Effectiveness of denosumab for fracture prevention in real-world postmenopausal women with osteoporosis: a retrospective cohort study.

To determine denosumab's effectiveness for fracture prevention among postmenopausal women with osteoporosis in East Asia, the risk of fracture was compared between patients continuing denosumab therapy versus patients discontinuing denosumab after one dose. The real-world effectiveness was observed to be consistent with the efficacy demonstrated in the phase III trial. INTRODUCTION: After therapeutic efficacy is demonstrated for subjects in global clinical trials, real-world evidence may provide complementary knowledge of therapeutic effectiveness in a heterogeneous mix of patients seen in clinical practice. This retrospective cohort study was conducted to compare the fracture risk in real-world clinical care received in Taiwan and Hong Kong between a treatment cohort (patients receiving denosumab 60 mg subcutaneously every 6 months) versus an off-treatment cohort (patients discontinuing after 1 dose of denosumab, which has no known clinical benefit) among real-world postmenopausal women. METHODS: This study included 38,906 and 2,835 postmenopausal women receiving denosumab in Taiwan and Hong Kong, respectively. The primary endpoint was hip fracture, and secondary endpoints were clinical vertebral and nonvertebral fractures. Propensity-score-matched analysis, adjusting for known covariates, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). The robustness of findings was evaluated with a series of sensitivity and quantitative bias analyses. RESULTS: In this study, 554 hip fractures were included in the primary Taiwan population analysis. The crude incidence rate was 0.9 per 100 person-years in the treatment cohort (n = 25,059) and 1.7 per 100 person-years in the off-treatment cohort (n = 13,847). After adjusting for prognostic differences between cohorts, denosumab reduced the risk of hip fractures by 38% (HR = 0.62, CI:0.52-0.75). Risk reductions of similar magnitude were observed for the secondary endpoints and for the analysis of the smaller Hong Kong population. CONCLUSION: The effectiveness of denosumab for fracture reduction among real-world postmenopausal women with osteoporosis was consistent with the efficacy demonstrated in a global clinical trial. REGISTRATION: EnCePP registration number: EUPAS26372; registration date: 12/11/2018.

Effectiveness of risedronate and alendronate on nonvertebral fractures: an observational study through 2 years of therapy.

UNLABELLED: This observational study showed that after 2 years, both risedronate and alendronate lowered the risk of hip and nonvertebral fractures compared with patients filling in a single bisphosphonate prescription. INTRODUCTION: Post hoc analyses of the placebo-controlled trials suggested earlier effects for risedronate (6-12 months) than for alendronate (18-24 months). The present study extends our 1-year observational data that confirmed an earlier fracture reduction with risedronate and evaluated the absolute and relative effectiveness of alendronate and risedronate in clinical practice over 2 years. METHODS: We observed three cohorts of women aged 65 years and older who initiated once-a-week dosing of bisphosphonate therapy; (1) patients adherent to alendronate (n = 21,615), (2) patients adherent to risedronate (n = 12,215), or (3) patients filling only a single bisphosphonate prescription (n = 5,390) as a referent population. Proportional hazard modeling compared the incidence of hip and nonvertebral fractures among the cohorts over 2 years after the initial prescription. RESULTS: In this cohort, we previously showed at 12 months a significant reduction of hip and nonvertebral fractures with risedronate but not with alendronate. At the end of 2 years, the cumulative incidence of hip fractures in the referent cohort was 1.9 %, and incidence of nonvertebral fractures was 6.3 %. Relative to the referent, 6 months after initiating therapy and continuing through 2 years, both risedronate and alendronate cohorts had approximately a 45 % lower incidence of hip fractures and a 30 % lower incidence of nonvertebral fractures. CONCLUSION: These observations suggest that both risedronate and alendronate are effective at reducing the risk of hip and nonvertebral fracture after 2 years of treatment and support the post hoc analyses of placebo-controlled trials indicating an earlier effect of risedronate.

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.

Longitudinal change in clinical fracture incidence after initiation of bisphosphonates.

SUMMARY: There are differences in the risk profile of patients prescribed alendronate, risedronate, or ibandronate. Observed reductions in fracture incidence over time suggest that the effectiveness of each bisphosphonate in clinical practice has been consistent with their efficacies demonstrated in randomized controlled trials. INTRODUCTION: Observational studies of bisphosphonate effectiveness for fracture prevention are subject to bias from unknown characteristics of baseline fracture risk at the start of therapy. The fracture incidence during the short period after starting a bisphosphonate and before any expected clinical benefit likely reflects baseline fracture risk. Bisphosphonate effectiveness may then be estimated by measuring the change in fracture incidence over time on therapy. METHODS: Administrative billing data were used to follow three cohorts of women aged 65 and older (total n = 210,144) after starting therapy either on alendronate, risedronate, or ibandronate in the USA between market introduction and 2006. Within each cohort, the baseline incidence of clinical fractures at the hip, vertebral, and nonvertebral sites was defined by the initial 3-month period after starting therapy. Relative to these baselines, we then compared the fracture incidence during the subsequent 12 months on therapy. RESULTS: At the start of therapy, the ibandronate cohort was younger and had fewer prior fractures than either the risedronate or alendronate cohorts. Accordingly, the baseline incidence of hip fractures was higher in the risedronate cohort (0.90 per 100 person-years) and in the alendronate cohort (0.77) than in the ibandronate cohort (0.64). Relative to the baseline incidence, fracture incidence was significantly lower in the subsequent 12 months in both cohorts of alendronate (18% lower at hip, 28% at nonvertebral sites, and 57% at vertebral sites) and risedronate (27% lower at hip, 21% at nonvertebral sites, and 54% at vertebral sites). In the ibandronate cohort, the fracture incidence was lower (31%) only at vertebral sites. CONCLUSIONS: Differences in the baseline fracture incidence among the cohorts may reflect differences in the risk profile of patients prescribed each bisphosphonate. The reductions observed in fracture incidence over time within each cohort suggest that the effectiveness of each bisphosphonate in clinical practice has been consistent with their efficacies demonstrated in randomized controlled trials.

Changes in amount and intracellular distribution of androgen receptor in human foreskin as a function of age.

To provide insight into the factors that control growth of the penis we measured the amount and intracellular distribution of specific high affinity androgen receptor in foreskins obtained at circumcision from 49 males varying in age from newborn to 59 yr. Total (cytosolic plus nuclear extract) androgen receptor decreased from approximately 40 fmol/g tissue weight in newborn foreskins to approximately 25 fmol/g by 1 yr of age. The amount of receptor rose in childhood to approximately 180 fmol/g in the late teenage years and fell thereafter to approximately 20-40 fmol/g in men older than 40 yr. The amount of receptor in the nuclear fraction increased at the time of puberty and subsequently decreased in parallel with the decline in total receptor level. These changes in androgen-receptor amount are similar when expressed per milligram DNA or per milligram protein.

The nature, incidence, and impact of eye injuries among US military personnel: implications for prevention.

OBJECTIVES: To assess incidence rates of eye injuries in the US Armed Forces and to identify demographic and occupational correlates of risk. DESIGN: Retrospective population-based study. SETTING: US military medical facilities worldwide. PARTICIPANTS: All individuals in the US Armed Forces during 1998. MAIN OUTCOME MEASURES: Incidence rates of hospitalizations and ambulatory visits for eye injuries. RESULTS: The incidence rate of ambulatory visits (983 per 100 000 person-years) for eye injuries was 58 times higher than the incidence rate of hospitalizations (17 per 100 000 person-years) for eye injuries. Orbital floor fractures, contusions, and open wounds to the ocular adnexa and orbit accounted for 85% of eye injuries resulting in hospitalization, while 80% of ambulatory visits were for superficial wounds and foreign bodies. Hospitalization rates varied widely across demographic subgroups. Men had twice the incidence rate as women, and the youngest age group (17-24 years) had 6 times the incidence rate of the oldest age group (35-65 years). Together, motor vehicle crashes and fights caused nearly half of the hospitalizations. Ambulatory rates varied significantly in relation to occupation but not to demography. Tradespeople (eg, metal body machinist, welder, and metalworker) had incidence rates 3 to 4 times higher than the overall population rate. CONCLUSIONS: Hospitalization and ambulatory data provide different views of the morbidity associated with eye injuries. General safety precautions and behavior modification, rather than eye-specific interventions, are indicated to prevent the most serious eye injuries. However, the consistent use of eye protection during known hazardous occupational activities could prevent much of the morbidity associated with the less serious, yet more common, eye injuries.

Certified safe farm: identifying and removing hazards on the farm.

This article describes the development of the Certified Safe Farm (CSF) on-farm safety review tools, characterizes the safety improvements among participating farms during the study period, and evaluates differences in background variables between low and high scoring farms. Average farm review scores on 185 study farms improved from 82 to 96 during the five-year study (0-100 scale, 85 required for CSF certification). A total of 1292 safety improvements were reported at an estimated cost of $650 per farm. A wide range of improvements were made, including adding 9 rollover protective structures (ROPS), 59 power take-off (PTO) master shields, and 207 slow-moving vehicle (SMV) emblems; improving lighting on 72 machines: placing 171 warning decals on machinery; shielding 77 moving parts; locking up 17 chemical storage areas, adding 83 lockout/tagout improvements; and making general housekeeping upgrades in 62 farm buildings. The local, trained farm reviewers and the CSF review process overall were well received by participating farmers. In addition to our earlier findings where higher farm review scores were associated with lower self-reported health outcome costs, we found that those with higher farm work hours, younger age, pork production in confinement, beef production, poultry production, and reported exposure to agrichemicals had higher farm review scores than those who did not have these characteristics. Overall, the farm review process functioned as expected. encouraging physical improvements in the farm environment, and contributing to the multi-faceted CSF intervention program.

Effectiveness of bisphosphonates on nonvertebral and hip fractures in the first year of therapy: the risedronate and alendronate (REAL) cohort study.

INTRODUCTION: Randomized clinical trials have shown that risedronate and alendronate reduce fractures among women with osteoporosis. The aim of this observational study was to observe, in clinical practice, the incidence of hip and nonvertebral fractures among women in the year following initiation of once-a-week dosing of either risedronate or alendronate. METHODS: Using records of health service utilization from July 2002 through September 2004, we created two cohorts: women (ages 65 and over) receiving risedronate (n = 12,215) or alendronate (n = 21,615). Cox proportional hazard modeling was used to compare the annual incidence of nonvertebral fractures and of hip fractures between cohorts, adjusting for potential differences in risk factors for fractures. RESULTS: There were 507 nonvertebral fractures and 109 hip fractures. Through one year of therapy, the incidence of nonvertebral fractures in the risedronate cohort (2.0%) was 18% lower (95% CI 2% - 32%) than in the alendronate cohort (2.3%). The incidence of hip fractures in the risedronate cohort (0.4%) was 43% lower (95% CI 13% - 63%) than in the alendronate cohort (0.6%). These results were consistent across a number of sensitivity analyses. CONCLUSION: Patients receiving risedronate have lower rates of hip and nonvertebral fractures during their first year of therapy than patients receiving alendronate.

Eleven years of experience with the inflatable penile prosthesis.

The 11-year experience with 395 consecutive patients in whom an inflatable prosthesis was implanted for the treatment of chronic erectile impotence is reported. Among these patients the most common etiology was vascular disease, followed by diabetes mellitus and radical pelvic surgery. The original American Medical Systems prosthesis with PPT cylinders shows a 61 per cent complication and revision rate with followup from 3 to 11 years. The newer inflatable prostheses manufactured since 1983 have needed revision in only 13 per cent of the patients followed to 4 years. Salvage procedures and increased product reliability have resulted in 97 per cent of the patients being satisfied. Five types of inflatable prostheses are compared and advantages are discussed.

Application of flow cytometry and fluorescent in situ hybridization for assessment of exposures to airborne bacteria.

Current limitations in the methodology for enumeration and identification of airborne bacteria compromise the precision and accuracy of bioaerosol exposure assessment. In this study, flow cytometry and fluorescent in situ hybridization (FISH) were evaluated for the assessment of exposures to airborne bacteria. Laboratory-generated two-component bioaerosols in exposures chambers and complex native bioaerosols in swine barns were sampled with two types of liquid impingers (all-glass impinger-30 and May 3-stage impinger). Aliquots of collection media were processed and enumerated by a standard culture technique, microscopy, or flow cytometry after nucleic acid staining with 4',6-diamidino-2-phenylindole (DAPI) and identified taxonomically by FISH. DAPI-labeled impinger samples yielded comparable estimates of bioaerosol concentrations when enumerated by microscopy or flow cytometry. The standard culture method underestimated bioaerosol concentrations by 2 orders of magnitude when compared to microscopy or flow cytometry. In the FISH method, aliquots of collection media were incubated with a probe universally complementary to eubacteria, a probe specific for several Pseudomonas species, and a probe complementary to eubacteria for detection of nonspecific binding. With these probes, FISH allowed quantitative identification of Pseudomonas aeruginosa and Escherichia coli bioaerosols in the exposure chamber without measurable nonspecific binding. Impinger samples from the swine barn demonstrated the efficacy of the FISH method for the identification of eubacteria in a complex organic dust. This work demonstrates the potential of emerging molecular techniques to complement traditional methods of bioaerosol exposure assessment.

Injuries in the Iowa Certified Safe Farm Study.

The aims of this article are to assess injury characteristics and risk factors in the Iowa Certified Safe Farm (CSF) program and to evaluate the effectiveness of CSF for reducing injuries. This intervention program includes a health screening, on-farm safety review, education, and monetary incentives. Cohorts of farmers in an intervention group (n = 152) and control group (n = 164) in northwestern Iowa were followed for a three-year period. During the follow-up, there were 318 injuries (42/100 person-years), of which 112 (15/100 person-years) required professional medical care. The monetary cost of injuries was $51,764 ($68 per farm per year). There were no differences in the self-reported injury rates and costs between the intervention and control groups. Raising livestock, poor general health, and exposures to dust and gas, noise, chemicals and pesticides, and lifting were among risk factors for injury. Most injuries in this study were related to animals, falls from elevation, slips/trips/falls, being struck by or struck against objects, lifting, and overexertion. Machinery was less prominent than generally reported in the literature. Hurry, fatigue, or stress were mentioned as the primary contributing factor in most injuries. These findings illustrate the need for new interventions to address a multitude of hazards in the farm work environment as well as management and organization of farm work.

Bioaerosol sampling in field studies: can samples be express mailed?

Bioaerosol sampling for viable microorganisms was conducted in 25 dairy barns in summer and in winter to examine the relationship of sample storage and shipping in determining bioaerosol concentrations separately for yeasts, molds, mesophilic bacteria, and thermophilic organisms. The study also compared the performance of three sampling methods--(1) all-glass impinger (AGI) used with peptone solution in both seasons and (2) betaine solution in winter; and (3) the nuclepore filtration and elution (NFE) method, using air filtration with subsequent elution and culturing--which were studied in a pairwise fashion with duplicate, simultaneous, side-by-side sampling. For each sample, one duplicate was analyzed within two hours in a laboratory less than 50 km from the sampling site, while the other was express-mailed to the authors' laboratory. Concentrations of all microorganisms measured by the AGI peptone method were unaffected by mailing in winter, but mesophilic bacteria increased in summer. AGI betaine samples were unchanged except for increased concentrations of molds after mailing in winter. Yeasts and mesophilic bacteria significantly decreased after mailing of NFE samples. Pairwise comparison of the sampling methods in winter yielded no significant differences in airborne concentrations for the yeasts, mesophilic bacteria, and thermophilic bacteria. Both AGI betaine and NFE methods had significantly greater concentrations of molds than AGI peptone. In summer, concentrations of yeasts and mesophilic bacteria were significantly greater with AGI peptone, as were molds with the NFE method.(ABSTRACT TRUNCATED AT 250 WORDS)