Resting heart rate and the risk of heart failure in healthy adults: the rotterdam study.

Background- An elevated resting heart rate is associated with rehospitalization for heart failure and is a modifiable risk factor in heart failure patients. We aimed to examine the association between resting heart rate and incident heart failure in a population-based cohort study of healthy adults without pre-existing overt heart disease. Methods and Results- We studied 4768 men and women aged ≥55 years from the population-based Rotterdam Study. We excluded participants with prevalent heart failure, coronary heart disease, pacemaker, atrial fibrillation, atrioventricular block, and those using β-blockers or calcium channel blockers. We used extended Cox models allowing for time-dependent variation of resting heart rate along follow-up. During a median of 14.6 years of follow-up, 656 participants developed heart failure. The risk of heart failure was higher in men with higher resting heart rate. For each increment of 10 beats per minute, the multivariable adjusted hazard ratios in men were 1.16 (95% confidence interval, 1.05-1.28; P=0.005) in the time-fixed heart rate model and 1.13 (95% confidence interval, 1.02-1.25; P=0.017) in the time-dependent heart rate model. The association could not be demonstrated in women (P for interaction=0.004). Censoring participants for incident coronary heart disease or using time-dependent models to account for the use of β-blockers or calcium channel blockers during follow-up did not alter the results. Conclusions- Baseline or persistent higher resting heart rate is an independent risk factor for the development of heart failure in healthy older men in the general population.

Prices of medicines: a case-study on the impact of the rate-of-return regulation in the United Kingdom

This work carries out an empirical evaluation of the impact of the main mechanism for regulating the prices of medicines in the UK on a variety ofpharmaceutical price indices. The empirical evidence shows that the overall impact of the rate of return cap appears to have been slight or even null, and in any case that the impact would differ across therapeutic areas. These empiricalfindings suggest that the price regulation has managed to encourage UK-based firms¿ diversification in many therapeutic areas

Analyse des taux de renvoi entre médecins praticiens: une revue de la littérature. [Analysis of referral rate between medical practitioners: a review of the literature].

The authors are discussing the results of the international literature with regards to referrals between ambulatory physicians. There are still few studies on this problem and the methodologies used are often too different to make valid comparisons. However, the earned results suggest more questions than they give answers to the determinants of the referral process. This can be explained by the multidimensionality of factors which are involved in the decision to refer a patient to another practitioner, particularly by the complex interaction between the characteristics of each patient, practitioner and the sanitary system itself.

Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.

Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.

Characteristics and outcome of 27 elbow periprosthetic joint infections: results from a 14-year cohort study of 358 elbow prostheses.

Elbow arthroplasty is increasingly performed in patients with rheumatic and post-traumatic arthritis. Data on elbow periprosthetic joint infection (PJI) are limited. We investigated the characteristics and outcome of elbow PJI in a 14-year cohort of total elbow arthroplasties in a single centre. Elbow prosthesis, which were implanted between 1994 and 2007 at Schulthess Clinic in Zurich, were retrospectively screened for infection. PJI was defined as periprosthetic purulence, the presence of sinus tract or microbial growth. A Kaplan-Meier survival method and Cox proportional hazard analysis were performed. Of 358 elbow prostheses, PJI was identified in 27 (7.5%). The median patient age (range) was 61 (39-82) years; 63% were females. Seventeen patients (63%) had a rheumatic disorder and ten (37%) had osteoarthritis. Debridement and implant retention was performed in 78%, followed by exchange or removal of the prosthesis (15%) or no surgery (7%).The relapse-free survival (95% CI) was 79% (63-95%) after 1 year and 65% (45-85%) after 2 years. The outcome after 2 years was significantly better when patients were treated according to the algorithm compared to patients who were not (100% vs. 33%, p <0.05). In 21 patients treated with debridement and retention, the cure rate was also higher when the algorithm was followed (100% vs. 11%, p <0.05). The findings of the present study suggest that the treatment algorithm developed for hip and knee PJI can be applied to elbow PJI. With proper patient selection and antimicrobial therapy, debridement and retention of the elbow prosthesis is associated with good treatment outcome.

Improvement of a testing apparatus for dynamometry: procedures for penetrometry and influence of strain rate to quantify the tensile strength of soil aggregates

Soil penetration resistance (PR) and the tensile strength of aggregates (TS) are commonly used to characterize the physical and structural conditions of agricultural soils. This study aimed to assess the functionality of a dynamometry apparatus by linear speed and position control automation of its mobile base to measure PR and TS. The proposed equipment was used for PR measurement in undisturbed samples of a clayey "Nitossolo Vermelho eutroférrico" (Kandiudalfic Eutrudox) under rubber trees sampled in two positions (within and between rows). These samples were also used to measure the volumetric soil water content and bulk density, and determine the soil resistance to penetration curve (SRPC). The TS was measured in a sandy loam "Latossolo Vermelho distrófico" (LVd) - Typic Haplustox - and in a very clayey "Nitossolo Vermelho distroférrico" (NVdf) - Typic Paleudalf - under different uses: LVd under "annual crops" and "native forest", NVdf under "annual crops" and "eucalyptus plantation" (> 30 years old). To measure TS, different strain rates were applied using two dynamometry testing devices: a reference machine (0.03 mm s-1), which has been widely used in other studies, and the proposed equipment (1.55 mm s-1). The determination coefficient values of the SRPC were high (R² > 0.9), regardless of the sampling position. Mean TS values in LVd and NVdf obtained with the proposed equipment did not differ (p > 0.05) from those of the reference testing apparatus, regardless of land use and soil type. Results indicate that PR and TS can be measured faster and accurately by the proposed procedure.

Polypharmacy as predictor of drug cost, length of hospital stay and mortality rate in nursing homes : a retrospective analysis of pharmacy medication records

Background and objectives: Polypharmacy (PP) is a typical con-sequence of multiple chronic conditions in elderly patients. PP is commonly defined as the use of multiple concurrent drug therapies although a standard definition is not used. The aims of this study were to assess the PP rate among nursing home (NH) residents using the data of the pharmacy medication records and to investigate the threshold level of PP as predictor of drug cost, length of hospital stay and mortality rate

Bond Development in Concrete Overlays, August 1995

Data collection to determine the rate of bond strength development between concrete overlays and existing pavements and the evaluation of nondestructive testing methods for determining concrete strength were the objectives of this study. Maturity meters and pulse velocity meters were employed to determine the rate of flexural strength gain and determine the time for opening of newly constructed pavements to traffic. Maturity measurements appear to provide a less destructive method of testing. Pulse velocity measurements do require care in the preparation of the test wells and operator care in testing. Both devices functioned well under adverse weather and construction conditions and can reduce construction traffic delay decisions. Deflection testing and strain gaging indicate differences in the reaction of the overlay and existing pavement under grouting versus nongrouted sections. Grouting did enhance the rate of bond development with Type I11 cement out performing the Type I1 grout section. Type I11 and Type I1 cement grouts enhanced resistance to cracking in uniformly supported pavements where joints are prepared prior to overlays achieving target flexural strengths. Torsional and direct shear testing provide additional ways of measuring bond development at different cure times. Detailed data analysis will be utilized by TRANSTEC, Inc. to develop a bonded overlay construction guidelines report.

Driving rate effects in avalanche-mediated first-order phase transitions

We study the driving-rate and temperature dependence of the power-law exponents that characterize the avalanche distribution in first-order phase transitions. Measurements of acoustic emission in structural transitions in Cu-Zn-Al and Cu-Al-Ni are presented. We show how the observed behavior emerges within a general framework of competing time scales of avalanche relaxation, driving rate, and thermal fluctuations. We confirm our findings by numerical simulations of a prototype model.

High rate of completion of preventive therapy for latent tuberculosis infection among asylum seekers in a Swiss Canton.

BACKGROUND: Preventive treatment may avoid future cases of tuberculosis among asylum seekers. The effectiveness of preventive treatment depends in large part on treatment completion. METHODS: In a prospective cohort study, asylum seekers of two of the Swiss Canton Vaud migration centres were screened with the Interferon Gamma Release Assay (IGRA). Those with a positive IGRA were referred for medical examination. Individuals with active or past tuberculosis were excluded. Preventive treatment was offered to all participants with positive IGRA but without active tuberculosis. The adherence was assessed during monthly follow-up. RESULTS: From a population of 393 adult migrants, 98 (24.9%) had a positive IGRA. Eleven did not attend the initial medical assessment. Of the 87 examined, eight presented with pulmonary disease (five of them received a full course of antituberculous therapy), two had a history of prior tuberculosis treatment and two had contraindications to treatment. Preventive treatment was offered to 75 individuals (4 months rifampicin in 74 and 9 months isoniazid in one), of whom 60 (80%) completed the treatment. CONCLUSIONS: The vulnerability and the volatility of this population make screening and observance of treatment difficult. It seems possible to obtain a high rate of completion using a short course of treatment in a closely monitored population living in stable housing conditions.

Comparison of the methane oxidation rate in four media

Landfill gas emissions are one of the main sources of anthropogenic methane (CH4), a major greenhouse gas. In this paper, an economically attractive alternative to minimize greenhouse gas emissions from municipal solid waste landfills was sought. This alternative consists in special biofilters as landfill covers with oxidative capacity in the presence of CH4. To improve the quality/cost ratio of the project, compost was chosen as one of the cover substrates and soil (Typic red yellow-silt-clay Podzolic) as the other. The performance of four substrates was studied in laboratory experiments: municipal solid waste (MSW) compost, soil, and two soil-compost at different proportions. This study aimed to evaluate the suitability and environmental compatibility as a means of CH4 oxidation in biofilters. Four biofilters were constructed in 60 cm PVC tubes with an internal diameter of 10 cm. Each filter contained 2.3 L of oxidizing substrate at the beginning of the experiment. The gas used was a mixture of CH4 and air introduced at the bottom of each biofilter, at a flow of 150 mL min-1, by a flow meter. One hundred days after the beginning of the experiment, the best biofilter was the MSW compost with an oxidation rate of 990 g m-3 day-1 , corresponding to an efficiency of 44 %. It can be concluded that the four substrates studied have satisfactory oxidative capacity, and the substrates can be used advantageously as cover substrate of MSW landfills.

Mutations in the epithelial Na+ channel ENaC outer pore disrupt amiloride block by increasing its dissociation rate.

The epithelial Na+ channel ENaC mediates transepithelial Na+ transport in the distal kidney, the colon, and the lung and is a key element for the maintenance of Na+ balance and the regulation of blood pressure. Mutagenesis studies have identified residues alphaS583 and the homologous betaG525 and gammaG537 in the outer pore entrance that are critical for ENaC block by the K+-sparing diuretic amiloride. The aim of the present study was to determine first, whether these residues are part of the amiloride binding site, and second, whether they are general determinants of ENaC block by amiloride and its derivatives. Kinetic analysis of the association and dissociation rates of amiloride and benzamil to ENaC showed that mutation of residue alphaS583C and the homologous betaG525C increased the dissociation rate of the drugs from the binding site, with little changes in their association rate. Thus, these mutations destabilize the binding interaction between the blockers and the receptor on the channel, favoring the unbinding of the ligand. This strongly suggests that they are part of the binding site. Because mutations of alphaS583, betaG525, and gammaG537 have similar effects on amiloride, benzamil, and triamterene block, we conclude that these three ENaC blockers share a common receptor within the ion channel pore.

Failure of surgical treatment in 115 infected total hip arthroplasties - analysis of a 12-year prosthetic joint cohort study (1999-2010)

Infection of total hip arthroplasties (THA) leads to significant long-termmorbidity and high healthcare costs. We evaluated the differentreasons for treatment failure using different surgical modalities in a12-year prosthetic joint infection cohort study.Method: All patients hospitalized at our institution with infected THAwere included either retrospectively (1999-2007) or prospectively(2008-2010). THA infection was defined as growth of the same microorganismin ≥2 tissue or synovial fluid culture, visible purulence, sinustract or acute inflammation on tissue histopathology. Outcome analysiswas performed at outpatient visits, followed by contacting patients,their relatives and/or treating physicians afterwards.Results: During the study period, 117 patients with THA were identified.We exclude 2 patients due to missing data. The median age was69 years (range, 33-102 years); 42% were women. THA was mainlyperformed for osteoarthritis (n = 84), followed by trauma (n = 22),necrosis (n = 4), dysplasia (n = 2), rheumatoid arthritis (n = 1), osteosarcoma(n = 1) and tuberculosis (n = 1). 28 infections occurred early(≤3 months), 25 delayed (3-24 months) and 63 late (≥24 months aftersurgery). Infected THA were treated with (i) two-stage exchange in59 patients (51%, cure rate: 93%), (ii) one-stage exchange in 5 (4.3%,cure rate: 100%), (iii) debridement with change of mobile parts in18 (17%, cure rate: 83%), (iv) debridement without change of mobileparts in 17 (14%, cure rate: 53% ), (v) Girdlestone in 13 (11%, curerate: 100%), and (vi) two-stage exchange followed by removal in 3(2.6%). Patients were followed for a mean of 3.9 years (range, 0.1 to 9years), 7 patients died unrelated to the infected THA. 15 patients (13%)needed additional operations, 1 for mechanical reasons (dislocationof spacer) and 14 for persistent infection: 11 treated with debridementand retention (8 without change and 3 with change of mobile parts)and 3 with two-stage exchange. The mean number of surgery was 2.2(range, 1 to 5). The infection was finally eradicated in all patients, butthe functional outcome remained unsatisfactory in 20% (persistentpain or impaired mobility due to spacer or Girdlestone situation).Conclusions: Non-respect of current treatment concept leads totreatment failure with subsequent operations. Precise analysis of eachtreatment failures can be used for improving the treatment algorithmleading to better results.