Overweight children have a greater proportion of fat mass relative to muscle mass in the upper limbs than in the lower limbs: implications for bone strength at the distal forearm

BACKGROUND: The influence of adiposity on upper-limb bone strength has rarely been studied in children, despite the high incidence of forearm fractures in this population. OBJECTIVE: The objective was to compare the influence of muscle and fat tissues on bone strength between the upper and lower limbs in prepubertal children. DESIGN: Bone mineral content, total bone cross-sectional area, cortical bone area (CoA), cortical thickness (CoTh) at the radius and tibia (4% and 66%, respectively), trabecular density (TrD), bone strength index (4% sites), cortical density (CoD), stress-strain index, and muscle and fat areas (66% sites) were measured by using peripheral quantitative computed tomography in 427 children (206 boys) aged 7-10 y. RESULTS: Overweight children (n = 93) had greater values for bone variables (0.3-1.3 SD; P < 0.0001) than did their normal-weight peers, except for CoD 66% and CoTh 4%. The between-group differences were 21-87% greater at the tibia than at the radius. After adjustment for muscle cross-sectional area, TrD 4%, bone mineral content, CoA, and CoTh 66% at the tibia remained greater in overweight children, whereas at the distal radius total bone cross-sectional area and CoTh were smaller in overweight children (P < 0.05). Overweight children had a greater fat-muscle ratio than did normal-weight children, particularly in the forearm (92 +/- 28% compared with 57 +/- 17%). Fat-muscle ratio correlated negatively with all bone variables, except for TrD and CoD, after adjustment for body weight (r = -0.17 to -0.54; P < 0.0001). CONCLUSIONS: Overweight children had stronger bones than did their normal-weight peers, largely because of greater muscle size. However, the overweight children had a high proportion of fat relative to muscle in the forearm, which is associated with reduced bone strength.

Vaccination of cystic fibrosis patients against Pseudomonas aeruginosa reduces the proportion of patients infected and delays time to infection

INTRODUCTION: Cystic fibrosis (CF) almost always leads to chronic airway infection with Pseudomonas aeruginosa. Despite advances in antibiotic therapy, after chronic infection rapid deterioration in lung function occurs, increasing morbidity and mortality. Prevention of infection by vaccination is desirable, but earlier trials produced disappointing results. The promising short term immunogenicity and safety of a new P. aeruginosa vaccine prompted us to evaluate its long term efficacy. We conducted a 10-year retrospective analysis of outcomes in a group of vaccinated patients. MATERIALS AND METHODS: In 1989-1990, 30 young children with CF, mean age 7 years, with no prior history of infection with P. aeruginosa, were vaccinated against P. aeruginosa with a polyvalent conjugate vaccine. We report the follow-up of 26 of these patients from 1989 to 2001. The patients were given yearly vaccine boosters. Comparisons were made with a CF patient control group matched for gender, age and, where possible, genetic mutation. Vaccinated patients and controls were attending a single CF clinic and received the same clinical management throughout the study period. Main outcomes were time to infection, proportion of patients infected, development of P. aeruginosa mucoid phenotype, lung function and body weight. RESULTS: The time to infection with P. aeruginosa was longer in the vaccination group than in the control group, and fewer vaccinated patients than controls became chronically infected (32% versus 72%; P < 0.001). The proportion of mucoid infections was higher in the control group (44%) than in the vaccinated group (25%). Patients >/=18 years of age at the end of the study had a lower mean forced expiratory volume at 1 s (FEV1) than did those 13-17 years of age, but this difference was small in the vaccinated group (73.6% versus 83.7%) compared with the controls (48.0% versus 78.7%). In the >/=18 year age category the mean FEV1% at 10 years was 73.6% (vaccinated) and 48.0% (controls) (P < 0.05). In the vaccinated group only 11 (44%) of 25 patients were underweight at the 10-year follow-up compared with 18 (72%) of 25 at the beginning of the study. In the control group 17 (68%) of 25 patients were underweight at 10-year follow-up compared with 16 (64%) of 25 at the beginning of the study. CONCLUSION: Regular vaccination of young CF patients for a period of 10 years with a polyvalent conjugate vaccine reduced the frequency of chronic infection with P. aeruginosa. This was associated with better preservation of lung function. Vaccinated patients gained more weight during the study period, a possible indication of an improved overall health status.

High proportion of healthcare-associated urinary tract infection in the absence of prior exposure to urinary catheter: a cross-sectional study

Exposure to urinary catheters is considered the most important risk factor for healthcare-associated urinary tract infection (UTI) and is associated with significant morbidity and substantial extra-costs. In this study, we assessed the impact of urinary catheterisation (UC) on symptomatic healthcare-associated UTI among hospitalized patients.

German Total Ankle Replacement Register of the German Foot and Ankle Society (D. A. F.) - presentation of design and reliability of the data as well as first results

INTRODUCTION Even though arthroplasty of the ankle joint is considered to be an established procedure, only about 1,300 endoprostheses are implanted in Germany annually. Arthrodeses of the ankle joint are performed almost three times more often. This may be due to the availability of the procedure - more than twice as many providers perform arthrodesis - as well as the postulated high frequency of revision procedures of arthroplasties in the literature. In those publications, however, there is often no clear differentiation between revision surgery with exchange of components, subsequent interventions due to complications and subsequent surgery not associated with complications. The German Orthopaedic Foot and Ankle Association's (D. A. F.) registry for total ankle replacement collects data pertaining to perioperative complications as well as cause, nature and extent of the subsequent interventions, and postoperative patient satisfaction. MATERIAL AND METHODS The D. A. F.'s total ankle replacement register is a nation-wide, voluntary registry. After giving written informed consent, the patients can be added to the database by participating providers. Data are collected during hospital stay for surgical treatment, during routine follow-up inspections and in the context of revision surgery. The information can be submitted in paper-based or online formats. The survey instruments are available as minimum data sets or scientific questionnaires which include patient-reported outcome measures (PROMs). The pseudonymous clinical data are collected and evaluated at the Institute for Evaluative Research in Medicine, University of Bern/Switzerland (IEFM). The patient-related data remain on the register's module server in North Rhine-Westphalia, Germany. The registry's methodology as well as the results of the revisions and patient satisfaction for 115 patients with a two year follow-up period are presented. Statistical analyses are performed with SAS™ (Version 9.4, SAS Institute, Inc., Cary, NC, USA). RESULTS About 2½ years after the register was launched there are 621 datasets on primary implantations, 1,427 on follow-ups and 121 records on re-operation available. 49 % of the patients received their implants due to post-traumatic osteoarthritis, 27 % because of a primary osteoarthritis and 15 % of patients suffered from a rheumatic disease. More than 90 % of the primary interventions proceeded without complications. Subsequent interventions were recorded for 84 patients, which corresponds to a rate of 13.5 % with respect to the primary implantations. It should be noted that these secondary procedures also include two-stage procedures not due to a complication. "True revisions" are interventions with exchange of components due to mechanical complications and/or infection and were present in 7.6 % of patients. 415 of the patients commented on their satisfaction with the operative result during the last follow-up: 89.9 % of patients evaluate their outcome as excellent or good, 9.4 % as moderate and only 0.7 % (3 patients) as poor. In these three cases a component loosening or symptomatic USG osteoarthritis was present. Two-year follow-up data using the American Orthopedic Foot and Ankle Society Ankle and Hindfoot Scale (AOFAS-AHS) are already available for 115 patients. The median AOFAS-AHS score increased from 33 points preoperatively to more than 80 points three to six months postoperatively. This increase remained nearly constant over the entire two-year follow-up period. CONCLUSION Covering less than 10 % of the approximately 240 providers in Germany and approximately 12 % of the annually implanted total ankle-replacements, the D. A. F.-register is still far from being seen as a national registry. Nevertheless, geographical coverage and inclusion of "high-" (more than 100 total ankle replacements a year) and "low-volume surgeons" (less than 5 total ankle replacements a year) make the register representative for Germany. The registry data show that the number of subsequent interventions and in particular the "true revision" procedures are markedly lower than the 20 % often postulated in the literature. In addition, a high level of patient satisfaction over the short and medium term is recorded. From the perspective of the authors, these results indicate that total ankle arthroplasty - given a correct indication and appropriate selection of patients - is not inferior to an ankle arthrodesis concerning patients' satisfaction and function. First valid survival rates can be expected about 10 years after the register's start.

Decreasing Proportion of Recent Infections among Newly Diagnosed HIV-1 Cases in Switzerland, 2008 to 2013 Based on Line-Immunoassay-Based Algorithms.

BACKGROUND: HIV surveillance requires monitoring of new HIV diagnoses and differentiation of incident and older infections. In 2008, Switzerland implemented a system for monitoring incident HIV infections based on the results of a line immunoassay (Inno-Lia) mandatorily conducted for HIV confirmation and type differentiation (HIV-1, HIV-2) of all newly diagnosed patients. Based on this system, we assessed the proportion of incident HIV infection among newly diagnosed cases in Switzerland during 2008-2013. METHODS AND RESULTS: Inno-Lia antibody reaction patterns recorded in anonymous HIV notifications to the federal health authority were classified by 10 published algorithms into incident (up to 12 months) or older infections. Utilizing these data, annual incident infection estimates were obtained in two ways, (i) based on the diagnostic performance of the algorithms and utilizing the relationship 'incident = true incident + false incident', (ii) based on the window-periods of the algorithms and utilizing the relationship 'Prevalence = Incidence x Duration'. From 2008-2013, 3'851 HIV notifications were received. Adult HIV-1 infections amounted to 3'809 cases, and 3'636 of them (95.5%) contained Inno-Lia data. Incident infection totals calculated were similar for the performance- and window-based methods, amounting on average to 1'755 (95% confidence interval, 1588-1923) and 1'790 cases (95% CI, 1679-1900), respectively. More than half of these were among men who had sex with men. Both methods showed a continuous decline of annual incident infections 2008-2013, totaling -59.5% and -50.2%, respectively. The decline of incident infections continued even in 2012, when a 15% increase in HIV notifications had been observed. This increase was entirely due to older infections. Overall declines 2008-2013 were of similar extent among the major transmission groups. CONCLUSIONS: Inno-Lia based incident HIV-1 infection surveillance proved useful and reliable. It represents a free, additional public health benefit of the use of this relatively costly test for HIV confirmation and type differentiation.

Design, expression, and processing of epitomized hepatitis C virus-encoded CTL epitopes

Hepatitis C virus (HCV) vaccine efficacy may crucially depend on immunogen length and coverage of viral sequence diversity. However, covering a considerable proportion of the circulating viral sequence variants would likely require long immunogens, which for the conserved portions of the viral genome, would contain unnecessarily redundant sequence information. In this study, we present the design and in vitro performance analysis of a novel "epitome" approach that compresses frequent immune targets of the cellular immune response against HCV into a shorter immunogen sequence. Compression of immunological information is achieved by partial overlapping shared sequence motifs between individual epitopes. At the same time, sequence diversity coverage is provided by taking advantage of emerging cross-reactivity patterns among epitope variants so that epitope variants associated with the broadest variant cross-recognition are preferentially included. The processing and presentation analysis of specific epitopes included in such a compressed, in vitro-expressed HCV epitome indicated effective processing of a majority of tested epitopes, although re-presentation of some epitopes may require refined sequence design. Together, the present study establishes the epitome approach as a potential powerful tool for vaccine immunogen design, especially suitable for the induction of cellular immune responses against highly variable pathogens.

Effects of variation in nest curtain design on pre-laying behaviour of domestic hens

Laying hens in loose-housing systems select a nest daily in which to lay their eggs among many identical looking nests, they often prefer corner nests. We investigated whether heterogeneity in nest curtain appearance – via colours and symbols – would influence nest selection and result in an even distribution of eggs among nests. We studied pre-laying behaviour in groups of 30 LSL hens across two consecutive trials with eight groups per trial. Half of the groups had access to six identical rollaway group-nests, while the others had access to six nests of the same type differing in outer appearance. Three colours (red, green, yellow) and three black symbols (cross, circle, rectangle) were used to create three different nest curtain designs per pen. Nest position and the side of entrance to the pens were changed at 28 and 30 weeks of age, respectively, whereby the order of changes was counterbalanced across trials. Nest positions were numbered 1–6, with nest position 1 representing the nest closest to the pen entrance. Eggs were counted per nest daily from week of age 18 to 33. Nest visits were recorded individually with an RFID system for the first 5 h of light throughout weeks 24–33. Hens with access to nests differing in curtain appearance entered fewer nests daily than hens with identical nests throughout the study but both groups entered more nests with increasing age. We found no other evidence that curtain appearance affected nest choice and hens were inconsistent in their daily nest selection. A high proportion of eggs were laid in corner nests especially during the first three weeks of lay. The number of visits per egg depended upon nest position and age: it increased with age and was higher after the nest position change than before in nest position 1, whereas it stayed stable over time in nest position 6. At 24 weeks of age, gregarious nest visits (hens visiting an occupied nest when there was at least one unoccupied nest) and solitary nest visits (hens visiting an unoccupied nest when there was at least one occupied nest) accounted for a similar amount of nest visits, however, after the door switch, gregarious nest visits made up more than half of all nest visits, while the number of solitary nest visits had decreased. The visual cues were too subtle or inadequate for hens to develop individual preferences while nest position, entrance side, age and nest occupancy affected the quantity and type of nest visits.

The Next 10 years in the Management of Peripheral Artery Disease: Perspectives from The 'PAD 2009' Conference

OBJECTIVES: To briefly inform on the conclusions from a conference on the next 10 years in the management of peripheral artery disease (PAD). DESIGN OF THE CONFERENCE: International participation, invited presentations and open discussion were based on the following issues: Why is PAD under-recognised? Health economic impact of PAD; funding of PAD research; changes of treatment options? Aspects on clinical trials and regulatory views; and the role of guidelines. RESULTS AND CONCLUSIONS: A relative lack of knowledge about cardiovascular risk and optimal management of PAD patients exists not only among the public, but also in parts of the health-care system. Specialists are required to act for improved information. More specific PAD research is needed for risk management and to apply the best possible evaluation of evidence for treatment strategies. Better strategies for funding are required based on, for example, public/private initiatives. The proportion of endovascular treatments is steadily increasing, more frequently based on observational studies than on randomised controlled trials. The role of guidelines is therefore important to guide the profession in the assessment of most relevant treatment.

The course of chronic and recurrent low back pain in the general population

Using latent class analysis (LCA), a previous study on patients attending primary care identified four courses of low back pain (LBP) over the subsequent 6 months. To date, no studies have used longitudinal pain recordings to examine the "natural" course of recurrent and chronic LBP in a population-based sample of individuals. This study examines the course of LBP in the general population and elaborates on the stability and criterion-related validity of the clusters derived. A random sample of 400 individuals reporting LBP in a population-based study was asked to complete a comprehensive questionnaire at the start and end of the year's survey, and 52 weekly pain diaries in between. The latter were analyzed using LCA. 305 individuals returned more than 50% of the diaries. Four clusters were identified (severe persistent, moderate persistent, mild persistent, and fluctuating). The clusters differed significantly with regards to pain and disability. Assessment of cluster stability showed that a considerable proportion of patients in the "fluctuating" group changed their classification over time. Three of the four clusters describing the typical course of pain matched the clusters described previously for patients in primary care. Due to the population-based design, this study achieves, for the first time, a close insight into the "natural" course of chronic and recurrent low back pain, including individuals that did not necessarily visit the general practitioner. The findings will help to understand better the nature of this pain in the general population.

Reporting of noninferiority trials was incomplete in trial registries

Objective To examine the registration of noninferiority trials, with a focus on the reporting of study design and noninferiority margins. Study Design and Setting Cross-sectional study of registry records of noninferiority trials published from 2005 to 2009 and records of noninferiority trials in the International Standard Randomized Controlled Trial Number (ISRCTN) or ClinicalTrials.gov trial registries. The main outcome was the proportion of records that reported the noninferiority design and margin. Results We analyzed 87 registry records of published noninferiority trials and 149 registry records describing noninferiority trials. Thirty-five (40%) of 87 records from published trials described the trial as a noninferiority trial; only two (2%) reported the noninferiority margin. Reporting of the noninferiority design was more frequent in the ISRCTN registry (13 of 18 records, 72%) compared with ClinicalTrials.gov (22 of 69 records, 32%; P = 0.002). Among the 149 records identified in the registries, 13 (9%) reported the noninferiority margin. Only one of the industry-sponsored trial compared with 11 of the publicly funded trials reported the margin (P = 0.001). Conclusion Most registry records of noninferiority trials do not mention the noninferiority design and do not include the noninferiority margin. The registration of noninferiority trials is unsatisfactory and must be improved.

Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity

Cellular immune responses during acute Hepatitis C virus (HCV) and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s) within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection. Of the total mutations observed 25% were within described CD8+ T-cell epitopes or at viral adaptation sites. Most mutations were maintained into the chronic phase of HCV infection (75%). The lack of reversion of adaptations and high proportion of silent substitutions suggests that HCV has structural and functional limitations that constrain evolution. These results were compared to the pattern of viral evolution observed in 98 subjects during a similar phase in HIV infection from a previous study. In contrast to HCV, evolution during acute HIV infection is marked by high levels of amino acid change relative to silent substitutions, including a higher proportion of adaptations, likely reflecting strong and continued CD8+ T-cell pressure combined with greater plasticity of the virus. Understanding viral escape dynamics for these two viruses is important for effective T cell vaccine design.

Evidence Based Development of a Novel Lateral Fibula Plate (VariAx Fibula) Using a Real CT Bone Data Based Optimization Process During Device Development

Development of novel implants in orthopaedic trauma surgery is based on limited datasets of cadaver trials or artificial bone models. A method has been developed whereby implants can be constructed in an evidence based method founded on a large anatomic database consisting of more than 2.000 datasets of bones extracted from CT scans. The aim of this study was the development and clinical application of an anatomically pre-contoured plate for the treatment of distal fibular fractures based on the anatomical database. 48 Caucasian and Asian bone models (left and right) from the database were used for the preliminary optimization process and validation of the fibula plate. The implant was constructed to fit bilaterally in a lateral position of the fibula. Then a biomechanical comparison of the designed implant to the current gold standard in the treatment of distal fibular fractures (locking 1/3 tubular plate) was conducted. Finally, a clinical surveillance study to evaluate the grade of implant fit achieved was performed. The results showed that with a virtual anatomic database it was possible to design a fibula plate with an optimized fit for a large proportion of the population. Biomechanical testing showed the novel fibula plate to be superior to 1/3 tubular plates in 4-point bending tests. The clinical application showed a very high degree of primary implant fit. Only in a small minority of cases further intra-operative implant bending was necessary. Therefore, the goal to develop an implant for the treatment of distal fibular fractures based on the evidence of a large anatomical database could be attained. Biomechanical testing showed good results regarding the stability and the clinical application confirmed the high grade of anatomical fit.

Sample sizes of studies on diagnostic accuracy: literature survey

OBJECTIVES: To determine sample sizes in studies on diagnostic accuracy and the proportion of studies that report calculations of sample size. DESIGN: Literature survey. DATA SOURCES: All issues of eight leading journals published in 2002. METHODS: Sample sizes, number of subgroup analyses, and how often studies reported calculations of sample size were extracted. RESULTS: 43 of 8999 articles were non-screening studies on diagnostic accuracy. The median sample size was 118 (interquartile range 71-350) and the median prevalence of the target condition was 43% (27-61%). The median number of patients with the target condition--needed to calculate a test's sensitivity--was 49 (28-91). The median number of patients without the target condition--needed to determine a test's specificity--was 76 (27-209). Two of the 43 studies (5%) reported a priori calculations of sample size. Twenty articles (47%) reported results for patient subgroups. The number of subgroups ranged from two to 19 (median four). No studies reported that sample size was calculated on the basis of preplanned analyses of subgroups. CONCLUSION: Few studies on diagnostic accuracy report considerations of sample size. The number of participants in most studies on diagnostic accuracy is probably too small to analyse variability of measures of accuracy across patient subgroups.