bluuebunny/crossref_metadata_2025 huggingface dataset:
MAPS of Ventricular Activation Time (VAT) Differences in Children on Peritoneal Dialysis — a Pilot Study
Authors: Laszki-Szcząchor Krystyna , Polak-Jonkisz Dorota , Zwolińska Danuta , Salomon Ewa , Filipowski Henryk , Sobieszczanska Małgorzata
Published: March 2014

Background

Decrement of glomerular filtration rate leads to many serious complications that cause both functional and structural impairments of the other organs. Long-term clinical observations of children and teenagers with end-stage renal disease (ESRD) showed that more than one third of those patients manifested various cardio-vascular conditions. The aim of the study was to analyze possible disturbances in the heart ventricular conduction system by using a technique of ventricular activation time (VAT) differences in ESRF children on peritoneal dialysis (PD) with normal electrocardiogram (ECG) examinations.

Material and methods

The study group comprised 10 ESRD children (mean age: 13.6 ± 2.31 years) on peritoneal dialysis – group I. The control group (group II) consisted of 26 age-matched healthy children with no clinical evidence of renal or cardiac disease and with normal 12-lead ECG recordings. Each of the ESRD patients was also subjected to the standard ECG examination. In order to capture possible heart conduction abnormalities, body surface potential mapping (BSPM) recordings were performed in PD patients between the successive dwells (‘on empty abdomen’) with a HPM-7100 Fukuda Denshi system. Based on the source ECG data, the original technique of a VAT difference map was then applied.

Results

Differences between VAT values for the two examined groups of children, controls and ESRD patients on PD, were significantly pronounced in the region of the right upper anterior thorax, the entire left thorax and nearly in the total back. Such a pattern of VAT delays indicates a pathological electric transmission in the intraventricular conduction system of the left anterior fascicle of His bundle.

Conclusion

1. VAT maps (isochrone maps) can be useful to detect abnormal spreading and depolarization through the heart ventricles. 2. Map of VAT value differences makes it possible to identify early disturbances in the left His bundle branch in ESRD children treated with peritoneal dialysis regardless of normal 12-lead ECG. 3. Further studies on a larger group of children with ESRD on PD are required to verify the preliminary observations presented herein.
Outcome of Acute Kidney Injury in Sudanese Children — An Experience from a Sub-Saharan African Unit
Authors: Abdelraheem Mohamed , Ali El-Tigani , Osman Rania , Ellidir Rashid , Bushara Amna , Hussein Rasha , Elgailany Shiraz , Bakhit Yassir , Karrar Mohamed , Watson Alan , Abu-Aisha Hasan
Published: March 2014

Background

Acute Kidney Injury (AKI) is an important cause of morbidity and mortality in developing countries. Although continuous renal replacement therapy is gaining more popularity worldwide, peritoneal dialysis (PD) in children remains an appropriate therapy for AKI in children for all age groups including neonates.

Methodology

We retrospectively reviewed all children who have been admitted with AKI at the pediatric nephrology unit, Soba University Hospital, Khartoum, during the period from January 2005 to December 2011.

Results

Over 7 years we recorded 659 children of whom 362 (54.9%) were male. The spectrum of age was variable with the majority being neonates, 178 (27.1%). The average patient admission rate was 94 patients per year, with an estimated incidence of 9.8 patients/million population/year. Common causes of AKI were sepsis 202 (30.8%), acute glomerulonephritis 75 (11.5%) and obstructive uropathy due to stones 56 (8.5%). The most common dialysis modality used was PD, 343 (52.4%), and peritonitis was reported in 53 (15.4%) patients. Recovery from AKI was achieved in 450 (68.9%) children, 37 (5.7%) went into chronic kidney disease (CKD), 33 (5.1%) referred to the pediatric surgery and 194 (29.7%) died.

Conclusion

In the setting of developing countries where AKI is a common cause of morbidity and mortality, reasonably equipped renal units with adequately trained medical staff may save many lives. International funding programs for communicable diseases and charity organizations should include AKI management in their programs. Acute PD remains the treatment modality of choice for AKI in developing countries.
Saha Suppresses Peritoneal Fibrosis in Mice
Authors: Io Kumiko , Nishino Tomoya , Obata Yoko , Kitamura Mineaki , Koji Takehiko , Kohno Shigeru
Published: March 2014

Objective

Long-term peritoneal dialysis causes peritoneal fibrosis in submesothelial areas. However, the mechanism of peritoneal fibrosis is unclear. Epigenetics is the mechanism to induce heritable changes without any changes in DNA sequences. Among epigenetic modifications, histone acetylation leads to the transcriptional activation of genes. Recent studies indicate that histone acetylation is involved in the progression of fibrosis. Therefore, we examined the effect of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, on the progression of peritoneal fibrosis in mice.

Methods

Peritoneal fibrosis was induced by the injection of chlorhexidine gluconate (CG) into the peritoneal cavity of mice every other day for 3 weeks. SAHA, or a dimethylsulfoxide and saline vehicle, was administered subcutaneously every day from the start of the CG injections for 3 weeks. Morphologic peritoneal changes were assessed by Masson's trichrome staining, and fibrosis-associated factors were assessed by immunohistochemistry.

Results

In CG-injected mice, a marked thickening of the submesothelial compact zone was observed. In contrast, the administration of SAHA suppressed the progression of submesothelial thickening and type III collagen accumulation in CG-injected mice. The numbers of fibroblast-specific protein-1-positive cells and α–smooth muscle actin α–positive cells were significantly decreased in the CG + SAHA group compared to that of the CG group. The level of histone acetylation was reduced in the peritoneum of the CG group, whereas it was increased in the CG + SAHA group.

Conclusions

Our results indicate that SAHA can suppress peritoneal thickening and fibrosis in mice through up-regulation of histone acetylation. These results suggest that SAHA may have therapeutic potential for treating peritoneal fibrosis.
MgCaCO3 Versus CaCO3 in Peritoneal Dialysis Patients – a Cross-over Pilot Trial
Authors: Evsanaa Baigalmaa , Liu Irene , Aliazardeh Babak , Mahdavi Sara , Bajwa Gursarn , Gula Jerry , Tam Michelle , Sze Elena , Roscoe Janet M. , Tam Paul Y. , Sikaneta Tabo
Published: March 2014

Background

Despite adverse effects such as constipation, vascular calcification, and hypercalcemia, calcium-based salts are relatively affordable and effective phosphate binders that remain in widespread use in the dialysis population. We conducted a pilot study examining whether the use of a combined magnesium/calcium-based binder was as effective as calcium carbonate at lowering serum phosphate levels in peritoneal dialysis (PD) patients.

Methods

This was a cross-over, investigator-masked pilot study in which prevalent PD patients received calcium carbonate alone (200 mg calcium per tablet) or calcium magnesium carbonate (100 mg calcium, 85 mg magnesium per tablet). Primary outcome was serum phosphate level at 3 months. Analysis was as per protocol.

Results

Twenty patients were recruited, 17 completed the study. Mean starting dose was 11.35 ± 7.04 pills per day of MgCaCO3 and 9.00 ± 4.97 pills per day of CaCO3. Mean phosphate levels fell from 2.13 mmol/L to 2.01 mmol/L (95% confidence interval (CI): 1.76 – 2.30, p = 0.361) in the MgCaCO3 group, and 1.81 mmol/L (95% CI: 1.56 – 2.0, p = 0.026) in the CaCO3 alone group. Six (35%) patients taking MgCaCO3 and 9 (54%) taking CaCO3 alone achieved Kidney Disease Outcomes Quality Initiative (KDOQI) serum phosphate targets at 3 months. Diarrhea developed in 9 patients taking MgCaCO3 and 3 taking CaCO3. Serum magnesium exceeded 1.4 mmol/L in 5 patients taking MgCaCO3 while serum calcium exceeded 2.65 mmol/L in 3 patients receiving CaCO3. When compared to the initial dose, the prescribed dose at 3 months was reduced by 44% (to 6.41 tablets/day) in the MgCaCO3 group and by 8% (to 8.24 pills per day) in the CaCO3 alone group.

Conclusion

Compared with CaCO3 alone, the preparation and dose of MgCaCO3 used in this pilot study was no better at lowering serum phosphate levels in PD patients, and was associated with more dose-limiting side effects.
Case Report of Cryptococcus Albidus Peritonitis in a Peritoneal Dialysis Patient and a Review of the Literature
Authors: Ragupathi Loheetha , Reyna Maria
Published: March 2014

Cryptococcus albidus is a saprophytic yeast linked to just 26 reports of human infection in the world literature. Here, we report the first case of C. albidus peritonitis, in a patient with end-stage renal disease and hepatitis C-associated cirrhosis who is on peritoneal dialysis. The patient was treated successfully with a week-long course of amphotericin B. Non-neoformans cryptococcal infections present a clinical challenge, because they are difficult to diagnose and lack established guidelines for treatment. We present a review of the literature on C. albidus infections and their treatment.
The Role of Monitoring Vancomycin Levels in Patients with Peritoneal Dialysis-Associated Peritonitis
Authors: Stevenson Sarah , Tang Wen , Cho Yeoungjee , Mudge David W. , Hawley Carmel M. , Badve Sunil V. , Johnson David W.
Published: March 2014

Background

There is limited available evidence regarding the role of monitoring serum vancomycin concentrations during treatment of peritoneal dialysis (PD)-associated peritonitis.

Methods

A total of 150 PD patients experiencing 256 episodes of either gram-positive or culture-negative peritonitis were included to investigate the relationship between measured serum vancomycin within the first week and clinical outcomes of cure, relapse, repeat or recurrence of peritonitis, catheter removal, temporary or permanent transfer to hemodialysis, hospitalization and death.

Results

Vancomycin was used as an initial empiric antibiotic in 54 gram-positive or culture-negative peritonitis episodes among 34 patients. The median number of serum vancomycin level measurements in the first week was 3 (interquartile range; IQR 1 - 4). The mean day-2 vancomycin level, measured in 34 (63%) episodes, was 17.5 ± 5.2 mg/L. Hospitalized patients were more likely to have serum vancomycin levels measured on day 2 and ≥ 3 measurements in the first week. The peritonitis cure rates were similar between patients with < 3 and ≥ 3 measurements in the first week (77% vs 57%, p = 0.12) and if day-2 vancomycin levels were measured or not (68% vs 65%, p = 0.84). The average day-2 (18.0 ± 5.9 vs 16.6 ± 3.2, p = 0.5), first-week average (18.6 ± 5.1 vs 18.6 ± 4.3, p = 0.9) and nadir (14.5 ± 4.1 vs 13.6 ± 4.2, p = 0.5) vancomycin levels were comparable in patients who did or did not achieve peritonitis cure. Similar results were observed for all other clinical outcomes.

Conclusion

The clinical outcomes of gram-positive and culture-negative peritonitis episodes are not associated with either the frequency or levels of serum vancomycin measurements in the first week of treatment when vancomycin is dosed according to International Society for Peritoneal Dialysis (ISPD) Guidelines.
Clinical Outcome of Home Hemodialysis in Patients with Previous Peritoneal Dialysis Exposure: Evaluation of the Integrated Home Dialysis Model
Authors: Nadeau-Fredette Annie-Claire , Bargman Joanne M. , Chan Christopher T.
Published: March 2014

Background

Home dialysis is a cost-effective modality of renal replacement therapy associated with excellent outcomes. Peritoneal dialysis (PD) is the most common home-based modality, but technique failure remains a problem. Transfer from PD to home hemodialysis (HHD) allows the patient to continue with a home-based modality, but the outcomes of patients transitioning to HHD after PD are largely unknown.

Methods

In a retrospective cohort study, including all consecutive HHD patients between January 1996 and December 2011, we evaluated the outcomes of patients with previous PD exposure compared to those without. The primary outcome was the cumulative patient and technique survival. Secondary outcomes included time to first hospitalization and hospitalization rate. Data were compared using the log-rank test and a multivariable Cox proportional hazards model.

Results

Among our cohort of 207 consecutive HHD patients, 35 (17%) had previous exposure to PD. Median renal replacement therapy (RRT) vintage (12.3 years, interquartile range (IQR) 8.5 – 18.9 vs 0.9 years, IQR 0.2 – 7.5, p < 0.001) and Charlson comorbidity index (CCI) (4, IQR 2 – 6 vs 3, IQR 2 – 4, p = 0.044) were higher among patients with PD exposure than those without. Despite the difference in vintage, cumulative patient and technique survival was similar in the two groups, in both unadjusted (log-rank p = 0.893) and Cox adjusted models (hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.51 – 2.59) for patients with PD exposure compared to those without. The time to first hospitalization was shorter in patients with previous PD exposure compared to PD-naïve patients (log-rank p = 0.021). This association was preserved in the Cox proportional model (HR 1.65, 95% CI 1.08 – 2.54).

Conclusion

Despite a higher burden of comorbidity, patients with previous PD exposure had similar cumulative patient and technique survival on HHD compared to those without PD exposure. Whenever possible, HHD should be considered in PD patients in need of a new dialysis modality.
Intraperitoneal Fluid Overestimates Hydration Status Assessment by Bioimpedance Spectroscopy
Authors: Arroyo David , Panizo Nayara , Abad Soraya , Vega Almudena , Rincón Abraham , De José Ana Pérez , López–Gómez Juan M.
Published: March 2014

Background

Bioimpedance spectroscopy (BIS) is a valuable tool to assess nutrition and volume status in peritoneal dialysis (PD) patients. However, data about the influence of intraperitoneal fluid on body composition measures are conflicting, and there is no clear consensus about whether the abdomen should be drained before the procedure. We designed a comparison study to detect the influence of intra-abdominal fluid on BIS results.

Methods

We performed 73 pairs of BIS measurements in 34 stable PD patients, first with the peritoneum filled with a 1.36% glucose dialysate solution and then after the solution was drained. Patients stayed in the supine position for 10 minutes before the BIS procedure, and the electrodes were not moved between measures. Clinical and demographic data were collected, as were analytic parameters of nutrition and volume status.

Results

Fluid overload is overestimated when BIS is performed with a full abdomen (1.82 ± 1.73 L vs 1.64 ± 1.68 L, p = 0.043). We also found a spurious overestimation in extracellular water (16.40 ± 3.21 L vs 16.24 ± 3.16 L, p < 0.001) and in relative overhydration (8.29% ± 6.96% vs 7.14% ± 6.79%, p = 0.017). No differences in intracellular water or parameters of nutrition were found. We observed negative correlations for the extracellular water overestimation with age ( r = –0.245, p = 0.037), serum B-type natriuretic peptide ( r = –0.366, p = 0.036), body mass index ( r = –0.248, p = 0.035), and lean tissue index ( r = –0.427, p = 0.001). The difference in extracellular water correlated only with body mass index ( r = –0.259, p = 0.039). We also found that, assessed at 50 KHz, whole-body impedance (–4.52 ± 8.37, p = 0.001) and phase angle (–0.08 ± 0.23 degrees, p = 0.002) were both lower when BIS was performed in patients with a full abdomen.

Conclusions

Fluid overload is overestimated by BIS when performed in patients with dialysate in the peritoneum. The observed differences are greater in younger, more poorly nourished, or less overhydrated patients. If more precise results are required, we suggest that the abdomen be drained before BIS is performed.
Removal of Different Classes of Uremic Toxins in APD vs CAPD: A Randomized Cross-Over Study
Authors: Eloot Sunny , Vanholder Raymond , Dequidt Clement , Van Biesen Wim
Published: March 2014

♦Aim

In this study, we investigated, and this for the different classes of uremic toxins, whether increasing dialysate volume by shifting from continuous ambulatory peritoneal dialysis (CAPD) to higher volume automated peritoneal dialysis (APD) increases total solute clearance.

♦Methods

Patients on peritoneal dialysis were randomized in a cross-over design to one 24-hour session of first a CAPD regimen (3*2 L of Physioneal 1.36% and 1*2 L of icodextrin) or APD (consisting of 5 cycles of 2 L Physioneal 1.36 and 1 cycle of 2 L Extraneal), and the other week the alternate regime, each patient serving as his/her own control. Dialysate, blood and urine samples were collected and frozen for later batch analysis of concentrations of urea, creatinine, phosphorus, uric acid, hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, indoxyl sulfate, indole acetic acid, and p-cresyl sulfate. For the protein-bound solutes, total and free fractions were determined. Total, peritoneal and renal clearance (K) and mass removal (MR) of each solute were calculated, using validated models.

♦Results

In 15 patients (11 male, 3 diabetics, 56 ± 16 years, 8 on CAPD, time on peritoneal dialysis 12 ± 14 months, and residual renal function of 9.9 ± 5.4 mL/min) dialysate over plasma ratio for creatinine (D/Pcrea) was 0.62 ± 0.10. Drained volume and obtained ultrafiltration were higher with APD vs CAPD (13.3 ± 0.5 L vs 8.5 ± 0.7 L and 1.3 ± 0.5 L vs 0.5 ± 0.7 L), whereas urine output was lower (1.0 ± 0.5 L vs 1.4 ± 0.6 L). Total clearance and MR tended to be higher for CAPD vs APD for all small and water soluble solutes, but mainly because of higher renal contribution, with no difference in the peritoneal contribution. For the protein-bound solutes, no differences in clearance or mass removal were observed.

♦Conclusion

Although the drained dialysate volume nearly doubled, APD did not result in better peritoneal clearance or solute removal vs classic CAPD. APD resulted in better ultrafiltration, but at the expense of residual urinary output and clearance.
Low-Polydispersity Glucose Polymers as Osmotic Agents for Peritoneal Dialysis
Authors: Leypoldt John K. , Hoff Catherine M. , Akonur Alp , Holmes Clifford J.
Published: March 2014

♦Background

Peritoneal dialysis (PD) solutions containing icodextrin as the osmotic agent have advantages during long dwells. The glucose polymers that constitute icodextrin are a heterogeneous mix of molecules with a polydispersity [ratio of weight-average to number-average molecular weight (Mw/Mn)] of approximately 2.6. The present study evaluates whether modifications in the polydispersity and concentration of glucose polymers can improve ultrafiltration (UF) without an associated increase in carbohydrate absorption (CA).

♦Methods

Computer simulations using a three-pore model of peritoneal transport during a long dwell in PD patients predict that, in general, compared with 7.5% icodextrin, glucose polymers with a Mw greater than or equal to 7.5 kDa, a polydispersity less than 2.6, and concentrations greater than 7% could achieve higher UF without higher CA. Based on the simulations, we hypothesized that, compared with 7.5% icodextrin, glucose polymers with a Mw of 18 – 19 kDa and a polydispersity of 2.0 at 11% concentration could achieve higher UF without a higher CA. We tested this hypothesis in experimental studies using 8-hour dwells in New Zealand White rabbits. In those studies, UF was measured by complete fluid collection, and CA was measured by subtracting the total carbohydrate in the collected fluid from the carbohydrate initially infused.

♦Results

The UF was higher with 11% 19 kDa glucose polymer than with 7.5% icodextrin (mean ± standard deviation: 89 ± 31 mL vs 49 ± 15 mL; p = 0.004) without higher CA (5.2 ± 0.9 g vs 5.0 ± 0.9 g, p = 0.7). Similar results were seen with the 11% 18 kDa glucose polymer, which, compared with 7.5% icodextrin, resulted in higher UF (mean ± standard deviation: 96 ± 18 mL vs 66 ± 17 mL; p < 0.001) without higher CA (4.8 ± 0.7 g vs 5.2 ± 0.6 g, p = 0.2).

♦Conclusions

The findings demonstrate that, compared with 7.5% icodextrin solution, long-dwell PD solutions containing 11% glucose polymers with a Mw of 18–19 kDa and a polydispersity of 2.0 can provide higher UF without higher CA.
Transitioning Youth with Rheumatic Conditions: Perspectives of Pediatric Rheumatology Providers in the United States and Canada
Authors: Chira Peter , Ronis Tova , Ardoin Stacy , White Patience
Published: March 2014

Objective.

To assess North American pediatric rheumatology providers’ perspectives on practices, barriers, and opportunities concerning the transition from pediatric-centered to adult-centered care.

Methods.

Childhood Arthritis and Rheumatology Research Alliance (CARRA) members completed a 25-item survey assessing current transition practices, transition policy awareness, and transitional care barriers and needs. Results were compared to the American Academy of Pediatrics (AAP) 2008 survey on transitional care.

Results.

Over half (158/288, 55%) of CARRA members completed the survey. Fewer than 10% are very familiar with AAP guidelines about transition care for youth with special healthcare needs. Eight percent have a formal written transition policy, but 42% use an informal approach. Patient request (75%) most frequently initiates transfer to adult care. Two major barriers to transition are fragmented adult medical care and lack of sufficient time to provide services. Compared with AAP survey participants, pediatric rheumatology providers are significantly more likely to help youth find an adult specialist (63% vs 45%) and discuss confidentiality and consent before age 18 (45% vs 33%), but are less likely to help with medical summary creation (16% vs 27%) or find a primary care provider (25% vs 47%). Outcomes ranked as “very important” in defining a successful transition are survival (76%), seeing an adult rheumatologist within 6 months of final pediatric rheumatology visit (66%), and maintaining insurance coverage (57%).

Conclusion.

This comprehensive survey of North American pediatric rheumatology providers regarding transitional care practices demonstrates deficiencies in education, resources, and a formalized process. Respondents support development of standardized rheumatology-specific transition practices.
Factors Associated with Major Cardiovascular Events in Patients with Systemic Necrotizing Vasculitides: Results of a Longterm Followup Study
Authors: Terrier Benjamin , Chironi Gilles , Pagnoux Christian , Cohen Pascal , Puéchal Xavier , Simon Alain , Mouthon Luc , Guillevin Loïc
Published: March 2014

Objective.

Systemic necrotizing vasculitides (SNV) are associated with more frequent subclinical atherosclerosis, suggesting that SNV might be associated with a higher risk of major cardiovascular events (MCVE). We aimed to identify factors predictive of MCVE in patients with SNV.

Methods.

Patients in remission from SNV were assessed for CV risk factors and subclinical atherosclerosis. MCVE was defined as myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, and/or death from CV causes. MCVE-free survival curves were compared using the log-rank test.

Results.

Forty-two patients were followed for 7.1 ± 2.6 years. Eight patients (18.9%) had MCVE. The respective 5- and 10-year MCVE rates were 9.5% and 26.8%. National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III)-defined high-risk status [hazard ratio (HR) 5.02 (95% CI: 1.17–27.4), p = 0.03], BMI > 30 kg/m2 [HR 4.84 (95% CI: 1.46–116), p = 0.02], and plaque detection in the abdominal aorta (p = 0.01) were significantly associated with MCVE. SNV characteristics, corticosteroid maintenance therapy, and C-reactive protein > 5 mg/l were not associated with MCVE. Plaque in the aorta was significantly associated with high-risk status (p < 0.001), while BMI and high-risk status were independent variables. Thus, a BMI > 30 kg/m2 and/or a high-risk status were strongly associated with MCVE (p = 0.004). Carotid intima-media thickness (IMT) identified patients with early MCVE and was correlated with the time to MCVE (r2 = 0.68, p = 0.01).

Conclusion.

These results suggest that factors associated with a higher MCVE risk in patients with SNV are NCEP/ATP III-defined high-risk status and BMI > 30 kg/m2. Carotid IMT could help identify patients with SNV at risk of early MCVE.
Associations Between Biomarkers of Joint Metabolism, Hand Osteoarthritis, and Hand Pain and Function: The Johnston County Osteoarthritis Project
Authors: Aslam Imran , Perjar Irina , Shi Xiaoyan A. , Renner Jordan B. , Kraus Virginia B. , Golightly Yvonne M. , Jordan Joanne M. , Nelson Amanda E.
Published: March 2014

Objective.

To determine the associations between joint metabolism biomarkers and hand radiographic osteoarthritis [(rOA), based on Kellgren Lawrence (KL) grade ≥ 2], symptoms, and function.

Methods.

Cross-sectional data were available for 663 participants (mean age 63 yrs, 63% white, 49% women). Three definitions of hand rOA were considered: (1) a composite measure involving at least 3 hand joints distributed bilaterally with 2 of 3 in the same joint group, including ≥ 1 distal interphalangeal joint, without metacarpophalangeal (MCP) swelling; (2) rOA in at least 1 joint of a group; and (3) number of joints with KL ≥ 2. We assessed hand symptoms and the 15-item Australian Canadian Hand Osteoarthritis Index (AUSCAN; Likert format). We measured serum cartilage oligomeric matrix protein (sCOMP), hyaluronic acid (sHA), carboxy-terminal propeptide of type II collagen, type II collagen degradation product, urinary C-terminal crosslinked telopeptide of type II collagen, and urinary N-terminal crosslinked telopeptide. Linear regression models were performed to assess associations between each biomarker with hand rOA, AUSCAN, and symptoms, adjusting for age, sex, race, current smoking/drinking status, body mass index, and hip and knee rOA.

Results.

In adjusted analyses, MCP (p < 0.0001) and carpometacarpal rOA (p = 0.003), and a higher number of hand joints with rOA (p = 0.009), were associated with higher levels of sHA. Positive associations were seen between AUSCAN and hand symptoms and levels of sCOMP (p ≤ 0.003) and sHA (p ≤ 0.048).

Conclusion.

Hand symptoms and higher AUSCAN scores were independently associated with higher levels of both sCOMP and sHA; hand rOA was associated only with sHA levels.
Vaccine Responses in Patients with Rheumatoid Arthritis Treated with Certolizumab Pegol: Results from a Single-blind Randomized Phase IV Trial
Authors: Kivitz Alan J. , Schechtman Joy , Texter Michele , Fichtner Andreas , de Longueville Marc , Chartash Elliot K.
Published: March 2014

Objective.

To evaluate the humoral immune response to pneumococcal and influenza vaccination in adults with rheumatoid arthritis (RA) receiving certolizumab pegol (CZP).

Methods.

In this 6-week, single-blind, placebo-controlled trial with optional 6-month open-label extension (NCT00993668), patients were stratified by concomitant methotrexate (MTX) use and randomized to receive CZP 400 mg (loading dose; according to CZP label) or placebo at weeks 0, 2, and 4. Pneumococcal (polysaccharide 23) and influenza vaccines were administered at Week 2. Satisfactory humoral immune response, defined as ≥ 2-fold titer increase in ≥ 3 of 6 pneumococcal antigens and ≥ 4-fold titer increase in ≥ 2 of 3 influenza antigens, were assessed independently 4 weeks after vaccination.

Results.

Following pneumococcal vaccination, 62.5% of placebo patients and 54.5% of CZP patients without effective titers at baseline achieved a humoral response (difference in proportions was −8.0 percentage points; 95% CI −22.5 to 6.6%). Following influenza vaccination, 61.4% of placebo and 53.5% of CZP patients without effective titers at baseline achieved a humoral response (difference in proportions: −8.0 percentage points; 95% CI −22.9 to 7.0%). In all patients, including those with effective titers at baseline, 58.2% of placebo and 53.3% of CZP patients developed satisfactory pneumococcal titers, and 54.1% of placebo and 50.5% of CZP patients developed satisfactory influenza antibody titers. Vaccine responses to pneumococcal and influenza antigens were reduced similarly in both treatment groups with concomitant MTX use.

Conclusion.

Humoral immune responses to pneumococcal and influenza vaccination are not impaired when given during the loading phase of CZP treatment in patients with RA. (ClinicalTrials.govNCT00993668).
Updating the OMERACT Filter: Implications for Imaging and Soluble Biomarkers
Authors: D’Agostino Maria-Antonietta , Boers Maarten , Kirwan John , van der Heijde Désirée , Østergaard Mikkel , Schett Georg , Landewé Robert B. , Maksymowych Walter P. , Naredo Esperanza , Dougados Maxime , Iagnocco Annamaria , Bingham Clifton O. , Brooks Peter M. , Beaton Dorcas E. , Gandjbakhch Frederique , Gossec Laure , Guillemin Francis , Hewlett Sarah E. , Kloppenburg Margreet , March Lyn , Mease Philip J. , Moller Ingrid , Simon Lee S. , Singh Jasvinder A. , Strand Vibeke , Wakefield Richard J. , Wells George A. , Tugwell Peter , Conaghan Philip G.
Published: March 2014

Objective.

The Outcome Measures in Rheumatology (OMERACT) Filter provides a framework for the validation of outcome measures for use in rheumatology clinical research. However, imaging and biochemical measures may face additional validation challenges because of their technical nature. The Imaging and Soluble Biomarker Session at OMERACT 11 aimed to provide a guide for the iterative development of an imaging or biochemical measurement instrument so it can be used in therapeutic assessment.

Methods.

A hierarchical structure was proposed, reflecting 3 dimensions needed for validating an imaging or biochemical measurement instrument: outcome domain(s), study setting, and performance of the instrument. Movement along the axes in any dimension reflects increasing validation. For a given test instrument, the 3-axis structure assesses the extent to which the instrument is a validated measure for the chosen domain, whether it assesses a patient-centered or disease-centered variable, and whether its technical performance is adequate in the context of its application. Some currently used imaging and soluble biomarkers for rheumatoid arthritis, spondyloarthritis, and knee osteoarthritis were then evaluated using the original OMERACT Filter and the newly proposed structure. Breakout groups critically reviewed the extent to which the candidate biomarkers complied with the proposed stepwise approach, as a way of examining the utility of the proposed 3-dimensional structure.

Results.

Although there was a broad acceptance of the value of the proposed structure in general, some areas for improvement were suggested including clarification of criteria for achieving a certain level of validation and how to deal with extension of the structure to areas beyond clinical trials.

Conclusion.

General support was obtained for a proposed tri-axis structure to assess validation of imaging and soluble biomarkers; nevertheless, additional work is required to better evaluate its place within the OMERACT Filter 2.0.
Conventional versus Piggyback Techniques: Do They Have Different Outcomes?
Authors: Ghazaly Mohamed , Davidson Brian R.
Published: March 2014

Background

Conventional orthotopic liver transplant includes resection of the recipient's native liver, together with the retrohepatic inferior vena cava, whereas with the piggyback technique, the recipient's vena cava is preserved and the donor's vena cava is anastomosed with the recipient's hepatic veins. So the caval flow is maintained during explantation, but on the other hand, the cava must be dissected completely from the liver, prolonging hepatic excision.

Objective

To compare outcomes of conventional versus piggyback techniques. Primary outcomes were serious adverse events or complications, and secondary outcomes were graft survival for 3 and 12 months, quality of life, days in the intensive care unit and in the hospital, and days spent receiving mechanical ventilation.

Materials and Methods

From January 3, 2007, to December 31, 2008, 120 liver transplant patients were divided into 2 groups: conventional (n = 93) and piggyback (n = 27).

Results

Intraoperative and postoperative complications, graft survival for 3 and 12 months, quality of life, and hospital stay did not differ significantly between the 2 groups. However, the stay in the intensive care unit (median, 2 vs 3 days; range, 1–101 vs 1–60 days) and the number of days on ventilatory support (median, 1 vs 2 days; range, 0–41 vs 1–60 days) were notably lower in the conventional group.

Conclusion

The conventional liver transplant technique had significantly better results than the piggyback technique in terms of length of stay in the intensive care unit and duration of mechanical ventilation.
Development of the National Living Donor Assistance Center: Reducing Financial Disincentives to Living Organ Donation
Authors: Warren Patricia H. , Gifford Kimberly A. , Hong Barry A. , Merion Robert M. , Ojo Akinlolu O.
Published: March 2014

Over the years, the transplant community has worked to advance the care of living organ donors; however, barriers remain, including the nonmedical expenses incurred by living donors. A new center, funded by a grant from the Health Resources and Services Administration (HRSA), was established to operate a nationwide system to remove these financial disincentives. The HRSA grant was awarded to an academic institution and the daily operations are managed by a transplant professional society. Expenses are reimbursed prospectively for financially needy living donors. Combining the legislative authority and economic resources of the federal government, the research experience of an academic institution, and the management know-how of a professional society has proven to be successful. To date, the center has received 3918 applications submitted by 199 different transplant centers and receives about 80 applications per month. On average, a donor spends $2767 for their travel expenses to the transplant center. Of the 3918 applications that have been submitted, 1941 of those applicants (50%) have completed their donor surgery.
Eleven‐Membered Fused‐Ring Low Band‐Gap Polymer with Enhanced Charge Carrier Mobility and Photovoltaic Performance
Authors: Li Yongxi , Yao Kai , Yip Hin‐Lap , Ding Fei‐Zhi , Xu Yun‐Xiang , Li Xiaosong , Chen Yu , Jen Alex K.‐Y.
Published: March 2014

A multi‐ring, ladder‐type low band‐gap polymer (PIDTCPDT‐DFBT) is developed to show enhanced light harvesting, charge transport, and photovoltaic performance. It possesses excellent planarity and enhanced effective conjugation length compared to the previously reported fused‐ring polymers. In order to understand the effect of extended fused‐ring on the electronic and optical properties of this polymer, a partially fused polymer PIDTT‐T‐DFBT is also synthesized for comparison. The fully rigidified polymer provides lower reorganizational energy, resulting in one order higher hole mobility than the reference polymer. The device made from PIDTCPDT‐DFBT also shows a quite promising power conversion efficiency of 6.46%. Its short‐circuit current (14.59 mA cm−2) is also among the highest reported for ladder‐type polymers. These results show that extending conjugation length in fused‐ring ladder polymers is an effective way to reduce band‐gap and improve charge transport for efficient photovoltaic devices.
Regio‐ and Stereoselective 1,2‐Dihydropyridine Alkylation/Addition Sequence for the Synthesis of Piperidines with Quaternary Centers
Authors: Duttwyler Simon , Chen Shuming , Lu Colin , Mercado Brandon Q. , Bergman Robert G. , Ellman Jonathan A.
Published: March 2014

The first example of C alkylation of 1,2‐dihydropyridines with alkyl triflates and Michael acceptors was developed to introduce quaternary carbon centers with high regio‐ and diastereoselectivity. Hydride or carbon nucleophile addition to the resultant iminium ion also proceeded with high diastereoselectivity. Carbon nucleophile addition results in an unprecedented level of substitution to provide piperidine rings with adjacent tetrasubstituted carbon atoms.
Effect of the crosslinking density and programming temperature on the shape fixity and shape recovery in epoxy–anhydride shape‐memory polymers
Authors: Wu Xue Lian , Kang Shu Feng , Xu Xiao Jing , Xiao Feng , Ge Xiao Lan
Published: March 2014

In addition to the fabrication of thermoset epoxy–anhydride shape‐memory polymers (SMPs), a systematic experimental investigation was conducted to characterize the crosslinking density, micromorphology, thermal properties, mechanical properties, and shape‐memory effects in the epoxy SMP system, with a focus on the influence of the crosslinking density and programming temperature on the shape‐fixity and shape‐recovery behaviors of the polymers. On the basis of the crosslinking density information determined by NMR technology, we concluded that the effect of the crosslinking density on the shape‐fixity behaviors was dependent on the programming temperature. The advantage of a nice combination of crosslinking density and programming temperature provided an effective approach to tailor the actual shape recovery within a wide range. The increasing crosslinking density significantly improved the shape‐recovery ratio, which could be further improved through a decrease in the programming, whereas the crosslinking density was more fundamental. This exploration should play an important role in the fabrication and applications of SMP materials. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40559.
Stereoselective Lewis Acid Mediated (3+2) Cycloadditions of N‐H‐ and N‐Sulfonylaziridines with Heterocumulenes
Authors: Craig Robert A. , O'Connor Nicholas R. , Goldberg Alexander F. G. , Stoltz Brian M.
Published: March 2014

Alkyl and aryl isothiocyanates and carbodiimides are effective substrates in (3+2) cycloadditions with N‐sulfonyl‐2‐substituted aziridines and 2‐phenylaziridine for the synthesis of iminothiazolidines and iminoimidazolidines. Additionally, the stereoselective (3+2) cycloaddition of N‐H‐ and N‐sulfonylaziridines with isothiocyanates can be accomplished, allowing for the synthesis of highly enantioenriched iminothiazolidines. Evidence for an intimate ion‐pair mechanism is presented herein in the context of these chemo‐, regio‐, and diastereoselective transformations. The demonstrated ability to remove the sulfonyl group from the heterocyclic products displays the utility of these compounds for further derivatization and application.
Exposure of trees to drought‐induced die‐off is defined by a common climatic threshold across different vegetation types
Authors: Mitchell Patrick J. , O'Grady Anthony P. , Hayes Keith R. , Pinkard Elizabeth A.
Published: March 2014

Increases in drought and temperature stress in forest and woodland ecosystems are thought to be responsible for the rise in episodic mortality events observed globally. However, key climatic drivers common to mortality events and the impacts of future extreme droughts on tree survival have not been evaluated. Here, we characterize climatic drivers associated with documented tree die‐off events across Australia using standardized climatic indices to represent the key dimensions of drought stress for a range of vegetation types. We identify a common probabilistic threshold associated with an increased risk of die‐off across all the sites that we examined. We show that observed die‐off events occur when water deficits and maximum temperatures are high and exist outside 98% of the observed range in drought intensity; this threshold was evident at all sites regardless of vegetation type and climate. The observed die‐off events also coincided with at least one heat wave (three consecutive days above the 90th percentile for maximum temperature), emphasizing a pivotal role of heat stress in amplifying tree die‐off and mortality processes. The joint drought intensity and maximum temperature distributions were modeled for each site to describe the co‐occurrence of both hot and dry conditions and evaluate future shifts in climatic thresholds associated with the die‐off events. Under a relatively dry and moderate warming scenario, the frequency of droughts capable of inducing significant tree die‐off across Australia could increase from 1 in 24 years to 1 in 15 years by 2050, accompanied by a doubling in the occurrence of associated heat waves. By defining commonalities in drought conditions capable of inducing tree die‐off, we show a strong interactive effect of water and high temperature stress and provide a consistent approach for assessing changes in the exposure of ecosystems to extreme drought events.
Asymmetric Synthesis of 3,4,6‐Trisubstituted 2,5‐Diketopiperazines by Using Dynamic Kinetic Resolution of α‐Bromo Tertiary Acetamides
Authors: Baek Jinho , Kang Seock Yong , Im Chan , Park Yong Sun
Published: March 2014

A new and efficient method for the asymmetric synthesis of 3,4,6‐trisubstituted 2,5‐diketopiperazines has been developed. The dynamic kinetic resolution of L‐amino‐acid‐derived α‐bromo tertiary amides in the nucleophilic substitution reaction with p‐anisidine and a subsequent deprotection‐cyclization process provides rapid access to diverse cis‐2,5‐diketopiperazines 5a–5o and proline‐containing trans‐2,5‐diketopiperazines 5p–5t in enantiomerically pure form in 45–67 % overall yields.
Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection
Authors: Kumada Hiromitsu , Suzuki Yoshiyuki , Ikeda Kenji , Toyota Joji , Karino Yoshiyasu , Chayama Kazuaki , Kawakami Yoshiiku , Ido Akio , Yamamoto Kazuhide , Takaguchi Koichi , Izumi Namiki , Koike Kazuhiko , Takehara Tetsuo , Kawada Norifumi , Sata Michio , Miyagoshi Hidetaka , Eley Timothy , McPhee Fiona , Damokosh Andrew , Ishikawa Hiroki , Hughes Eric
Published: March 2014

All-oral combinations of direct-acting antivirals may improve efficacy and safety outcomes for patients with hepatitis C virus (HCV) infection, particularly those who are poor candidates for current interferon/ribavirin-based regimens. In this open-label, phase 3 study, 135 interferon-ineligible/intolerant and 87 nonresponder patients with chronic HCV genotype 1b infection were enrolled at 24 centers in Japan. Patients received daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily for 24 weeks. The primary endpoint was sustained virologic response 24 weeks after treatment (SVR24). This study is registered with ClinicalTrials.gov (NCT01497834). SVR24 was achieved by 87.4% of interferon-ineligible/intolerant patients and 80.5% of nonresponder (null and partial) patients; rates were similar in cirrhosis (90.9%) and noncirrhosis (84.0%) patients, and in patients with IL28B CC (84.5%) or non-CC (84.8%) genotypes. Fourteen patients in each group (12.6%) discontinued dual therapy, mainly due to adverse events or lack of efficacy. Nine nonresponder patients received additional treatment with peginterferon/ribavirin per protocol-defined criteria. The rate of serious adverse events was low (5.9%) and varied among patients. The most common adverse events were nasopharyngitis, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST), headache, diarrhea, and pyrexia. Conclusion: Interferon-free, ribavirin-free all-oral therapy with daclatasvir and asunaprevir for 24 weeks is well tolerated and can achieve a high rate of SVR in patients with HCV genotype 1b who were ineligible, intolerant, or had not responded to prior interferon-based therapy. (Hepatology 2014;59:2083–2091)
A finite mixture method for outlier detection and robustness in meta‐analysis
Authors: Beath Ken J.
Published: March 2014

When performing a meta‐analysis unexplained variation above that predicted by within study variation is usually modeled by a random effect. However, in some cases, this is not sufficient to explain all the variation because of outlier or unusual studies. A previously described method is to define an outlier as a study requiring a higher random effects variance and testing each study sequentially. An extension is described where the studies are considered to be a finite mixture of outliers and non‐outliers, allowing any number of outlier studies and the use of standard mixture model techniques. The bootstrap likelihood ratio test is used to determine if there are any outliers present by comparing models with and without outliers, and the outlier studies are identified using posterior predicted probabilities. The estimation of the overall treatment effect is then determined including all observations but with the outliers down‐weighted. This has the advantage that studies that are marginal outliers are still included in the meta‐analysis but with an appropriate weighting. The method is applied to examples from meta‐analysis and meta‐regression. Copyright © 2014 John Wiley & Sons, Ltd.
MRI‐based myelin water imaging: A technical review
Authors: Alonso‐Ortiz Eva , Levesque Ives R. , Pike G. Bruce
Published: March 2014

Multiexponential T2 relaxation time measurement in the central nervous system shows a component that originates from water trapped between the lipid bilayers of myelin. This myelin water component is of significant interest as it provides a myelin‐specific MRI signal of value in assessing myelin changes in cerebral white matter in vivo. In this article, the various acquisition and analysis strategies proposed to date for myelin water imaging are reviewed and research conducted into their validity and clinical applicability is presented. Comparisons between the imaging methods are made with a discussion regarding potential difficulties and model limitations. Magn Reson Med 73:70–81, 2015. © 2014 Wiley Periodicals, Inc.
Novel patterned layer to enhance conversion efficiency of amorphous silicon thin‐film solar cells
Authors: Kim Yang Doo , Han Kang‐Soo , Shin Ju‐Hyeon , Cho Joong‐Yeon , Im Chan , Lee Heon
Published: March 2014

The substrate of an a‐Si:H solar cell with microscale surface roughness generally shows high diffuse transmittance; however, it also has detrimental effects, including low open‐circuit voltage and fill factor (FF). We applied planarization to the rough surface using spin‐coating of ZnO nanoparticles dispersed in an ethanol‐based solution. The resulting conversion efficiency of the solar cell increased by ∼18% owing to the higher open‐circuit voltage and FF, with a small decrease in the diffused transmittance.
The Risk Management of Minimum Return Guarantees
Authors: Mahayni Antje , Schlögl Erik
Published: March 2014

Contracts paying a guaranteed minimum rate of return and a fraction of a positive excess rate, which is specified relative to a benchmark portfolio, are closely related to unit-linked life-insurance products and can be considered as alternatives to direct investment in the underlying benchmark. They contain an embedded power option, and the key issue is the tractable and realistic hedging of this option, in order to rigorously justify valuation by arbitrage arguments and prevent the guarantees from becoming uncontrollable liabilities to the issuer. We show how to determine the contract parameters conservatively and implement robust risk-management strategies.
They’re Natural and Everywhere: How Evaluative Practices Permeate the Organization
Authors: Maier Florentine , Brandl Julia
Published: March 2014

How do evaluative practices become natural and ubiquitous in an organization? In this paper we integrate findings from previous empirical work on the adoption of evaluative practices in organizations with insights from institutional theory and social psychology research for advancing the understanding of possible states of evaluative practices within organizations and the processes through which organizations become permeated by evaluative practices. Our conceptual model suggests that once evaluative practices have gained a foothold in an organization, they tend to be applied to an increasing number of organizational problems and become taken for granted.