High-power Raman lasing and efficient anti-Stokes generation in mm-sized crystalline disk resonators.

We have previously experimentally observed high-power Stokes and second-order Stokes output from a mm-sized CaF2 disk using stimulated Raman scattering. A pump laser at a wavelength of 1.06 µm was coupled via a tapered fiber to the whispering gallery modes (WGM) of the disk. In this Letter, we extend this work and demonstrate the production of the first anti-Stokes sideband at power levels as high as 60 µW in near continuous-wave (CW) operation. The result is a four-component Raman comb at the output, with a wavelength range covering from 1.023 to 1.14 µm. We discuss the threshold dependence of the observed Raman lines on the crystal orientation and provide experimental validation. These advances enable the use of such mm-sized resonators as compact, efficient sources for terahertz-level frequency modulation.

The impact of transvaginal, mesh-augmented level one apical repair on anorectal dysfunction due to pelvic organ prolapse.

INTRODUCTION AND HYPOTHESIS: The objective was to investigate the symptom prevalence of anorectal dysfunction (AD) in women with pelvic organ prolapse (POP) and whether symptom improvement can be achieved by pelvic floor surgery. METHODS: Secondary analysis of the Propel Study data from 277 women with POP stage II-IV regarding bothersome AD symptoms, which were assessed using the Pelvic Floor Distress Inventory (PFDI) questionnaire preoperatively, and 6, 12, and 24 months after transvaginal prolapse repair with Elevate anterior and posterior. RESULTS: Prevalence of AD was high in the study cohort (14.4-56.3%) and could be reduced significantly throughout a 2-year follow-up (cure rates 44.3-83.1%). AD symptoms decreased in a similar manner after posterior/apical fixation to the way they did after anterior/apical fixation (e.g., feeling of incomplete bowel emptying 66.7% to 25.5% vs 46.5% to 10.7% respectively). Hemorrhoids and loss of loose stool decreased even more after anterior/apical fixation than after posterior/apical fixation. Even though AD symptoms decreased significantly more in patients with POP stage III-IV, there was still a considerable improvement in patients with POP stage II (e.g., pain when passing stool 31.1 to 7.7% vs 21.4 to 0% respectively). Notably, even symptoms of hemorrhoids and rectal prolapse improved substantially (cure rates 44.2% and 70.1% respectively). CONCLUSIONS: Symptoms of AD were frequent in our study cohort, and they significantly improved after vaginal mesh-augmented sacrospinous prolapse repair with Elevate anterior and posterior throughout the follow-up period. Anterior/apical fixation showed results that were almost as good as those after posterior/apical fixation. Patients with POP stage II experienced considerable symptom improvement, but cure rates were significantly higher in patients with POP stage III-IV. Vaginal mesh-augmented prolapse repair with good apical fixation is efficacious in resolving AD symptoms with low de novo rates in women suffering of POP.

Recommendations for the conduct of economic evaluations in osteoporosis: outcomes of an experts' consensus meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the US branch of the International Osteoporosis Foundation.

Economic evaluations are increasingly used to assess the value of health interventions, but variable quality and heterogeneity limit the use of these evaluations by decision-makers. These recommendations provide guidance for the design, conduct, and reporting of economic evaluations in osteoporosis to improve their transparency, comparability, and methodologic standards. INTRODUCTION: This paper aims to provide recommendations for the conduct of economic evaluations in osteoporosis in order to improve their transparency, comparability, and methodologic standards. METHODS: A working group was convened by the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis to make recommendations for the design, conduct, and reporting of economic evaluations in osteoporosis, to define an osteoporosis-specific reference case to serve a minimum standard for all economic analyses in osteoporosis, to discuss methodologic challenges and initiate a call for research. A literature review, a face-to-face meeting in New York City (including 11 experts), and a review/approval by a larger group of experts worldwide (including 23 experts in total) were conducted. RESULTS: Recommendations on the type of economic evaluation, methods for economic evaluation, modeling aspects, base-case analysis and population, excess mortality, fracture costs and disutility, treatment characteristics, and model validation were provided. Recommendations for reporting economic evaluations in osteoporosis were also made and an osteoporosis-specific checklist was designed that includes items to report when performing an economic evaluation in osteoporosis. Further, 12 minimum criteria for economic evaluations in osteoporosis were identified and 12 methodologic challenges and need for further research were discussed. CONCLUSION: While the working group acknowledges challenges and the need for further research, these recommendations are intended to supplement general and national guidelines for economic evaluations, improve transparency, quality, and comparability of economic evaluations in osteoporosis, and maintain methodologic standards to increase their use by decision-makers.

Plasma metabolite profiles in children with current asthma.

BACKGROUND: Identifying metabolomic profiles of children with asthma has the potential to increase understanding of asthma pathophysiology. OBJECTIVE: To identify differences in plasma metabolites between children with and without current asthma at mid-childhood. METHODS: We used untargeted mass spectrometry to measure plasma metabolites in 237 children (46 current asthma cases and 191 controls) in Project Viva, a birth cohort from eastern Massachusetts, USA. Current asthma was assessed at mid-childhood (mean age 8.0 years). The ability of a broad spectrum metabolic profile to distinguish between cases and controls was assessed using partial least squares discriminant analysis. We used logistic regression models to identify individual metabolites that were differentially abundant by case-control status. We tested significant metabolites for replication in 411 children from the VDAART clinical trial. RESULTS: There was no evidence of a systematic difference in the metabolome of children reporting current asthma vs. healthy controls according to partial least squares discriminant analysis. However, several metabolites were associated with odds of current asthma at a nominally significant threshold (P < .05), including a metabolite of nicotinamide (N1-Methyl-2-pyridone-5-carboxamide (Odds Ratio (OR) = 2.8 (95% CI 1.1-8.0)), a pyrimidine metabolite (5,6-dihydrothymine (OR = 0.4 (95% CI 0.2-0.9)), bile constituents (biliverdin (OR = 0.4 (95%CI 0.1-0.9), taurocholate (OR = 2.0 (95% CI 1.2-3.4)), two peptides likely derived from fibrinopeptide A (ORs from 1.6 to 1.7), and a gut microbiome metabolite (p-cresol sulphate OR = 0.5 (95% CI 0.2-0.9)). The associations for N1-Methyl-2-pyridone-5-carboxamide and p-cresol sulphate replicated in the independent VDAART population (one-sided P values = .03-.04). CONCLUSIONS AND CLINICAL RELEVANCE: Current asthma is nominally associated with altered levels of several metabolites, including metabolites in the nicotinamide pathway, and a bacterial metabolite derived from the gut microbiome.

Continuous-wave modulation of a femtosecond oscillator using coherent molecules.

We describe a new method to broaden the frequency spectrum of a femtosecond oscillator in the continuous-wave (CW) domain. The method relies on modulating the femtosecond laser using four-wave mixing inside a Raman-based optical modulator. We prepare the modulator by placing deuterium molecules inside a high-finesse cavity and driving their fundamental vibrational transition using intense pump and Stokes lasers that are locked to the cavity modes. With the molecules prepared, any laser within the optical region of the spectrum can pass through the system and be modulated in a single pass. This constitutes a CW optical modulator at a frequency of 90 THz with a steady-state single-pass efficiency of ∼10-6 and transient (10 µs-time-scale) single-pass efficiency of ∼10-4. Using our modulator, we broaden the initial Ti:sapphire spectrum centered at 800 nm and produce upshifted and downshifted sidebands centered at wavelengths of 650 nm and 1.04 µm, respectively.

Extended C-band tunable multi-channel InP-based coherent receiver PICs.

Fully integrated monolithic, multi-channel InP-based coherent receiver PICs and transceiver modules with extended C-band tunability are described. These PICs operate at 33 and 44 Gbaud per channel under dual polarization (DP) 16-QAM modulation. Fourteen-channel monolithic InP receiver PICs show integration and data rate scaling capability to operate at 44 Gbaud under DP 16-QAM modulation for combined 4.9 Tb/s total capacity. Six channel simultaneous operation of a commercial transceiver module at 33 Gbaud is demonstrated for a variety of modulation formats including DP 16-QAM for >1.2Tbit/s aggregate data capacity.

The importance of physical function to people with osteoporosis.

There is increasing need to understand patient outcomes in osteoporosis. This article discusses that fracture in osteoporosis can lead to a cycle of impairment, driven by complex psychosocial factors, having a profound impact on physical function/activity which accumulates over time. More information is required on how treatments impact physical function. INTRODUCTION: There is increasing need to understand patient-centred outcomes in osteoporosis (OP) clinical research and management. This multi-method paper provides insight on the effect of OP on patients' physical function and everyday activity. METHODS: Data were collected from three sources: (1) targeted literature review on OP and physical function, conducted in MEDLINE, Embase and PsycINFO; (2) secondary thematic analysis of transcripts from patient interviews, conducted to develop a patient-reported outcome instrument. Transcripts were re-coded to focus on OP impact on daily activities and physical function for those with and without fracture history; and (3) discussions of the literature review and secondary qualitative analysis results with three clinical experts to review and interpret the importance and implications of the findings. RESULTS: Results suggest that OP, particularly with fracture, can have profound impacts on physical function/activity. These impacts accumulate over time through a cycle of impairment, as fracture leads to longer term detriments in physical function, including loss of muscle, activity avoidance and reduced physical capacity, which in turn leads to greater risk of fracture and potential for further physical restrictions. The cycle of impairment is complex, as other physical, psychosocial and treatment-related factors, such as comorbidities, fears and beliefs about physical activity and fracture risk influence physical function and everyday activity. CONCLUSION: More information on how treatments impact physical function would benefit healthcare professionals and persons with OP in making treatment decisions and improving treatment compliance/persistence, as these impacts may be more salient to patients than fracture incidence.

International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates.

Adherence to oral bisphosphonates is low. A screening strategy is proposed based on the response of biochemical markers of bone turnover after 3 months of therapy. If no change is observed, the clinician should reassess the adherence to the treatment and also other potential issues with the drug. INTRODUCTION: Low adherence to oral bisphosphonates is a common problem that jeopardizes the efficacy of treatment of osteoporosis. No clear screening strategy for the assessment of compliance is widely accepted in these patients. METHODS: The International Osteoporosis Foundation and the European Calcified Tissue Society have convened a working group to propose a screening strategy to detect a lack of adherence to these drugs. The question to answer was whether the bone turnover markers (BTMs) PINP and CTX can be used to identify low adherence in patients with postmenopausal osteoporosis initiating oral bisphosphonates for osteoporosis. The findings of the TRIO study specifically address this question and were used as the basis for testing the hypothesis. RESULTS: Based on the findings of the TRIO study, specifically addressing this question, the working group recommends measuring PINP and CTX at baseline and 3 months after starting therapy to check for a decrease above the least significant change (decrease of more than 38% for PINP and 56% for CTX). Detection rate for the measurement of PINP is 84%, for CTX 87% and, if variation in at least one is considered when measuring both, the level of detection is 94.5%. CONCLUSIONS: If a significant decrease is observed, the treatment can continue, but if no decrease occurs, the clinician should reassess to identify problems with the treatment, mainly low adherence.

Developmental determinants in non-communicable chronic diseases and ageing.

Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of an ageing population and (ii) develop effective novel prevention strategies. It is important to compare the trajectories of respiratory diseases with those of other chronic diseases.

Asthma and allergy development: contrasting influences of yeasts and other fungal exposures.

BACKGROUND: Infancy is a developmental stage with heightened susceptibility to environmental influences on the risk of chronic childhood disease. Few birth cohort studies have detailed measures of fungal diversity data in infants' bedrooms, limiting the potential to measure long-term associations of these complex exposures with development of asthma or allergy. OBJECTIVE: We evaluated the relation of home fungal levels in infancy to repeated measures of wheeze and development of asthma and rhinitis by age 13, and sensitization by age 12 years. METHODS: In the Epidemiology of Home Allergens and Asthma prospective birth cohort study, we recruited 408 children with family history of allergic disease or asthma. When children were aged 2-3 months, we measured culturable fungi in bedroom air and dust, and in outdoor air. Main outcomes included ascertainment of symptoms/disease onset by questionnaire from birth through age 13. We estimated hazard ratios and, for wheeze and sensitization, odds ratios for an interquartile increase in log-transformed fungal concentrations, adjusting for other outcome predictors and potential confounders. RESULTS: Elevated levels of yeasts in bedroom floor dust were associated with reduced: i) wheeze at any age; ii) fungal sensitization; and iii) asthma development by age 13 (hazard ratio (HR) = 0.86; 95% confidence interval (CI), [0.75 to 0.98]). Outdoor airborne Cladosporium and dustborne Aspergillus predicted increased rhinitis. Risk of fungal sensitization by age 12, in response to environmental Alternaria and Aspergillus, was elevated in children with a maternal history of fungal sensitization. CONCLUSIONS AND CLINICAL RELEVANCE: Despite the irritant and allergenic properties of fungi, early-life elevated dust yeast exposures or their components may be protective against allergy and asthma in children at risk for these outcomes. Ascertainment of fungal components associated with immunoprotective effects may have therapeutic relevance for asthma.

Persistence at 12 months with denosumab in postmenopausal women with osteoporosis: interim results from a prospective observational study.

UNLABELLED: To determine persistence with subcutaneous denosumab every 6 months in women being treated for osteoporosis, we conducted a single-arm prospective, observational study in the United States and Canada. Among 935 patients enrolled, 12-month persistence was 82%, with 66 patients (7%) reporting serious adverse events and 19 patients (2%) reporting fractures. INTRODUCTION: Increased persistence with osteoporosis therapy is associated with reduced fracture risk. Denosumab reduced fracture risk in clinical trials; persistence in community settings is undetermined. This study evaluates persistence with denosumab in community practice in the United States (US) and Canada. METHODS: In a 24-month multicenter, prospective, single-arm, observational study, women being treated for osteoporosis were enrolled ≤4 weeks after the first subcutaneous injection of denosumab. For this 12-month prespecified interim analysis, endpoints include persistence (one injection at study entry and another within 6 months + 8 weeks), attributes associated with persistence (univariate analysis), and serious adverse events (SAEs). RESULTS: Among 935 patients (mean age 71 years), mean baseline T-scores were -2.18 (femoral neck) and -2.00 (lumbar spine); 50% of patients had experienced osteoporotic fracture(s). At 12 months, 82 % of patients were persistent with denosumab. Baseline factors significantly (p < 0.05) associated with higher persistence included use of osteoporosis medications >5 years previously, lumbar spine T-score > -2.5, and treatment by female physicians (US). Lower persistence was associated (p < 0.05) with psychiatric diagnoses including depression, southern US residence, being divorced, separated, or widowed (US), and prior hip fracture (Canada). SAEs were reported in 66 patients (7%); no SAEs of osteonecrosis of the jaw, atypical femoral fracture, fracture healing complications, hypocalcemia, eczema, or hypersensitivity were reported. Nineteen patients (2%) reported osteoporotic fractures. CONCLUSIONS: The 12-month persistence observed in this single-arm open-label study of US and Canadian community practice extends the evidence regarding denosumab's potential role in reducing fracture risk in postmenopausal women with osteoporosis.

Cardiorespiratory responses to haemolytic anaemia in rainbow trout Oncorhynchus mykiss.

To quantify cardiorespiratory response to experimental anaemia in rainbow trout Oncorhynchus mykiss, a 24 h phenylhydrazine treatment was used to reduce haematocrit to almost one third of its initial value over 4-5 days. In response, relative blood velocity in the ventral aorta (an index of cardiac output) progressively increased to more than double to its normocythaemic value and there was no significant change in routine oxygen uptake. Thus, the primary compensatory response to anaemia was an increase in cardiac output.

ß-2 adrenergic receptor gene methylation is associated with decreased asthma severity in inner-city schoolchildren: asthma and rhinitis.

BACKGROUND: Genetic variation in the ß-2 adrenergic receptor gene (ADRB2) has been implicated in asthma severity and control with conflicting results. Epigenetic variation in the ADRB2 may play an important role in asthma phenotype. OBJECTIVE: We aimed to evaluate whether DNA methylation of ADRB2 is associated with asthma phenotypes in inner-city school-aged children. METHODS: Multiple CpG sites in the promoter region of ADRB2 gene were analysed in 177 children enrolled in the School Inner-City Asthma Study. Blood- or saliva-derived DNA was measured by bisulphite-polymerase chain reaction pyrosequencing assay. Average percentage DNA methylation across the sites was evaluated for association with asthma severity (report of dyspnoea, night-time symptoms, rescue medication use, and baseline spirometry) and morbidity (school absences and unscheduled healthcare visits). Three clades composed of highly correlated methylation sites within the methylated segment of ADRB2 were further analysed. RESULTS: Methylation of individual sites generally ranged from 0% to 6% with average percentage methylation across sites of 2.4%. Univariate analyses strongly favoured the association of higher percentage methylation with lower asthma severity measured by report of dyspnoea. Furthermore, there was a non-significant trend towards less rescue medication use, night-time symptoms, school absences, activity limitation due to asthma, and improved lung function measurements with increased methylation. Multivariate analysis demonstrated methylation of ADRB2 gene significantly associated with less dyspnoea (odds ratio (OR) 0.2, 95% confidence interval (CI), 0.1-0.6, P = 0.002). Each of the three clades of methylation sites showed a strong, but not statistically significant, effect on decreased dyspnoea. CONCLUSIONS AND CLINICAL RELEVANCE: DNA methylation in the ADRB2 gene is associated with decreased asthma symptom severity, suggesting a role for methylation in asthma phenotypes.

Development of the Osteoporosis Assessment Questionnaire--physical Function (OPAQ-PF): an osteoporosis-targeted, patient-reported outcomes (PRO) measure of physical function.

UNLABELLED: We have developed a short, patient-reported outcome questionnaire--the Osteoporosis Assessment Questionnaire--Physical Function (OPAQ-PF)--that assesses the impact of osteoporosis on physical function. OPAQ-PF contains 15 items in three domains (mobility, physical positions, and transfers) and has content validity in osteoporosis patients with and without a history of fracture. INTRODUCTION: This paper describes the development of the Osteoporosis Assessment Questionnaire--Physical Function (OPAQ-PF), a patient-reported outcome (PRO) questionnaire based on OPAQ v.2.0 (60 items, 14 domains) that assesses the impact of osteoporosis on physical function. METHODS: OPAQ v.2.0 was administered to patients with osteoporosis. Item response theory methodology and clinical judgment were used to retain/eliminate items. The resulting instrument was modified during two sets of concept elicitation and cognitive debriefing interviews with osteoporosis patients. RESULTS: Item response theory-based analysis of OPAQ v.2.0 (n = 1,478) coupled with clinician input resulted in the generation of a 21-item, six-domain instrument with a frequency response format. Interview data from 32 participants were used to modify this version and led to generation of the final instrument, OPAQ-PF. This final version has a severity response format and contains 15 items in three domains (mobility, physical positions, and transfers) that group together to provide an overall assessment of physical function in patients with osteoporosis. Twenty-two of the 32 interview participants (69 %) had previously sustained a fracture. Symptoms occurred primarily in these patients. CONCLUSIONS: OPAQ-PF represents a brief, focused, PRO instrument that assesses physical function in patients with osteoporosis, specifically related to mobility, physical positions, and transfers. This questionnaire has content validity in osteoporosis patients who have, and have not, sustained a prior fracture.

Osteoporosis Assessment Questionnaire-Physical Function (OPAQ-PF): a psychometrically validated osteoporosis-targeted patient reported outcome measure of daily activities of physical function.

UNLABELLED: The purpose of this study was to evaluate the measurement properties of the Osteoporosis Assessment Questionnaire-Physical Functioning (OPAQ-PF). Based on this study, the OPAQ-PF has confirmed unidimensionality and acceptable reliability, construct validity, and sensitivity to change in a recent fracture/no recent fracture osteoporosis sample. METHODS: Dimensionality was established through exploratory and confirmatory factor analysis. Patients completed three patient reported outcome (PRO) measures and four performance-based measures (PBMs) at baseline to enable an evaluation of construct validity. Patients without a recent fracture completed the OPAQ-PF 2 weeks after baseline to enable an evaluation of test-retest reliability. Ability to detect change and interpretation of change were investigated following completion of the OPAQ-PF 12 and 24 weeks postbaseline by patients with a recent fracture. RESULTS: A prospective psychometric validation study in 144 postmenopausal women, with moderate to severe osteoporosis, 37 of whom had experienced a recent fragility fracture (<6 weeks). Unidimensionality was established for the OPAQ-PF by factor analysis. The OPAQ-PF had good internal consistency (α = 0.974) and test-retest reliability (mean intraclass correlation coefficient (ICC) 0.993. The OPAQ-PF differentiated between patients with/without recent fracture, and by severity of osteoarthritis; it correlated strongly with hypothesized-related scales and PBMs (r > 0.3, p < 0.001). Ability to detect change was established with high correlations between changes in OPAQ-PF score and changes in global concept scores in recent fracture patients (r ≥ 0.6, 24-week change). Effect size of change on OPAQ-PF score increased by level of global change (p < 0.001). Anchor-based methods identified an OPAQ-PF change of 10 at an individual patient level and 20 at a group level as meaningful to patients. CONCLUSIONS: The OPAQ-PF has confirmed unidimensionality and acceptable reliability, construct validity, and sensitivity to change in a recent fracture/no recent fracture osteoporosis sample.

The effects of urban green space and road proximity to indoor traffic-related PM2.5, NO2, and BC exposure in inner-city schools.

BACKGROUND: Since there are known adverse health impacts of traffic-related air pollution, while at the same time there are potential health benefits from greenness, it is important to examine more closely the impacts of these factors on indoor air quality in urban schools. OBJECTIVE: This study investigates the association of road proximity and urban greenness to indoor traffic-related fine particulate matter (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) in inner-city schools. METHODS: PM2.5, NO2, and BC were measured indoors at 74 schools and outdoors at a central urban over a 10-year period. Seasonal urban greenness was estimated using the Normalized Difference Vegetation Index (NDVI) with 270 and 1230 m buffers. The associations between indoor traffic-related air pollution and road proximity and greenness were investigated with mixed-effects models. RESULTS: The analysis showed linear decays of indoor traffic-related PM2.5, NO2, and BC by 60%, 35%, and 22%, respectively for schools located at a greater distance from major roads. The results further showed that surrounding school greenness at 270 m buffer was significantly associated (p < 0.05) with lower indoor traffic-related PM2.5: -0.068 (95% CI: -0.124, -0.013), NO2: -0.139 (95% CI: -0.185, -0.092), and BC: -0.060 (95% CI: -0.115, -0.005). These associations were stronger for surrounding greenness at a greater distance from the schools (buffer 1230 m) PM2.5: -0.101 (95% CI: -0.156, -0.046) NO2: -0.122 (95% CI: -0.169, -0.075) BC: -0.080 (95% CI: -0.136, -0.026). These inverse associations were stronger after fully adjusting for regional pollution and meteorological conditions. IMPACT STATEMENT: More than 90% of children under the age of 15 worldwide are exposed to elevated air pollution levels exceeding the WHO's guidelines. The study investigates the impact that urban infrastructure and greenness, in particular green areas and road proximity, have on indoor exposures to traffic-related PM2.5, NO2, and BC in inner-city schools. By examining a 10-year period the study provides insights for air quality management, into how road proximity and greenness at different buffers from the school locations can affect indoor exposure.

Oral bisphosphonates reduce the risk of clinical fractures in glucocorticoid-induced osteoporosis in clinical practice.

UNLABELLED: This study aims to estimate bisphosphonate effectiveness by comparing fracture incidence over time on therapy in glucocorticoid-induced osteoporosis (GIO). From this observational study, alendronate and risedronate decreased clinical vertebral and nonvertebral fractures over time. The effectiveness of each bisphosphonate is consistent with their efficacies demonstrated on surrogate markers in randomized controlled trials (RCTs). INTRODUCTION: This study aims to estimate bisphosphonate effectiveness by comparing fracture incidence over time on therapy with fracture incidence during a short period after starting a therapy. METHODS: The study population was a subgroup of a larger cohort study comprising two cohorts of women aged ≥65 years, prescribed with alendronate or risedronate. Within the two study cohorts, 11,007 women were identified as having received glucocorticoids. Within each cohort, the baseline incidence of clinical fractures at nonvertebral and vertebral sites was defined by the initial 3-month period after starting therapy. Relative to these baseline data, we then compared the fracture incidence during the subsequent 12 months on therapy. RESULTS: The baseline incidence of clinical nonvertebral and vertebral fractures was similar in the alendronate cohort (5.22 and 5.79/100 person-years, respectively) and in the risedronate cohort (5.51 and 5.68/100 person-years, respectively). Relative to the baseline incidence, fracture incidence was significantly lower in the subsequent 12 months in both cohorts of alendronate (33 % lower at nonvertebral sites and 59 % at vertebral sites) and risedronate (28 % lower at nonvertebral sites and 54 % at vertebral sites). CONCLUSION: From this observational study not designed to compare drugs, both alendronate and risedronate decreased clinical vertebral and nonvertebral fractures over time. The reductions observed in fracture incidence, within each cohort, suggest that the effectiveness of each bisphosphonate in clinical practice is consistent with their efficacies demonstrated on surrogate markers in randomized controlled trials.

Patient weighting of osteoporosis medication attributes across racial and ethnic groups: a study of osteoporosis medication preferences using conjoint analysis.

UNLABELLED: We studied the ranking of osteoporosis (OP) medication attributes in a convenience sample of four different racial/ethnic groups in the United States. Our study showed that postmenopausal women differ in the ranking of OP medication attributes based on age, educational level, income, and prior fracture history. INTRODUCTION: Decision making about OP medication-related behavior relies heavily on patient preferences about specific medication attributes. Patients may decide to initiate, change, or stop therapies based on ranking of perceived attributes of the therapy and their personal attitudes toward those attributes. We used MaxDiff, a form of conjoint analysis (Ryan and Farrar 2000), to explore patient weighting of attributes across four racial/ethnic groups at two sites in the United States and defined four critical attributes that influence such decisions (safety, efficacy, cost, and convenience) from qualitative interviews. METHODS: We recruited a sample of 367 Postmenopausal (PM) women at risk of OP fractures from four racial/ethnic groups: Caucasian (n = 100), African American (n = 100), Asian American (n = 82), and Hispanic American (n = 85). Respondents completed a laptop-based questionnaire that included demographic items, several short scales on medical care preference and OP patient perceptions, and a MaxDiff procedure that determines comparative ranking of attributes either as least important or most important to their decisions. RESULTS: MaxDiff analyses were done to evaluate the relative weight of specific statements for each participant and to determine whether racial/ethnic groups differed across dimensions. Overall, participants in all four groups rated efficacy > safety > cost > convenience. CONCLUSIONS: Although there were no significant differences among the racial/ethnic groups on overall ranking of attributes, subgroup analyses revealed significant impact of age, education, income, and prior fracture on these decisions. The findings from this study suggest that postmenopausal women differ in their ranking of OP medication attributes, and healthcare providers must account for personal preferences in their communication about and selection of OP medications.

Primary non-adherence to bisphosphonates in an integrated healthcare setting.

UNLABELLED: We estimated primary non-adherence to oral bisphosphonate medication and examined the factors associated with primary non-adherence. Nearly 30% of women did not pick up their new bisphosphonate within 60 days. Identifying barriers and developing interventions that address patients' needs and concerns at the time a new medication is prescribed are warranted. INTRODUCTION: To estimate primary non-adherence to oral bisphosphonate medications using electronic medical record data in a large, integrated healthcare delivery system and to describe patient and prescribing provider factors associated with primary non-adherence. METHODS: Women aged 55 years and older enrolled in Kaiser Permanente Southern California (KPSC) with a new prescription for oral bisphosphonates between December 1, 2009 and March 31, 2011 were identified. Primary non-adherence was defined as failure to pick up the new prescription within 60 days of the order date. Multivariable logistic regression models were used to investigate patient factors (demographics, healthcare utilization, and health conditions) and prescribing provider characteristics (demographics, years in practice, and specialty) associated with primary non-adherence. RESULTS: We identified 8,454 eligible women with a new bisphosphonate order. Among these women, 2,497 (29.5%) did not pick up their bisphosphonate prescription within 60 days of the order date. In multivariable analyses, older age and emergency department utilization were associated with increased odds of primary non-adherence while prescription medication use and hospitalizations were associated with lower odds of primary non-adherence. Prescribing providers practicing 10 or more years had lower odds of primary non-adherent patients compared with providers practicing less than 10 years. Internal medicine and rheumatology providers had lower odds of primary non-adherent patients than primary care providers. CONCLUSION: This study found that nearly one in three women failed to pick up their new bisphosphonate prescription within 60 days. Identifying barriers and developing interventions aimed at reducing the number of primary non-adherent patients to bisphosphonate prescriptions are warranted.

Wheeze in infancy: protection associated with yeasts in house dust contrasts with increased risk associated with yeasts in indoor air and other fungal taxa.

BACKGROUND: While fungal exposures are assumed to provoke wheeze through irritant or allergenic mechanisms, little is known about the differential effects of indoor and outdoor fungi on early-life wheeze. METHODS: In a Boston prospective birth cohort of 499 at-risk infants, culturable fungi in bedroom air and dust and outdoor air were measured at the age of 2-3 months. Wheeze was determined using bimonthly telephone questionnaires. Odds ratios were estimated for an interquartile increase in fungal natural log-transformed concentrations, adjusting for predictors of wheeze and potential confounders. RESULTS: Increased odds of 'any wheeze' (≥1 vs 0 episodes) by age one were positively associated with indoor dust Alternaria [odds ratio (OR) = 1.83; 95% confidence interval (CI), 1.07-3.14], Penicillium [OR = 1.18; (0.98-1.43)], and Cladosporium [OR = 1.47; (1.16-1.85)]; indoor air Penicillium [OR = 1.26; (0.92-1.74)]; and outdoor air Cladosporium [OR = 1.68; (1.04-2.72)]. In contrast, indoor dust yeasts were protective [OR = 0.78; (0.66-0.93)]. 'Frequent wheeze' (≥2 vs <2 episodes) by age one was borderline associated with dust yeasts [OR = 0.86; (0.70-1.04)] and indoor air yeasts [OR = 1.53; (0.93-2.53)]. Alternaria concentration was associated with any wheeze for children with maternal mold sensitization [OR = 9.16; (1.37-61.22)], but not for those without maternal mold sensitization [OR = 1.32; (0.79-2.20)]. CONCLUSIONS: While wheeze rates were higher with exposures to fungal taxa considered to be irritant or allergenic in sensitive subjects, yeasts in the home had a strong protective association with wheeze in infancy. Molecular microbiologic studies may elucidate specific components of innate microbiologic stimulants that lead to contrasting effects on wheeze development.