Berkeley Madonna Version 10-A simulation package for solving mathematical models.

Berkeley Madonna is a software program that provides an easy and intuitive environment for graphically building and numerically solving mathematical equations. Our users range from college undergraduates with little or no mathematical experience to academic researchers and professionals building and simulating sophisticated mathematical models that represent complex systems in the biological, chemical, and engineering fields. Here we briefly describe our recent advances including a new Java-based user interface introduced in Version 9 and our transition from a 32- to 64-bit architecture with the release of Version 10. We take the reader through an example tutorial that illustrates how to construct a mathematical model in Berkeley Madonna while highlighting some of the recent changes to the software. Specifically, we construct a standard pharmacokinetic model of the antifungal medication amphotericin B taken from the literature and discuss aspects related to model building, key numerical considerations, data fitting, and graphical visualization. We end by discussing planned functionality and features intended for future releases.

Cost-effectiveness of secondary fracture prevention intervention for Medicare beneficiaries.

BACKGROUND: Secondary fracture prevention intervention such as fracture liaison services are effective for increasing osteoporosis treatment rates, but are not currently widely used in the United States. We evaluated the cost-effectiveness of secondary fracture prevention intervention after osteoporotic fracture for Medicare beneficiaries. METHODS: An individual-level state-transition microsimulation model was developed to evaluate the cost-effectiveness of secondary fracture prevention intervention compared with usual care for U.S. Medicare patients aged 65 and older who experience a new osteoporotic fracture. Patients who initiated pharmacotherapy and remained adherent were assumed to be treated for 5 years. Outcome measures included subsequent fractures, average lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios in 2020 U.S. dollars per QALY gained. The model time horizon was lifetime, and analysis perspective was payer. RESULTS: Base-case analysis results showed that the secondary fracture prevention intervention strategy was both more effective and less expensive than usual care-thus, it was cost-saving. Model findings indicated that the intervention would reduce the number of expected fractures by approximately 5% over a 5-year period, preventing approximately 30,000 fractures for 1 million patients. Secondary fracture prevention intervention resulted in an average cost savings of $418 and an increase in QALYs of 0.0299 per patient over the lifetime; for 1 million patients who receive the intervention instead of usual care, expected cost savings for Medicare would be $418 million dollars. One-way and probabilistic sensitivity analyses supported base-case findings of cost savings. CONCLUSION: Secondary fracture prevention intervention for Medicare beneficiaries after a new osteoporotic fracture is very likely to both improve health outcomes and reduce healthcare costs compared with usual care. Expansion of its use for this population is strongly recommended.

How Can We Improve Osteoporosis Care? A Systematic Review and Meta-Analysis of the Efficacy of Quality Improvement Strategies for Osteoporosis.

Although osteoporosis affects 10 million people in the United States, screening and treatment rates remain low. We performed a systematic review and meta-analysis of the efficacy of quality improvement strategies to improve osteoporosis screening (bone mineral density [BMD]/dual-energy X-ray absorptiometry [DXA] testing) and/or treatment (pharmacotherapy) initiation rates. We developed broad literature search strategies for PubMed, Embase, and Cochrane Library databases, and applied inclusion/exclusion criteria to select relevant studies. Random-effects meta-analyses were performed for outcomes of BMD/DXA testing and/or osteoporosis treatment. Forty-three randomized clinical studies met inclusion criteria. For increasing BMD/DXA testing in patients with recent or prior fracture, meta-analyses demonstrated several efficacious strategies, including orthopedic surgeon or fracture clinic initiation of osteoporosis evaluation or management (risk difference 44%, 95% confidence interval [CI] 26%-63%), fracture liaison service/case management (risk difference 43%, 95% CI 23%-64%), multifaceted interventions targeting providers and patients (risk difference 24%, 95% CI 15%-32%), and patient education and/or activation (risk difference 16%, 95% CI 6%-26%). For increasing osteoporosis treatment in patients with recent or prior fracture, meta-analyses demonstrated significant efficacy for interventions of fracture liaison service/case management (risk difference 20%, 95% CI 1%-40%) and multifaceted interventions targeting providers and patients (risk difference 12%, 95% CI 6%-17%). The only quality improvement strategy for which meta-analysis findings demonstrated significant improvement of osteoporosis care for patient populations including individuals without prior fracture was patient self-scheduling of DXA plus education, for increasing the outcome of BMD testing (risk difference 13%, 95% CI 7%-18%). The meta-analyses findings were limited by small number of studies in each analysis; high between-study heterogeneity; sensitivity to removal of individual studies; and unclear risk of bias of included studies. Despite the limitations of the current body of evidence, our findings indicate there are several strategies that appear worthwhile to enact to try to improve osteoporosis screening and/or treatment rates. © 2018 American Society for Bone and Mineral Research.

Osteoporosis Treatment Efficacy for Men: A Systematic Review and Meta-Analysis.

OBJECTIVES: To evaluate the efficacy of treatment options to reduce osteoporotic fracture risk in men. DESIGN: Systematic review and meta-analysis. SETTING: Randomized clinical trials that evaluated the efficacy of a treatment for osteoporosis or low bone mineral density for adult men and reported fracture outcomes. PARTICIPANTS: Men. MEASUREMENTS: PubMed, Embase, and the Cochrane Library databases were searched for relevant studies. Information was extracted from included studies on participant sociodemographic characteristics, number of male participants, treatment evaluated, comparator for evaluated treatment, study duration, and fracture outcomes. Risk of bias of individual studies was assessed using measures recommended by the Cochrane Collaboration. RESULTS: Twenty-four articles reporting results for 22 studies (including 4,868 male participants) met strict inclusion criteria. Fixed-effects meta-analyses using the Mantel-Haenszel method demonstrated significantly lower risk of vertebral fractures with alendronate (relative risk (RR) = 0.328, 95% confidence interval (CI) = 0.155-0.692) and risedronate (RR = 0.428, 95% CI = 0.245-0.746) but not with calcitonin (RR = 0.272, 95% CI = 0.046-1.608) or denosumab (RR = 0.256, 95% CI = 0.029-2.238) than in controls. For bisphosphonates as a treatment category, meta-analyses demonstrated significantly lower risk of vertebral fractures (RR = 0.368, 95% CI = 0.252-0.537) and nonvertebral fractures (RR = 0.604, 95% CI = 0.404-0.904) than in controls. The meta-analysis finding that bisphosphonates significantly reduce nonvertebral fracture risk was not robust to sensitivity analysis. CONCLUSION: Bisphosphonates reduce the risk of vertebral and possibly nonvertebral fractures for men with osteoporosis. Further studies are needed to evaluate the efficacy of bisphosphonates for reducing nonvertebral fracture risk and the efficacy of nonbisphosphonates for reducing vertebral and nonvertebral fracture risk in men with osteoporosis.

A mathematical model of osteoclast acidification during bone resorption.

Bone resorption by osteoclasts occurs through the creation of a sealed extracellular compartment (ECC), or pit, adjacent to the bone that is subsequently acidified through a complex biological process. The low pH of the pit dissolves the bone mineral and activates acid proteases that further break down the bone matrix. There are many ion channels, transporters, and soluble proteins involved in osteoclast mediated resorption, and in the past few years, there has been an increased understanding of the identity and properties of some key proteins such as the ClC-7 Cl-/H+ antiporter and the HV1 proton channel. Here we present a detailed mathematical model of osteoclast acidification that includes the influence of many of the key regulatory proteins. The primary enzyme responsible for acidification is the vacuolar H+-ATPase (V-ATPase), which pumps protons from the cytoplasm into the pit. Unlike the acidification of small lysosomes, the pit is so large that protons become depleted from the cytoplasm. Hence, proton buffering and production in the cytoplasm by carbonic anhydrase II (CAII) is potentially important for proper acidification. We employ an ordinary differential equations (ODE)-based model that accounts for the changes in ionic species in the cytoplasm and the resorptive pit. Additionally, our model tracks ionic flow between the cytoplasm and the extracellular solution surrounding the cell. Whenever possible, the properties of individual channels and transporters are calibrated based on electrophysiological measurements, and physical properties of the cell, such as buffering capacity, surface areas, and volumes, are estimated based on available data. Our model reproduces many of the experimental findings regarding the role of key proteins in the acidification process, and it allows us to estimate, among other things, number of active pumps, protons moved, and the influence of particular mutations implicated in disease.

Systematic Review and Meta-Analysis of Inhaled Toxicants from Waterpipe and Cigarette Smoking.

OBJECTIVE: Waterpipe tobacco smoking (WTS) is an emerging trend worldwide. To inform public health policy and educational programming, we systematically reviewed the biomedical literature to compute the inhaled smoke volume, nicotine, tar, and carbon monoxide (CO) associated with a single WTS session and a single cigarette. METHODS: We searched seven biomedical bibliographic databases for controlled laboratory or natural environment studies designed to mimic human tobacco consumption. Included studies quantified the mainstream smoke of a single cigarette and/or single WTS session for smoke volume, nicotine, tar, and/or CO. We conducted meta-analyses to calculate summary estimates for the inhalation of each unique substance for each mode of tobacco consumption. We assessed between-study heterogeneity using chi-squared and I-squared statistics. RESULTS: Sufficient data from 17 studies were available to derive pooled estimates for inhalation of each exposure via each smoking method. Two researchers working independently abstracted measurement of smoke volume in liters, and nicotine, tar, and CO in milligrams. All numbers included in meta-analyses matched precisely between the two researchers (100% agreement, Cohen's k=1.00). Whereas one WTS session was associated with 74.1 liters of smoke inhalation (95% confidence interval [CI] 38.2, 110.0), one cigarette was associated with 0.6 liters of smoke (95% CI 0.5, 0.7). One WTS session was also associated with higher levels of nicotine, tar, and CO. CONCLUSIONS: One WTS session consistently exposed users to larger smoke volumes and higher levels of tobacco toxicants compared with one cigarette. These computed estimates may be valuable to emphasize in prevention programming.

Cost-Effectiveness of Osteoporosis Screening Strategies for Men.

Osteoporosis affects many men, with significant morbidity and mortality. However, the best osteoporosis screening strategies for men are unknown. We developed an individual-level state-transition cost-effectiveness model with a lifetime time horizon to identify the cost-effectiveness of different osteoporosis screening strategies for US men involving various screening tests (dual-energy X-ray absorptiometry [DXA]; the Osteoporosis Self-Assessment Tool [OST]; or a fracture risk assessment strategy using age, femoral neck bone mineral density [BMD], and Vertebral Fracture Assessment [VFA]); screening initiation ages (50, 60, 70, or 80 years); and repeat screening intervals (5 years or 10 years). In base-case analysis, no screening was a less effective option than all other strategies evaluated; furthermore, no screening was more expensive than all strategies that involved screening with DXA or the OST risk assessment instrument, and thus no screening was "dominated" by screening with DXA or OST at all evaluated screening initiation ages and repeat screening intervals. Screening strategies that most frequently appeared as most cost-effective in base-case analyses and one-way sensitivity analyses when assuming willingness-to-pay of $50,000/quality-adjusted life-year (QALY) or $100,000/QALY included screening initiation at age 50 years with the fracture risk assessment strategy and repeat screening every 10 years; screening initiation at age 50 years with fracture risk assessment and repeat screening every 5 years; and screening initiation at age 50 years with DXA and repeat screening every 5 years. In conclusion, expansion of osteoporosis screening for US men to initiate routine screening at age 50 or 60 years would be expected to be effective and of good value for improving health outcomes. A fracture risk assessment strategy using variables of age, femoral neck BMD, and VFA is likely to be the most effective of the evaluated strategies within accepted cost-effectiveness parameters. DXA and OST are also reasonable screening options, albeit likely slightly less effective than the evaluated fracture risk assessment strategy. © 2016 American Society for Bone and Mineral Research.

A model of lysosomal pH regulation.

Lysosomes must maintain an acidic luminal pH to activate hydrolytic enzymes and degrade internalized macromolecules. Acidification requires the vacuolar-type H(+)-ATPase to pump protons into the lumen and a counterion flux to neutralize the membrane potential created by proton accumulation. Early experiments suggested that the counterion was chloride, and more recently a pathway consistent with the ClC-7 Cl(-)/H(+) antiporter was identified. However, reports that the steady-state luminal pH is unaffected in ClC-7 knockout mice raise questions regarding the identity of the carrier and the counterion. Here, we measure the current-voltage characteristics of a mammalian ClC-7 antiporter, and we use its transport properties, together with other key ion regulating elements, to construct a mathematical model of lysosomal pH regulation. We show that results of in vitro lysosome experiments can only be explained by the presence of ClC-7, and that ClC-7 promotes greater acidification than Cl(-), K(+), or Na(+) channels. Our models predict strikingly different lysosomal K(+) dynamics depending on the major counterion pathways. However, given the lack of experimental data concerning acidification in vivo, the model cannot definitively rule out any given mechanism, but the model does provide concrete predictions for additional experiments that would clarify the identity of the counterion and its carrier.

Impact of total shoulder arthroplasty on generic and shoulder-specific health-related quality-of-life measures: a systematic literature review and meta-analysis.

BACKGROUND: Total shoulder arthroplasty is increasingly used in the treatment of arthritis. However, the effect of total shoulder arthroplasty on health-related quality of life has not been fully established. The goal of this systematic review and meta-analysis was to characterize the change in generic and shoulder-specific health-related quality-of-life measures resulting from total shoulder arthroplasty. METHODS: We identified published studies reporting preoperative and postoperative health-related quality-of-life outcomes for patients receiving total shoulder arthroplasty. Health-related quality-of-life measures were identified, and meta-analysis was used to calculate standardized mean differences (SMDs, reflective of the effect size) and 95% confidence intervals for each scale. RESULTS: Twenty studies (1576 total shoulder replacements) met the inclusion criteria. Outcome measures were analyzed after an average postoperative follow-up duration of 3.7 ± 2.2 years. The Short Form-36 demonstrated significant improvement in physical component summary scores (SMD = 0.7, p < 0.001) but not in mental component summary scores (SMD = 0.2, p = 0.37). Significant improvements were observed in the visual analog scale score for pain (SMD = -2.5, p < 0.001) and scores on three shoulder-specific measures: the Constant score (SMD = 2.7, p < 0.001), American Shoulder and Elbow Surgeons score (SMD = 2.9, p < 0.001), and Simple Shoulder Test (SMD = 2.3, p < 0.001). CONCLUSIONS: Total shoulder arthroplasty leads to significant improvements in scores for function and pain. Shoulder-specific measures of function consistently showed the greatest degree of improvement, with large effect sizes. Total shoulder arthroplasty also leads to significant improvements in overall physical well-being, with a moderate-to-large effect size.

Role of video games in improving health-related outcomes: a systematic review.

CONTEXT: Video games represent a multibillion-dollar industry in the U.S. Although video gaming has been associated with many negative health consequences, it also may be useful for therapeutic purposes. The goal of this study was to determine whether video games may be useful in improving health outcomes. EVIDENCE ACQUISITION: Literature searches were performed in February 2010 in six databases: the Center on Media and Child Health Database of Research, MEDLINE, CINAHL, PsycINFO, EMBASE, and the Cochrane Central Register of Controlled Trials. Reference lists were hand-searched to identify additional studies. Only RCTs that tested the effect of video games on a positive, clinically relevant health consequence were included. Study selection criteria were strictly defined and applied by two researchers working independently. Study background information (e.g., location, funding source); sample data (e.g., number of study participants, demographics); intervention and control details; outcomes data; and quality measures were abstracted independently by two researchers. EVIDENCE SYNTHESIS: Of 1452 articles retrieved using the current search strategy, 38 met all criteria for inclusion. Eligible studies used video games to provide physical therapy, psychological therapy, improved disease self-management, health education, distraction from discomfort, increased physical activity, and skills training for clinicians. Among the 38 studies, a total of 195 health outcomes were examined. Video games improved 69% of psychological therapy outcomes, 59% of physical therapy outcomes, 50% of physical activity outcomes, 46% of clinician skills outcomes, 42% of health education outcomes, 42% of pain distraction outcomes, and 37% of disease self-management outcomes. Study quality was generally poor; for example, two thirds (66%) of studies had follow-up periods of <12 weeks, and only 11% of studies blinded researchers. CONCLUSIONS: There is potential promise for video games to improve health outcomes, particularly in the areas of psychological therapy and physical therapy. RCTs with appropriate rigor will help build evidence in this emerging area.

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment.

INTRODUCTION: Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women. METHODS: Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA), and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through $800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs); and incremental cost-effectiveness ratios (ICERs) in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed. RESULTS: Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days). When assuming alendronate costs of $400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from $714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of $50,000/QALY at all alendronate costs evaluated. CONCLUSIONS: Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost-saving at annual alendronate costs of $200 or less.

FRAX or fiction: determining optimal screening strategies for treatment of osteoporosis in residents in long-term care facilities.

OBJECTIVES: To examine screening strategies for osteoporosis and fractures for treatment of long-term care residents. DESIGN: Cross-sectional analysis to examine screening strategies for treatment. SETTING: Assisted living and skilled care facilities. PARTICIPANTS: Two hundred two frail women aged 65 and older (mean 85), excluding those receiving bisphosphonates. MEASUREMENTS: Clinical fractures of the hip or spine (Clin Fx); Clin Fx or bone mineral density (BMD); Clin Fx, BMD, or vertebral fractures (VF) assessed according to dual-energy X-ray absorptiometry-based vertebral fracture assessments; fracture risk algorithm using femoral neck BMD (FRAX-FN); fracture risk algorithm using body mass index (FRAX-BMI); or Clin Fx or heel ultrasound (heel US). RESULTS: Treatment eligibility ranged from 17% (Clin Fx) to 98% (FRAX-BMI). VFs were found in 47%, 74% of which were silent. Criteria with Clin Fx, BMD, or VF identified 73% of study participants for treatment. FRAX-FN suggested treatment in 81% but would have missed approximately 10% of individuals with silent VFs. Clin Fx or heel US suggested that 39% of participants were eligible for treatment. CONCLUSION: Long-term care residents eligible for osteoporosis treatment ranged from fewer than 20% to roughly all residents depending on screening criteria. VFs are common and identify a subset of residents missed by conventional BMD scans or FRAX-FN. A reasonable clinical approach could consider treatment for those with Clin Fx of the hip or spine, radiological evidence of a VF, or osteoporosis according to BMD classification. Prospective studies are needed to determine optimal screening strategies for treatment in this cohort.

Cost-effectiveness of different screening strategies for osteoporosis in postmenopausal women.

BACKGROUND: The best strategies to screen postmenopausal women for osteoporosis are not clear. OBJECTIVE: To identify the cost-effectiveness of various screening strategies. DESIGN: Individual-level state-transition cost-effectiveness model. DATA SOURCES: Published literature. TARGET POPULATION: U.S. women aged 55 years or older. TIME HORIZON: Lifetime. PERSPECTIVE: Payer. INTERVENTION: Screening strategies composed of alternative tests (central dual-energy x-ray absorptiometry [DXA], calcaneal quantitative ultrasonography [QUS], and the Simple Calculated Osteoporosis Risk Estimation [SCORE] tool) initiation ages, treatment thresholds, and rescreening intervals. Oral bisphosphonate treatment was assumed, with a base-case adherence rate of 50% and a 5-year on/off treatment pattern. OUTCOME MEASURES: Incremental cost-effectiveness ratios (2010 U.S. dollars per quality-adjusted life-year [QALY] gained). RESULTS OF BASE-CASE ANALYSIS: At all evaluated ages, screening was superior to not screening. In general, quality-adjusted life-days gained with screening tended to increase with age. At all initiation ages, the best strategy with an incremental cost-effectiveness ratio (ICER) of less than $50,000 per QALY was DXA screening with a T-score threshold of -2.5 or less for treatment and with follow-up screening every 5 years. Across screening initiation ages, the best strategy with an ICER less than $50,000 per QALY was initiation of screening at age 55 years by using DXA -2.5 with rescreening every 5 years. The best strategy with an ICER less than $100,000 per QALY was initiation of screening at age 55 years by using DXA with a T-score threshold of -2.0 or less for treatment and then rescreening every 10 years. No other strategy that involved treatment of women with osteopenia had an ICER less than $100,000 per QALY. Many other strategies, including strategies with SCORE or QUS prescreening, were also cost-effective, and in general the differences in effectiveness and costs between evaluated strategies was small. RESULTS OF SENSITIVITY ANALYSIS: Probabilistic sensitivity analysis did not reveal a consistently superior strategy. LIMITATIONS: Data were primarily from white women. Screening initiation at ages younger than 55 years were not examined. Only osteoporotic fractures of the hip, vertebrae, and wrist were modeled. CONCLUSION: Many strategies for postmenopausal osteoporosis screening are effective and cost-effective, including strategies involving screening initiation at age 55 years. No strategy substantially outperforms another. PRIMARY FUNDING SOURCE: National Center for Research Resources.

Immunostimulant activity of noni (Morinda citrifolia) on T and B lymphocytes.

Morinda citrifolia Linn (Rubiaceae) is a traditional medicinal herb that has been purported to be beneficial in the treatment of infections due to its immune enhancing properties. However, detailed studies highlighting the effect of different compounds isolated from the plant on the immune system are lacking. In this study, the stimulatory effects of the extracts and fractions of M. citrifolia fruits on important components of the adaptive immune system such as T lymphocytes and B lymphocytes were studied. The effects of the plant extracts on lymphocytes were assessed by in vitro (MTT assay) and in vivo (cell mediated immune response) techniques. Results of the MTT study indicated that the hydroalcoholic (0.5 and 1.0 mg/mL) and aqueous extracts (0.5 and 1.0 mg/mL) significantly (p < 0.05) increased in vitro splenocyte proliferation to the extent of 43.6, 54.5, 32.7, and 36.4%, respectively. Moreover, the hydroalcoholic (200 mg/kg) and the aqueous (200 mg/kg) extracts significantly (p < 0.05) increased the cell-mediated immune response to the extent of 33.52 and 18.56%, respectively. The fractions F I, F II, and F III failed to elicit a significant stimulatory effect on lymphocytes in the in vitro and in vivo studies. The effect of the extractives of M. citrifolia fruits on B-cells was measured by the delayed type hypersensitivity method. The study revealed that the hydroalcoholic extract (200 mg/kg) and fraction F I (40 mg/kg) significantly increased the humoral response to the extent of 33.33 and 35.12%, respectively. The results of this study confirm the cellular and humoral immunostimulant properties of M. citrifolia fruits and justify its usage in traditional medicine.

Health Beliefs about Osteoporosis and Osteoporosis Screening in Older Women and Men.

OBJECTIVE: To examine older adults' beliefs about osteoporosis and osteoporosis screening to identify barriers to screening. DESIGN: Cross-sectional mailed survey. SETTING: Western Pennsylvania. METHODS: Surveys were mailed to 1830 women and men aged 60 years and older. The survey assessed sociodemographic characteristics, osteoporosis and general health-related characteristics, and beliefs about osteoporosis severity, susceptibility, screening self-efficacy, and screening response efficacy. Analyses included Wilcoxon rank-sum tests to compare belief dimension scores, and multivariable ordinal logistic regression analyses to evaluate association between osteoporosis beliefs and potential explanatory variables. RESULTS: Surveys were completed by 1268 individuals (69.3 per cent). Mean age of respondents was 73.3 years, and most were female (58.7 per cent). Individuals demonstrated greatest belief in the severity of osteoporosis and least belief in personal susceptibility (P <.001). Older individuals believed less strongly than younger individuals in osteoporosis severity (OR, 0.95 per 1-year increase in age; 95 per cent CI, 0.92-0.97) and response efficacy (OR, 0.97 per 1-year increase in age; 95 per cent CI, 0.95-0.99). Women believed more strongly than men in osteoporosis susceptibility (OR, 1.87; 95 per cent CI, 1.38-2.53) and screening self-efficacy (OR, 2.87; 95 per cent CI, 1.17-7.07). Individuals with high self-rated health status had greater belief than those with low self-rated health status in screening self-efficacy (OR, 3.59; 95 per cent CI, 1.89-6.83). CONCLUSION: Older adults demonstrate several beliefs that may be barriers to osteoporosis screening, including low belief in susceptibility to osteoporosis. These beliefs should be targeted with patient education to improve screening rates.

Osteoporosis screening preferences of older adults.

We aimed to examine older adults' osteoporosis screening test preferences, willingness to travel for screening, and willingness to pay for screening. A survey was mailed to 1830 women and men aged 60 yr or older in Pennsylvania, assessing screening test preference (among dual-energy X-ray absorptiometry [DXA], heel quantitative ultrasound [QUS], and risk-assessment tools), willingness to travel 20 miles for a better screening test, and willingness to pay $100 for a better screening test, as well as socio-demographic and health-related characteristics. Analyses included descriptive statistics and multivariable logistic regression analyses to evaluate association between screening test preference, willingness to travel, willingness to pay, and potential explanatory variables. Surveys were completed by 1268 individuals (69.3%). Most respondents indicated a screening test preference (73.9%) and, of these, 78.1% preferred DXA. 78.8% of the respondents indicated that they may be willing to travel 20 miles for a better test, and 51.2% indicated that they may be willing to pay $100 for a better test. Similar trends were observed in analyses including only individuals who had not had prior osteoporosis testing or diagnosis. Many older individuals would prefer the "best" test for osteoporosis screening, and may be willing to travel or pay more to obtain a better test.

Factors associated with osteoporosis screening and recommendations for osteoporosis screening in older adults.

BACKGROUND: Osteoporosis screening rates are low, and it is unclear which patient factors are associated with screening and physician recommendations for screening. OBJECTIVE: To identify patient characteristics associated with osteoporosis screening recommendations and receipt of screening in older adults. DESIGN: Cross-sectional mailed survey. PARTICIPANTS: Women and men > or =60 years old living in or near western Pennsylvania. MEASUREMENTS: Sociodemographic characteristics and osteoporosis-related data, including risk factors, physician recommendations for screening, and receipt of screening. Multivariable logistic regression analyses were performed to determine odds ratios for receipt of screening and screening recommendations for individuals with particular osteoporosis risk factors, adjusting for sociodemographic and other risk factors. RESULTS: Surveys were completed by 1,268 of the 1,830 adults to whom surveys were mailed (69.3%). Most respondents were white (92.9%), female (58.7%), and believed they were in good to excellent health (88.2%). Only 47.6% said their physician recommended osteoporosis screening, and 62.6% of all respondents reported being screened. Screening recommendations were less likely for older respondents than younger ones (OR, 0.87 per 5-year increase in age; 95% CI, 0.77-0.97). Individuals with osteoporosis risk factors of a history of oral steroid use for >1 month, height loss >2.54 cm, or history of low-trauma fracture were no more likely to report screening recommendations than individuals without these characteristics. Receipt of screening was no more likely for more elderly respondents or respondents with a history of oral steroid use for >1 month than for respondents without these characteristics. CONCLUSIONS: Individuals with several known osteoporosis risk factors are not being sufficiently targeted for screening.

Risk of hypospadias in offspring of women using loratadine during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Loratadine, a second-generation antihistamine, is commonly used to treat seasonal allergies. Some studies have suggested that use of loratadine by pregnant women increases the risk of hypospadias in male offspring. OBJECTIVE: This meta-analysis was designed to assess the strength of the association between loratadine and hypospadias. METHODS: To locate pertinent articles published in any language from January 1989 until August 2007, we searched electronic databases (MEDLINE, OVID, EMBASE, SCOPUS, TOXLINE Special, ReproTox, TERIS, CINAHL and others), conference proceedings and bibliographies. Studies were eligible for this analysis if they were cohort, case-control or case series studies that reported the incidence of hypospadias in the offspring of women who were or were not exposed to loratadine during pregnancy. Two authors independently extracted information on study design, participant characteristics, measures of outcome, control for potential confounding factors and risk estimates using a standardized data collection form. The Newcastle-Ottawa Scale was then used to assess the quality of each study. We used a random-effects meta-analysis model to combine the risk data. RESULTS: In 1402 potentially relevant titles, we found three case-control studies and seven cohort studies that reported the incidence of hypospadias or other congenital malformations in offspring of women who did or did not use loratadine during pregnancy. Together the studies in our meta-analysis provided information about 453 053 male births in Brazil, Canada, Denmark, Israel, Italy, Sweden, the UK and the US.Of 2694 male infants born to women using loratadine, 39 (1.4%) had hypospadias. Of 450 413 male infants born to women not using loratadine, 4231 (0.9%) had hypospadias. Women who used loratadine during pregnancy were not significantly more likely to have a son with hypospadias (unadjusted odds ratio [OR] 1.27, 95% CI 0.73, 2.23; adjusted OR 1.28, 95% CI 0.69, 2.39). CONCLUSION: The results of our systematic review and meta-analysis of controlled observational studies indicate that the use of loratadine during pregnancy does not significantly increase the risk of hypospadias in male offspring.

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.

Quality improvement strategies for hypertension management: a systematic review.

BACKGROUND: Care remains suboptimal for many patients with hypertension. PURPOSE: The purpose of this study was to assess the effectiveness of quality improvement (QI) strategies in lowering blood pressure. DATA SOURCES: MEDLINE, Cochrane databases, and article bibliographies were searched for this study. STUDY SELECTION: Trials, controlled before-after studies, and interrupted time series evaluating QI interventions targeting hypertension control and reporting blood pressure outcomes were studied. DATA EXTRACTION: Two reviewers abstracted data and classified QI strategies into categories: provider education, provider reminders, facilitated relay of clinical information, patient education, self-management, patient reminders, audit and feedback, team change, or financial incentives were extracted. DATA SYNTHESIS: Forty-four articles reporting 57 comparisons underwent quantitative analysis. Patients in the intervention groups experienced median reductions in systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were 4.5 mm Hg (interquartile range [IQR]: 1.5 to 11.0) and 2.1 mm Hg (IQR: -0.2 to 5.0) greater than observed for control patients. Median increases in the percentage of individuals achieving target goals for SBP and DBP were 16.2% (IQR: 10.3 to 32.2) and 6.0% (IQR: 1.5 to 17.5). Interventions that included team change as a QI strategy were associated with the largest reductions in blood pressure outcomes. All team change studies included assignment of some responsibilities to a health professional other than the patient's physician. LIMITATIONS: Not all QI strategies have been assessed equally, which limits the power to compare differences in effects between strategies. CONCLUSION: QI strategies are associated with improved hypertension control. A focus on hypertension by someone in addition to the patient's physician was associated with substantial improvement. Future research should examine the contributions of individual QI strategies and their relative costs.