Clinician reported ease of use for a novel fibrin sealant patch for hemostasis: results from four randomized controlled trials.

BACKGROUND: In addition to rapid and sustained efficacy, ease of use is also an important characteristic of topical hemostats. OBJECTIVES: To evaluate clinician-reported ease of use for the Evarrest fibrin sealant patch across various surgical bleeding situations. METHODS: An ease of use questionnaire (EUQ) was validated and administered in four randomized studies comparing the fibrin sealant patch to standard of care (SoC) in soft tissue and hepatic surgical bleeding. Three of these randomized studies have been previously published and all have been registered (NCT00658723; NCT00977925; NCT01166243; NCT01993888). The EUQ is a 19 item instrument evaluating clinician's preferences on five subscales: product ease of use, satisfaction with product properties and efficiency, confidence in product efficacy, global confidence, and global satisfaction. A pair-wise meta-analysis using a random effects model was conducted on EUQ scores for trials that reported data for both treatment arms. Individual scores are presented for each trial. RESULTS: The fibrin sealant patch demonstrated numerically greater scores than SoC in all EUQ subscales. The meta-analysis demonstrated that fibrin sealant patch scores improved for all subscales compared with SoC: satisfaction with product properties (mean difference [MD] = 0.38, 95% CI: 0.04 to 0.73; P = 0.03), confidence in efficacy (MD = 1.10, 95% CI: 0.47 to 1.74; P = 0.0007), global confidence (MD = 0.57, 95% CI: 0.05 to 1.10, P = 0.03), global satisfaction (MD = 0.79, 95% CI: 0.32 to 1.26, P = 0.001), and ease of use (MD = 0.33, 95% CI: -0.29 to 0.94; P = 0.23). Fibrin sealant patch single arm trial results aligned with these findings. CONCLUSIONS: Physicians consistently reported high EUQ scores for the fibrin sealant patch across surgical bleeding populations. An important limitation of this study was that the composition of SoC varied across studies and EUQ data were only available for the SoC in two of four trials. Future studies should evaluate ease of use for other hemostats and across other surgical subspecialties, as data are currently limited.

A meta-analysis of the efficacy and safety of unboosted atazanavir compared with ritonavir-boosted protease inhibitor maintenance therapy in HIV-infected adults with established virological suppression after induction.

OBJECTIVES: Treatment simplification involving induction with a ritonavir (RTV)-boosted protease inhibitor (PI) replaced by a nonboosted PI (i.e. atazanavir) has been shown to be a viable option for long-term antiretroviral therapy. To evaluate the clinical evidence for this approach, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating efficacy and safety in patients with established virological suppression. METHODS: Several databases were searched without limits on time or language. Searches of conferences were also conducted. RCTs were included if they compared a PI/RTV regimen to unboosted atazanavir, after induction with PI/RTV. The meta-analysis was conducted using a random effects model for the proportion achieving virological suppression (i.e. HIV RNA < 50 and <400 HIV-1 RNA copies/mL), CD4 cell counts, lipid levels and liver function tests. Dichotomous outcomes were reported as risk ratios (RRs) and continuous outcomes as mean differences (MDs). RESULTS: Five studies (n = 1249) met the inclusion criteria. The meta-analysis demonstrated no statistically significant difference in efficacy (i.e. HIV RNA < 50 copies/mL) between PI/RTV and unboosted atazanavir [RR = 1.04; 95% confidence interval (CI) 0.99 to 1.10], with no heterogeneity. Findings were similar in a subanalysis of studies where atazanavir/RTV was the only PI/RTV used during induction. Additional efficacy results support these findings. A significant reduction in total cholesterol (P < 0.00001), triglycerides (P = 0.0002), low-density lipoprotein (LDL) cholesterol (P = 0.009) and hyperbilirubinaemia (P = 0.02) was observed with unboosted atazanavir vs. PI/RTV. CONCLUSIONS: The meta-analysis demonstrated that switching patients with virological suppression from an RTV-boosted PI to unboosted atazanavir leads to improvements in safety (i.e. blood parameter abnormalities) without sacrificing virological efficacy.

Cost-effectiveness of prophylactic vaccination against human papillomavirus 16/18 for the prevention of cervical cancer: adaptation of an existing cohort model to the situation in the Netherlands.

Cervical cancer is one of the most prevalent cancers among women worldwide. Implementation of an HPV-vaccination strategy targeting the major oncogenic types 16 and 18 that cause cervical cancer is generally expected to significantly reduce the burden of cervical cancer disease. Here we estimate the costs, savings and health gains with the addition of HPV-16/18 vaccination to the already existing Dutch screening programme. In the base-case analysis, it was estimated that implementation of an HPV-16/18 vaccine would result in an incremental cost-effectiveness ratio (ICER) of euro22,700 per life-year gained (LYG). In sensitivity analysis, the robustness of our finding of favourable cost-effectiveness was established. The ICER appeared sensitive to the vaccine price, discount rate and duration of vaccine-induced protection. From our results, it validly follows that immunization of 12-year-old Dutch girls against HPV-16/18 infection is a cost-effective strategy for protecting against cervical cancer.

Estimating the long-term impact of a prophylactic human papillomavirus 16/18 vaccine on the burden of cervical cancer in the UK.

To predict the public health impact on cervical disease by introducing human papillomavirus (HPV) vaccination in the United Kingdom, we developed a mathematical model that can be used to reflect the impact of vaccination in different countries with existing screening programmes. Its use is discussed in the context of the United Kingdom. The model was calibrated with published data. The impact of vaccination on cervical cancer and deaths, precancerous lesions and screening outcomes were estimated for a vaccinated cohort of 12-year-old girls, among which it is estimated that there would be a reduction of 66% in the prevalence of high-grade precancerous lesions and a 76% reduction in cervical cancer deaths. Estimates for various other measures of the population effects of vaccination are also presented. We concluded that it is feasible to forecast the potential effects of HPV vaccination in the context of an existing national screening programme. Results suggest a sizable reduction in the incidence of cervical cancer and related deaths. Areas for future research include investigation of the beneficial effects of HPV vaccination on infection transmission and epidemic dynamics, as well as HPV-related neoplasms in other sites.

Prevalence of vertebral fractures among patients with chronic obstructive pulmonary disease in Canada.

PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) may be at higher risk for osteoporosis. The primary objective of this case-control study was to determine the prevalence of vertebral fractures among patients with COPD admitted to acute care compared with a gender- and age-matched control group. SUBJECTS AND METHODS: Subjects were identified by chart reviews from an acute care hospital in Hamilton, Ontario, in 1999, including patients who were over 50 years old. In total, 127 patients with ICD-9 codes specifying COPD were randomly selected and compared with 127 gender- and age-matched controls. Chest radiographs were interpreted by two radiologists who defined and graded vertebral fractures using Genant's method. Medications taken, or prescribed at discharge, were recorded from charts. RESULTS: The overall prevalence of at least one vertebral fracture was found to be 34/127 (26.8%) in the COPD patients compared with 30/127 (23.6%) in the controls ( p=0.556). A significantly greater proportion of COPD patients had at least one severe vertebral fracture (OR=3.75, 95% CI 1.24 to 11.3). Review of hospital chest X-ray reports indicated that only 12 of 64 (18.8%) patients with vertebral fractures identified by the study radiologists actually had a vertebral fracture noted in the report. The proportion of COPD patients with vertebral fractures who were discharged on osteoporosis therapy was 5/27 (18.5%). There was a suggestion of lower lung function, as measured by forced vital capacity (FVC%), in patients with severe vertebral fractures ( p=0.067). CONCLUSIONS: These data indicate that: (1) There is an increased proportion of COPD patients with severe vertebral fracture, and (2) Documentation and treatment of osteoporosis in acute care COPD patients is low. Therefore, there is a need to target this high-risk group for osteoporosis screening and potential clinical management.

Efficacy of home-based exercise for improving quality of life among elderly women with symptomatic osteoporosis-related vertebral fractures.

This randomized controlled trial was designed to investigate the effect of a 6-month home-based exercise program versus control (usual activities) on quality of life for postmenopausal women with osteoporosis who had at least one vertebral fracture. Twelve-month assessments of outcomes were completed to determine if women would continue exercising with minimal supervision and if benefit could be sustained. The home exercise program followed a "lifestyle exercise" approach where participants completed exercises 60 min per day, 3 days a week and could complete exercises in small periods of time throughout the day. Exercise activities included stretching, strength training and aerobics (i.e. walking). Participants were assessed at baseline, 6 months, and 12 months using the Osteoporosis Quality of Life Questionnaire (OQLQ), the Sickness Impact Profile (SIP), a balance test, and the Timed Up And Go test. Bone mineral density was assessed at baseline and 12 months for both the lumbar spine and femoral neck. Quality of life (OQLQ) improved over 6 months in the exercise group compared to the control group in the domains of symptoms (P=0.003), emotion (P=0.01) and leisure (P=0.03). Results from the balance test indicated a greater effect in the exercise group over 12 months (P<0.05). There were no significant differences between groups in measures of Timed Up and Go, SIP at 6 and 12 months, and femoral neck and lumbar spine bone mineral density at 12 months. Home-based exercise with minimal supervision improves quality of life in elderly women with vertebral fractures. Future research is needed to determine if home exercise programs reduce falls and fall-related injuries in the elderly.

All patients with inflammatory bowel disease should have bone density assessment: pro.

Bone loss is a common problem for individuals with inflammatory bowel disease. Corticosteroids play an important role in the development of osteoporosis in these patients; however, active disease and longer disease duration also appear to increase the risk of osteoporosis. Given the current burden of osteoporosis, bone mineral density is recommended.

Evaluation of the association between St. John's wort and elevated thyroid-stimulating hormone.

STUDY OBJECTIVE: To evaluate whether St. John's wort is associated with an elevation in thyroid-stimulating hormone (TSH) levels. DESIGN: Retrospective case-control study SETTING: Hamilton, Ontario; September 1998-May 1999. SUBJECTS: Thirty-seven subjects with elevated TSH levels and 37 age- (+/- 6 yrs) and gender-matched subjects with normal TSH levels who resided in the same region. MEASUREMENTS AND MAIN RESULTS: Exposure to St. John's wort during the 3-6 months before TSH measurement was assessed through a telephone interview. A total of 4 of 37 subjects with elevated TSH levels and 2 of 37 subjects with normal TSH levels had taken St. John's wort in that time period. The odds ratio for elevated TSH levels associated with taking St. John's wort was 2.12 (95% confidence interval [CI] 0.36-12.36). CONCLUSION: This study suggests a probable association between St. John's wort and elevated TSH levels. However, because of the wide CIs surrounding the point estimate (which crosses unity), further investigation, including a large, prospective cohort study, is warranted.