Randomised Controlled Trial to determine the appropriate time to initiate peritoneal dialysis after insertion of catheter to minimise complications (Timely PD study)

Background. The most appropriate time to initiate dialysis after surgical insertion of Tenckhoff catheters is not clear in the literature. There is the possibility of peritoneal dialysis (PD) complications such as leakage and infection if dialysis is started too soon after insertion. However, much morbidity and expense could be saved by reducing dependency on haemodialysis (HD) by earlier initiation of PD post catheter insertion. Previous studies are observational and mostly compare immediate with delayed use. The primary objective is to determine the safest and shortest time interval between surgical placement of a Tenckhoff catheter and starting PD. Methods/Design. This is a randomised controlled trial of patients who will start PD after insertion of Tenckhoff catheter at Royal Brisbane and Women's Hospital (RBWH) or Rockhampton Base Hospital (RBH) who meet the inclusion criteria. Patients will be stratified by site and diabetic status. The patients will be randomised to one of three treatment groups. Group 1 will start PD one week after Tenckhoff catheter insertion, group 2 at two weeks and group 3 at four weeks. Nurses and physicians will be blinded to the randomised allocation. The primary end point is the complication rate (leaks and infection) after initiation of PD. Discussion. The study will determine the most appropriate time to initiate PD after placement of a Tenckhoff catheter

Potentially toxic metals in historic landfill sites: Implications for grazing animals

Municipal waste disposal is an increasing global problem, frequently solved by the use of landfill sites. Following closure, such sites contain a legacy of pollutants and must be managed to provide a safe and useful end life. The soils and vegetation from four historic landfill sites were analysed to determine the extent of pollution by potentially toxic metals (PTMs). Data were subsequently assessed to determine if post closure uses involving grazing were safe for the animals. The heaviest and widest spread soil contamination was due to Ni. Concentrations at all sites exceeded the 95th percentile value for rural soils, in one case by a factor of 30. Cu and Pb contamination was identified at some sites, but no evidence of Al or Zn contamination was found. Oral bioaccessibility testing showed that the availability of Ni in soil was exceedingly low, whilst that of Cu and Pb was high. Concentrations in plant shoots differed significantly amongst the sites, but interspecific differences in shoot concentration were only significant in the case of Cu. The results indicated that exposure levels to grazers would be at or below tolerable levels, indicating that it is generally safe to graze historic landfill. However, animals could be exposed to higher levels of PTMs than would be expected from rural locations, and grazing under conditions where soil consumption may be high could result in levels of exposure to Al, Ni and Pb exceeding tolerable levels. © Springer International Publishing 2014

Women’s, partners’ and healthcare providers’ views and experiences of assisted vaginal birth: a systematic mixed methods review

Background When certain complications arise during the second stage of labour, assisted vaginal delivery (AVD), a vaginal birth with forceps or vacuum extractor, can effectively improve outcomes by ending prolonged labour or by ensuring rapid birth in response to maternal or fetal compromise. In recent decades, the use of AVD has decreased in many settings in favour of caesarean section (CS). This review aimed to improve understanding of experiences, barriers and facilitators for AVD use. Methods Systematic searches of eight databases using predefined search terms to identify studies reporting views and experiences of maternity service users, their partners, health care providers, policymakers, and funders in relation to AVD. Relevant studies were assessed for methodological quality. Qualitative findings were synthesised using a meta-ethnographic approach. Confidence in review findings was assessed using GRADE CERQual. Findings from quantitative studies were synthesised narratively and assessed using an adaptation of CERQual. Qualitative and quantitative review findings were triangulated using a convergence coding matrix. Results Forty-two studies (published 1985–2019) were included: six qualitative, one mixed-method and 35 quantitative. Thirty-five were from high-income countries, and seven from LMIC settings. Confidence in the findings was moderate or low. Spontaneous vaginal birth was most likely to be associated with positive short and long-term outcomes, and emergency CS least likely. Views and experiences of AVD tended to fall somewhere between these two extremes. Where indicated, AVD can be an effective, acceptable alternative to caesarean section. There was agreement or partial agreement across qualitative studies and surveys that the experience of AVD is impacted by the unexpected nature of events and, particularly in high-income settings, unmet expectations. Positive relationships, good communication, involvement in decision-making, and (believing in) the reason for intervention were important mediators of birth experience. Professional attitudes and skills (development) were simultaneously barriers and facilitators of AVD in quantitative studies. Conclusions Information, positive interaction and communication with providers and respectful care are facilitators for acceptance of AVD. Barriers include lack of training and skills for decision-making and use of instruments

PTEN/MMAC1 expression in melanoma resection specimens

PTEN/MMAC1, a tumour suppressor gene located on chromosome 10q23.3, has been found to be deleted in several types of human malignancies. As the chromosomal region 10q22-qter commonly is affected by losses in melanomas, we addressed this gene as tumour suppressor candidate in melanomas. Investigating PTEN/MMAC1 expression at mRNA level by semi-quantitative reverse transcription-polymerase chain reaction, we did not find a statistically significant down-regulation in melanoma resection specimens in comparison to acquired melanocytic nevi from which melanomas quite often are known to arise. Upon immunohistochemistry, PTEN/MMAC1 protein expression in melanomas was not lost. Sequencing the PTEN/MMAC1 cDNAs in 26 melanoma resection specimens (21 primary melanomas, five metastases), we detected three point mutations and two nucleotide deletions which did not represent genetic polymorphisms. With respect to the predicted protein sequences, all three point mutations were silent whereas the two frame shifts at the extreme C-terminus resulted in a loss of the putative PDZ-targeting consensus sequence. As loss of this motif possibly impairs localization and function of PTEN/MMAC1 in the two corresponding primary tumours, alterations of this tumour suppressor protein may participate in some melanomas

Confusion and Conflict in Assessing the Physical Activity Status of Middle-Aged Men

BACKGROUND: Physical activity (including exercise) is prescribed for health and there are various recommendations that can be used to gauge physical activity status. The objective of the current study was to determine whether twelve commonly-used physical activity recommendations similarly classified middle-aged men as sufficiently active for general health. METHODS AND FINDINGS: We examined the commonality in the classification of physical activity status between twelve variations of physical activity recommendations for general health in ninety men aged 45-64 years. Physical activity was assessed using synchronised accelerometry and heart rate. Using different guidelines but the same raw data, the proportion of men defined as active ranged from to 11% to 98% for individual recommendations (median 73%, IQR 30% to 87%). There was very poor absolute agreement between the recommendations, with an intraclass correlation coefficient (A,1) of 0.24 (95% CI, 0.15 to 0.34). Only 8% of men met all 12 recommendations and would therefore be unanimously classified as active and only one man failed to meet every recommendation and would therefore be unanimously classified as not sufficiently active. The wide variability in physical activity classification was explained by ostensibly subtle differences between the 12 recommendations for thresholds related to activity volume (time or energy), distribution (e.g., number of days of the week), moderate intensity cut-point (e.g., 3 vs. 4 metabolic equivalents or METs), and duration (including bout length). CONCLUSIONS: Physical activity status varies enormously depending on the physical activity recommendation that is applied and even ostensibly small differences have a major impact. Approximately nine out of every ten men in the present study could be variably described as either active or not sufficiently active. Either the effective dose or prescription that underlies each physical activity recommendation is different or each recommendation is seeking the same prescriptive outcome but with variable success

The INeS study: prevention of multiple pregnancies: a randomised controlled trial comparing IUI COH versus IVF e SET versus MNC IVF in couples with unexplained or mild male subfertility

BACKGROUND Multiple pregnancies are high risk pregnancies with higher chances of maternal and neonatal mortality and morbidity. In the past decades the number of multiple pregnancies has increased. This trend is partly due to the fact that women start family planning at an increased age, but also due to the increased use of ART. Couples with unexplained or mild male subfertility generally receive intrauterine insemination IUI with controlled hormonal stimulation (IUI COH). The cumulative pregnancy rate is 40%, with a 10% multiple pregnancy rate. This study aims to reveal whether alternative treatments such as IVF elective Single Embryo Transfer (IVF e SET) or Modified Natural Cycle IVF (MNC IVF) can reduce the number of multiple pregnancy rates, but uphold similar pregnancy rates as IUI COH in couples with mild male or unexplained subfertility. Secondly, the aim is to perform a cost effective analyses and assess treatment preference of these couples. METHODS/DESIGN We plan a multicentre randomised controlled clinical trial in the Netherlands comparing six cycles of intra-uterine insemination with controlled ovarian hyperstimulation or six cycles of Modified Natural Cycle (MNC) IVF or three cycles with IVF-elective Single Embryo Transfer (eSET) plus cryo-cycles within a time frame of 12 months. Couples with unexplained subfertility or mild male subfertility and a poor prognosis for treatment independent pregnancy will be included. Women with anovulatory cycles, severe endometriosis, double sided tubal pathology or serious endocrine illness will be excluded. Our primary outcome is the birth of a healthy singleton. Secondary outcomes are multiple pregnancy, treatment costs, and patient experiences in each treatment arm. The analysis will be performed according tot the intention to treat principle. We will test for non-inferiority of the three arms with respect to live birth. As we accept a 12.5% loss in pregnancy rate in one of the two IVF arms to prevent multiple pregnancies, we need 200 couples per arm (600 couples in total). DISCUSSION Determining the safest and most cost-effective treatment will ensure optimal chances of pregnancy for subfertile couples with substantially diminished perinatal and maternal complications. Should patients find the most cost-effective treatment acceptable or even preferable, this could imply the need for a world wide shift in the primary treatment. TRIAL REGISTRATION Current Controlled Trials ISRCTN 52843371Alexandra J Bensdorp, Els Slappendel, Carolien Koks, Jur Oosterhuis, Annemieke Hoek, Peter Hompes, Frank Broekmans, Harold Verhoeve, Jan Peter de Bruin, Janne Meije van Weert, Maaike Traas, Jacques Maas, Nicole Beckers, Sjoerd Repping, Ben W Mol, Fulco van der Veen and Madelon van Wel

In Patients with Established RA, Positive Effects of a Randomised Three Month WBV Therapy Intervention on Functional Ability, Bone Mineral Density and Fatigue Are Sustained for up to Six Months

Functional ability is often impaired for people with rheumatoid arthritis (RA), rendering these patients highly sedentary. Additionally, patients with RA often take medication known to negatively affect bone mass. Thus improving functional ability and bone health in this group of patients is important. The aim of this study was to investigate the effects of whole body vibration (WBV) therapy in patients with stable, established RA. Thirty one females with RA were randomly assigned to a control group (CON, n = 15) who continued with their normal activities or a WBV group (n = 16) who underwent a three month WBV therapy intervention, consisting of 15 minutes of intermittent vibration, performed twice per week. Patients were assessed at baseline, three months, and three months post intervention for functional ability using the modified Health Assessment Questionnaire; for RA disease activity using the Clinical Disease Activity Index, for quality of life using self-report fatigue and pain scores; for physical activity profiles using accelerometry, and for BMD and body composition using DXA. Patients in both groups were matched for all variables at baseline. After the intervention period, functional ability was significantly improved in the WBV group (1.22(0.19) to 0.92(0.19), p = 0.02). Hip BMD was significantly reduced in the CON group (0.97(0.05) to 0.84(0.05) g.cm-2, p = 0.01), while no decreases were seen in the WBV group (1.01(0.05) to 0.94(0.05) g.cm-2, p = 0.50). Despite no change in RA disease activity in either group at either follow up, fatigue levels were improved in the WBV group (4.4(0.63) to 1.1(0.65), yet remained unchanged in the CON group at both follow ups (p = 0.01). Ten minute bouts of light to moderate physical activity were significantly reduced in the CON group after the intervention (2.8(0.61) to 1.8(0.64) bouts per day, p = 0.01), and were preserved in the WBV group (3.1(0.59) to 3.0(0.61) bouts per day, p = 0.70). Intermittent WBV shows promise for sustained improvements in functional ability, for attenuating loss of bone mass at the hip, as well as for decreasing fatigue in patients with established RA. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201405000823418

Linking disease epidemiology and livestock productivity: the case of bovine respiratory disease in France

Concerns are growing over the impact of livestock farming on environment and public health. The livestock industry is faced with the double constraint of limiting its use of natural resources and antimicrobials while ensuring its economic sustainability. In this context, reliable methods are needed to evaluate the effect of the prevention of endemic animal diseases on the productivity of livestock production systems. In this study, an epidemiological and productivity model was used to link changes in Bovine Respiratory Disease (BRD) incidence with the productivity of the beef and dairy cattle sectors in France. Cattle production parameters significantly affected by BRD were selected through literature review. Previous field study results and national cattle performance estimates were used to infer growth performances, mortality rates and carcass quality in the cattle affected and not affected by BRD. A steady-state deterministic herd production model was used to predict the productivity of the dairy and beef sector and their defined compartments (breeding-fattening, feedlot young bulls, and feedlot veal) in case of BRD incidence reduction by 20%, 50% or 100%. Results suggested that BRD should be controlled at a priority in beef breeding farms as eradication of BRD in beef calves would increase the whole beef sector’s productivity by 4.7–5.5% while eradication in other production stages would result in lower productivity gain in their respective sectors. However, the analysis performed at compartment level showed that, in both the beef and dairy sector, young bull and veal feedlot enterprises derive more economic benefits from BRD eradication for their own compartment (increase in productivity of 8.7–12.8% for beef young bulls) than the breeding farms (increase in productivity of 5.1–6% for beef calves), which may limit the investments in BRD control

Heterogeneity of fractional anisotropy and mean diffusivity measurements by in vivo diffusion tensor imaging in normal human hearts

Background: Cardiac diffusion tensor imaging (cDTI) by cardiovascular magnetic resonance has the potential to assess microstructural changes through measures of fractional anisotropy (FA) and mean diffusivity (MD). However, normal variation in regional and transmural FA and MD is not well described. Methods: Twenty normal subjects were scanned using an optimised cDTI sequence at 3T in systole. FA and MD were quantified in 3 transmural layers and 4 regional myocardial walls. Results: FA was higher in the mesocardium (0.46 ±0.04) than the endocardium (0.40 ±0.04, p≤0.001) and epicardium (0.39 ±0.04, p≤0.001). On regional analysis, the FA in the septum was greater than the lateral wall (0.44 ±0.03 vs 0.40 ±0.05 p = 0.04). There was a transmural gradient in MD increasing towards the endocardium (epicardium 0.87 ±0.07 vs endocardium 0.91 ±0.08×10-3 mm2/s, p = 0.04). With the lateral wall (0.87 ± 0.08×10-3 mm2/s) as the reference, the MD was higher in the anterior wall (0.92 ±0.08×10-3 mm2/s, p = 0.016) and septum (0.92 ±0.07×10-3 mm2/s, p = 0.028). Transmurally the signal to noise ratio (SNR) was greatest in the mesocardium (14.5 ±2.5 vs endocardium 13.1 ±2.2, p<0.001; vs epicardium 12.0 ± 2.4, p<0.001) and regionally in the septum (16.0 ±3.4 vs lateral wall 11.5 ± 1.5, p<0.001). Transmural analysis suggested a relative reduction in the rate of change in helical angle (HA) within the mesocardium. Conclusions: In vivo FA and MD measurements in normal human heart are heterogeneous, varying significantly transmurally and regionally. Contributors to this heterogeneity are many, complex and interactive, but include SNR, variations in cardiac microstructure, partial volume effects and strain. These data indicate that the potential clinical use of FA and MD would require measurement standardisation by myocardial region and layer, unless pathological changes substantially exceed the normal variation identified