Search

Background: breast cancer has a significant heritable basis, of which ∼60% remains unexplained. Testing for BRCA1/BRCA2 offers useful discrimination of breast cancer risk within families, and identification of additional breast cancer susceptibility genes could offer clinical utility. Patients and methods: we included 2135 invasive breast cancer cases recruited via the Breast and Ovarian Cancer Susceptibility study, a retrospective UK study of familial breast cancer. Eligibility criteria: female, BRCA-negative, white European ethnicity, and one of: (i) breast cancer family history, (ii) bilateral disease, (iii) young age of onset (Results: 159/2135 (7.4%) cases had a qualifying variant in an established breast cancer susceptibility gene, with minimal evidence of signal in other cancer susceptibility genes. Known breast cancer susceptibility genes PALB2, CHEK2, and ATM were the only genes to retain statistical significance after correcting for multiple testing. Due to the enrichment of hereditary cases in the series, we had good power (>80%) to detect a gene of BRCA1-like risk [odds ratio (OR) = 10.6] down to a population minor allele frequency of 4.6 × 10 −5 (1 in 10 799, less than one-tenth that of BRCA1)and of PALB2-like risk (OR = 5.0) down to a population minor allele frequency of 2.8 × 10 −4 (1 in 1779, less than half that of PALB2). Power was lower for identification of novel moderate penetrance genes (OR = 2-3) like CHEK2 and ATM. Conclusions: this is the largest case-control whole-exome analysis of enriched breast cancer published to date. Whilst additional breast cancer susceptibility genes likely exist, those of high penetrance are likely to be of very low mutational frequency. Contention exists regarding the clinical utility of such genes.

We conducted a preregistered multilaboratory project ( k = 36; N = 3,531) to assess the size and robustness of ego-depletion effects using a novel replication method, termed the paradigmatic replication approach. Each laboratory implemented one of two procedures that was intended to manipulate self-control and tested performance on a subsequent measure of self-control. Confirmatory tests found a nonsignificant result ( d = 0.06). Confirmatory Bayesian meta-analyses using an informed-prior hypothesis (δ = 0.30, SD = 0.15) found that the data were 4 times more likely under the null than the alternative hypothesis. Hence, preregistered analyses did not find evidence for a depletion effect. Exploratory analyses on the full sample (i.e., ignoring exclusion criteria) found a statistically significant effect ( d = 0.08); Bayesian analyses showed that the data were about equally likely under the null and informed-prior hypotheses. Exploratory moderator tests suggested that the depletion effect was larger for participants who reported more fatigue but was not moderated by trait self-control, willpower beliefs, or action orientation.

A 65-year-old man with diabetes, end-stage renal disease on hemodialysis, coronary artery disease, and a prosthetic aortic valve. He presented to the emergency department with hypothermia (96.6°F), several weeks of anorexia and chills, and bilateral lower extremity tissue necrosis with erythema and edema (Figure 1A). He had a peripherally inserted central catheter (PICC) line 8 weeks prior placed at another hospital for treatment of cellulitis. Laboratory results revealed anemia, azotemia, and leukocytosis (19,200 WBCs/mm

The extent to which physical therapy (PT) is used after meniscectomy is unknown. The objective of this study was to estimate the extent to which PT is implemented after meniscectomy and to identify factors associated with its utilization.The Mariner PearlDiver database was queried to identify patients who underwent uncomplicated meniscectomy. The number of PT visits for each patient was tabulated. Logistic regressions were used to compare demographic factors associated with no use of PT and use of nine or more PT visits.In total, 92,291 patients met inclusion criteria. Of these patients, 72.21% did not use PT and 27.8% used 1 or more PT visits. Of the patients who used PT, 19.76% had 1 to 8 PT visits and 8.03% had 9 or more PT visits. Older age and noncommercial insurance types were associated with no PT use. Male sex, Medicaid, and Medicare were associated with markedly lower odds of increased PT utilization.PT is used in the minority of the time after meniscectomy. Among patients who do use PT, however, notable variation exists in the amount of PT visits used. Patient age, sex, insurance status, and geographic variables were independently associated with PT utilization.

Sternal cleft (SC) is a rare congenital anomaly, occurring with associated developmental anomalies or in isolation. Surgery to reconstruct the sternum is indicated to protect the visceral organs from trauma, to ensure healthy cardiopulmonary function and growth, and to reconstruct the anterior chest wall. Although infection recognized as a postoperative complication following chest wall reconstruction, spontaneous mediastinal infection is rare. To the authors' knowledge, there is only 1 reported case of spontaneous mediastinal infection with concomitant SC in the literature. Here, the authors present a unique case of a medically complicated infant with a SC who presented with a spontaneous mediastinal abscess.

Development of novel anti-tuberculosis combination regimens that increase efficacy and reduce treatment timelines will improve patient compliance, limit side-effects, reduce costs, and enhance cure rates. Such advancements would significantly improve the global TB burden and reduce drug resistance acquisition. Bioenergetics has received considerable attention in recent years as a fertile area for anti-tuberculosis drug discovery. Targeting the electron transport chain (ETC) and oxidative phosphorylation machinery promises not only to kill growing cells but also metabolically dormant bacilli that are inherently more drug tolerant. Over the last two decades, a broad array of drugs targeting various ETC components have been developed. Here, we provide a focused review of the current state of art of bioenergetic inhibitors of Mtb with an in-depth analysis of the metabolic and bioenergetic disruptions caused by specific target inhibition as well as their synergistic and antagonistic interactions with other drugs. This foundation is then used to explore the reigning theories on the mechanisms of antibiotic-induced cell death and we discuss how bioenergetic inhibitors in particular fail to be adequately described by these models. These discussions lead us to develop a clear roadmap for new lines of investigation to better understand the mechanisms of action of these drugs with complex mechanisms as well as how to leverage that knowledge for the development of novel, rationally-designed combination therapies to cure TB.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an infectious disease of recent origin with high transmissibility and mortality. The resulting COVID-19 pandemic has impacted the United States the most, in terms of the number of confirmed cases and fatalities. How other aspects of public health will be impacted by this disease has yet to be fully realized. Sexually transmitted diseases (STDs), already a major public health crisis, will likely be significantly affected by this pandemic. We address some of the potential implications for STDs in the setting of widespread COVID-19, discussing the sexual transmission of COVID-19 itself, STD co-infection with COVID-19, and changes in STD prevalence secondary to COVID-19. (

Bacterial infections still present a significant concern in orthopedic and dental implant failure. Previous investigations have focused on modifying the surface texture, roughness, or coating implants with antibiotics to provide enhanced anti-bacterial properties. However, they have demonstrated limited success. In this study, we attempted to engineer the titanium (Ti) alloy surface biomimetically at the nano level using alkaline hydrothermal treatment (AHT) inspired by cicada's wing structure. Two modified surfaces of Ti plates were developed using 4 and 8-hr AHT at 230°C. We found that the control plates showed a relatively smooth surface, with little artifacts on the surface. In contrast, 4-hr AHT and 8-hr AHT plates showed nano-spikes of heights around 250-350 and 100-1,250 nm, respectively, that were distributed randomly all over the surface. We found a statistically significant (p < 0.05) number of non-viable cells for both S. aureus and P. aeruginosa bacterial strains when incubated for 1 hr in a dynamic environment when compared with the control group. The 8-hr AHT groups killed 38.97% more S. aureus in static culture and 11.27% in a dynamic environment than the 4-hr AHT. Overall, the findings indicate that the nanostructures generated on titanium by the AHT showed significant bactericidal properties. We, therefore, recommend conducting alkaline hydrothermal treatment on the surfaces for future orthopedic and dental metallic implants.

Masks are coverings of the face that serve a variety of purposes. Throughout history, they have been used for religious ceremonies, theatric entertainment, protection of identity, and as a tool to limit the spread of infectious diseases. The development of masks in the medical setting has evolved along with our understanding of the mode of disease transmission, material science, and population health dynamics. The simple barrier face mask, surgical mask, and filtering facepiece respirator are each appropriate in different settings. Establishing evidence-based guidance behind the use of masks is essential, particularly in public health crises.

Background: Patients often have quadriceps or hamstring weakness after anterior cruciate ligament reconstruction (ACLR), despite postoperative physical therapy regimens; however, little evidence exists connecting nerve blocks and ACLR outcomes. Purpose: To compare muscle strength at return to play in patients who received a nerve block with ACLR and determine whether a specific block type affected subjective knee function. Study Design: Cohort study; Level of evidence, 3. Methods: Patients were recruited 5 to 7 months after primary, isolated ACLR and completed bilateral isokinetic strength tests of the knee extensor/flexor groups as a single-session return-to-sport test. Subjective outcomes were assessed with the International Knee Documentation Committee (IKDC) score. Strength was expressed as torque normalized to mass (N·m/kg) and limb symmetry index as involved/uninvolved torque. Chart review was used to determine the type of nerve block and graft used. Nerve block types were classified as knee extensor motor (femoral nerve), knee flexor motor (sciatic nerve), or isolated sensory (adductor canal block/saphenous nerve). A 1-way analysis of covariance controlling for graft type was used. Results: A total of 169 patients were included. Graft type distribution consisted of 102 (60.4%) ipsilateral bone–patellar tendon–bone (BTB) and 67 (39.6%) ipsilateral hamstring tendon. Nerve block type distribution consisted of 38 (22.5%) femoral, 25 (14.8%) saphenous, 45 (26.6%) femoral and sciatic, and 61 (36.1%) saphenous and sciatic. No significant difference was found in knee extensor strength ( P = .113) or symmetry ( P = .860) between patients with knee extensor motor blocks (1.57 ± 0.45 N·m/kg; 70.1% ± 15.3%) and those without (1.47 ± 0.47 N·m/kg; 69.6% ± 18.8%). A significant difference was found between patients with knee flexor motor blocks (0.83 ± 0.26 N·m/kg) and those without (0.92 ± 0.27 N·m/kg) for normalized knee flexor strength ( P = .21) but not knee flexor symmetry ( P = .592). Controlling for graft type, there were no differences in subjective knee function (IKDC score) between all nerve block groups ( P = .57). Conclusion: Our data showed that use of a sciatic nerve block with ACLR in patients with hamstring and BTB grafts influences persistent knee flexor strength deficits at time of return to sports. Although the cause of postoperative muscular weakness is multifactorial, this study adds to the growing body of evidence suggesting that perioperative nerve blocks affect muscle strength and functional rehabilitation after ACLR.

A concerted action on the part of international agencies and national governments has resulted in the near-eradication of poliomyelitis. However, both the oral polio vaccine (OPV) and the inactivated polio vaccine (IPV) have deficiencies which make them suboptimal for use after global eradication. OPV is composed of attenuated Sabin strains and stimulates robust immunity, but may revert to neurovirulent forms in the intestine which can be shed and infect susceptible contacts. The majority of IPV products are manufactured using pathogenic strains inactivated with formalin. Upon eradication, the production of large quantities of pathogenic virus will present an increased biosecurity hazard. A logical ideal endgame vaccine would be an inactivated form of an attenuated strain that could afford protective immunity while safely producing larger numbers of doses per unit of virus stock than current vaccines. We report here the development of an ionizing radiation (IR)-inactivated Sabin-based vaccine using a reconstituted Mn-decapeptide (MDP) antioxidant complex derived from the radioresistant bacterium Deinococcus radiodurans. In bacteria, Mn2+-peptide antioxidants protect proteins from oxidative damage caused by extreme radiation exposure. Here we show for the first time, that MDP can protect immunogenic neutralizing epitopes in picornaviruses. MDP protects epitopes in Polio Virus 1 and 2 Sabin strains (PV1-S and PV2-S, respectively), but viral genomic RNA is not protected during supralethal irradiation. IR-inactivated Sabin viruses stimulated equivalent or improved neutralizing antibody responses in Wistar rats compared to the commercially used IPV products. Our approach reduces the biosecurity risk of the current PV vaccine production method by utilizing the Sabin strains instead of the wild type neurovirulent strains. Additionally, the IR-inactivation approach could provide a simpler, faster and less costly process for producing a more immunogenic IPV. Gamma-irradiation is a well-known method of virus inactivation and this vaccine approach could be adapted to any pathogen of interest.

Magnetic resonance imaging (MRI) is a cornerstone in multiple sclerosis (MS) diagnostics and monitoring. Ultra-high field (UHF) MRI is being increasingly used and becoming more accessible. Due to the small diameter and mobility of the spinal cord, imaging this structure at ultra-high fields poses additional challenges compared to brain imaging. Here we review the potential benefits for the MS field by providing a literature overview of the use UHF spinal cord MRI in MS research and we elaborate on the challenges that are faced. Benefits include increased signal- and contrast-to-noise, enabling for higher spatial resolutions, which can improve MS lesion sensitivity in both the spinal white matter as well as grey matter. Additionally, these benefits can aid imaging of microstructural abnormalities in the spinal cord in MS using advanced MRI techniques like functional imaging, MR spectroscopy and diffusion-based techniques. Technical challenges include increased magnetic field inhomogeneities, distortions from physiological motion and optimalisation of sequences. Approaches including parallel imaging techniques, real time shimming and retrospective compensation of physiological motion are making it increasingly possible to unravel the potential of spinal cord UHF MRI in the context of MS research.

Functional mapping of cerebral blood volume (CBV) changes has the potential to reveal brain activity with high localization specificity at the level of cortical layers and columns. Non-invasive CBV imaging using Vascular Space Occupancy (VASO) at ultra-high magnetic field strengths promises high spatial specificity but poses unique challenges in human applications. As such, 9.4 T B1+ and B0 inhomogeneities limit efficient blood tagging, while the specific absorption rate (SAR) constraints limit the application of VASO-specific RF pulses. Moreover, short T2* values at 9.4 T require short readout duration, and long T1 values at 9.4 T can cause blood-inflow contaminations. In this study, we investigated the applicability of layer-dependent CBV-fMRI at 9.4 T in humans. We addressed the aforementioned challenges by combining multiple technical advancements: temporally alternating pTx B1+ shimming parameters, advanced adiabatic RF-pulses, 3D-EPI signal readout, optimized GRAPPA acquisition and reconstruction, and stability-optimized RF channel combination. We found that a combination of suitable advanced methodology alleviates the challenges and potential artifacts, and that VASO fMRI provides reliable measures of CBV change across cortical layers in humans at 9.4 T. The localization specificity of CBV-fMRI, combined with the high sensitivity of 9.4 T, makes this method an important tool for future studies investigating cortical micro-circuitry in humans.

Patients with craniosynostosis with subnormal vision due to papilledema and/or exposure-related corneal decompensation are well documented in the literature; however, there is only a single prior documented case of vision compromise secondary to anterior segment dysgenesis and glaucoma in this patient population. This report highlights a case of syndromic craniosynostosis with advanced corneal decompensation and anterior segment dysgenesis that was masked and ultimately delayed the diagnosis of congenital glaucoma.

Item does not contain fulltext OBJECTIVES: The use of 7 Tesla (T) magnetic resonance imaging (MRI) has recently shown great potential for high-resolution soft-tissue neuroimaging and visualization of microvascularization in glioblastoma (GBM). We have designed a clinical trial to explore the value of 7 T MRI in radiation treatment of GBM. For this aim we performed a preparatory study to investigate the technical feasibility of incorporating 7 T MR images into the neurosurgical navigation and radiotherapy treatment planning (RTP) systems via qualitative and quantitative assessment of the image quality. MATERIALS AND METHODS: The MR images were acquired with a Siemens Magnetom 7 T whole-body scanner and a Nova Medical 32-channel head coil. The 7 T MRI pulse sequences included magnetization-prepared two rapid acquisition gradient echoes (MP2RAGE), T2-SPACE, SPACE-FLAIR and gradient echo sequences (GRE). A pilot study with three healthy volunteers and an anthropomorphic 3D phantom was used to assess image quality and geometrical image accuracy. RESULTS: The MRI scans were well tolerated by the volunteers. Susceptibility artefacts were observed in both the cortex and subcortical white matter at close proximity to air-tissue interfaces. Regional loss of signal and contrast could be minimized by the use of dielectric pads. Image transfer and processing did not degrade image quality. The system-related spatial uncertainty of geometrical distortion-corrected MP2RAGE pulse sequences was

OBJECTIVE: This study evaluates the inter-site and intra-site reproducibility of 7 Tesla brain imaging and compares it to literature values for other field strengths.MATERIALS AND METHODS: The same two subjects were imaged at eight different 7 T sites. MP2RAGE, TSE, TOF, SWI, EPI as well as B1 and B0 field maps were analyzed quantitatively to assess inter-site reproducibility. Intra-site reproducibility was measured with rescans at three sites.RESULTS: Quantitative measures of MP2RAGE scans showed high agreement. Inter-site and intra-site reproducibility errors were comparable to 1.5 and 3 T. Other sequences also showed high reproducibility between the sites, but differences were also revealed. The different RF coils used were the main source for systematic differences between the sites.CONCLUSION: Our results show for the first time that multi-center brain imaging studies of the supratentorial brain can be performed at 7 T with high reproducibility and similar reliability as at 3T. This study develops the basis for future large-scale 7 T multi-site studies.

BACKGROUND: Biocompatible peritoneal dialysis (PD) solutions, including neutral pH, low glucose degradation product (GDP) solutions and icodextrin, have previously been shown to favourably influence some patient‐level outcomes, albeit based on generally sub‐optimal quality studies. Several additional randomised controlled trials (RCT) evaluating biocompatible solutions in PD patients have been published recently. This is an update of a review first published in 2014. OBJECTIVES: This review aimed to look at the benefits and harms of biocompatible PD solutions in comparison to standard PD solutions in patients receiving PD. SEARCH METHODS: The Cochrane Kidney and Transplant Specialised Register was searched up to 12 February 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All RCTs and quasi‐RCTs in adults and children comparing the effects of biocompatible PD solutions (neutral pH, lactate‐buffered, low GDP; neutral pH, bicarbonate(± lactate)‐buffered, low GDP; glucose polymer (icodextrin)) in PD were included. Studies of amino acid‐based solutions were excluded. DATA COLLECTION AND ANALYSIS: Two authors extracted data on study quality and outcomes. Summary effect estimates were obtained using a random‐effects model, and results were expressed as risk ratios and 95% confidence intervals (CI) for categorical variables, and mean differences (MD) or standardised mean differences (SMD) and 95% CI for continuous variables. MAIN RESULTS: This review update included 42 eligible studies (3262 participants), including six new studies (543 participants). Overall, 29 studies (1971 participants) compared neutral pH, low GDP PD solution with conventional PD solution, and 13 studies (1291 participants) compared icodextrin with conventional PD solution. Risk of bias was assessed as high for sequence generation in three studies, allocation concealment in three studies, attrition bias in 21 studies, and selective outcome reporting bias in 16 studies. Neutral pH, low GDP versus conventional glucose PD solution Use of neutral pH, low GDP PD solutions improved residual renal function (RRF) preservation (15 studies, 835 participants: SMD 0.19, 95% CI 0.05 to 0.33; high certainty evidence). This approximated to a mean difference in glomerular filtration rate of 0.54 mL/min/1.73 m(2) (95% CI 0.14 to 0.93). Better preservation of RRF was evident at all follow‐up durations with progressively greater preservation observed with increasing follow up duration. Neutral pH, low GDP PD solution use also improved residual urine volume preservation (11 studies, 791 participants: MD 114.37 mL/day, 95% CI 47.09 to 181.65; high certainty evidence). In low certainty evidence, neutral pH, low GDP solutions may make little or no difference to 4‐hour peritoneal ultrafiltration (9 studies, 414 participants: SMD ‐0.42, 95% CI ‐0.74 to ‐0.10) which approximated to a mean difference in peritoneal ultrafiltration of 69.72 mL (16.60 to 122.00 mL) lower, and may increase dialysate:plasma creatinine ratio (10 studies, 746 participants: MD 0.01, 95% CI 0.00 to 0.03), technique failure or death compared with conventional PD solutions. It is uncertain whether neutral pH, low GDP PD solution use led to any differences in peritonitis occurrence, hospitalisation, adverse events (6 studies, 519 participants) or inflow pain (1 study, 58 participants: RR 0.51, 95% CI 0.24 to 1.08). Glucose polymer (icodextrin) versus conventional glucose PD solution In moderate certainty evidence, icodextrin probably reduced episodes of uncontrolled fluid overload (2 studies, 100 participants: RR 0.30, 95% CI 0.15 to 0.59) and augmented peritoneal ultrafiltration (4 studies, 102 participants: MD 448.54 mL/d, 95% CI 289.28 to 607.80) without compromising RRF (4 studies, 114 participants: SMD 0.12, 95% CI ‐0.26 to 0.49; low certainty evidence) which approximated to a mean creatinine clearance of 0.30 mL/min/1.73m(2) higher (0.65 lower to 1.23 higher) or urine output (3 studies, 69 participants: MD ‐88.88 mL/d, 95% CI ‐356.88 to 179.12; low certainty evidence). It is uncertain whether icodextrin use led to any differences in adverse events (5 studies, 816 participants) technique failure or death. AUTHORS' CONCLUSIONS: This updated review strengthens evidence that neutral pH, low GDP PD solution improves RRF and urine volume preservation with high certainty. These effects may be related to increased peritoneal solute transport and reduced peritoneal ultrafiltration, although the evidence for these outcomes is of low certainty due to significant heterogeneity and suboptimal methodological quality. Icodextrin prescription increased peritoneal ultrafiltration and mitigated uncontrolled fluid overload with moderate certainty. The effects of either neutral pH, low GDP solution or icodextrin on peritonitis, technique survival and patient survival remain uncertain and require further high quality, adequately powered RCTs.

Competency standards for nurses who specialize in the care of burn-injured patients are lacking. Currently, there are no nationally agreed on standards that define safe and competent burn nursing practice. In 2014, nurse members of the American Burn Association proposed the Burn Nurse Competency Initiative (BNCI) with the intent of establishing a core set of competency standards for burn nursing. The BNCI used the Delphi technique of consensus building with input from up to 178 registered nurse burn care experts. This article describes the multistaged consensus-building process used and provides a final list of competencies. These newly created competencies now define professional practice standards for burn nurses. Their creation completes one of the essential steps required for burn nursing to be recognized as a specialty.

Objective: A fine structure of the corpus callosum (CC), consisting of radial lines, is seen in historical anatomical atlases as far back as that of Vicq d'Azyr (1786). This study examines a similar pattern observed in vivo using high-resolution MR images at 7 T. Methods: 8 healthy subjects were examined with 7.0-T MRI. Anatomical images were collected with a gradient echo scan with 0.5-mm isotropic resolution, which were rated for visibility of the radial pattern. In addition, the second eigenvector of the diffusion tensor images was examined. Results: The fine radial lines are detected not only in the sagittal view but also in the axial view of the in vivo MR images. From this, it is likely that these structures are two-dimensional ribbons. Interestingly, and confirming the structural nature of these stripes, the second eigenvector of the diffusion tensor imaging data shows an extremely similar pattern of oriented foliate structure. A similar modular structure involving transient septa has been observed previously in histological sections of human fetal CC. Conclusion: The separate sets of data—the atlas of Klingler, anatomical images and second eigenvector images—all indicate a ribbon-like arrangement of the fibres in the CC. As such, they closely match the structures shown in the drawn atlases of as old as 1786. Advances in knowledge: This ribbon arrangement of fibres in the CC, previously unseen in CT or lower field MRI, can now be observed in vivo. This appears to match over two centuries of ex vivo observations.

Cost-effective strategies to maintain healthy active lifestyle in aging populations are required to address the global burden of age-related diseases. ASPREE will examine whether the potential primary prevention benefits of low dose aspirin outweigh the risks in older healthy individuals. Our primary hypothesis is that daily oral 100. mg enteric-coated aspirin will extend a composite primary endpoint termed 'disability-free life' including onset of dementia, total mortality, or persistent disability in at least one of the Katz Activities of Daily Living in 19,000 healthy participants aged 65. years and above ('US minorities') and 70. years and above (non-'US minorities'). ASPREE is a double-blind, randomized, placebo-controlled trial of oral 100. mg enteric-coated acetyl salicylic acid (ASA) or matching placebo being conducted in Australian and US community settings on individuals free of dementia, disability and cardiovascular disease (CVD) events. Secondary endpoints are all-cause and cause specific mortality, fatal and non-fatal cardiovascular events, fatal and non-fatal cancer (excluding non-melanoma skin cancer), dementia, mild cognitive impairment, depression, physical disability, and clinically significant bleeding. To 20 September 2013 14,383 participants have been recruited. Recruitment and study completion are anticipated in July 2014 and December 2018 respectively. In contrast to other aspirin trials that have largely focused on cardiovascular endpoints, ASPREE has a unique composite primary endpoint to better capture the overall risk and benefit of aspirin to extend healthy independent lifespan in older adults in the US and Australia.

Background. Although icodextrin has been shown to augment peritoneal ultrafiltration in peritoneal dialysis (PD) patients, its impact upon other clinical end points, such as technique survival, remains uncertain. This systematic review evaluated the effect of icodextrin use on patient level clinical outcomes. Methods. The Cochrane CENTRAL Registry, MEDLINE, Embase and reference lists were searched (last search 13 September 2012) for randomized controlled trials of icodextrin versus glucose in the long dwell exchange. Summary estimates of effect were obtained using a random effects model. Results. Eleven eligible trials (1222 patients) were identified. There was a significant reduction in episodes of uncontrolled fluid overload [two trials; 100 patients; relative risk (RR) 0.30, 95% confidence interval (CI) 0.15-0.59] and improvement in peritoneal ultrafiltration [four trials; 102 patients; mean difference (MD) 448.54 mL/day, 95% CI 289.28-607.80] without compromising residual renal function [four trials; 114 patients; standardized MD (SMD) 0.12, 95% CI -0.26 to 0.49] or urine output (three trials; 69 patients; MD -88.88, 95% CI -356.88 to 179.12) with icodextrin use for up to 2 years. There was no significant effect on peritonitis incidence (five trials; 607 patients; RR 0.97, 95% CI 0.76-1.23), peritoneal creatinine clearance (three trials; 237 patients; SMD 0.36, 95% CI -0.24 to 0.96), technique failure (three trials; 290 patients; RR 0.58, 95% CI 0.28-1.20), patient survival (six trials; 816 patients; RR 0.82, 95% CI 0.32-2.13) or adverse events. Conclusions. Icodextrin prescription improved peritoneal ultrafiltration, mitigated uncontrolled fluid overload and was not associated with increased risk of adverse events. No effects of icodextrin on technique or patient survival were observed, although trial sample sizes and follow-up durations were limited.

There has been little study to date of daily variation in cardiac death in dialysis patients and whether such variation differs according to dialysis modality and session frequency.Observational cohort study using ANZDATA (Australia and New Zealand Dialysis and Transplant) Registry data.All adult patients with end-stage kidney failure treated by dialysis in Australia and New Zealand who died between 1999 and 2008.Timing of death (day of week), dialysis modality, hemodialysis (HD) session frequency, and demographic, clinical, and facility variables.Cardiac and noncardiac mortality.14,636 adult dialysis patients died during the study period (HD, n = 10,338; peritoneal dialysis [PD], n = 4,298). Cardiac death accounted for 40% of deaths and was significantly more likely to occur on Mondays in in-center HD patients receiving 3 or fewer dialysis sessions per week (n = 9,503; adjusted OR, 1.26; 95% CI, 1.14-1.40; P0.001 compared with the mean odds of cardiac death for all days of the week). This daily variation in cardiac death was not seen in PD patients, in-center HD patients receiving more than 3 sessions per week (n = 251), or home HD patients (n = 573). Subgroup analyses showed that deaths related to hyperkalemia and myocardial infarction also were associated with daily variation in risk in HD patients. This pattern was not seen for vascular, infective, malignant, dialysis therapy withdrawal, or other deaths.Limited covariate adjustment. Residual confounding and coding bias could not be excluded. Possible type 2 statistical error due to limited sample size of home HD and enhanced-frequency HD cohorts.Daily variation in the pattern of cardiac deaths was observed in HD patients receiving 3 or fewer dialysis sessions per week, but not in PD, home HD, and HD patients receiving more than 3 sessions per week.

Burn injuries have a major influence on the survivors' physical and psychological functioning. In pediatric burns, the consequences persist long after the injury. The objective of this study is to evaluate an existing yoga kids program to gain better understanding of the physical and psychosocial effects of a yoga practice among children with burn injuries. Thirty campers participated in a series of four (1 hour) yoga sessions during the summer of 2014. Nationally trained Instructors had taught children's yoga in the Southwestern United States for at least 10 years. A Yoga Evaluation Questionnaire, designed for children, was used to evaluate perceptions of somatic and cognitive anxiety before and after each Yoga session. Camper's age ranged from 6 to 12 years old with burn severities ranging from 5 to 75%. A dependent samples t-test was used to test for differences between composite pre- and postintervention scores for both somatic and cognitive anxiety. Significant effects emerged for somatic anxiety t(29) = -4.24, P < .001, d = 0.77, and cognitive anxiety t(29) = -4.188, P < .001, d = 0.76. For both cognitive and somatic anxiety, the postintervention composite mean scores were significantly higher, indicating a decrease in somatic and cognitive anxiety. This study suggests that participation in a Yoga program may lower perceptions of cognitive and somatic anxiety in pediatric burn survivors. Further, Yoga is one technique that may compliment the short- and long-term treatment of burn injuries.

Purpose In order to fully benefit from the improved signal‐to‐noise and contrast‐to‐noise ratios at 9.4T, the challenges of B1+ inhomogeneity and the long acquisition time of high‐resolution 2D gradient‐recalled echo (GRE) imaging were addressed. Theory and Methods Flip angle homogenized excitations were achieved by parallel transmission (pTx) of 3‐spoke pulses, designed by magnitude least‐squares optimization in a slice‐by‐slice fashion; the acquisition time reduction was achieved by simultaneous multislice (SMS) pulses. The slice‐specific spokes complex radiofrequency scaling factors were applied to sinc waveforms on a per‐channel basis and combined with the other pulses in an SMS slice group to form the final SMS‐pTX pulse. Optimal spokes locations were derived from simulations. Results Flip angle maps from presaturation TurboFLASH showed improvement of flip angle homogenization with 3‐spoke pulses over CP‐mode excitation (normalized root‐mean‐square error [NRMSE] 0.357) as well as comparable excitation homogeneity across the single‐band (NRMSE 0.119), SMS‐2 (NRMSE 0.137), and SMS‐3 (NRMSE 0.132) 3‐spoke pulses. The application of the 3‐spoke SMS‐3 pulses in a 48‐slice GRE protocol, which has an in‐plane resolution of 0.28 × 0.28 mm, resulted in a 50% reduction of scan duration (total acquisition time 6:52 min including reference scans). Conclusion Time‐efficient flip angle homogenized high‐resolution GRE imaging at 9.4T was accomplished by using slice‐specific SMS‐pTx spokes excitations. Magn Reson Med 78:1050–1058, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

OBJECTIVES: To overcome the challenges of B0 and RF excitation inhomogeneity at ultra-high field MRI, a workflow for volumetric B0 and flip-angle homogenisation was implemented on a human 9.4 T scanner.MATERIALS AND METHODS: Imaging was performed with a 9.4 T human MR scanner (Siemens Medical Solutions, Erlangen, Germany) using a 16-channel parallel transmission system. B0- and B1-mapping were done using a dual-echo GRE and transmit phase-encoded DREAM, respectively. B0 shims and a small-tip-angle-approximation kT-points pulse were calculated with an off-line routine and applied to acquire T1- and T 2 (*) -weighted images with MPRAGE and 3D EPI, respectively.RESULTS: Over six in vivo acquisitions, the B0-distribution in a region-of-interest defined by a brain mask was reduced down to a full-width-half-maximum of 0.10 ± 0.01 ppm (39 ± 2 Hz). Utilising the kT-points pulses, the normalised RMSE of the excitation was decreased from CP-mode's 30.5 ± 0.9 to 9.2 ± 0.7 % with all B 1 (+) voids eliminated. The SNR inhomogeneities and contrast variations in the T1- and T 2 (*) -weighted volumetric images were greatly reduced which led to successful tissue segmentation of the T1-weighted image.CONCLUSION: A 15-minute B0- and flip-angle homogenisation workflow, including the B0- and B1-map acquisitions, was successfully implemented and enabled us to reduce intensity and contrast variations as well as echo-planar image distortions in 9.4 T images.

Peritonitis is a major complication of peritoneal dialysis, but the relationship between peritonitis and mortality among these patients is not well understood. In this case-crossover study, we included the 1316 patients who received peritoneal dialysis in Australia and New Zealand from May 2004 through December 2009 and either died on peritoneal dialysis or within 30 days of transfer to hemodialysis. Each patient served as his or her own control. The mean age was 70 years, and the mean time receiving peritoneal dialysis was 3 years. In total, there were 1446 reported episodes of peritonitis with 27% of patients having ≥ 2 episodes. Compared with the rest of the year, there were significantly increased odds of peritonitis during the 120 days before death, although the magnitude of this association was much greater during the 30 days before death. Compared with a 30-day window 6 months before death, the odds for peritonitis was six-fold higher during the 30 days immediately before death (odds ratio, 6.2; 95% confidence interval, 4.4-8.7). In conclusion, peritonitis significantly associates with mortality in peritoneal dialysis patients. The increased odds extend up to 120 days after an episode of peritonitis but the magnitude is greater during the initial 30 days.

Background Determinants and outcomes of peritoneal dialysis (PD)-associated peritonitis occurring within 4 weeks of completion of therapy of a prior episode caused by the same (relapse) or different organism (recurrence) recently have been characterized. However, determinants and outcomes of peritonitis occurring more than 4 weeks after treatment of a prior episode caused by the same (repeated) or different organism (nonrepeated) are poorly understood. Study Design Observational cohort study using Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) data. Setting & Participants All Australian PD patients between October 1, 2003, and December 31, 2007, with first episodes of repeated or nonrepeated peritonitis. Predictors Repeated versus nonrepeated peritonitis, according to International Society of PD (ISPD) criteria. Outcomes & Measurements Relapse, hospitalization, catheter removal, hemodialysis transfer, and death. Results After a peritonitis episode, the probability that a subsequent episode represented repeated rather than nonrepeated peritonitis was highest in the second month (41%), then progressively decreased to a stable level of 14% from 6 months onward. When first episodes of repeated (n = 245) or nonrepeated peritonitis (n = 824) were analyzed, repeated peritonitis was predicted independently by a shorter elapsed time from the prior episode (adjusted OR per day elapsed, 0.91; 95% CI, 0.88-0.94). Staphylococcus aureus and coagulase-negative staphylococcus were isolated more frequently in repeated peritonitis, whereas Gram-negative, streptococcal, and fungal organisms were recovered more frequently in nonrepeated peritonitis. Using multivariate logistic regression, repeated peritonitis was associated independently with higher relapse (OR, 5.41; 95% CI, 3.72-7.89) and lower hospitalization rates (OR, 0.63; 95% CI, 0.46-0.85), but catheter removal, hemodialysis transfer, and death rates similar to nonrepeated peritonitis. Limitations Limited covariate adjustment. Residual confounding and coding bias could not be excluded. Conclusions Repeated and nonrepeated peritonitis episodes are caused by different spectra of micro-organisms and have different outcomes. Study findings suggest that the ISPD definition for repeated peritonitis should be limited to 6 months.

Summary Background and objectives Hepatitis C virus (HCV) infection is associated with increased mortality and morbidity in end-stage renal failure (ESRF) patients. Despite a lower incidence and risk of transmission of HCV infection with peritoneal dialysis (PD), the optimal dialysis modality for HCV-infected ESRF patients is not known. The aim of this study was to evaluate the impact of dialysis modality on the survival of HCV-infected ESRF patients. Design, setting, participants, & measurements The study included all adult incident ESRF patients in Australia and New Zealand who commenced dialysis between January 1, 1994, and December 31, 2008, and were HCV antibody-positive at the time of dialysis commencement. Time to all-cause mortality was compared between hemodialysis (HD) and PD according to modality assignment at day 90, using Cox proportional hazards model analysis. Results A total of 424 HCV-infected ESRF patients commenced dialysis during the study period and survived for at least 90 days (PD n = 134; HD n = 290). Mortality rates were comparable between PD and HD in the first year (10.7 versus 13.8 deaths per 100 patient-years, respectively; adjusted hazard ratio [HR] 0.65, 95% CI 0.34 to 1.26) and thereafter (20 versus 15.9 deaths per 100 patient-years, respectively; HR 1.27, 95% CI 0.86 to 1.88). Conclusions The survival of HCV-infected ESRF patients is comparable between PD and HD.

Aminoglycosides offer several potential benefits in their treatment of peritoneal dialysis (PD)-associated peritonitis, including low cost, activity against Gram-negative organisms (including Pseudomonas aeruginosa), synergistic bactericidal activity against some Gram-positive organisms (such as Staphylococci) and relatively low propensity to promote antimicrobial resistance. However, there is limited conflicting evidence that aminoglycosides may accelerate loss of residual renal function (RRF) in PD patients. The aim of this study was to study the effect of aminoglycoside use on slope of decline in RRF.The study included 2715 Australian patients receiving PD between October 2003 and December 2007 in whom at least two measurements of renal creatinine clearance were available. Patients were divided according to tertiles of slope of RRF decline (rapid, intermediate and slow). The primary outcome was the slope of RRF over time in patients who received aminoglycosides for PD peritonitis versus those who did not.A total of 1412 patients (52%) experienced at least one episode of PD peritonitis. An aminoglycoside was used as the initial empiric antibiotic in 1075 patients. The slopes of RRF decline were similar in patients treated and not treated with at least one course of aminoglycoside (median [interquartile range] -0.26 [-1.17 to 0.04] mL/min/1.73 m(2)/month versus -0.22 [-1.11 to 0.01] mL/min/1.73 m(2)/month, P = 0.9). The slopes of RRF decline were also similar in patients receiving repeated courses of aminoglycoside.Empiric treatment with aminoglycoside for peritonitis was not associated with an adverse effect on RRF in PD patients.

Non-Pseudomonas Gram-negative (NPGN) peritonitis is a frequent, serious complication of peritoneal dialysis; however, previous reports have been limited to small, single-center studies. To gain insight on the frequency, predictors, treatment, and outcomes of NPGN peritonitis, we analyzed data in the ANZDATA registry of all adult Australian peritoneal dialysis patients over a 39-month period using multivariate logistic and multilevel Poisson regressions. There were 837 episodes of NPGN peritonitis (23.3% of all peritonitis) that occurred in 256 patients. The most common organism isolated was Escherichia coli, but included Klebsiella, Enterobacter, Serratia, Acinetobacter, Proteus, and Citrobacter, with multiple organisms identified in a quarter of the patients. The principal risk factor was older age, with poorer clinical outcome predicted by older age and polymicrobial peritonitis. The overall antibiotic cure rate was 59%. NPGN peritonitis was associated with significantly higher risks of hospitalization, catheter removal, permanent transfer to hemodialysis, and death compared to other organisms contributing to peritonitis. Underlying bowel perforation requiring surgery was uncommon. Hence, we show that NPGN peritonitis is a frequent, serious complication of peritoneal dialysis, which is frequently associated with significant risks, including death. Its cure with antibiotics alone is less likely when multiple organisms are involved.

Staphylococcus aureus peritonitis is a serious complication of peritoneal dialysis (PD). Since reports of the course and treatment of S. aureus peritonitis have generally been limited to small, single-center studies, the aim of the current investigation was to examine the frequency, predictors, treatment, and clinical outcomes of this condition in all 4675 patients receiving PD in Australia between 1 October 2003 and 31 December 2006. 3594 episodes of peritonitis occurred in 1984 patients and 503 (14%) episodes of S. aureus peritonitis occurred in 355 (8%) individuals. 273 (77%) patients experienced 1 episode of S. aureus peritonitis, 52 (15%) experienced 2 episodes, 19 (5%) experienced 3 episodes, and 11 (3%) experienced 4 or more episodes. The predominant antibiotics used as initial empiric therapy were vancomycin (61%) and cephazolin (31%). Once S. aureus was isolated and identified, the prescription of vancomycin did not appreciably change for methicillin-sensitive S. aureus (MSSA) peritonitis (59%) and increased for methicillin-resistant S. aureus (MRSA) peritonitis (84%). S. aureus peritonitis was associated with a higher rate of relapse than non-S. aureus peritonitis (20% vs 13%, p < 0.001) but comparable rates of hospitalization (67% vs 70%, p = 0.2), catheter removal (23% vs 21%, p = 0.4), hemodialysis transfer (18% vs 18%, p = 0.6), and death (2.2% vs 2.3%, p = 0.9). MRSA peritonitis was independently predictive of an increased risk of permanent hemodialysis transfer [odds ratio (OR) 2.11, 95% confidence interval (CI) 1.17 – 3.82] and tended to be associated with an increased risk of hospitalization (OR 2.00, 95% CI 0.96 – 4.19). The initial empiric antibiotic choice between vancomycin and cephazolin was not significantly associated with clinical outcomes, but serious adverse outcomes were more likely if vancomycin was not used for subsequent treatment of MRSA peritonitis. In conclusion, S. aureus peritonitis is a serious complication of PD, involves a small proportion of patients, and is associated with a high rate of relapse and repeat episodes. Other adverse clinical outcomes are similar to those for peritonitis overall but are significantly worse for MRSA peritonitis. Empiric initial therapy with either vancomycin or cephazolin results in comparable outcomes, provided vancomycin is prescribed when MRSA is isolated and identified.

Coagulase-negative staphylococcal (CNS) peritonitis is the most common cause of peritoneal dialysis (PD)-associated peritonitis. Previous reports of this important condition have been sparse and generally limited to single-centre studies.The frequency, predictors, treatment and clinical outcomes of CNS peritonitis were examined by multivariate logistic regression and multilevel Poisson regression in all adult PD patients in Australia between 2003 and 2006.A total of 936 episodes of CNS peritonitis (constituting 26% of all peritonitis episodes) occurred in 620 individuals. The observed rate of CNS peritonitis was 0.16 episodes per patient-year. Lower rates of CNS peritonitis were independently predicted by Asian racial origin (adjusted odds ratio [OR], 0.52; 95% CI, 0.35-0.79), renovascular nephrosclerosis (OR, 0.40; 95% CI, 0.18-0.86), early referral to a renal unit prior to dialysis commencement (OR, 0.38; 95% CI, 0.19-0.79) and treatment with automated PD at any time during the PD career (OR, 0.79; 95% CI, 0.66-0.96). The majority of CNS peritonitis episodes were initially treated with intraperitoneal vancomycin or cephazolin in combination with gentamicin. This regimen was changed in 533 (57%) individuals after a median period of 3 days, most commonly to vancomycin monotherapy. The median total antibiotic course duration was 14 days. Compared with other forms of peritonitis, CNS episodes were significantly more likely to be cured by antibiotics alone (76 vs 64%, P0.001) and less likely to be complicated by hospitalization (61 vs 73%, P0.001), catheter removal (10 vs 26%, P0.001), temporary haemodialysis (2 vs 5%, P0.001), permanent haemodialysis transfer (9 vs 21%, P0.001) and death (1.0 vs 2.7%, P = 0.002). CNS peritonitis was also associated with a shorter duration of hospitalization, a longer time to catheter removal and a shorter duration of temporary haemodialysis. Catheter removal and permanent haemodialysis transfer were independently predicted by polymicrobial peritonitis and initial empiric administration of vancomycin (compared with cephalosporins). CNS peritonitis was associated with a higher relapse rate (17 vs 13%, P = 0.003) and relapsed CNS peritonitis was associated with a higher catheter removal rate (22 vs 7%, P0.001). Repeat peritonitis occurred in 194 (31%) individuals and the highest risk was in the second month after completion of antibiotic treatment for CNS peritonitis (OR, 1.87; 95% CI, 1.39-2.51 compared with2 months).CNS peritonitis is a common complication with a relatively benign outcome compared with other forms of PD-associated peritonitis. Relapsed and repeat peritonitis are relatively common and are associated with worse outcomes.

Automated peritoneal dialysis (APD) is widely recommended for the management of high transporters by the International Society of Peritoneal Dialysis (ISPD), although there have been no adequate studies to date comparing the outcomes of APD and continuous ambulatory peritoneal dialysis (CAPD) in this high risk group.The relative impact of APD versus CAPD on patient and technique survival rates was examined by both intention-to-treat (PD modality at Day 90) and 'as-treated' time-varying Cox proportional hazards model analyses in all patients who started PD in Australia or New Zealand between 1 April 1999 and 31 March 2004 and who had baseline peritoneal equilibration tests confirming the presence of high peritoneal transport status.During the study period, 4128 patients commenced PD. Of these, 628 patients were high transporters on PD at Day 90 (486 on APD and 142 on CAPD). Compared to high transporters treated with CAPD, APD-treated high transporters were more likely to be younger and Caucasian, and less likely to be diabetic. On multivariate intention-to-treat analysis, APD treatment was associated with superior survival [adjusted hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.35-0.87] and comparable death-censored technique survival (HR 0.88, 95% CI 0.64-1.21). Superior survival of high transporters treated with APD versus CAPD was also confirmed in supplemental as-treated analysis (HR 0.72, 95% CI 0.54-0.96), matched case-control analysis (HR 0.60, 95% CI 0.36-0.96) and subgroup analysis of high transporters treated entirely with APD versus those treated entirely with CAPD (HR 0.29, 95% CI 0.14-0.60). There were no statistically significant differences in patient survival or death-censored technique survival between APD and CAPD for any other transport group, except for low transporters, who experienced a higher mortality rate on APD compared with CAPD (HR 2.19, 95% CI 1.02-4.70).APD treatment is associated with a significant survival advantage in high transporters compared with CAPD. However, APD treatment is associated with inferior survival in low transporters.

Fungal peritonitis is a serious complication of peritoneal dialysis but previous reports on this have been limited to small, single-center studies. Using all Australian peritoneal dialysis patients, we measured predictors, treatments, and outcomes of this condition by logistic regression and multilevel, multivariate Poisson regression. This encompassed 66 centers over a 4-year period that included 162 episodes of fungal peritonitis (4.5% of all peritonitis episodes) that occurred in 158 individuals. Candida albicans (25%) and other Candida species (44%) were the most common fungi isolated. Fungal peritonitis was independently predicted by indigenous race and prior treatment of bacterial peritonitis. Peritonitis episodes occurring after 7 and 60 days of treatment for previous bacterial peritonitis decreases in the probability of fungal peritonitis 23 and 6%, respectively. Compared with other organisms, fungal peritonitis was associated with significantly higher rates of hospitalization, catheter removal, transfer to permanent hemodialysis, and death. The risks of repeat fungal peritonitis and death were lowest with catheter removal combined with antifungal therapy when compared to either intervention alone. Our study shows that fungal peritonitis is a serious complication of peritoneal dialysis and should be strongly suspected in the context of recent antibiotic treatment for bacterial peritonitis.

Background. Infection due to Corynebacterium species has been reported with increasing frequency over recent decades. The impacts of enhanced laboratory detection together with widespread use of new peritoneal dialysis (PD) connection technology and antimicrobial prophylaxis strategies on Corynebacterium PD-associated peritonitis have not been well studied. Methods. We investigated the frequency, predictors, treatment and clinical outcomes of Corynebacterium peritonitis in all Australian adult patients involving 66 centres who were receiving PD between 1 October 2003 and 31 December 2006. Results. Eighty-two episodes of Corynebacterium peritonitis (2.3% of all peritonitis episodes) occurred in 65 (1.4%) PD patients. Ten (15%) patients experienced more than one episode of Corynebacterium peritonitis and additional organisms were isolated in 12 (15%) episodes of Corynebacterium peritonitis. The incidence of Corynebacterium peritonitis was significantly and independently predicted only by BMI: RR 2.72 (95% CI 1.38–5.36) for the highest tertile BMI compared with the lowest tertile. The overall cure rate with antibiotics alone was 67%, which was similar to that of peritonitis due to other organisms. Vancomycin was the most common antimicrobial agent administered in the initial empiric and subsequent antibiotic regimens, although outcomes were similar regardless of antimicrobial schedule. Corynebacterium peritonitis not infrequently resulted in relapse (18%), repeat peritonitis (15%), hospitalization (70%), catheter removal (21%), permanent haemodialysis transfer (15%) and death (2%). The individuals who had their catheters removed more than 1 week after the onset of Corynebacterium peritonitis had a significantly higher risk of permanent haemodialysis transfer than those who had their catheters removed within 1 week (90% versus 43%, P < 0.05). Conclusions. Corynebacterium is an uncommon but significant cause of PD-associated peritonitis. Complete cure with antibiotics alone is possible in the majority of patients, and rates of adverse outcomes are comparable to those seen with peritonitis due to other organisms. Use of vancomycin rather than cephazolin as empiric therapy does not impact outcomes, and a 2-week course of antibiotic therapy appears sufficient. If catheter removal is required, outcomes are improved by removing the catheter within 1 week of peritonitis onset.

Background Primary hepatitis B virus (HBV) vaccination through the intramuscular (IM) route is less efficacious in dialysis patients than in the general population. Previous studies suggest improved seroconversion with intradermal (ID) vaccination. Study Design Prospective open-label randomized controlled trial. Setting & Participants Hemodialysis patients nonresponsive to primary HBV vaccination. Intervention Revaccination with either ID (5 μg of vaccine every week for 8 weeks) or IM (40 μg of vaccine at weeks 1 and 8) HBV vaccine. Outcomes Primary outcome: proportion of patients achieving HBV surface antibody (anti-HBs) titer of 10 IU/L or greater within 2 months of vaccination course. Secondary outcomes: time to seroconversion, predictors of seroconversion, peak antibody titer, duration of seroprotection, and safety and tolerability of vaccine. Measurements Anti-HBs titer to 24 months. Results 59 patients were analyzed. Seroconversion rates were 79% ID versus 40% IM (P = 0.002). The unadjusted odds ratio for seroconversion for ID versus IM was 5.5 (95% confidence interval [CI], 1.6 to 18.4) and increased with adjustment for baseline differences. The only factor predictive of seroconversion was the ID vaccination route. The geometric mean peak antibody titer was significantly greater in the ID versus IM group: 239 IU/L (95% CI, 131 to 434) versus 78 IU/L (95% CI, 36 to 168; P Limitations Inability to distinguish whether the mechanism of the greater efficacy of ID vaccination was the cumulative effect of multiple injections or route of administration; use of anti-HBs as a surrogate marker of protection; lack of evidence of long-term protection. Conclusions Significantly greater seroconversion rates and peak antibody titers can be achieved with ID compared with IM vaccination in hemodialysis patients nonresponsive to primary vaccination. ID vaccination should become the standard of care in this setting.

The aim of the present investigation is to compare rates, types, causes, and timing of infectious death in incident peritoneal dialysis (PD) and hemodialysis (HD) patients in Australia and New Zealand.Observational cohort study using the Australian and New Zealand Dialysis and Transplant Registry data.The study included all patients starting dialysis therapy between April 1, 1995, and December 31, 2005.Dialysis modality.Rates of and time to infectious death were compared by using Poisson regression, Kaplan-Meier, and competing risks multivariate Cox proportional hazards model analyses.21,935 patients started dialysis therapy (first treatment PD, n = 6,020; HD, n = 15,915) during the study period, and 1,163 patients (5.1%) died of infectious causes (PD, 529 patients; 7.6% versus HD, 634 patients; 4.2%). Incidence rates of infectious mortality in PD and HD patients were 2.8 and 1.7/100 patient-years, respectively (incidence rate ratio PD versus HD, 1.66; 95% confidence interval [CI], 1.47 to 1.86). After performing competing risks multivariate Cox analyses allowing for an interaction between time on study and modality because of identified nonproportionality of hazards, PD consistently was associated with increased hazard of death from infection compared with HD after 6 months of treatment (6 months hazard ratio [HR], 1.08; 95% CI, 0.76 to 1.54; 6 months to 2 years HR, 1.31; 95% CI, 1.09 to 1.59; 2 to 6 years HR, 1.51; 95% CI, 1.26 to 1.80;6 years HR, 2.76; 95% CI, 1.76 to 4.33). This increased risk of infectious death in PD patients was largely accounted for by an increased risk of death caused by bacterial or fungal peritonitis.Patients were not randomly assigned to their initial dialysis modality. Residual confounding and coding bias could not be excluded.Dialysis modality selection significantly influences risks, types, causes, and timing of fatal infections experienced by patients with end-stage kidney disease in Australia and New Zealand.

Functional magnetic resonance imaging (fMRI) has become a powerful tool for studying the normal and diseased human brain. The application of fMRI in detecting neuronal signals in the trigeminal system, however, has been hindered by low detection sensitivity due to activation artifacts caused by cardiac pulse-induced brain and brainstem movement. A variety of cardiac gating techniques have been proposed to overcome this issue, typically by phase locking the sampling to a particular time point during each cardiac cycle. We sought to compare different cardiac gating strategies for trigeminal system fMRI. In the present study, we used tactile stimuli to elicit brainstem and thalamus activation and compared the fMRI results obtained without cardiac gating and with three different cardiac gating strategies: single-echo with TR of 3 or 9 heartbeats (HBs) and dual-echo T2*-mapping EPI (TR = 2 HBs, TE = 21/55 ms). The dual-echo T2* mapping and the single-echo with TR of 2 and 3 HBs cardiac-gated fMRI techniques both increased detection rate of fMRI activation in brainstem. Activation in the brainstem and the thalamus was best detected by cardiac-gated dual-echo EPI.

SUMMARY: Aim: Nocturnal haemodialysis (NHD) is a new haemodialysis (HD) modality that has been shown to have many benefits when compared with conventional haemodialysis (CHD). Previous results from our NHD programme have demonstrated a 7% fall in the postdialysis serum albumin concentration when compared with the pre-HD levels. A similar, physiological, 9% haemodilution of albumin is seen in normal individuals on assuming a supine posture. Method: In this observational study, the intradialytic change in the concentration of 11 serum proteins (total protein, albumin, alkaline phosphatase, gamma glutamyl transferase, alanine transaminase, amylase, transferrin, complement factors 3 and 4, free thyroxine and C-reactive protein (CRP)) was measured in 10 patients on NHD and in 10 age- and sex-matched controls on CHD. The ultrafiltration rate (UFR) was also recorded. Results: We demonstrated an intradialytic fall in the total protein (0.63%), albumin (2.40%), alkaline phosphatase (1.84%), amylase (8.82%), complement factor 3 (2.73%) and CRP (8.19%) in patients on NHD. This was of a lesser magnitude than that occurring in the pilot study but still approximated the physiological fall in serum proteins occurring with overnight recumbency in normal individuals. In contrast, all serum proteins measured rose during CHD, reflecting intravascular volume contraction and haemoconcentration. The UFR was significantly lower in NHD than CHD (234.52 ± 20.90 mL/h vs 435.38 ± 38.44 mL/h, P

The clinical usefulness of hemodialysis catheters is limited by increased infectious morbidity and mortality. Topical antiseptic agents, such as mupirocin, are effective at reducing this risk but have been reported to select for antibiotic-resistant strains. The aim of the present study was to determine the efficacy and the safety of exit-site application of a standardized antibacterial honey versus mupirocin in preventing catheter-associated infections. A randomized, controlled trial was performed comparing the effect of thrice-weekly exit-site application of Medihoney versus mupirocin on infection rates in patients who were receiving hemodialysis via tunneled, cuffed central venous catheters. A total of 101 patients were enrolled. The incidences of catheter-associated bacteremias in honey-treated (n = 51) and mupirocin-treated (n = 50) patients were comparable (0.97 versus 0.85 episodes per 1000 catheter-days, respectively; NS). On Cox proportional hazards model analysis, the use of honey was not significantly associated with bacteremia-free survival (unadjusted hazard ratio, 0.94; 95% confidence interval, 0.27 to 3.24; P = 0.92). No exit-site infections occurred. During the study period, 2% of staphylococcal isolates within the hospital were mupirocin resistant. Thrice-weekly application of standardized antibacterial honey to hemodialysis catheter exit sites was safe, cheap, and effective and resulted in a comparable rate of catheter-associated infection to that obtained with mupirocin (although the study was not adequately powered to assess therapeutic equivalence). The effectiveness of honey against antibiotic-resistant microorganisms and its low likelihood of selecting for further resistant strains suggest that this agent may represent a satisfactory alternative means of chemoprophylaxis in patients with central venous catheters.

Elevated white cell count at commencement of peritoneal dialysis predicts overall and cardiac mortality.BackgroundHigher total white blood cell counts (WCC) have been shown in the general population to be strongly and independently predictive of coronary heart disease and all-cause mortality. The aim of the present study was to evaluate the prognostic value of WCC in patients commencing peritoneal dialysis (PD).MethodsA cohort of 323 patients (mean age 55.1 ± 17.7 years, 54% male, 81% Caucasian) commencing PD at the Princess Alexandra Hospital between January 1, 1998 and March 31, 2003 were prospectively followed until death, completion of PD therapy, or otherwise to the end of the study (January 2, 2004), at which point data were censored. Individuals with failed renal transplants (N = 17) and those with acute infections at the time of PD onset (N = 12) were not included. A multivariate Cox's proportional hazards model was applied to calculate hazard ratios and adjusted survival curves for time to death or cardiac death, adjusting for baseline demographic, clinical, and laboratory characteristics.ResultsMedian actuarial patient survival was 3.9 years [95% confidence interval (CI) 3.2–4.7 years]. The highest quartile of WCC (>9.4 × 109/L) was significantly and independently associated with increased risks of both death from all causes [adjusted hazard ratio (HR) 2.27, 95% CI 1.09–4.74, P < 0.05] and cardiac death (HR 3.75, 95% CI 1.2–11.8, P < 0.05). Other adverse risk factors included older age, lower serum albumin, and the presence of coronary artery disease. Similar associations were found between mortality and PMN count, but not lymphocyte count.ConclusionElevated baseline WCC or PMN count at the commencement of PD (in the absence of acute infection) strongly predicts all-cause and cardiovascular mortality. These data suggest that new PD patients with higher WCC may warrant closer monitoring and extra attention to modifiable cardiovascular risk factors.

An eight-channel receive-only brain coil and table-top detunable volume transmit coil were developed and tested at 7 T for human imaging. Optimization of this device required attention to sources of interaction between the array elements, between the transmit and receive coils and minimization of common mode currents on the coaxial cables. Circular receive coils (85 mm dia.) were designed on a flexible former to fit tightly around the head and within a 270-mm diameter TEM transmit volume coil. In the near cortex, the array provided a fivefold increase in SNR compared to a TEM transmit-receive coil, a gain larger than that seen in comparable coils at 3 T. The higher SNR gain is likely due to strong dielectric effects, which cause the volume coil to perform poorly in the cortex compared to centrally. The sensitivity and coverage of the array is demonstrated with high-resolution images of the brain cortex.

Several strategies have been used to increase the biostability of medical-grade polyurethanes while maintaining biocompatibility and mechanical properties. One approach is to chemically modify or replace the susceptible soft segment. Currently, poly(carbonate urethanes) (PCUs) are being evaluated as a replacement of poly(ether urethanes) (PEUs) in medical devices because of the increased oxidative stability of the polycarbonate soft segment. Preliminary in vivo and in vitro studies have reported improved biostability of PCUs over PEUs. Although several studies have reported evidence of in vitro degradation of these new polyurethanes, there has been no evidence of significant in vivo degradation that validates a degradation mechanism. In this study, the effect of soft segment chemistry on the phase morphology, mechanical properties, and in vivo response of commercial-grade PEU and PCU elastomers was examined. Results from dynamic mechanical testing and infrared spectroscopy suggested that the phase separation was better in PCU as compared with PEU. In addition, the higher modulus and reduced ultimate elongation of PCU was attributed to the reduced flexibility of the polycarbonate soft segment. Following material characterization, the in vivo biostability and biocompatibility of PEU and PCU were studied using a subcutaneous cage implant protocol. The results from the cage implant study and cell culture experiments indicated that monocytes adhere, differentiate, and fuse to form foreign body giant cells on both polyurethanes. It is now generally accepted that the reactive oxygen species released by these adherent macrophages and foreign body giant cells initiate PEU biodegradation. Attenuated total reflectance-Fourier transform infrared analysis of explanted samples provided evidence of chain scission and crosslinking in both polyurethanes. This indicated that the PCU was also susceptible to biodegradation by agents released from adherent cells. These results reinforce the need to evaluate and understand the biodegradation mechanisms of PCUs.

Background Peritonitis is a common complication of peritoneal dialysis (PD) that is associated with significant morbidity including death, hospitalisation, and need to change from PD to haemodialysis. Treatment is aimed to reduce morbidity and recurrence. This is an update of a review first published in 2008. Objectives To evaluate the benefits and harms of treatments for PD-associated peritonitis. Search methods For this review update we searched the Cochrane Renal Group's Specialised Register to March 2014 through contact with the Trials Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE, and handsearching conference proceedings. Selection criteria We included randomised controlled trials (RCTs) and quasi-RCTs assessing the treatment of peritonitis in PD patients (adults and children). We included any study that evaluated: administration of an antibiotic by different routes (e.g. oral, intraperitoneal (IP), intravenous (IV)); dose of an antibiotic agent; different schedules of administration of antimicrobial agents; comparisons of different regimens of antimicrobial agents; any other intervention including fibrinolytic agents, peritoneal lavage and early catheter removal. Data collection and analysis Multiple authors independently extracted data on study risk of bias and outcomes. Statistical analyses were performed using the random effects model. We expressed summarised treatment estimates as a risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) with 95% CI for continuous outcomes. Main results We identified 42 eligible studies in 2433 participants: antimicrobial agents (36 studies); urokinase (4 studies), peritoneal lavage (1 study), and IP immunoglobulin (1 study). We did not identify any optimal antibiotic agent or combination of agents. IP glycopeptides (vancomycin or teicoplanin) had uncertain effects on primary treatment response, relapse rates, and need for catheter removal compared to first generation cephalosporins, although glycopeptide regimens were more likely to achieve a complete cure (3 studies, 370 episodes: RR 1.66, 95% CI 1.01 to 2.72). For relapsing or persistent peritonitis, simultaneous catheter removal and replacement was better than urokinase at reducing treatment failure rates (RR 2.35, 95% CI 1.13 to 4.91) although evidence was limited to a single small study. Continuous and intermittent IP antibiotic dosing schedules had similar treatment failure and relapse rates. IP antibiotics were superior to IV antibiotics in reducing treatment failure in one small study (RR 3.52, 95% CI 1.26 to 9.81). Longer duration treatment (21 days of IV vancomycin and IP gentamicin) had uncertain effects on risk of treatment relapse compared with 10 days treatment (1 study, 49 patients: RR 1.56, 95% CI 0.60 to 3.95) although may have increased ototoxicity. In general, review conclusions were based on a small number of studies with few events in which risk of bias was generally high; interventions were heterogeneous, and outcome definitions were often inconsistent. There were no RCTs evaluating optimal timing of catheter removal and data for automated PD were absent. Authors' conclusions Many of the studies evaluating treatment of PD-related peritonitis are small, out-dated, of poor quality, and had inconsistent definitions and dosing regimens. IP administration of antibiotics was superior to IV administration for treating PD-associated peritonitis and glycopeptides appear optimal for complete cure of peritonitis, although evidence for this finding was assessed as low quality. PD catheter removal may be the best treatment for relapsing or persistent peritonitis. Evidence was insufficient to identify the optimal agent, route or duration of antibiotics to treat peritonitis. No specific antibiotic appears to have superior efficacy for preventing treatment failure or relapse of peritonitis, but evidence is limited to few trials. The role of routine peritoneal lavage or urokinase is uncertain.