Tao Fan

Epidemiology of falls and osteoporotic fractures: a systematic review

Background and methods Fractures in elderly populations result from the combination of falls and osteoporosis. We report a systematic review of studies indexed in PubMed reporting annual rates of low-trauma falls and associated osteoporotic fractures among older community-dwelling people (age ≥ 50 years). An osteoporotic fracture was defined as either a fracture resulting from a low-impact fall in subjects with clinical osteoporosis, a fall resulting in an investigator-defined osteoporotic fracture, or a fall resulting in a low-trauma fracture. Rates are presented using descriptive statistics. Meta-analysis was conducted for statistically homogeneous data sets. Results The median (range) annual fall prevalence rates (median proportion of people who experienced one or more falls during the past year) for cohorts of women and men (10 determinations), women alone (seven determinations), and men alone (four determinations) were, respectively, 0.334 (0.217–0.625), 0.460 (0.372–0.517), and 0.349 (0.284–0.526). In studies that reported fall prevalence rates for Western men and women separately (four determinations), the pooled risk ratio (95% confidence interval [CI]) for men versus women was 0.805 (95% CI 0.721–0.900). The ranges of fall prevalence rates in East Asian women (two studies) and East Asian men (two studies) were, respectively, 0.163–0.258 and 0.087–0.184. The risk ratio (95% CI) for fall prevalence in East Asian men versus women was 0.634 (0.479–0.838) in studies (two determinations) reporting results for East Asian men and women separately. In cohorts of Western women and men (five determinations), the pooled rate (95% CI) of low-impact falls resulting in fractures was 0.041 (0.031–0.054). The proportion of low-trauma fractures attributable to falls among the Western community-dwelling elderly was within the range of 0.860–0.950 for fractures at all sites or the hip (five determinations). A range of 0.716–0.924 of all fractures were osteoporotic (eight determinations). Conclusion Fall rates are higher in women than in men in Western community-dwelling populations and lower in East Asian populations. Extrapolated to the US population, the statistics imply that low-impact falls cause approximately 0.53 million osteoporotic fractures annually among the US community-dwelling elderly.

Efficacy of vitamin D3 supplementation in preventing fractures in elderly women: A meta-analysis

Abstract Background: The efficacy of vitamin D3 in preventing fractures and falls has been explored in a number of clinical trials. However, recent evidence revealed new questions about the adequate doses of vitamin D3 supplementation and its efficacy in fracture prevention independent of calcium supplements for various types of fractures. Objective: To conduct a meta-analysis to estimate the effectiveness of 800 IU daily vitamin D3 supplementation for increasing bone mineral density (BMD) and preventing fractures in postmenopausal women. Methods: Medline and EMBASE were searched for controlled trials comparing the effectiveness of cholecalciferol (vitamin D3) against placebo with or without background calcium supplementation in the treatment of postmenopausal women. Results: Eight controlled trials evaluating the effect of vitamin D3 supplementation with or without calcium were assessed. Of 12 658 women included in a Bayesian meta-analysis, 6089 received vitamin D3 (with or without calcium) and 6569 received placebo (with or without calcium). Compared to placebo, vitamin D3 with calcium supplementation showed beneficial effects on the incidence of non-vertebral (odds ratio [OR] 0.77, 95% credibility limit [CL] 0.6–0.93) and hip (OR 0.70, 95% CL 0.53–0.90) fractures, while the effects on non-vertebral-non-hip fractures (OR 0.84, 95% CL 0.67–1.04) % point increase) were associated with more uncertainty. Vitamin D3 supplementation showed a 70% probability of being a better treatment than placebo for the prevention of non-vertebral fractures, hip fractures, and non-vertebral, non-hip fractures. Compared to calcium supplementation, vitamin D3 plus calcium reduced non-vertebral fractures (OR 0.68, 95% CL 0.43–1.01) and non-vertebral, non-hip fractures (OR 0.64, 95% CL 0.38–0.99), but did not reduce hip fractures (OR 1.03, 95% CL 0.39–2.25). Key limitations to this analysis include a small number of studies and heterogeneity in the study populations. Conclusions: This meta-analysis supports the use of vitamin D3 of 800 IU daily to reduce the incidence of osteoporotic non-vertebral, hip, and non-vertebral-non-hip fractures in elderly women. Vitamin D3 with calcium appears to achieve benefits above those attained with calcium supplementation alone for non-vertebral and non-vertebral-non-hip fractures.

Prescribing patterns of asthma controller therapy for children in UK primary care: a cross-sectional observational study

BackgroundAsthma management guidelines recommend a stepwise approach to instituting and adjusting anti-inflammatory controller therapy for children with asthma. The objective of this retrospective observational study was to describe prescribing patterns of asthma controller therapies for children in a primary care setting.MethodsData from the UK General Practice Research Database were examined for children with recorded asthma or recurrent wheezing who, from September 2006 through February 2007, were ≤ 14 years old at the time of a first asthma controller prescription after ≥ 6 months without a controller prescription. We evaluated demographic characteristics, asthma duration, comorbidities, asthma-related health care resource use, and prescribed daily dose of controller medication. In addition, physicians for 635 randomly selected patients completed a survey retrospectively classifying asthma severity at the prescription date and describing therapy and health care utilization for 6 prior months.ResultsWe identified 10,004 children, 5942 (59.4%) of them boys, of mean (SD) age of 8.0 (3.8) years. Asthma controller prescriptions were for inhaled corticosteroid (ICS) monotherapy for 9059 (90.6%) children; ICS plus long-acting β2-agonist (LABA) for 698 (7.0%); leukotriene antagonist monotherapy for 91 (0.9%); ICS plus leukotriene antagonist for 55 (0.6%); and other therapy for 101 (1.0%), including 45 (0.45%) children who were prescribed LABA as monotherapy. High doses of ICS (> 400 μg) were prescribed for 44/2140 (2.1%) children < 5 years old and for 420/7452 (5.6%) children ≥ 5 years. Physicians reported asthma severity as intermittent for 346/635 (55%) patients and as mild, moderate, and severe persistent for 159 (25%), 71 (11%), and 11 (2%), respectively (severity data missing for 48 [8%]). The baseline characteristics and controller therapy prescriptions of the survey cohort were similar to those of the full cohort.ConclusionsPhysician classifications of asthma severity did not always correspond to guideline recommendations, as leukotriene receptor antagonists were rarely used and high-dose ICS or add-on LABA was prescribed even in intermittent and mild disease. In UK primary care, monotherapy with ICS is the most common controller therapy at all levels of asthma severity.

Estimation of resource utilization associated with osteoporotic hip fracture and level of post-acute care in China

ABSTRACT Objective: Research suggests that the incidence and cost of treating osteoporotic hip fracture (OHF) in China is rising. The purpose of this study was to estimate resource utilization associated with OHF, including hospital length of stay (LOS) and inpatient costs, and to examine the level of post-acute care for osteoporosis among patients hospitalized for OHF in Shanghai, China. Methods: This was a retrospective study of 2855 patients aged 50 years and older who were hospitalized for bone fragility hip fractures in 13 districts of Shanghai in the 2000. One hundred and one patients were randomly selected and interviewed to determine the treatments and associated costs for the 6-month period following hospitalization. Log linear regressions with bootstrapping resampling were conducted for LOS and hospital cost data to estimate the average LOS and associated costs after adjusting for demographic and comorbid characteristics. Results: Hospital records of 2855 patients (mean age, 73.6 ± 9.9 years) were reviewed. For women, mean LOS (35 days) was longer for those greater than 60 years of age; however, mean cost of hospital stay (15 082 RMB) increased to a peak at age 65–74 years (18 932 RMB). For men, mean LOS (34 days) and mean cost of hospitalization (13 149 RMB) both increased with age. Only 14% of patients hospitalized for OHF received treatment for osteoporosis. Due to the small number of patients and sampling that was taken largely for geographical convenience, care should be taken when generalizing these data into other areas of China. Conclusions: OHF is associated with substantial resource utilization in Shanghai, China. Although patients hospitalized with OHF should be considered for osteoporosis therapy to alleviate economic and patient burden, most patients with OHF received no such treatment.

Calcium and vitamin D intake by postmenopausal women with osteoporosis in France

Abstract Objective: To assess dietary calcium and vitamin D intake and their relationship with prescription medication and nutritional supplement use among postmenopausal women with osteoporosis in France. Research design and methods: Telephone interviews were conducted with 207 postmenopausal women with osteoporosis referred by a random sample of physicians from a French national list. Based on a French food frequency questionnaire, patients reported their daily food intake and frequency as well as their use of prescription medications and nutritional supplements. Results: Average daily dietary vitamin D intake was only 144.8 IU (SD 84.6, p < 0.01 compared to the recommended 800 IU), with 30% of the sample taking a vitamin D supplement. No participant had more than 500 IU vitamin D daily from food alone and 78% had less than 200 IU per day. A total of 51% of patients took no vitamin D supplements and had less than 5 hours of sun exposure in a week. Patients who were receiving osteoporosis medications and those who were not had comparable vitamin D intake. The average daily dietary calcium intake was 966.4 mg (SD 273.7, p < 0.01 compared to the 800 mg recommended). Calcium supplements were taken by 38% of participants and older patients tended to take more. Limitations of the study include convenience sampling and patient self-report. Conclusions: Daily vitamin D intake among this sample of postmenopausal osteoporotic women in France was significantly lower than recommended dosages. At least 50% of these patients might benefit by adding vitamin D to their current therapy.

Persistence with weekly and monthly bisphosphonates among postmenopausal women: analysis of a US pharmacy claims administrative database

Background Bisphosphonates are available in daily, weekly, and monthly dosing formulations to treat postmenopausal osteoporosis. Some researchers suggested that adherence to monthly bisphosphonate might be different from that with weekly or daily bisphosphonate because of different dosing regimens. However, the actual persistency rates in regular practice settings are unknown. Objectives To compare persistence rates with alendronate 70 mg once weekly (AOW), risedronate 35 mg once weekly (ROW), and ibandronate 150 mg once monthly (IOM) in a US pharmacy claims database. Methods In this retrospective cohort study, pharmacy claims data of patients with new bisphosphonate prescriptions were extracted for women aged ≥ 50 years who had an AOW, ROW, or IOM prescription (index prescription) between December 30, 2004 and May 31, 2005 (the index period) and did not have the index Rx during the previous 12 months. Patients’ records were reviewed for at least 5 months from their index date to November 2, 2005 (the follow-up period). Patients were considered persistent if they neither discontinued (failed to refill the index Rx within a 45-day period following the last supply day of the previous dispensing) nor switched (changed to another bisphosphonate) during the follow-up period. Medication-possession ratio was defined as days with index prescription supplies/total days of follow-up. Results Among 44,635 patients, 25,207 (56.5%) received prescriptions of AOW, 18,689 (41.9%) ROW, and 739 (1.7%) IOM as the index prescription. In all, 35.1% of AOW patients, 32.5% of ROW patients, and 30.4% of IOM patients (P < 0.0001 AOW vs ROW or IOM) had persisted with their initial therapy, whereas 64.0% of AOW, 66.4% of ROW, and 68.2% of IOM patients discontinued (P < 0.0001) during follow-up. The medication-possession ratio (days with index prescription supplies/total days of follow-up) was significantly higher for AOW (0.55) compared with ROW (0.52) and IOM (0.51, P < 0.05). By Kaplan–Meier analysis, the time for 50% of patients to discontinue therapy was also significantly longer with AOW (109 days) compared with ROW (95 days, P < 0.05) or IOM (58 days, P < 0.05). Conclusion In a real-world clinical setting, although persistence with all treatments was suboptimal, patients receiving prescriptions for once-weekly alendronate were more likely to be persistent than those receiving prescriptions for once-weekly risedronate or once-monthly ibandronate.

Frequency of diagnosis and treatment of allergic rhinitis among adults with asthma in Germany, France, and the UK: National Health and Wellness Survey

ABSTRACT Background: Concomitant allergic rhinitis (AR) adds to the symptomatic burden of asthma. Scope: To determine the proportion of adults with concomitant asthma and AR whose AR is diagnosed and/or treated, data were derived from a cross-sectional, stratified, random sample of 26,468 adults from France, Germany and the UK, participants in the 2004 web-based National Health and Wellness Survey. Patients were drawn from the database if they reported (1) experiencing asthma in the prior 12 months, (2) a physician diagnosis of asthma, and (3) ever experiencing ‘nasal allergies/hay fever’ (physician diagnosed or self-reported symptoms). Findings: Of 1139 patients with asthma who reported AR, 203 (18%) did not have a diagnosis of AR. Of these, 86 (42%) pursued over-the-counter self-treatment for AR, and 117 (58%) remained untreated. Of 936 patients who reported diagnosed AR, 471 (50%) received AR prescriptions, 200 (21%) pursued over-the-counter self-treatment, and 265 (28%) remained untreated. Overall, 34% of patients with asthma and diagnosed or self-reported AR were not treated for AR. There were no significant differences in QoL over the prior 4 weeks, nor healthcare resource use over the prior 6 months between patients treated and those not treated for AR. Conclusion: Based on self-reported data, despite global treatment guidelines recommending evaluation and treatment of AR among patients with asthma, AR was not diagnosed for 1 in 5 patients, and AR was not treated for 1 in 3 patients with asthma.

Calcium and vitamin D intake by postmenopausal women with osteoporosis in Spain: an observational calcium and vitamin D intake (CaVIT) study

Background Osteoporotic fractures are important causes of morbidity, mortality, and increased health care costs. However, the risk of osteoporotic fractures can be decreased, with clinical studies supporting the use of calcium and vitamin D supplements to promote bone health. Vitamin D insufficiency is widespread, particularly among postmenopausal women with osteoporosis, and this indicates that dietary intake is suboptimal, even though vitamin D supplements are widely available. Methods We conducted an observational study, using telephone surveys, to estimate vitamin D and calcium intake and the use of prescription osteoporosis medications in Spanish women aged ≥ 50 years with osteoporosis. Results Among the study participants, mean dietary calcium intake was 1239 mg/day and generally appeared sufficient in terms of the recommended daily intake guidance documents. Participants aged ≥ 75 years had a significantly lower mean dietary calcium intake (988 mg/day), thus one-half were below the level advised by the World Health Organization. Daily calcium intake was also lower in participants who were not taking prescription medications for bone health. Dietary vitamin D intake was 167 IU/day, which is well below both the established target dose (400 IU/day) and the more recent, higher guideline recommended for postmenopausal women (800–1300 IU/day). Dietary vitamin D intake was even lower for participants aged ≥ 75 years (120 IU/day) and was not related to the use of bone health prescription medications. Conclusion These results support the need for greater promotion of the benefits of higher vitamin D intake in Spanish women with osteoporosis.

Rates of asthma attacks in patients with previously inadequately controlled mild asthma treated in clinical practice with combination drug therapy: an exploratory post-hoc analysis

BackgroundDifferences could exist in the likelihood of asthma attacks in patients treated with inhaled corticosteroid (ICS), long-acting beta-agonist (LABA), and montelukast (MON) (ICS/LABA/MON) and patients treated with an inhaled corticosteroid (ICS) and montelukast (MON) (ICS/MON).MethodsThis was a post-hoc analysis of a pretest-posttest retrospective cohort study. Patients with mild persistent asthma and allergic rhinitis, who were taking an ICS either alone or in combination with a LABA, started concomitant MON treatment as part of their routine care. Rates of asthma- and allergic rhinitis-related medical resource use in the 12-months after the initial (index) MON prescription were compared in the ICS/MON and ICS/LABA/MON groups. An asthma attack was defined as an asthma-related hospitalization, ER visit, or use of an oral corticosteroid.ResultsOf the total of 344 patients, 181 (53%) received ICS/MON and 163 (47%) received ICS/LABA/MON in the post-index period for means of 10.5 and 11.4 months, respectively, (P < 0.05). Short-acting beta-agonists were used by 74.6% in the ICS/MON and 71.8% in the ICS/LABA/MON groups (P > 0.05). An asthma attack occurred in 4.4% of the ICS/MON group and 6.8% of the ICS/LABA/MON group (P > 0.05). The adjusted odds of an asthma attack in the post-index period in the ICS/LABA/MON group relative to the ICS/MON group was 1.24, 95% confidence interval 0.35–4.44.ConclusionIn this observational study of combination drug treatment of mild persistent asthma and allergic rhinitis, no difference was observed between LABA/ICS/MON combination therapy and the ICS/MON combination without LABA use, for the rate of asthma attacks over one year.

Comparison of infliximab and ustekinumab for the treatment of moderate-to-severe psoriasis: an indirect comparison meta-analysis

Correspondence: Tao Fan Global Health Outcomes, Merck & Co, Inc., One Merck Drive, WS2E-76, Whitehouse Station, NJ, USA Tel +1 908 423 4627 Fax +1 908 735 1688 Email tao.fan@merck.com Objectives: As no direct comparisons have been made between infliximab and ustekinumab, the present study’s aim was to estimate these drugs’ relative efficacy in the treatment of moderate-to-severe psoriasis. Methods: Eleven randomized controlled trials of infliximab 5 mg/kg and ustekinumab 45 mg or 90 mg, reporting Psoriasis Area and Severity Index (PASI) 75 and PASI 90 end points, were identified from a systematic literature review. Of these, five were excluded because they had inappropriate intervention (n = 1), inappropriate patient population (n = 3), or a small sample size (n = 1). Ultimately, six studies were included in the networks. Log odds ratio (OR) of achieving PASI 75 or PASI 90 was used as the treatment effect in fixedand random-effects mixed treatment comparison meta-analysis. Results: Based on the results of the random-effects model, when compared to infliximab 5 mg/kg, the OR of ustekinumab 90 mg and ustekinumab 45 mg achieving a PASI 75 following 12 weeks of treatment was 0.57 CrI (0.19, 1.29) and 0.44 (0.15, 0.99), respectively. Similarly, the odds of achieving PASI 90 was 0.77 (0.09, 2.70) for ustekinumab 90 mg and 0.63 (0.07, 2.20) for ustekinumab 45 mg. Infliximab 5 mg/kg had the highest probability of being the most effective of all treatments considered, in attaining a PASI 75 (92%) and PASI 90 response (76%). Ustekinumab 90 mg had the highest probability of being ranked second in attaining a PASI 75 (84%) and PASI 90 response (62%). Results from the randomand fixed-effects models were consistent. Conclusion: A greater proportion of patients with plaque psoriasis are expected to achieve a PASI 75 or PASI 90 response when treated with infliximab 5 mg/kg than with ustekinumab 90 mg or 45 mg.