Indicators for the total number of melanocytic naevi : an adjunct for screening campaigns. Observational study on 292 patients.

BACKGROUND: The presence of multiple melanocytic naevi is a strong risk factor for melanoma. Use of the whole body naevus count to identify at-risk patients is impractical. OBJECTIVES: To (i) identify a valid anatomical predictor of total naevus count; (ii) determine the number of naevi that most accurately predict total naevus count above 25, 50 and 100; and (iii) evaluate determinants of multiple melanocytic naevi and atypical naevi. METHODS: Clinical data from 292 consecutive Spanish patients consulting for skin lesions requiring debriding were collected throughout 2009 and 2010. Correlations between site-specific and whole body naevus counts were analysed. Cut-offs to predict total naevus counts were determined using the area under the receiver operating characteristic curve. RESULTS: The studied population was young (median age 31 years, interquartile range 28-43). The naevus count on the right arm correlated best with the total nevus count (R(2) 0·80 for men, 0·86 for women). Presence of at least five naevi on the right arm was the strongest determinant of a total naevus count above 50 [odds ratio (OR) 34·4, 95% confidence interval (CI) 13·9-85·0] and of having at least one atypical naevus (OR 5·7, 95% CI 2·4-13·5). Cut-off values of 6, 8 and 11 naevi on the right arm best predicted total naevus count above 25, 50 and 100, respectively. CONCLUSIONS: Our results support the arm as a practical and reliable site to estimate the total naevus count when screening or phenotyping large populations. Threshold values for the number of naevi on the arm are proposed to help identify patients for melanoma screening.

Trends of pre-hospital emergency medical services activity over 10 years : a population-based registry analysis

BACKGROUND: The number of requests to pre-hospital emergency medical services (PEMS) has increased in Europe over the last 20 years, but epidemiology of PEMS interventions has little be investigated. The aim of this analysis was to describe time trends of PEMS activity in a region of western Switzerland. METHODS: Use of data routinely and prospectively collected for PEMS intervention in the Canton of Vaud, Switzerland, from 2001 to 2010. This Swiss Canton comprises approximately 10% of the whole Swiss population. RESULTS: We observed a 40% increase in the number of requests to PEMS between 2001 and 2010. The overall rate of requests was 35/1000 inhabitants for ambulance services and 10/1000 for medical interventions (SMUR), with the highest rate among people aged ≥ 80. Most frequent reasons for the intervention were related to medical problems, predominantly unconsciousness, chest pain respiratory distress, or cardiac arrest, whereas severe trauma interventions decreased over time. Overall, 89% were alive after 48 h. The survival rate after 48 h increased regularly for cardiac arrest or myocardial infarction. CONCLUSION: Routine prospective data collection of prehospital emergency interventions and monitoring of activity was feasible over time. The results we found add to the understanding of determinants of PEMS use and need to be considered to plan use of emergency health services in the near future. More comprehensive analysis of the quality of services and patient safety supported by indicators are also required, which might help to develop prehospital emergency services and new processes of care.

Prevalence of frailty indicators and association with socioeconomic status in middle-aged and older adults in a swiss region with universal health insurance coverage : a population-based cross-sectional study

Frailty prevalence in older adults has been reported but is largely unknown in middle-aged adults. We determined the prevalence of frailty indicators among middle-aged and older adults from a general Swiss population characterized by universal health insurance coverage and assessed the determinants of frailty with a special focus on socioeconomic status. Participants aged 50 and more from the population-based 2006-2010 Bus Santé study were included (N = 2,930). Four frailty indicators (weakness, shrinking, exhaustion, and low activity) were measured according to standard definitions. Multivariate logistic regressions were used to determine associations. Overall, 63.5%, 28.7%, and 7.8% participants presented no frailty indicators, one frailty indicator, and two or more frailty indicators, respectively. Among middle-aged participants (50-65 years), 75.1%, 22.2%, and 2.7% presented 0, 1, and 2 or more frailty indicators. The number of frailty indicators was positively associated with age, hypertension, and current smoking and negatively associated with male gender, body mass index, waist-to-hip ratio, and serum total cholesterol level. Lower income level but not education was associated with higher number of frailty indicators. Frailty indicators are frequently encountered in both older and middle-aged adults from the Swiss general population. Despite universal health insurance coverage, household income is independently associated with frailty.

Cost-effectiveness analysis in Chagas' disease vectors control interventions

After a large scale field trial performed in central Brazil envisaging the control of Chagas' disease vectors in an endemic area colonized by Triatoma infestans and T. sordida the cost-effectiveness analysis for each insecticide/formulation was performed. It considered the operational costs and the prices of insecticides and formulations, related to the activity and persistence of each one. The end point was considered to be less than 90% of domicilliary unitis (house + annexes) free of infestation. The results showed good cost-effectiveness for a slow-release emulsifiable suspension (SRES) based on PVA and containing malathion as active ingredient, as well as for the pyrethroids tested in this assay-cyfluthrin, cypermethrin, deltamethrin and permethrin.

Challenging recommended oral and intravenous voriconazole doses for improved efficacy and safety: population pharmacokinetics-based analysis of adult patients with invasive fungal infections.

BACKGROUND: Recommended oral voriconazole (VRC) doses are lower than intravenous doses. Because plasma concentrations impact efficacy and safety of therapy, optimizing individual drug exposure may improve these outcomes. METHODS: A population pharmacokinetic analysis (NONMEM) was performed on 505 plasma concentration measurements involving 55 patients with invasive mycoses who received recommended VRC doses. RESULTS: A 1-compartment model with first-order absorption and elimination best fitted the data. VRC clearance was 5.2 L/h, the volume of distribution was 92 L, the absorption rate constant was 1.1 hour(-1), and oral bioavailability was 0.63. Severe cholestasis decreased VRC elimination by 52%. A large interpatient variability was observed on clearance (coefficient of variation [CV], 40%) and bioavailability (CV 84%), and an interoccasion variability was observed on bioavailability (CV, 93%). Lack of response to therapy occurred in 12 of 55 patients (22%), and grade 3 neurotoxicity occurred in 5 of 55 patients (9%). A logistic multivariate regression analysis revealed an independent association between VRC trough concentrations and probability of response or neurotoxicity by identifying a therapeutic range of 1.5 mg/L (>85% probability of response) to 4.5 mg/L (<15% probability of neurotoxicity). Population-based simulations with the recommended 200 mg oral or 300 mg intravenous twice-daily regimens predicted probabilities of 49% and 87%, respectively, for achievement of 1.5 mg/L and of 8% and 37%, respectively, for achievement of 4.5 mg/L. With 300-400 mg twice-daily oral doses and 200-300 mg twice-daily intravenous doses, the predicted probabilities of achieving the lower target concentration were 68%-78% for the oral regimen and 70%-87% for the intravenous regimen, and the predicted probabilities of achieving the upper target concentration were 19%-29% for the oral regimen and 18%-37% for the intravenous regimen. CONCLUSIONS: Higher oral than intravenous VRC doses, followed by individualized adjustments based on measured plasma concentrations, improve achievement of the therapeutic target that maximizes the probability of therapeutic response and minimizes the probability of neurotoxicity. These findings challenge dose recommendations for VRC.

New roles for community pharmacists in modern health care systems: a challenge for pharmacy education and research.

The academic activities led by the Unit of Community Pharmacy can be classified as translational. Our group is interested in person-centered pharmaceutical services aimed at a more responsible use of drugs (effectiveness, safety, efficiency) in collaboration with physicians and other health care professionals in a primary care setting. The following domains of education and research are high priorities for our group: medication therapy management, medication adherence, integrated care, individualization of therapies, care management for the elderly and e-health.

Sorting out measures and definitions of screening participation to improve comparability: The example of colorectal cancer.

Participation is a key indicator of the potential effectiveness of any population-based intervention. Defining, measuring and reporting participation in cancer screening programmes has become more heterogeneous as the number and diversity of interventions have increased, and the purposes of this benchmarking parameter have broadened. This study, centred on colorectal cancer, addresses current issues that affect the increasingly complex task of comparing screening participation across settings. Reports from programmes with a defined target population and active invitation scheme, published between 2005 and 2012, were reviewed. Differences in defining and measuring participation were identified and quantified, and participation indicators were grouped by aims of measure and temporal dimensions. We found that consistent terminology, clear and complete reporting of participation definition and systematic documentation of coverage by invitation were lacking. Further, adherence to definitions proposed in the 2010 European Guidelines for Quality Assurance in Colorectal Cancer Screening was suboptimal. Ineligible individuals represented 1% to 15% of invitations, and variable criteria for ineligibility yielded differences in participation estimates that could obscure the interpretation of colorectal cancer screening participation internationally. Excluding ineligible individuals from the reference population enhances comparability of participation measures. Standardised measures of cumulative participation to compare screening protocols with different intervals and inclusion of time since invitation in definitions are urgently needed to improve international comparability of colorectal cancer screening participation. Recommendations to improve comparability of participation indicators in cancer screening interventions are made.

The effectiveness of tipi in the treatment of hip and knee osteoarthritis: a preliminary report

Osteoarthritis (OA) is a common painful inflammatory condition occurring mainly in the later half of life. Hipe and knee are the joints mostly affected. Petiveria alliacea (tipi) popularly known as an anti-rheumatic medicine, has been used by OA patients to relief pain. This one-week cross-over double-blind trial has preliminary evaluated the analgesic effect of tipi tea in 14 patients with hip and knee OA. Imperata exaltata (sape) was used as the Placebo tea. The pain assessments that were made at baseline and before the start of the second treatment period by treatment groups were comparable. While taking tipi or placebo tea patients experienced a statistically significant improvement in pain on motion and pain at night. The comparison between the improvements reported while on tipi and placebo tea, however, did not disclose any statistically significant difference. At the conclusion of the study 7 patients preferred tipi tea and 6 preferred placebo tea (NS). Two patients reported insomnia, one durign placebo treatment and the other during tipi treatment. In this preliminary report both teas succeeded in the aim of relieving pain.

A randomized controlled clinical trial evaluating the performance and safety of platelets treated with MIRASOL pathogen reduction technology.

BACKGROUND: Pathogen reduction of platelets (PRT-PLTs) using riboflavin and ultraviolet light treatment has undergone Phase 1 and 2 studies examining efficacy and safety. This randomized controlled clinical trial (RCT) assessed the efficacy and safety of PRT-PLTs using the 1-hour corrected count increment (CCI(1hour) ) as the primary outcome. STUDY DESIGN AND METHODS: A noninferiority RCT was performed where patients with chemotherapy-induced thrombocytopenia (six centers) were randomly allocated to receive PRT-PLTs (Mirasol PRT, CaridianBCT Biotechnologies) or reference platelet (PLT) products. The treatment period was 28 days followed by a 28-day follow-up (safety) period. The primary outcome was the CCI(1hour) determined using up to the first eight on-protocol PLT transfusions given during the treatment period. RESULTS: A total of 118 patients were randomly assigned (60 to PRT-PLTs; 58 to reference). Four patients per group did not require PLT transfusions leaving 110 patients in the analysis (56 PRT-PLTs; 54 reference). A total of 541 on-protocol PLT transfusions were given (303 PRT-PLTs; 238 reference). The least square mean CCI was 11,725 (standard error [SE], 1.140) for PRT-PLTs and 16,939 (SE, 1.149) for the reference group (difference, -5214; 95% confidence interval, -7542 to -2887; p<0.0001 for a test of the null hypothesis of no difference between the two groups). CONCLUSION: The study failed to show noninferiority of PRT-PLTs based on predefined CCI criteria. PLT and red blood cell utilization in the two groups was not significantly different suggesting that the slightly lower CCIs (PRT-PLTs) did not increase blood product utilization. Safety data showed similar findings in the two groups. Further studies are required to determine if the lower CCI observed with PRT-PLTs translates into an increased risk of bleeding.

IL28B polymorphism is significantly correlated with ifn anti-viral effectiveness already on first day of pegylated interferon-alpha and ribavirin therapy of chronic HCV infection

Background and Aims: Recently, single nucleotide polymorphisms (SNPs) in IL28B were shown to correlate with response to pegylated interferon-a (IFN) and ribavirin therapy of chronic HCV infection. However, the cause for the SNPs effect on therapy response and its application for direct anti-viral (DAV) treatment are not clear. Here, we analyze early HCV kinetics as function of IL28B SNPs to determine its specific effect on viral dynamics. Methods: IL28B SNPs rs8099917, rs12979860 and rs12980275 were genotyped in 252 chronically HCV infected Caucasian naïve patients (67% HCV genotype 1, 28% genotype 2-3) receiving peginterferonalfa- 2a (180 mg/qw) plus ribavirin (1000-1200 mg/qd) in the DITTO study. HCV-RNA was measured (LD = 50 IU/ml) frequently during first 28 days. Results: RVR was achieved in 33% of genotype 1 patients with genotype CC at rs12979860 versus 12-16% for genotypes TT and CT (P < 0.03). Significant (P < 0.001) difference in viral decline was observed already at day 1 (see Figure). First phase decline was significantly (P < 0.001) larger in patients with genotype CC (2.0 log) than for TT and CT genotypes (0.6 and 0.8), indicating IFN anti-viral effectiveness in blocking virion production of 99% versus 75-84%. There was no significant association between second phase slope and rs12979860 genotype in patients with a first phase decline larger than 1 log. HCV kinetics as function of IL28b SNP. The same trend (not shown) was observed for HCV genotype 2-3 patients with different SNP genotype distribution that may indicate differential selection pressure as function of HCV genotype. Similar results were observed for SNPs rs8099917 and rs12980275, with a strong linkage disequilibrium among the 3 loci allowing to define the composite haplotype best associated with IFN effectiveness. Conclusions: IFN effectiveness in blocking virion production/ release is strongly affected by IL28B SNPs, but not other viral dynamic properties such as infected cell loss rate. Thus, IFN based therapy, as standard-of-care or in combination with DAV, should consider IL28B SNPs for prediction and personalized treatment, while response to pure DAV treatment may be less affected by IL28B SNPs. Additional analyses are undergoing to pinpoint the SNP effect on IFN anti-viral effectiveness.

Comparative cost-effectiveness analyses of cardiovascular magnetic resonance and coronary angiography combined with fractional flow reserve for the diagnosis of coronary artery disease.

BACKGROUND: According to recent guidelines, patients with coronary artery disease (CAD) should undergo revascularization if significant myocardial ischemia is present. Both, cardiovascular magnetic resonance (CMR) and fractional flow reserve (FFR) allow for a reliable ischemia assessment and in combination with anatomical information provided by invasive coronary angiography (CXA), such a work-up sets the basis for a decision to revascularize or not. The cost-effectiveness ratio of these two strategies is compared. METHODS: Strategy 1) CMR to assess ischemia followed by CXA in ischemia-positive patients (CMR + CXA), Strategy 2) CXA followed by FFR in angiographically positive stenoses (CXA + FFR). The costs, evaluated from the third party payer perspective in Switzerland, Germany, the United Kingdom (UK), and the United States (US), included public prices of the different outpatient procedures and costs induced by procedural complications and by diagnostic errors. The effectiveness criterion was the correct identification of hemodynamically significant coronary lesion(s) (= significant CAD) complemented by full anatomical information. Test performances were derived from the published literature. Cost-effectiveness ratios for both strategies were compared for hypothetical cohorts with different pretest likelihood of significant CAD. RESULTS: CMR + CXA and CXA + FFR were equally cost-effective at a pretest likelihood of CAD of 62% in Switzerland, 65% in Germany, 83% in the UK, and 82% in the US with costs of CHF 5'794, euro 1'517, £ 2'680, and $ 2'179 per patient correctly diagnosed. Below these thresholds, CMR + CXA showed lower costs per patient correctly diagnosed than CXA + FFR. CONCLUSIONS: The CMR + CXA strategy is more cost-effective than CXA + FFR below a CAD prevalence of 62%, 65%, 83%, and 82% for the Swiss, the German, the UK, and the US health care systems, respectively. These findings may help to optimize resource utilization in the diagnosis of CAD.

Adiposity indicators and blood pressure in children: nothing beyond body mass index?

Obesity is a major risk factor for elevated blood pressure in children. For instance, in a school-based study of 5207 children aged 10-12 years, the prevalence of hypertension, which is sustained elevated blood pressure over several visits, was 1.5%, 3.9% and 17.5% in normal weight, overweight and obese children, respectively. High body mass index (BMI) is commonly used to define overweight and obesity. However, because BMI is merely a proxy for adiposity, there is a longstanding debate about its performance to predict elevated blood pressure (or any other health conditions associated with adiposity) and whether other adiposity indicators, such as waist circumference, waist-to-hip ratio or hip circumference, should not be preferred... In this study, 7.4% of boys and 6.4% of girls had elevated blood pressure. The adiposity indicators were highly correlated to each other, apart from weight, waist-to-hip ratio and skinfold thickness z-scores. All indicators were associated with blood pressure. The ability to identify children with elevated blood pressure, assessed by the area under the receiver operating curve (AUC) statistic, was superior for BMI, body adiposity index and waist-to-height ratio z-scores compared with other indicators. BMI z-scores had a slightly higher AUC than other indicators. The authors concluded that BMIz-scores could be a better predictor of elevated blood pressure in children than other adiposity indicators.

Study design for technology assessment: critical issues.

The epidemiological methods have become useful tools for the assessment of the effectiveness and safety of health care technologies. The experimental methods, namely the randomized controlled trials (RCT), give the best evidence of the effect of a technology. However, the ethical issues and the very nature of the intervention under study sometimes make it difficult to carry out an RCT. Therefore, quasi-experimental and non-experimental study designs are also applied. The critical issues concerning these designs are discussed. The results of evaluative studies are of importance for decision-makers in health policy. The measurements of the impact of a medical technology should go beyond a statement of its effectiveness, because the essential outcome of an intervention or programme is the health status and quality of life of the individuals and populations concerned.