Cost analysis of self-monitoring blood glucose in nonintensively managed type 2 diabetes.

OBJECTIVES: To compare health care resource utilization (HCRU) and costs between self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) users in adults with nonintensively managed type 2 diabetes (T2D). STUDY DESIGN: Retrospective analysis of the MarketScan Databases. METHODS: Adults with T2D using SMBG or initiating CGM between January 2018 and March 2019 were eligible for inclusion. Inclusion criteria were (1) 2 consecutive claims for T2D or 1 claim for T2D and a claim for glucose-lowering therapy, (2) at least 1 pharmacy claim for SMBG strips or CGM sensors, and (3) continuous enrollment for 1 year before and after the index date. Individuals with evidence of CGM in the preindex period, pregnancy, use of rapid-acting insulin or glucagon, type 1 diabetes, gestational diabetes, or secondary diabetes at any time during the study period were excluded. SMBG and CGM patients were matched using propensity score, and all-cause HCRU and costs during a 1-year period were compared. RESULTS: A total of 3498 patients were included in each matched cohort. The per-patient per-year (PPPY) all-cause cost was $20,542 in CGM users vs $19,349 in SMBG users (P < .001). The PPPY cost of glucose-lowering medication was $6312 in CGM users vs $5606 in SMBG users (P < .001). No significant differences in the number of emergency department visits or hospitalizations were observed, but CGM users had more all-cause outpatient visits and office visits with an endocrinologist. CONCLUSIONS: In adults with nonintensively managed T2D, SMBG appears to be less costly than CGM and is associated with lower pharmacy costs.

Economic evaluation of aclidinium bromide in the management of moderate to severe COPD: an analysis over 5 years.

PURPOSE: Aclidinium bromide is a long-acting muscarinic antagonistic used in maintenance treatment of chronic obstructive pulmonary disease (COPD). A model-based health economic study evaluated the cost-effectiveness of aclidinium 400 µg bid as an alternative to tiotropium 18 µg od for this indication in the US. PATIENTS AND METHODS: PATIENT CHARACTERISTICS IN THIS MODEL REFLECT THOSE IN THE ACLIDINIUM CLINICAL STUDIES: age >40 years, stable moderate-to-severe COPD, current or ex-smokers (>10 pack-years), post-salbutamol forced expiratory volume in 1 second (FEV1) ≥30% and <80% of predicted normal value, and FEV1/forced vital capacity <70%. The model consists of five main health states indicating severity of COPD and the level of utility, resource use, and costs. Treatment efficacy over 5 years was modeled using FEV1% predicted; a network meta-analysis comparing aclidinium and tiotropium was used to estimate disease progression during the first 24 weeks, and results from the UPLIFT trial were used for time points after 24 weeks. Quality of life was assessed using utility scores in US patients from the UPLIFT trial. Cost-effectiveness was assessed as the incremental cost per quality-adjusted life year (QALY) gained. RESULTS: Over 5 years, QALYs were 3.50 for aclidinium versus 3.49 for tiotropium; life years accumulated were 4.52 for both. In this economic model, aclidinium versus tiotropium showed marginally fewer exacerbations (3.364 versus 3.390, respectively) and mean total health care costs (US$126,274 versus US$128,591, respectively). In all scenario analyses performed (discount factors of 0% and 6% for benefits and costs; time horizon of 1 year; mapping St George's Respiratory Questionnaire to European Quality of Life-5 Dimensions; excluding pharmacy costs, COPD-related cost only; cost of exacerbations; including ACCORD II trial in the network meta-analysis), aclidinium was associated with lower costs and marginally greater QALYs versus tiotropium. CONCLUSION: Aclidinium is potentially cost-effective compared with tiotropium for maintenance treatment of moderate-to-severe COPD.

Relative efficacy of bivalirudin versus heparin monotherapy in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: a network meta-analysis.

In the absence of head-to-head clinical data, the objective of this study was to indirectly compare the efficacy and safety of a bivalirudin-based anticoagulation strategy with that of heparin monotherapy in patients with ST-elevation myocardial infarction (STEMI) intended for primary percutaneous coronary intervention. A systematic literature review was performed to identify randomized controlled trials to build a network of bivalirudin and heparin monotherapy strategies in STEMI patients using heparin, with glycoprotein IIb/IIIa inhibitor as a common reference strategy. At 30 days, the bivalirudin-based strategy was expected to result in lower mortality rates than heparin monotherapy (odds ratio [OR], 0.55; credible limit [CrL], 0.32-0.95). This relationship was sustained at 1 year. At 30 days, the risk for stroke (OR, 0.88; CrL, 0.37-2.13), myocardial infarction (OR, 0.79; CrL, 0.40-1.55), and thrombolysis in myocardial infarction major and minor bleedings (OR, 0.66; CrL, 0.45-0.98) tended to be numerically reduced with bivalirudin in comparison with heparin monotherapy. For patients with STEMI intended for primary percutaneous coronary intervention, bivalirudin is associated with lower mortality rates in comparison with heparin monotherapy. This study suggests that bivalirudin is more effective and safer than heparin monotherapy and should therefore be preferred over heparin monotherapy.

Efficacy of once-daily indacaterol relative to alternative bronchodilators in COPD: a patient-level mixed treatment comparison.

OBJECTIVE: Indacaterol was evaluated versus placebo, formoterol, and salmeterol in randomized controlled trials. No direct comparisons, however, are available for indacaterol 150 µg with formoterol or indacaterol 300 µg with salmeterol. Indacaterol trial evidence was synthesized to provide coherent estimates of indacaterol 150 µg and indacaterol 300 µg relative to formoterol, salmeterol, and tiotropium. METHODS: Four randomized controlled trials were combined with Bayesian mixed treatment comparisons by using individual patient-level data. End points of interest were trough forced expiratory volume in 1 second (FEV(1)), St. George's Respiratory Questionnaire (SGRQ) total score and response (≥ 4 points), and Transition Dyspnea Index total score and response (≥ 1 point). RESULTS: Indacaterol 150 µg demonstrated a higher FEV(1) than did formoterol at 12 weeks and 6 months (0.10 L difference; 95% credible interval [CrI] = 0.06-0.14), as did indacaterol 300 µg versus salmeterol (0.06 L difference at 12 weeks; CrI = 0.02-0.10; 0.06 L at 6 months; CrI = 0.02-0.11). Regarding SGRQ, indacaterol 150 µg demonstrated a comparable proportion of responders versus formoterol, as did indacaterol 300 µg versus salmeterol. In comparison to tiotropium, indacaterol 150 µg demonstrated a greater proportion of responders (odds ratio = 1.52 at 12 weeks; CrI 1.15-2.00). For Transition Dyspnea Index, indacaterol 150 µg and formoterol showed a similar response. Indacaterol 300 µg was more efficacious than salmeterol (odds ratio = 1.65 at 12 weeks; CrI 1.16-2.34). Overall, indacaterol 150 µg showed the greatest efficacy for SGRQ and indacaterol 300 µg for FEV(1) and Transition Dyspnea Index. CONCLUSION: Indacaterol is expected to be comparable to formoterol, salmeterol, and tiotropium, providing higher FEV(1) than formoterol and salmeterol and greater improvement in the SGRQ total score than tiotropium. Indacaterol 150 µg provided comparable improvement in dyspnea, while indacaterol 300 µg demonstrated the greatest response overall.

Indirect treatment comparison of abatacept with methotrexate versus other biologic agents for active rheumatoid arthritis despite methotrexate therapy in the United kingdom.

OBJECTIVE: To compare the efficacy of abatacept and alternative biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) in the United Kingdom. METHODS: A systematic literature search identified 11 individual studies investigating the efficacy of abatacept, infliximab, adalimumab, etanercept, certolizumab pegol, and golimumab in adult patients with RA that did not respond to MTX. The clinical trials included in this analysis were similar in trial design, baseline patient characteristics, and background therapy (i.e., MTX). The key clinical endpoints of interest were the Health Assessment Questionnaire (HAQ) change from baseline (CFB) and the American College of Rheumatology (ACR) responses at 6 months (24-28 weeks). Results were analyzed using Bayesian network metaanalysis methods, and were expressed as differences in HAQ CFB and ACR20/50/70 relative risks, with 95% credible limits (CrL). RESULTS: Analysis of HAQ CFB at 6 months showed that abatacept is more efficacious than placebo [mean difference in HAQ CFB: -0.30 (95% CrL -0.42; -0.16)] and comparable to all other biologic agents, in patients receiving MTX as background treatment. Abatacept is also expected to result in a higher proportion of ACR responders compared to placebo, with relative risks ranging from 1.90 (95% CrL 1.24; 2.57) for ACR20 to 3.72 (95% CrL 1.50; 10.52) for ACR70, and to result in comparable proportions of ACR responders as other biologic agents, at 6 months. CONCLUSION: Abatacept is expected to result in improvement in functional status comparable to other recommended biologic agents in patients with RA who are unresponsive to MTX in the UK.

Abatacept with methotrexate versus other biologic agents in treatment of patients with active rheumatoid arthritis despite methotrexate: a network meta-analysis.

INTRODUCTION: The goal of this study was to compare the efficacy in terms of Health Assessment Questionnaire change from baseline (HAQ CFB), 50% improvement in American College of Rheumatology criterion (ACR-50) and Disease Activity Score in 28 joints (DAS28) defined remission (< 2.6) between abatacept and other biologic disease modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX-IR). METHODS: A systematic literature review identified controlled trials investigating the efficacy of abatacept (three studies), etanercept (two studies), infliximab (two), adalimumab (two), certolizumab pegol (two) ritixumab (three), and tocilizumab (two) in MTX-IR patients with RA. The clinical trials included in this analysis were similar with respect to trial design, baseline patient characteristics and background therapy (MTX). The key clinical endpoints of interest were HAQ CFB, ACR-50 and DAS28 < 2.6 measured at 24 and 52 weeks. The results were analysed using network meta-analysis methods that enabled calculation of an estimate for expected relative effect of comparative treatments. Analysis results were expressed as the difference in HAQ CFB score and odds ratio (OR) of achieving an ACR-50 and DAS28 response and associated 95% credible intervals (CrI). RESULTS: The analysis of HAQ CFB at 24 weeks and 52 weeks showed that abatacept in combination with MTX is expected to be more efficacious than MTX monotherapy and is expected to show a comparable efficacy relative to other biologic DMARDs in combination with MTX. Further, abatacept showed comparable ACR-50 and DAS28 < 2.6 response rates with other biologic DMARDs at 24 and 52 weeks, except for ACR-50 compared to certolizumab pegol at 52 weeks and for DAS28 < 2.6 compared to tocilizumab at 24 weeks. Sensitivity analyses confirmed the robustness of the findings. CONCLUSIONS: Abatacept in combination with MTX is expected to result in a comparable change from baseline in HAQ score and comparable ACR-50 and DAS28 < 2.6 response rates in MTX-IR patients compared to other approved biologic agents.

Costo efectividad de Abatacept en comparación con otras terapias biológicas para el tratamiento de la artritis reumatoide moderada a severamente activa en pacientes que han fallado al tratamiento con metotrexato en EsSalud para el año 2010 / Cost-effectiveness of abatacept compared to other biological agents for the treatment of moderately to severely active rheumatoid arthritis in patients who failed with methotrexate in Peruvian Social Security during 2010

Objetivo: Estimar la costo efectividad de Abatacept combinado con Metotrexato (MTX) en comparación a otras DARMEs biológicas, en combinación con MTX, en pacientes con AR moderada a severamente activa. Materiales y métodos: Se adaptó un modelo de secuencias de tratamiento para la representación de la invalidez en términos del índice HAQ en un horizonte de 5 años de enfermedad para una cohorte de 1 000 pacientes. Abatacept en combinación con MTX se comparó contra etanercept, rituximab, infliximab, adalimumab y tocilizumab, todas asociadas a MTX. Resultados: El costo de tratamiento con Abatacept es de S/. 169 263 y su efectividad es de 1.96 AVAC. Respecto a etanercept, adalimumab, infliximab y tocilizumab, abatacept se ha mostrado más efectivo en términos de AVACs y menos costoso. Respecto a rituximab, abatacept presenta un índice de costo efectividad incremental de S/ 75 493 por AVAC ganado. Conclusiones: abatacept es dominante frente a Etanercept, Adalimumab, Infliximab y Tocilizumab, desde la perspectiva del Seguro Social de Salud (EsSalud) para el tratamiento de pacientes con AR moderada a severamente activa que han fallado a MTX.

Objective: To estimate the cost-effectiveness of Abatacept in combination with Methotrexate (MTX) versus other biologic DMARDs in combination with MTX in patients with moderately to severely active rheumatoid arthritis. Materials and methods: A sequential therapy model was adapted for representing disability using the HAQ Index in a 5-year horizon period for a 1000-patient cohort. Abatacept in combination with MTX was compared against etanercept, rituximab, infliximab, adalimumab, and tocilizumab, all of them combined with MTX. Results: The cost of abatacept therapy was S/. 169 263 and its effectiveness was found to be 1.96 QALY. Compared to etanercept, adalimumab, infliximab and tocilizumab, abatacept has shown to be the most effective agent in terms of QALYs and the least expensive. Compared to rituximab, abatacept has an incremental cost effectiveness ratio of S/. 75 493 per QALY gained. Conclusions: According to this model, abatacept was found to be superior compared to etanercept, adalimumab, infliximab, and tocilizumab, from the Peruvian Social Security (EsSalud) perspective for the treatment of moderately to severely active Rheumatoid Arthritis in patients who failed using a MTX-based therapy.

The efficacy of bisphosphonates in the prevention of vertebral, hip, and nonvertebral-nonhip fractures in osteoporosis: a network meta-analysis.

OBJECTIVE: To evaluate the efficacy of available bisphosphonate therapies regarding the prevention of vertebral, hip, and nonvertebral-nonhip fractures in postmenopausal women with osteoporosis. METHODS: Eight randomized placebo controlled trials investigating the effects of zoledronic acid (1 study), alendronate (3), ibandronate (1), risedronate (2), and etidronate (1) in terms of fractures with a follow-up of 3 years (or 2 years if used for registration purposes) were identified with a systematic literature search. The endpoints of interest were morphometric vertebral fractures, hip fractures, and nonvertebral-nonhip fractures. Results of all trials were analyzed simultaneously with a Bayesian network meta-analysis by which the relative treatment effect of 1 intervention to another can be obtained in the absence of head-to-head evidence. Given the estimated treatment effects and their uncertainty, the Bayesian approach allowed for calculations of the probability of which bisphosphonate is best in terms of overall fracture reductions by weighting the impact of each by type of fracture on costs, quality of life, and incidence. RESULTS: There is a 79% probability that zoledronic acid shows the greatest reduction in vertebral fractures of all bisphophonates compared. Zoledronic acid showed a relative risk (RR) of 0.30 (95% Credible Interval 0.23-0.37) relative to placebo, an RR of 0.55 (0.41-0.76) relative to alendronate, an RR of 0.50 (0.36-0.70) relative to risedronate, and an RR of 0.58 (0.37-0.92) relative to ibandronate. Regarding hip fractures, there is a 47% probability that zoledronic acid shows the greatest risk reduction, followed by alendronate (36%) and risedronate (11%). RRs of zoledronic acid relative to placebo, alendronate, and risedronate were 0.58 (0.41-0.82), 0.95 (0.54-1.68), and 0.73 (0.37-1.44), respectively. Risedronate showed the greatest reduction in nonvertebral-nonhip fractures, followed by zoledronic acid. The RR of zoledronic acid relative to risedronate was 1.28 (0.87-1.90). Overall, there was a 94% probability that zoledronic acid showed the greatest reduction in any fracture. Weighting the impact of the different type of fractures by incidence, cost, or quality of life showed similar results. CONCLUSION: Of the available bisphosphonates for osteoporosis, zoledronic acid has the highest probability of offering the best overall fracture protection.

Manipulative therapy in addition to usual medical care accelerates recovery of shoulder complaints at higher costs: economic outcomes of a randomized trial.

BACKGROUND: Shoulder complaints are common in primary care and have unfavourable long term prognosis. Our objective was to evaluate the clinical effectiveness of manipulative therapy of the cervicothoracic spine and the adjacent ribs in addition to usual medical care (UMC) by the general practitioner in the treatment of shoulder complaints. METHODS: This economic evaluation was conducted alongside a randomized trial in primary care. Included were 150 patients with shoulder complaints and a dysfunction of the cervicothoracic spine and adjacent ribs. Patients were treated with UMC (NSAID's, corticosteroid injection or referral to physical therapy) and were allocated at random (yes/no) to manipulative therapy (manipulation and mobilization). Patient perceived recovery, severity of main complaint, shoulder pain, disability and general health were outcome measures. Data about direct and indirect costs were collected by means of a cost diary. RESULTS: Manipulative therapy as add-on to UMC accelerated recovery on all outcome measures included. At 26 weeks after randomization, both groups reported similar recovery rates (41% vs. 38%), but the difference between groups in improvement of severity of the main complaint, shoulder pain and disability sustained. Compared to the UMC group the total costs were higher in the manipulative group (€1167 vs. €555). This is explained mainly by the costs of the manipulative therapy itself and the higher costs due sick leave from work. The cost effectiveness ratio showed that additional manipulative treatment is more costly but also more effective than UMC alone. The cost-effectiveness acceptability curve shows that a 50%-probability of recovery with AMT within 6 months after initiation of treatment is achieved at €2876. CONCLUSION: Manipulative therapy in addition to UMC accelerates recovery and is more effective than UMC alone on the long term, but is associated with higher costs. INTERNATIONAL STANDARD RANDOMIZED CONTROLLED TRIAL NUMBER REGISTER: ISRCTN11216.

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

BACKGROUND: The efficacy of vitamin D(3) 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 D(3) 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 D(3) 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 D(3)) against placebo with or without background calcium supplementation in the treatment of postmenopausal women. RESULTS: Eight controlled trials evaluating the effect of vitamin D(3) supplementation with or without calcium were assessed. Of 12 658 women included in a Bayesian meta-analysis, 6089 received vitamin D(3) (with or without calcium) and 6569 received placebo (with or without calcium). Compared to placebo, vitamin D(3) 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 D(3) 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 D(3) 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 D(3) with calcium appears to achieve benefits above those attained with calcium supplementation alone for non-vertebral and non-vertebral-non-hip fractures.

Indirect comparison of tocilizumab and other biologic agents in patients with rheumatoid arthritis and inadequate response to disease-modifying antirheumatic drugs.

OBJECTIVES: To compare the patterns of American College of Rheumatology (ACR) response between tocilizumab and other biologic agents in patients with rheumatoid arthritis who have inadequate response to disease-modifying antirheumatic drugs (DMARD-IR). METHODS: Systematic literature review identified similarly designed double-blind, randomized, placebo-controlled trials over an 18-year period that investigated the effectiveness of abatacept (2), rituximab (2), and TNF-alpha inhibitors etanercept, infliximab, and adalimumab (11) in DMARD-IR patients; data from 3 placebo-controlled, phase 3 trials for tocilizumab, a newly developed IL-6 inhibitor, were included. The endpoint of interest was ACR20/50/70 response criteria at 24 to 30 weeks. Results were analyzed simultaneously using Bayesian mixed-treatment comparison techniques. Nonoverlapping ACR response rates (ACR70) for each agent were compared among treatments to identify differences in ACR response pattern. Separate analyses of overlapping ACR20/50/70 responses were conducted to identify the source of any differences. Results were expressed as relative risk of ACR20/50/70 response and associated 95% credible interval (CrI). RESULTS: Patterns across nonoverlapping ACR response levels varied significantly across treatments. In subsequent analyses, the effectiveness of tocilizumab appeared to be comparable to that of other biologic agents for ACR20 and ACR50 responses but greater for ACR70. Specifically, tocilizumab had greater ACR70 responses than both TNF-alpha inhibitors (relative risk = 1.8; CrI = 1.2, 2.6) and abatacept (relative risk = 2.0; CrI = 1.3, 3.1). CONCLUSIONS: Among DMARD-IR patients, tocilizumab shows a pattern of response that differs from that of other biologic agents. Post-hoc analyses suggest that the difference lies in a higher likelihood of ACR70 response with tocilizumab.

Manipulative therapy in addition to usual care for patients with shoulder complaints: results of physical examination outcomes in a randomized controlled trial.

OBJECTIVE: The purpose of this study was to examine the effect of manipulative therapy on the shoulder girdle, in addition to usual care provided by the general practitioner, on the outcomes of physical examination tests for the treatment of shoulder complaints. METHODS: This was a randomized controlled trial in a primary care setting in the Netherlands. A total of 150 participants were recruited from December 2000 until December 2002. All patients received usual care by the general practitioner. Usual care included one or more of the following depending on the needs of the patient: information/advice, oral analgesics or nonsteroidal antiinflammatory drugs, corticosteroid injections, exercises, and massage. In addition to usual care, the intervention group received manipulative therapy, up to 6 treatment sessions in a 12-week period. Twenty-four physical examination tests were done at baseline and after 6, 12, and 26 weeks. Factor analysis was done to reduce the number of outcome measures. RESULTS: The factor analysis resulted in 4 factors: "shoulder pain," "neck pain," "shoulder mobility," and "neck mobility." At 6 weeks, no significant differences between groups were found. At 12 weeks, the mean changes of all 4 factors favored the intervention group; the factors "shoulder pain" and "neck pain" reached statistical significance (95% confidence interval [CI], 0.1-2.1). At 26 weeks, differences in the factors "shoulder pain" (95% CI, 0.0-2.6), "shoulder mobility" (95% CI, 0.2-1.7), and "mobility neck" (95% CI, 0.2-1.3) statistically favored the intervention group. CONCLUSION: In this pragmatic study, manipulative therapy, in addition to usual care by the general practitioner, diminished severity of shoulder pain and neck pain and improved shoulder and neck mobility.

Prevention of vertebral fractures in osteoporosis: mixed treatment comparison of bisphosphonate therapies.

OBJECTIVE: The objective was to compare the efficacy of bisphosphonates regarding the prevention of vertebral fractures in postmenopausal women with osteoporosis. METHODS: Seven randomized placebo controlled trials investigating the effects of zoledronic acid (one study), alendronate (three studies), ibandronate (one study), and risedronate (two studies) in terms of fractures with a follow-up of 3 years were identified with a systematic literature search. The endpoint of interest was vertebral fractures. Results of all trials were analyzed simultaneously with a Bayesian mixed treatment comparison (MTC). With MTC the relative treatment effect of one intervention to another can be obtained in the absence of head-to-head evidence. MTC can be considered a valid method when included studies are comparable regarding effect modifying baseline patient and study characteristics. RESULTS: There is a 98% probability that zoledronic acid shows the greatest reduction in vertebral fractures of all four bisphophonates compared. Zoledronic acid showed an OR of 0.28 (95% Credible Interval 0.22; 0.35) relative to placebo, an OR of 0.57 (0.36; 0.92) relative to ibandronate, an OR of 0.54 (0.39; 0.75) relative to alendronate, and an OR of 0.49 (0.34; 0.69) relative to risedronate. Alendronate, ibandronate, and risedronate showed comparable vertebral fracture reductions. Indirect comparisons using a conservative random effects model supported these findings. CONCLUSION: An indirect comparison of findings from placebo controlled randomized studies indicates that zoledronic acid provides a greater vertebral fracture risk reduction in postmenopausal women with osteoporosis than ibandronate, alendronate, or risedronate.

Interobserver reliability of physical examination of shoulder girdle.

The object of this study was to assess interobserver reliability in 23 tests concerning physical examination of the shoulder girdle. A physical therapist and a physical therapist/manual therapist independently performed a physical examination of the shoulder girdle in 91 patients with shoulder complaints of varying severity and duration. The observers assessed 23 items in total: active and passive abductions, passive external rotation, hand in neck (HIN) test, hand in back (HIB) test, impingement test according to Neer, springing test of the first rib and joint play test of the acromioclavicular joint. The interobserver reliability was evaluated by means of a Cohen's Kappa, the weighted Kappa and the intraclass correlation (ICC). Criteria for acceptable reliability were: Kappa value>or=0.60, ICC>or=0.75 or an absolute agreement>or=80%. The results showed that Kappa values varied from 0.09 (springing test first rib, stiffness) to 0.66 (springing test first rib, pain), weighted Kappa varied from 0.35 (pain during HIB) to 0.73 (range of motion HIB) and ICC varied from 0.54 (abduction passive starting point painful arc) to 0.96 (active and passive ranges of motion in abduction). In total 11 (48%) items fulfilled the criteria of acceptable reliability. In conclusion, there appears to be a great deal of variation in the reliability of the tests used in the physical examination of the shoulder girdle. Over 50% of the tests did not meet the statistical criteria for acceptable reliability.

Bayesian meta-analysis of multiple treatment comparisons: an introduction to mixed treatment comparisons.

Recently, mixed treatment comparisons (MTC) have been presented as an extension of traditional meta-analysis by including multiple different pairwise comparisons across a range of different interventions. MTC allow for indirect comparisons and can therefore provide very useful information for clinical and reimbursement decision-making in the absence of head-to-head data. In this article, we provide an introductory overview of MTC illustrated with example analyses of different drug treatments in rheumatoid arthritis using a continuous patient-reported end point. As a background, we start with an overview of the traditional meta-analyses for pairwise trials, and the difference between a traditional approach and a Bayesian approach. Next, the Bayesian MTC for continuous outcomes are presented. We finish with a discussion of how MTC can best be presented in order to maximize acceptance by target audiences, i.e., clinicians and market access decision-makers.

Cost-effectiveness of a fixed dose combination of alendronate and cholecalciferol in the treatment and prevention of osteoporosis in the United Kingdom and The Netherlands.

OBJECTIVE: To evaluate the cost-effectiveness of a fixed dose combination of alendronate 70 mg and cholecalciferol 2800 IU (alendronate/vitamin D3; Fosavance) versus no treatment, alendronate with dietary vitamin D supplements and ibandronate in the treatment of osteoporosis in the UK and Netherlands. METHODS: A patient simulation model was developed. One-year cycles included health states related to hip, vertebral, wrist and proximal humerus fractures, as well as death due to hip fractures and other causes. Effect of treatment was extracted from alendronate and ibandronate clinical trials. Direct costs and utilities were derived from other literature. Analyses were performed for women with a history of vertebral fractures and osteoporosis aged 50, 60, 70 and 80 years. Probabilistic sensitivity analyses were undertaken to estimate the uncertainty of outcomes. RESULTS: In the UK, alendronate/vitamin D3 was cost-effective compared to no treatment in women 70 years and older with osteoporosis ( pound17 439 per quality-adjusted life year [QALY] gained) and women 60 years and older with a history of vertebral fractures ( pound29 283 per QALY gained). For women 80 years of age alendronate/vitamin D3 was cost-saving combined with QALY gains. Alendronate/vitamin D3 was cost-saving relative to alendronate with dietary supplements. Relative to ibandronate, alendronate/vitamin D3 was cost-effective in women 50 years ( pound19 095 per QALY gained) and economically dominant in women 60 years or older. Comparable results were observed for the Netherlands. CONCLUSIONS: Given the underlying assumptions and data used, this economic modelling study showed that alendronate/vitamin D3 is cost-effective in women 70 years or older with osteoporosis and in women 60 years or older with a history of vertebral fractures in the UK and Netherlands. Alendronate/vitamin D3 is economically dominant over ibandronate in women with a history of vertebral fractures aged 60 and over and cost-saving relative to alendronate with dietary supplements.

Assessment of the cervical range of motion over time, differences between results of the Flock of Birds and the EDI-320: a comparison between an electromagnetic tracking system and an electronic inclinometer.

The objective of this study was to analyse cervical range of motion, assessed over time by means of a digital inclinometer (EDI-320) and a three-dimensional electromagnetic tracking device (Flock of Birds). The maximum active cervical range of motion was assessed with two measurement devices in three sessions over time, with 6-week intervals. In total, 26 women and 24 men (mean age: 44.4, SD: 9.9) without known pathology of the cervical spine participated. Four movements were measured axial rotation with the cervical spine in a flexed and in an extended position, flexion-extension, and lateral bending. The results showed that the factor time was significant for rotation in extension and rotation in flexion. The factor device was significant for all movements measured, and the interaction term between time and device was significant for all movements except rotation in extension. The Flock of Birds measured significantly higher ranges of motion on all motions except for lateral bending. A substantial variation in cervical range of motion was observed over time (ranging from -5.6 to 8.1) as well as between devices (ranging from -13.1 to 29.9). Substantial and significant differences in cervical range of motion were found over time as well as differences between the Flock of Birds and the EDI-320.

Interobserver reliability of neck-mobility measurement by means of the flock-of-birds electromagnetic tracking system.

OBJECTIVE: To establish the interobserver reliability for measuring neck mobility in human subjects by means of an electromagnetic tracking device, the Flock-of-Birds system. METHODS: Two observers independently and in random order assessed the cervical range-of-motion in 30 subjects with a dysfunction in the neck and shoulder region (symptomatic subjects) and 30 subjects without known pathology (asymptomatic subjects). Measurements included rotation in neutral position, in flexed position and in extended position, flexion-extension, and lateral bending (all active and passive). Reliability was analyzed by intraclass correlation coefficient (ICC) and agreement by limits of agreement and percentage of paired observations within 5 degrees, 10 degrees, and 15 degrees. RESULTS: For asymptomatic subjects, the ICC varied from 0.57 to 0.85, and the limits of agreement varied between 14.5 degrees and 27.0 degrees. The percentage of paired observations within 5 degrees, 10 degrees, and 15 degrees ranged from 31% to 57%, 58% to 90%, and 78% to 93%, respectively. For symptomatic subjects, the ICC varied from 0.36 to 0.91, and the limits of agreement varied between 9.6 degrees and 37.8 degrees. The percentage of paired observations within 5 degrees, 10 degrees, and 15 degrees ranged from 17% to 60%, 33% to 93%, and 50% to 97%, respectively. CONCLUSIONS: Despite the use of a standardized protocol and a sophisticated measurement system, the interobserver reliability of neck mobility was variable in quality, with reliability being good in rotation in neutral position, flexion-extension, and lateral bending.

Variation in the cervical range of motion over time measured by the "flock of birds" electromagnetic tracking system.

STUDY DESIGN: Observational longitudinal study. OBJECTIVE: To establish the normal variation over time for active and passive cervical range of motion (ROM) measured with the Flock of Birds electromagnetic tracking system (FOB). SUMMARY OF BACKGROUND DATA: Data about normal variation of cervical ROM over time are scarce but important for the interpretation of study results. METHODS: Forty-eight subjects without a manifest dysfunction in neck and shoulder region (asymptomatic group) and 58 subjects with a dysfunction in the neck and shoulder region (symptomatic group) participated in this study. Cervical active and passive ROM was assessed in three different sessions 6 weeks apart. The following movements were measured: flexion-extension, lateral bending, and axial rotation in neutral, flexed, and extended position. RESULTS: A wide range of variation of active and passive cervical ROM was found at the 6- and 12-week measurement in the asymptomatic group as well as in the symptomatic group. Highest variation was found during passive ROM testing as compared with active ROM testing. The symptomatic group showed larger variation than the asymptomatic group. CONCLUSIONS: Cervical range of motion varies considerably over time. This variation should be taken into account when results of therapeutic trials with respect to cervical ROM are interpreted.

Manipulative therapy in addition to usual medical care for patients with shoulder dysfunction and pain: a randomized, controlled trial.

BACKGROUND: Dysfunction of the cervicothoracic spine and the adjacent ribs (also called the shoulder girdle) is considered to predict occurrence and poor outcome of shoulder symptoms. It can be treated with manipulative therapy, but scientific evidence for the effectiveness of such therapy is lacking. OBJECTIVE: To study the effectiveness of manipulative therapy for the shoulder girdle in addition to usual medical care for relief of shoulder pain and dysfunction. DESIGN: Randomized, controlled trial. SETTING: General practices in Groningen, the Netherlands. PATIENTS: 150 patients with shoulder symptoms and dysfunction of the shoulder girdle. INTERVENTIONS: All patients received usual medical care from their general practitioners. Only the intervention group received additional manipulative therapy, up to 6 treatment sessions in a 12-week period. MEASUREMENTS: Patient-perceived recovery, severity of the main complaint, shoulder pain, shoulder disability, and general health. Data were collected during and at the end of the treatment period (at 6 and 12 weeks) and during the follow-up period (at 26 and 52 weeks). RESULTS: During treatment (6 weeks), no significant differences were found between study groups. After completion of treatment (12 weeks), 43% of the intervention group and 21% of the control group reported full recovery. After 52 weeks, approximately the same difference in recovery rate (17 percentage points) was seen between groups. During the intervention and follow-up periods, a consistent between-group difference in severity of the main complaint, shoulder pain and disability, and general health favored additional manipulative therapy. LIMITATIONS: The sample size was small, and assessment of end points was subjective. CONCLUSION: Manipulative therapy for the shoulder girdle in addition to usual medical care accelerates recovery of shoulder symptoms.