses.

Decision Support Techniques↗

PubMed2005

Cost-effectiveness of defending against bioterrorism: a comparison of vaccination and antibiotic prophylaxis against anthrax.

BACKGROUND: Weaponized Bacillus anthracis is one of the few biological agents that can cause death and disease in sufficient numbers to devastate an urban setting. OBJECTIVE: To evaluate the cost-effectiveness of strategies for prophylaxis and treatment of an aerosolized B. anthracis bioterror attack. DESIGN: Decision analytic model. DATA SOURCES: We derived probabilities of anthrax exposure, vaccine and treatment characteristics, and their costs and associated clinical outcomes from the medical literature and bioterrorism-preparedness experts. TARGET POPULATION: Persons living and working in a large metropolitan U.S. city. TIME HORIZON: Patient lifetime. PERSPECTIVE: Societal. INTERVENTION: We evaluated 4 postattack strategies: no prophylaxis, vaccination alone, antibiotic prophylaxis alone, or vaccination and antibiotic prophylaxis, as well as preattack vaccination versus no vaccination. OUTCOME MEASURES: Costs, quality-adjusted life-years, life-years, and incremental cost-effectiveness. RESULTS OF BASE-CASE ANALYSIS: If an aerosolized B. anthracis bioweapon attack occurs, postexposure prophylactic vaccination and antibiotic therapy for those potentially exposed is the most effective (0.33 life-year gained per person) and least costly (355 dollars saved per person) strategy, as compared with vaccination alone. At low baseline probabilities of attack and exposure, mass previous vaccination of a metropolitan population is more costly (815 million dollars for a city of 5 million people) and not more effective than no vaccination. RESULTS OF SENSITIVITY ANALYSIS: If prophylactic antibiotics cannot be promptly distributed after exposure, previous vaccination may become cost-effective. LIMITATIONS: The probability of exposure and disease critically depends on the probability and mechanism of bioweapon release. CONCLUSIONS: In the event of an aerosolized B. anthracis bioweapon attack over an unvaccinated metropolitan U.S. population, postattack prophylactic vaccination and antibiotic therapy is the most effective and least expensive strategy.

Anthrax↗

PubMed2005

Elevated late-night salivary cortisol levels in elderly male type 2 diabetic veterans.

OBJECTIVE: Late-night salivary cortisol (LNSC) is reportedly highly accurate for the diagnosis of Cushing's syndrome (CS). However, diagnostic thresholds for abnormal results are based on healthy, young populations and limited data are available on its use in elderly populations with chronic medical conditions. The purpose of this study was to evaluate LNSC levels in elderly male veterans with and without diabetes. DESIGN: Prospective evaluation of LNSC levels in male veterans. PATIENTS: One hundred and fifty-four participants with type 2 diabetes and 52 participants without diabetes. MEASUREMENTS: Participants underwent outpatient LNSC (2300 h) testing. Participants with elevated LNSC (> or = 4.3 nmol/l) underwent secondary testing, including 24-h urine free cortisol (24UFC, > 60 microg/day) and dexamethasone suppression testing (DST, serum cortisol > 50 nmol/l). Participants with positive secondary testing had a morning ACTH level analysed and either pituitary or adrenal imaging performed. RESULTS: One hundred and forty-one diabetics and 46 controls (mean age 61 years) returned samples (91% overall). Average LNSC levels (nmol/l) in diabetics were significantly higher than in nondiabetics [median (interquartile range): 2.6 (1.8-4.1) vs. 1.6 (1.0-2.0)] and in those aged > or = 60 compared to < 60 [2.7 (2.0-4.3) vs. 1.9 (1.4-2.9)] (P < 0.001 for both). Thirty-one participants required secondary testing. Seventy-nine per cent of participants who underwent secondary testing had normal 24UFC and DST. No cases of CS have been diagnosed to date. Increasing age [odds ratio (OR) 2.0 per decade], current diabetes mellitus (OR 4.4), and elevated blood pressure (OR 1.3 per 10 mmHg increase in systolic blood pressure) were associated with abnormal LNSC results (P < 0.05 for each). CONCLUSIONS: LNSC has been shown to be sensitive and specific in diagnosing CS in certain high-risk populations, primarily the young and middle-aged. The development of age- and comorbidity-adjusted thresholds may be warranted for LNSC testing in elderly subjects and in those with significant comorbidity.

Aged↗

PubMed2004

Systematic review: surveillance systems for early detection of bioterrorism-related diseases.

BACKGROUND: Given the threat of bioterrorism and the increasing availability of electronic data for surveillance, surveillance systems for the early detection of illnesses and syndromes potentially related to bioterrorism have proliferated. PURPOSE: To critically evaluate the potential utility of existing surveillance systems for illnesses and syndromes related to bioterrorism. DATA SOURCES: Databases of peer-reviewed articles (for example, MEDLINE for articles published from January 1985 to April 2002) and Web sites of relevant government and nongovernment agencies. STUDY SELECTION: Reports that described or evaluated systems for collecting, analyzing, or presenting surveillance data for bioterrorism-related illnesses or syndromes. DATA EXTRACTION: From each included article, the authors abstracted information about the type of surveillance data collected; method of collection, analysis, and presentation of surveillance data; and outcomes of evaluations of the system. DATA SYNTHESIS: 17,510 article citations and 8088 government and nongovernmental Web sites were reviewed. From these, the authors included 115 systems that collect various surveillance reports, including 9 syndromic surveillance systems, 20 systems collecting bioterrorism detector data, 13 systems collecting influenza-related data, and 23 systems collecting laboratory and antimicrobial resistance data. Only the systems collecting syndromic surveillance data and detection system data were designed, at least in part, for bioterrorism preparedness applications. Syndromic surveillance systems have been deployed for both event-based and continuous bioterrorism surveillance. Few surveillance systems have been comprehensively evaluated. Only 3 systems have had both sensitivity and specificity evaluated. LIMITATIONS: Data from some existing surveillance systems (particularly those developed by the military) may not be publicly available. CONCLUSIONS: Few surveillance systems have been specifically designed for collecting and analyzing data for the early detection of a bioterrorist event. Because current evaluations of surveillance systems for detecting bioterrorism and emerging infections are insufficient to characterize the timeliness or sensitivity and specificity, clinical and public health decision making based on these systems may be compromised.

Bioterrorism↗

PubMed2004

Evaluating detection and diagnostic decision support systems for bioterrorism response.

We evaluated the usefulness of detection systems and diagnostic decision support systems for bioterrorism response. We performed a systematic review by searching relevant databases (e.g., MEDLINE) and Web sites for reports of detection systems and diagnostic decision support systems that could be used during bioterrorism responses. We reviewed over 24,000 citations and identified 55 detection systems and 23 diagnostic decision support systems. Only 35 systems have been evaluated: 4 reported both sensitivity and specificity, 13 were compared to a reference standard, and 31 were evaluated for their timeliness. Most evaluations of detection systems and some evaluations of diagnostic systems for bioterrorism responses are critically deficient. Because false-positive and false-negative rates are unknown for most systems, decision making on the basis of these systems is seriously compromised. We describe a framework for the design of future evaluations of such systems.

Bioterrorism↗

PubMed2003

Efficacy and safety of low-carbohydrate diets: a systematic review.

CONTEXT: Low-carbohydrate diets have been popularized without detailed evidence of their efficacy or safety. The literature has no clear consensus as to what amount of carbohydrates per day constitutes a low-carbohydrate diet. OBJECTIVE: To evaluate changes in weight, serum lipids, fasting serum glucose, and fasting serum insulin levels, and blood pressure among adults using low-carbohydrate diets in the outpatient setting. DATA SOURCES: We performed MEDLINE and bibliographic searches for English-language studies published between January 1, 1966, and February 15, 2003, with key words such as low carbohydrate, ketogenic, and diet. STUDY SELECTION: We included articles describing adult, outpatient recipients of low-carbohydrate diets of 4 days or more in duration and 500 kcal/d or more, and which reported both carbohydrate content and total calories consumed. Literature searches identified 2609 potentially relevant articles of low-carbohydrate diets. We included 107 articles describing 94 dietary interventions reporting data for 3268 participants; 663 participants received diets of 60 g/d or less of carbohydrates--of whom only 71 received 20 g/d or less of carbohydrates. Study variables (eg, number of participants, design of dietary evaluation), participant variables (eg, age, sex, baseline weight, fasting serum glucose level), diet variables (eg, carbohydrate content, caloric content, duration) were abstracted from each study. DATA EXTRACTION: Two authors independently reviewed articles meeting inclusion criteria and abstracted data onto pretested abstraction forms. DATA SYNTHESIS: The included studies were highly heterogeneous with respect to design, carbohydrate content (range, 0-901 g/d), total caloric content (range, 525-4629 kcal/d), diet duration (range, 4-365 days), and participant characteristics (eg, baseline weight range, 57-217 kg). No study evaluated diets of 60 g/d or less of carbohydrates in participants with a mean age older than 53.1 years. Only 5 studies (nonrandomized and no comparison groups) evaluated these diets for more than 90 days. Among obese patients, weight loss was associated with longer diet duration (P =.002), restriction of calorie intake (P =.03), but not with reduced carbohydrate content (P =.90). Low-carbohydrate diets had no significant adverse effect on serum lipid, fasting serum glucose, and fasting serum insulin levels, or blood pressure. CONCLUSIONS: There is insufficient evidence to make recommendations for or against the use of low-carbohydrate diets, particularly among participants older than age 50 years, for use longer than 90 days, or for diets of 20 g/d or less of carbohydrates. Among the published studies, participant weight loss while using low-carbohydrate diets was principally associated with decreased caloric intake and increased diet duration but not with reduced carbohydrate content.

Blood Glucose↗

PubMedDate not supplied

A conceptual framework for evaluating information technologies and decision support systems for bioterrorism preparedness and response.

OBJECTIVES: The authors sought to develop a conceptual framework for evaluating whether existing information technologies and decision support systems (IT/DSSs) would assist the key decisions faced by clinicians and public health officials preparing for and responding to bioterrorism. METHODS: They reviewed reports of natural and bioterrorism related infectious outbreaks, bioterrorism preparedness exercises, and advice from experts to identify the key decisions, tasks, and information needs of clinicians and public health officials during a bioterrorism response. The authors used task decomposition to identify the subtasks and data requirements of IT/DSSs designed to facilitate a bioterrorism response. They used the results of the task decomposition to develop evaluation criteria for IT/DSSs for bioterrorism preparedness. They then applied these evaluation criteria to 341 reports of 217 existing IT/DSSs that could be used to support a bioterrorism response. MAIN RESULTS: In response to bioterrorism, clinicians must make decisions in 4 critical domains (diagnosis, management, prevention, and reporting to public health), and public health officials must make decisions in 4 other domains (interpretation of bioterrorism surveillance data, outbreak investigation, outbreak control, and communication). The time horizons and utility functions for these decisions differ. From the task decomposition, the authors identified critical subtasks for each of the 8 decisions. For example, interpretation of diagnostic tests is an important subtask of diagnostic decision making that requires an understanding of the tests' sensitivity and specificity. Therefore, an evaluation criterion applied to reports of diagnostic IT/DSSs for bioterrorism asked whether the reports described the systems' sensitivity and specificity. Of the 217 existing IT/DSSs that could be used to respond to bioterrorism, 79 studies evaluated 58 systems for at least 1 performance metric. CONCLUSIONS: The authors identified 8 key decisions that clinicians and public health officials must make in response to bioterrorism. When applying the evaluation system to 217 currently available IT/DSSs that could potentially support the decisions of clinicians and public health officials, the authors found that the literature provides little information about the accuracy of these systems.

Bioterrorism↗

PubMedDate not supplied

Invariance and inconsistency in utility ratings.

PURPOSE: To assess utilities of composite health states for dependence in activities of daily living (ADLs) for invariance (i.e., when subjects provide a utility of 1 for all health states) and order inconsistency (i.e., when subjects order their utilities such that their utility for a combination of ADL dependencies is greater than their utility for any subset of the combination). METHODS: Each of the 400 subjects, age 65 y and older, enrolled in one of several regional medical centers of the Kaiser Permanente Medical Care Program of Northern California and provided standard-gamble utilities for single ADL dependencies (e.g., bathing, dressing, continence) and for dependence in 8 other combinations of ADL dependencies. For order-inconsistent responses, the authors calculated the maximum magnitude of inconsistency as the maximum difference between the utility for the combined ADL dependence health state and that of its inconsistent subset. RESULTS: A total of 76 subjects (19%) gave a utility of 1.0 for all health states presented to them; 19 (5%) gave the same utility other than 1.0 for all health states; 130 (33%) gave at least 1 utility < 1.0 and had no order inconsistencies; and 175 (44%) had at least 1 order inconsistency. Invariance was associated with a Mini-Mental Status Examination score < 28.6 (P = 0.01), with education < 12 y (P = 0.004), with race/ethnicity other than non-Hispanic White/Caucasian (P = 0.001), and with shorter time spent on the utility elicitation task (P < 0.0001). Among the inconsistent subjects, 69% had a maximal magnitude of inconsistency that was within 1 standard deviation of the mean utilities. The maximal magnitude of inconsistency was associated with longer time spent on the elicitation task (P < 0.0001) and race/ethnicity other than non-Hispanic White/Caucasian (P = 0.005). The mean (s) utility for dependence in continence among consistent subjects who were not invariant (0.88 [0.24]) was higher than among inconsistent subjects (0.80 [0.27]; P = 0.01). CONCLUSIONS: Invariance and order inconsistencies in utility ratings for complex health states occur frequently. Utilities of consistent subjects may differ from those of inconsistent subjects. Utility assessments should attempt to measure and report these patterns.

Activities of Daily Living↗