Introduction of a Chiral Biphenanthrene-Diol Unit to Achieve Circularly Polarized Thermally Activated Delayed Fluorescence.

Circularly polarized luminescence (CPL) materials are promising candidates for future display technology. However, such highly efficient emitters suffer from the issues of difficult chiral separation and low photoluminescence quantum yield (PLQY). In this work, the chiral 4,4'-biphenanthrene-3,3'-diol (BIPOL) unit was introduced into a thermally activated delayed fluorescence (TADF) framework for the first time. We presented two series of enantiomers, R/S-o-DCzBPNCN and R/S-p-DCzBPNCN, and the synthesis of enantiopure BIPOL can be prepared via normal column chromatography. Notably, o-DCzBPNCN showed narrow singlet-triplet gap of 0.05 eV, efficient TADF, and high PLQYs of 82 % in doped films. In addition, R/S-o-DCzBPNCN exhibited high luminescence dissymmetry factor (gPL ) values of -1.94×10-2 /+1.91×10-2 in doped films. The strategy of BIPOL introduction offers a new approach to organic emitters with stereospecific synthesis, TADF, and chiroptical properties.

Salmon Bias and Preterm Birth Among Western Immigrants in China.

Introduction Immigrants from Western industrialized countries are rarely found in immigrant studies. Our primary objective was to calculate the rate of cesarean delivery, 5-min Apgar score <7, and preterm birth among Chinese and Western women. Our secondary objective was to examine whether there are significant differences in terms of risk factors between Western immigrants who chose to deliver in their country of citizenship compared to those who chose to deliver in China. Methods Single-center retrospective cohort study in Shanghai, China. Multivariate logistic regression models used delivery outcome, and place of delivery (China vs. country of citizenship) as outcome variables. Results Preterm birth occurred at a rate of 3.82% among Chinese citizens, 4.12% among Chinese-born Western citizens, and 6.54% among non-Chinese-born Western citizens. After adjustment, preterm birth <37 weeks was more frequent among non-Chinese-born Western citizens compared with Chinese citizens, with an odds ratio of 1.82 (Confidence Interval 1.20-2.78), p = 0.005. Variables statistically associated with giving birth in China were maternal age ≥35 years and being Chinese-born Western, as well as the absence of medical or obstetrical conditions. Discussion Western immigrants have overall good obstetrical outcomes in China, and this could be partly explained by selective immigration, but also by the Salmon bias, as women with risk factors tend to return to their country of citizenship for the delivery. However, the preterm birth rate was higher among Western women than in their Chinese counterparts, and further research is needed.

Vaginal birth after caesarean delivery in Chinese women and Western immigrants in Shanghai.

Recent studies show a steep rise in caesarean sections in China. Most couples are now eligible to apply for a second child. This retrospective cohort study compares the prevalence of trial of labour and vaginal birth after caesarean section among Chinese and foreign women in Shanghai. In total, 135 of 368 women underwent trial of labour (36.68%), and of those, 77 (57.04%) had a vaginal birth. After inclusion in a multivariate model, factors associated with trial of labour were maternal age <35 years with an adjusted odds ratio of 2.58 (1.49-4.46), absence of a history of ≥3 abortions (2.22 (1.08-4.57)), and European citizenship (1.94 (1.05-3.59)). The prevalence of trial of labour and vaginal birth seems to mirror rates found in countries of origin, but despite a high rate of caesarean section, Chinese women had a higher rate of vaginal birth after caesarean section than North American and Australian women, in particular. Impact statement What is already known on this subject: Caesarean section (CS) rates are rising worldwide. Repeat CS contributes largely to these rates, although vaginal birth after CS (VBAC) rates varies widely between countries. What the results of this study add: North American and Australian women who deliver in Shanghai have low rates of attempted trial of labour after CS (TOLAC) and VBAC, with European women having the highest rate of TOLAC, followed by Chinese women. Implications for clinical practice and/or further research: These findings might reflect different levels of acceptance in line with respective national trends. Studies evaluating the influence of cultural norms on birth preferences after CS are needed. Further research is also needed to assess the overall acceptance of TOLAC in the context of the softening of the one-child policy in China.

Profiling risk for acute rejection in kidney transplantation: recipient age is a robust risk factor.

Careful management of immunosuppression is paramount to prevent acute rejection in kidney transplantation. We studied a cohort of 139,875 kidney transplant recipients from the Organ Procurement and Transplantation Network (OPTN) database between 2002 and 2013. We confirmed the analysis with a cohort of 35,277 who received thymoglobulin induction with tacrolimus maintenance, and a third cohort of 12,161 recipients who received basiliximab induction with tacrolimus maintenance. We performed multivariate logistic regression analyses on data from all three cohorts and identified independent risk factors for treated acute rejection at 1 year. Recipient age was a robust risk factor for rejection in all three cohorts in a dose response pattern. Young age (18-25 years) was among the strongest risk factors for rejection in all three cohorts; thymoglobulin cohort: OR 1.87 (1.59-2.19); basiliximab cohort: OR 2.41 (1.89-3.05); and inclusive cohort: OR 1.97 (1.83-2.12). The opposite was true for old age (65-69 years); thymoglobulin cohort: OR 0.69 (0.59-0.81); basiliximab cohort: OR 0.77 (0.62-0.96); and inclusive cohort: OR 0.75 (0.70-0.80). This study is unique because it is the largest and most comprehensive multivariate analysis that demonstrates recipient age is a robust risk factor for acute rejection in an inverse dose response pattern.

Are organic foods safer or healthier than conventional alternatives?: a systematic review.

BACKGROUND: The health benefits of organic foods are unclear. PURPOSE: To review evidence comparing the health effects of organic and conventional foods. DATA SOURCES: MEDLINE (January 1966 to May 2011), EMBASE, CAB Direct, Agricola, TOXNET, Cochrane Library (January 1966 to May 2009), and bibliographies of retrieved articles. STUDY SELECTION: English-language reports of comparisons of organically and conventionally grown food or of populations consuming these foods. DATA EXTRACTION: 2 independent investigators extracted data on methods, health outcomes, and nutrient and contaminant levels. DATA SYNTHESIS: 17 studies in humans and 223 studies of nutrient and contaminant levels in foods met inclusion criteria. Only 3 of the human studies examined clinical outcomes, finding no significant differences between populations by food type for allergic outcomes (eczema, wheeze, atopic sensitization) or symptomatic Campylobacter infection. Two studies reported significantly lower urinary pesticide levels among children consuming organic versus conventional diets, but studies of biomarker and nutrient levels in serum, urine, breast milk, and semen in adults did not identify clinically meaningful differences. All estimates of differences in nutrient and contaminant levels in foods were highly heterogeneous except for the estimate for phosphorus; phosphorus levels were significantly higher than in conventional produce, although this difference is not clinically significant. The risk for contamination with detectable pesticide residues was lower among organic than conventional produce (risk difference, 30% [CI, -37% to -23%]), but differences in risk for exceeding maximum allowed limits were small. Escherichia coli contamination risk did not differ between organic and conventional produce. Bacterial contamination of retail chicken and pork was common but unrelated to farming method. However, the risk for isolating bacteria resistant to 3 or more antibiotics was higher in conventional than in organic chicken and pork (risk difference, 33% [CI, 21% to 45%]). LIMITATION: Studies were heterogeneous and limited in number, and publication bias may be present. CONCLUSION: The published literature lacks strong evidence that organic foods are significantly more nutritious than conventional foods. Consumption of organic foods may reduce exposure to pesticide residues and antibiotic-resistant bacteria. PRIMARY FUNDING SOURCE: None.

Successful long-term treatment of Cushing disease with mifepristone (RU486).

OBJECTIVE: We describe a girl with Cushing disease for whom surgery and radiation treatments failed and the subsequent clinical course with mifepristone therapy. METHODS: We present the patient's clinical, biochemical, and imaging findings. RESULTS: A 16-year-old girl presented with classic Cushing disease. After transsphenoidal surgery, Cyberknife radiosurgery, ketoconazole, and metyrapone did not control her disease, and she was prescribed mifepristone, which was titrated to a maximal dosage of 1200 mg daily with subsequent symptom improvement. Mifepristone (RU486) is a high-affinity, nonselective antagonist of the glucocorticoid receptor. There is limited literature on its use as an off-label medication to treat refractory Cushing disease. Over her 8-year treatment with mifepristone, her therapy was complicated by hypertension and hypokalemia requiring spironolactone and potassium chloride. She received a 2-month drug holiday every 4 to 6 months to allow for withdrawal menstrual bleeding with medroxyprogesterone acetate. Urinary cortisol, serum cortisol, and corticotropin levels remained elevated during mifepristone drug holidays. While on mifepristone, her signs and symptoms of Cushing disease resolved. Repeated magnetic resonance imaging demonstrated stable appearance of the residual pituitary mass. Bilateral adrenalectomy was performed, and mifepristone was discontinued after 95 months of medical therapy. CONCLUSIONS: We describe the longest duration of mifepristone therapy thus reported for the treatment of refractory Cushing disease. Mifepristone effectively controlled all signs and symptoms of hypercortisolism. Menstruating women who take the drug on a long-term basis should receive periodic drug holidays to allow for menses. The lack of reliable serum biomarkers to monitor the success of mifepristone therapy requires careful clinical judgment and may make its use difficult in Cushing disease.

Validation of FRC, a fracture risk assessment tool, in a cohort of older men: the Osteoporotic Fractures in Men (MrOS) Study.

We evaluated the performance of the Fracture Risk Calculator (FRC) in 5893 men who participated in the baseline visit (March 2000-April 2002) of the Osteoporotic Fractures in Men Study. FRC estimates for 10-yr hip and major osteoporotic (hip, clinical spine, forearm, and shoulder) fractures were calculated and compared with observed 10-yr fracture probabilities. Possible enhancement of the tool's performance when bone mineral density (BMD) was included was evaluated by comparing areas under receiver operating characteristic curves and by Net Reclassification Improvement (NRI). A total of 5893 men were followed-up for an average of 8.4 yr. For most quintiles of predicted fracture risk, the ratios of observed to predicted probabilities were close to unity. Area under the curves improved when BMD was included (p<0.001; 0.79 vs 0.71 for hip fracture and 0.70 vs 0.66 for major osteoporotic fracture, respectively). Using National Osteoporosis Foundation clinical treatment thresholds, BMD inclusion increased NRI significantly, 8.5% (p<0.01) for hip and 4.0% (p=0.01) for major osteoporotic fracture. We conclude that the FRC calibrates well with hip and major osteoporotic fractures observed among older men. Further, addition of BMD to the fracture risk calculation improves the tool's performance.

Clinical review: The effect of vitamin D on falls: a systematic review and meta-analysis.

CONTEXT: Vitamin D affects bone and muscle health and likely reduces the risk of falls in the elderly. OBJECTIVE: The aim of this systematic review is to summarize the existing evidence on vitamin D use and the risk of falls. DATA SOURCES: We searched electronic databases from inception through August 2010. STUDY SELECTION: Eligible studies were randomized controlled trials in which the intervention was vitamin D and the incidence of falls was reported. DATA EXTRACTION: Reviewers working in duplicate and independently extracted study characteristics, quality, and outcomes data. DATA SYNTHESIS: Odds ratio and associated 95% confidence interval were estimated from each study and pooled using the random effects model. RESULTS: We found 26 eligible trials of moderate quality that enrolled 45,782 participants, the majority of which were elderly and female. Vitamin D use was associated with statistically significant reduction in the risk of falls (odds ratio for suffering at least one fall, 0.86; 95% confidence interval, 0.77-0.96). This effect was more prominent in patients who were vitamin D deficient at baseline and in studies in which calcium was coadministered with vitamin D. The quality of evidence was low to moderate because of heterogeneity and publication bias. CONCLUSIONS: Vitamin D combined with calcium reduces the risk of falls. The reduction in studies without calcium coadministration did not reach statistical significance. The majority of the evidence is derived from trials enrolling elderly women.

Vitamin D and cardiovascular outcomes: a systematic review and meta-analysis.

CONTEXT: Several studies found association between vitamin D levels and hypertension, coronary artery calcification, and heart disease. OBJECTIVE: The aim of this study was to summarize the evidence on the effect of vitamin D on cardiovascular outcomes. DESIGN AND METHODS: We searched electronic databases from inception through August 2010 for randomized trials. Reviewers working in duplicate and independently extracted study characteristics, quality, and the outcomes of interest. Random-effects meta-analysis was used to pool the relative risks (RR) and the weighted mean differences across trials. RESULTS: We found 51 eligible trials with moderate quality. Vitamin D was associated with nonsignificant effects on the patient-important outcomes of death [RR, 0.96; 95% confidence interval (CI), 0.93, 1.00; P = 0.08], myocardial infarction (RR, 1.02; 95% CI, 0.93, 1.13; P = 0.64), and stroke (RR, 1.05; 95% CI, 0.88, 1.25; P = 0.59). These analyses were associated with minimal heterogeneity. There were no significant changes in the surrogate outcomes of lipid fractions, glucose, or diastolic or systolic blood pressure. The latter analyses were associated with significant heterogeneity, and the pooled estimates were trivial in absolute terms. CONCLUSIONS: Trial data available to date are unable to demonstrate a statistically significant reduction in mortality and cardiovascular risk associated with vitamin D. The quality of the available evidence is low to moderate at best.

The cost-effectiveness of hormone therapy in younger and older postmenopausal women.

PURPOSE: To evaluate the health and economic outcomes of hormone therapy in younger and older postmenopausal women. METHODS: We developed a cost-effectiveness model to evaluate outcomes associated with hormone therapy in younger and older postmenopausal women, using data sources from published literature through March 2008. The target population was 50-year-old and 65-year-old women given hormone therapy or no therapy, and then followed over their lifetime. Primary outcomes measured were quality-adjusted life-years (QALYs) and incremental cost per QALY gained. RESULTS: For the base-case analysis, hormone therapy for 15 years in the younger cohort resulted in a gain of 1.49 QALYs with an incremental cost of $2438 per QALY gained, compared with no therapy. The results for younger women were robust to all sensitivity analyses, and treatment remained highly cost-effective (<$10,000 per QALY gained) within the range of individual assumptions used. Treatment durations of 5 years and 30 years also were highly cost-effective. In the older cohort, treatment for 15 years resulted in a net gain of 0.11 QALYs with a cost of $27,953 per QALY gained. However, a loss of QALYs was seen in the first 9 years. The results for older women were sensitive to many of the assumptions used. CONCLUSIONS: Hormone therapy for 5 to 30 years in younger postmenopausal women increases quality-adjusted life-years and is cost-effective. Hormone therapy started in later years results in a loss of quality-adjusted life for several years before a net gain can be realized.

Screening for osteoporosis in men: a systematic review for an American College of Physicians guideline.

BACKGROUND: Screening for low bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is the primary way to identify asymptomatic men who might benefit from osteoporosis treatment. Identifying men at risk for low BMD and fracture can help clinicians determine which men should be tested. PURPOSE: To identify which asymptomatic men should receive DXA BMD testing, this systematic review evaluates 1) risk factors for osteoporotic fracture in men that may be mediated through low BMD and 2) the performance of non-DXA tests in identifying men with low BMD. DATA SOURCES: Studies identified through the MEDLINE database (1990 to July 2007). STUDY SELECTION: Articles that assessed risk factors for osteoporotic fracture in men or evaluated a non-DXA screening test against a gold standard of DXA. DATA EXTRACTION: Researchers performed independent dual abstractions for each article, determined performance characteristics of screening tests, and assessed the quality of included articles. DATA SYNTHESIS: A published meta-analysis of 167 studies evaluating risk factors for low BMD-related fracture in men and women found high-risk factors to be increased age (>70 years), low body weight (body mass index <20 to 25 kg/m2), weight loss (>10%), physical inactivity, prolonged corticosteroid use, and previous osteoporotic fracture. An additional 102 studies assessing 15 other proposed risk factors were reviewed; most had insufficient evidence in men to draw conclusions. Twenty diagnostic study articles were reviewed. At a T-score threshold of -1.0, calcaneal ultrasonography had a sensitivity of 75% and specificity of 66% for identifying DXA-determined osteoporosis (DXA T-score, -2.5). At a risk score threshold of -1, the Osteoporosis Self-Assessment Screening Tool had a sensitivity of 81% and specificity of 68% to identify DXA-determined osteoporosis. LIMITATION: Data on other screening tests, including radiography, and bone geometry variables, were sparse. CONCLUSION: Key risk factors for low BMD-mediated fracture include increased age, low body weight, weight loss, physical inactivity, prolonged corticosteroid use, previous osteoporotic fracture, and androgen deprivation therapy. Non-DXA tests either are too insensitive or have insufficient data to reach conclusions.

Systematic review: the effects of growth hormone on athletic performance.

BACKGROUND: Human growth hormone is reportedly used to enhance athletic performance, although its safety and efficacy for this purpose are poorly understood. PURPOSE: To evaluate evidence about the effects of growth hormone on athletic performance in physically fit, young individuals. DATA SOURCES: MEDLINE, EMBASE, SPORTDiscus, and Cochrane Collaboration databases were searched for English-language studies published between January 1966 and October 2007. STUDY SELECTION: Randomized, controlled trials that compared growth hormone treatment with no growth hormone treatment in community-dwelling healthy participants between 13 and 45 years of age. DATA EXTRACTION: 2 authors independently reviewed articles and abstracted data. DATA SYNTHESIS: 44 articles describing 27 study samples met inclusion criteria; 303 participants received growth hormone, representing 13.3 person-years of treatment. Participants were young (mean age, 27 years [SD, 3]), lean (mean body mass index, 24 kg/m2 [SD, 2]), and physically fit (mean maximum oxygen uptake, 51 mL/kg of body weight per minute [SD, 8]). Growth hormone dosage (mean, 36 microg/kg per day [SD, 21]) and treatment duration (mean, 20 days [SD, 18] for studies giving growth hormone for >1 day) varied. Lean body mass increased in growth hormone recipients compared with participants who did not receive growth hormone (increase, 2.1 kg [95% CI, 1.3 to 2.9 kg]), but strength and exercise capacity did not seem to improve. Lactate levels during exercise were statistically significantly higher in 2 of 3 studies that evaluated this outcome. Growth hormone-treated participants more frequently experienced soft tissue edema and fatigue than did those not treated with growth hormone. LIMITATIONS: Few studies evaluated athletic performance. Growth hormone protocols in the studies may not reflect real-world doses and regimens. CONCLUSION: Claims that growth hormone enhances physical performance are not supported by the scientific literature. Although the limited available evidence suggests that growth hormone increases lean body mass, it may not improve strength; in addition, it may worsen exercise capacity and increase adverse events. More research is needed to conclusively determine the effects of growth hormone on athletic performance.

Effects of bedding systems selected by manual muscle testing on sleep and sleep-related respiratory disturbances.

In this study, we investigated the feasibility of applying manual muscle testing (MMT) for bedding selection and examined the bedding effect on sleep. Four lay testers with limited training in MMT performed muscle tests for the selection of the bedding systems from five different mattresses and eight different pillows for 14 participants with mild sleep-related respiratory disturbances. For each participant individually, two bedding systems-one inducing stronger muscle forces and the other inducing weaker forces-were selected. The tester-participant pairs showed 85% and 100% agreement, respectively, for the selection of mattresses and pillows that induced the strongest muscle forces. The firmness of the mattress and the height of the pillow were significantly correlated with the body weight and body mass index of the participants for the selected strong bedding system but not for the weak bedding system. Finally, differences were observed between the strong and the weak bedding systems with regard to sleep-related respiratory disturbances and the percentage of slow-wave sleep. It was concluded that MMT can be performed by inexperienced testers for the selection of bedding systems.

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.

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.

The cost-effectiveness of therapy with teriparatide and alendronate in women with severe osteoporosis.

BACKGROUND: Teriparatide is a promising new agent for the treatment of osteoporosis. METHODS: The objective of this study was to evaluate the cost-effectiveness of teriparatide-based strategies compared with alendronate sodium for the first-line treatment of high-risk osteoporotic women. We developed a microsimulation with a societal perspective. Key data sources include the Study of Osteoporotic Fractures, the Fracture Intervention Trial, and the Fracture Prevention Trial. We evaluated postmenopausal white women with low bone density and prevalent vertebral fracture. The interventions were usual care (UC) (calcium or vitamin D supplementation) compared with 3 strategies: 5 years of alendronate therapy, 2 years of teriparatide therapy, and 2 years of teriparatide therapy followed by 5 years of alendronate therapy (sequential teriparatide/alendronate). The main outcome measure was cost per quality-adjusted life-year (QALY). RESULTS: For the base-case analysis, the cost of alendronate treatment was 11,600 dollars per QALY compared with UC. The cost of sequential teriparatide/alendronate therapy was 156,500 dollars per QALY compared with alendronate. Teriparatide treatment alone was more expensive and produced a smaller increase in QALYs than alendronate. For sensitivity analysis, teriparatide alone was less cost-effective than alendronate even if its efficacy lasted 15 years after treatment cessation. Sequential teriparatide/alendronate therapy was less cost-effective than alendronate even if fractures were eliminated during the alendronate phase, although its cost-effectiveness was less than 50,000 dollars per QALY if the price of teriparatide decreased 60%, if used in elderly women with T scores of -4.0 or less, or if 6 months of teriparatide therapy had comparable efficacy to 2 years of treatment. CONCLUSIONS: Alendronate compares favorably to interventions accepted as cost-effective. Therapy with teriparatide alone is more expensive and produces a smaller increase in QALYs than therapy with alendronate. Sequential teriparatide/alendronate therapy appear expensive but could become more cost-effective with reductions in teriparatide price, with restriction to use in exceptionally high-risk women, or if short courses of treatment have comparable efficacy to that observed in clinical trials.

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.

Pediatric anthrax: implications for bioterrorism preparedness.

OBJECTIVES: To systematically review the literature about children with anthrax to describe their clinical course, treatment responses, and the predictors of disease progression and mortality. DATA SOURCES: MEDLINE (1966-2005), 14 selected journal indexes (1900-1966) and bibliographies of all retrieved articles. REVIEW METHODS: We sought case reports of pediatric anthrax published between 1900 and 2005 meeting predefined criteria. We abstracted three types of data from the English-language reports: (1) Patient information (e.g., age, gender, nationality), (2) symptom and disease progression information (e.g., whether the patient developed meningitis); (3) treatment information (e.g., treatments received, year of treatment). We compared the clinical symptoms and disease progression variables for the pediatric cases with data on adult anthrax cases reviewed previously. RESULTS: We identified 246 titles of potentially relevant articles from our MEDLINE(R) search and 2253 additional references from our manual search of the bibliographies of retrieved articles and the indexes of the 14 selected journals. We included 62 case reports of pediatric anthrax including two inhalational cases, 20 gastrointestinal cases, 37 cutaneous cases, and three atypical cases. Anthrax is a relatively common and historically well-recognized disease and yet rarely reported among children, suggesting the possibility of significant under-diagnosis, underreporting, and/or publication bias. Children with anthrax present with a wide range of clinical signs and symptoms, which differ somewhat from the presenting features of adults with anthrax. Like adults, children with gastrointestinal anthrax have two distinct clinical presentations: Upper tract disease characterized by dysphagia and oropharyngeal findings and lower tract disease characterized by fever, abdominal pain, and nausea and vomiting. Additionally, children with inhalational disease may have "atypical" presentations including primary meningoencephalitis. Children with inhalational anthrax have abnormal chest roentgenograms; however, children with other forms of anthrax usually have normal roentgenograms. Nineteen of the 30 children (63%) who received penicillin-based antibiotics survived; whereas nine of 11 children (82%) who received anthrax antiserum survived. CONCLUSIONS: There is a broad spectrum of clinical signs and symptoms associated with pediatric anthrax. The limited data available regarding disease progression and treatment responses for children infected with anthrax suggest some differences from adult populations. Preparedness planning efforts should specifically address the needs of pediatric victims.

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.