Peritoneal dialysis (PD)-related peritonitis carries high morbidity for PD patients. Understanding the characteristics and risk factors for peritonitis can guide regional development of prevention ...strategies. We describe peritonitis rates and the associations of selected facility practices with peritonitis risk among countries participating in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS).
Observational prospective cohort study.
7,051 adult PD patients in 209 facilities across 7 countries (Australia, New Zealand, Canada, Japan, Thailand, United Kingdom, United States).
Facility characteristics (census count, facility age, nurse to patient ratio) and selected facility practices (use of automated PD, use of icodextrin or biocompatible PD solutions, antibiotic prophylaxis strategies, duration of PD training).
Peritonitis rate (by country, overall and variation across facilities), microbiology patterns.
Poisson rate estimation, proportional rate models adjusted for selected patient case-mix variables.
2,272 peritonitis episodes were identified in 7,051 patients (crude rate, 0.28 episodes/patient-year). Facility peritonitis rates were variable within each country and exceeded 0.50/patient-year in 10% of facilities. Overall peritonitis rates, in episodes per patient-year, were 0.40 (95% CI, 0.36-0.46) in Thailand, 0.38 (95% CI, 0.32-0.46) in the United Kingdom, 0.35 (95% CI, 0.30-0.40) in Australia/New Zealand, 0.29 (95% CI, 0.26-0.32) in Canada, 0.27 (95% CI, 0.25-0.30) in Japan, and 0.26 (95% CI, 0.24-0.27) in the United States. The microbiology of peritonitis was similar across countries, except in Thailand, where Gram-negative infections and culture-negative peritonitis were more common. Facility size was positively associated with risk for peritonitis in Japan (rate ratio RR per 10 patients, 1.07; 95% CI, 1.04-1.09). Lower peritonitis risk was observed in facilities that had higher automated PD use (RR per 10 percentage points greater, 0.95; 95% CI, 0.91-1.00), facilities that used antibiotics at catheter insertion (RR, 0.83; 95% CI, 0.69-0.99), and facilities with PD training duration of 6 or more (vs <6) days (RR, 0.81; 95% CI, 0.68-0.96). Lower peritonitis risk was seen in facilities that used topical exit-site mupirocin or aminoglycoside ointment, but this association did not achieve conventional levels of statistical significance (RR, 0.79; 95% CI, 0.62-1.01).
Sampling variation, selection bias (rate estimates), and residual confounding (associations).
Important international differences exist in the risk for peritonitis that may result from varied and potentially modifiable treatment practices. These findings may inform future guidelines in potentially setting lower maximally acceptable peritonitis rates.
Display omitted
The role of the T cell in asthma Robinson, Douglas S., MD, FRCP
Journal of allergy and clinical immunology,
12/2010, Letnik:
126, Številka:
6
Journal Article
Recenzirano
Since the initial detection of TH 2 cytokines in asthmatic airways, our understanding of the complexity of T-cell subtypes and flexibility and of the potential role of airway structural cells in the ...immunopathology of asthma has increased. Cytokines derived from airway epithelium, including IL-25, IL-33, and thymic stromal lymphopoietin, might be important drivers of TH 2-type inflammation in asthma. The balance between effector TH 2 cells and suppressive regulatory T cells is skewed toward a proinflammatory TH 2 response in atopy and asthma, and there is much interest in how to redress this equilibrium. Novel T-cell subsets, including TH 17, TH 9, and TH 22, have been described, although their role in asthma remains unclear. Other T cells, including natural killer T cells, γδ T cells, and CD8 T cells, have also been implicated in asthma, although their importance remains to be confirmed. Therapeutic strategies aimed at TH 2 cytokines are beginning to bear fruit in patients with asthma, although like many biologic agents, these might need specific targeting at subgroups of patients. Strategies directed specifically at the T cells are currently being evaluated, including novel forms of allergen immunotherapy. T cells remain an exciting potential target for new treatments in patients with asthma.
Upper tract urothelial carcinoma (UTUC) is characterized by a distinctly aggressive clinical phenotype. To define the biological features driving this phenotype, we performed an integrated analysis ...of whole-exome and RNA sequencing of UTUC. Here we report several key insights from our molecular dissection of this disease: 1) Most UTUCs are luminal-papillary; 2) UTUC has a T-cell depleted immune contexture; 3) High FGFR3 expression is enriched in UTUC and correlates with its T-cell depleted immune microenvironment; 4) Sporadic UTUC is characterized by a lower total mutational burden than urothelial carcinoma of the bladder. Our findings lay the foundation for a deeper understanding of UTUC biology and provide a rationale for the development of UTUC-specific treatment strategies.
Background There is limited information about the clinical and prognostic significance of patient-reported recovery time. Study Design Prospective cohort study. Setting & Participants 6,040 patients ...in the DOPPS (Dialysis Outcomes and Practice Patterns Study). Predictor Answer to question “How long does it take you to recover from a dialysis session?” categorized as follows: fewer than 2, 2-6, 7-12, or longer than 12 hours. Outcomes & Measurements Cross-sectional and longitudinal associations between recovery time and patient characteristics, hemodialysis treatment variables, health-related quality of life (HRQoL), and hospitalization and mortality. Results 32% reported recovery time shorter than 2 hours; 41%, 2-6 hours; 17%, 7-12 hours; and 10%, longer than 12 hours. Using proportional odds (ordinal) logistic regression, shorter recovery time was associated with male sex, full-time employment, and higher serum albumin level. Longer recovery time was associated with older age, dialysis vintage, body mass index, diabetes, and psychiatric disorder. Greater intradialytic weight loss, longer dialysis session length, and lower dialysate sodium concentration were associated with longer recovery time. In facilities that used uniform dialysate sodium concentrations for ≥90% of patients, the adjusted OR of longer recovery time, comparing dialysate sodium concentration < 140 vs 140 mEq/L, was 1.72 (95% CI, 1.37-2.16). Recovery time was correlated positively with symptoms of kidney failure and kidney disease burden score and inversely with HRQoL mental and physical component summary scores. Using Cox regression, adjusting for potential confounders not influenced by recovery time, it was associated positively with first hospitalization and mortality (adjusted HRs for recovery time > 12 vs 2-6 hours 1.22 95% CI, 1.09-1.37 and 1.47 95% CI, 1.19-1.83, respectively). Limitations Answers are subjective and not supported by physiologic measurements. Conclusions Recovery time can be used to identify patients with poorer HRQoL and higher risks of hospitalization and mortality. Interventions to reduce recovery time and possibly improve clinical outcomes, such as increasing dialysate sodium concentration, need to be tested in randomized trials.
Background Poor nutritional status and both hyper- and hypophosphatemia are associated with increased mortality in maintenance hemodialysis (HD) patients. We assessed associations of phosphate binder ...prescription with survival and indicators of nutritional status in maintenance HD patients. Study Design Prospective cohort study (DOPPS Dialysis Outcomes and Practice Patterns Study), 1996-2008. Setting & Participants 23,898 maintenance HD patients at 923 facilities in 12 countries. Predictors Patient-level phosphate binder prescription and case-mix–adjusted facility percentage of phosphate binder prescription using an instrumental-variable analysis. Outcome All-cause mortality. Results Overall, 88% of patients were prescribed phosphate binders. Distributions of age, comorbid conditions, and other characteristics showed small differences between facilities with higher and lower percentages of phosphate binder prescription. Patient-level phosphate binder prescription was associated strongly at baseline with indicators of better nutrition, ie, higher values for serum creatinine, albumin, normalized protein catabolic rate, and body mass index and absence of cachectic appearance. Overall, patients prescribed phosphate binders had 25% lower mortality (HR, 0.75; 95% CI, 0.68-0.83) when adjusted for serum phosphorus level and other covariates; further adjustment for nutritional indicators attenuated this association (HR, 0.88; 95% CI, 0.80-0.97). However, this inverse association was observed for only patients with serum phosphorus levels ≥3.5 mg/dL. In the instrumental-variable analysis, case-mix–adjusted facility percentage of phosphate binder prescription (range, 23%-100%) was associated positively with better nutritional status and inversely with mortality (HR for 10% more phosphate binders, 0.93; 95% CI, 0.89-0.96). Further adjustment for nutritional indicators reduced this association to an HR of 0.95 (95% CI, 0.92-0.99). Limitations Results were based on phosphate binder prescription; phosphate binder and nutritional data were cross-sectional; dietary restriction was not assessed; observational design limits causal inference due to possible residual confounding. Conclusions Longer survival and better nutritional status were observed for maintenance HD patients prescribed phosphate binders and in facilities with a greater percentage of phosphate binder prescription. Understanding the mechanisms for explaining this effect and ruling out possible residual confounding require additional research.
Background CD4+ CD25+ regulatory T cells can inhibit excessive T-cell responses in vivo . We have previously demonstrated that prophylactic administration of CD4+ CD25+ regulatory T cells suppresses ...the development of acute allergen-induced airway inflammation in vivo. Objective We sought to determine the effect of therapeutic transfer of CD4+ CD25+ regulatory T cells on established pulmonary inflammation and the subsequent development of airway remodeling. Methods CD4+ CD25+ cells were transferred after the onset of allergic inflammation, and airway challenges were continued to induce chronic inflammation and airway remodeling. Results Administration of CD4+ CD25+ regulatory T cells reduced established lung eosinophilia, TH 2 infiltration, and expression of IL-5, IL-13, and TGF-β. Moreover, subsequent mucus hypersecretion and peribronchial collagen deposition were reduced after prolonged challenge. In contrast, transfer of CD4+ CD25+ regulatory T cells had no effect on established airway hyperreactivity either 7 days or 4 weeks after transfer. Conclusions In this study we demonstrate for the first time that therapeutic transfer of CD4+ CD25+ regulatory T cells can resolve features of chronic allergen-induced inflammation and prevent development of airway remodeling.
Sudden death is common in hemodialysis patients, but whether modifiable practices affect the risk of sudden death remains unclear.
This study analyzed 37,765 participants in 12 countries in the ...Dialysis Outcomes and Practice Patterns Study to explore the association of the following practices with sudden death (due to cardiac arrhythmia, cardiac arrest, and/or hyperkalemia): treatment time TT <210 minutes, Kt/V <1.2, ultrafiltration volume >5.7% of postdialysis weight, low dialysate potassium K(D) <3), and prescription of Q wave/T wave interval-prolonging drugs. Cox regression was used to estimate effects on mortality, adjusting for potential confounders. An instrumental variable approach was used to further control for unmeasured patient-level confounding.
There were 9046 deaths, 26% of which were sudden (crude mortality rate, 15.3/100 patient-years; median follow-up, 1.59 years). Associations with sudden death included hazard ratios of 1.13 for short TT, 1.15 for large ultrafiltration volume, and 1.10 for low Kt/V. Compared with K(D) ≥3 mEq/L, the sudden death rate was higher for K(D) ≤1.5 and K(D)=2-2.5 mEq/L. The instrumental variable approach yielded generally consistent findings. The sudden death rate was elevated for patients taking amiodarone, but not other Q wave/T wave interval-prolonging drugs.
This study identified modifiable dialysis practices associated with higher risk of sudden death, including short TT, large ultrafiltration volume, and low K(D). Because K(D) <3 mEq/L is common and easy to change, K(D) tailoring may prevent some sudden deaths. This hypothesis merits testing in clinical trials.
Asthma treatment guidelines recommend increasing corticosteroid dose to control symptoms and reduce exacerbations. This approach is potentially flawed because symptomatic asthma can occur without ...corticosteroid responsive type-2 (T2)-driven eosinophilic inflammation, and inappropriately high-dose corticosteroid treatment might have little therapeutic benefit with increased risk of side-effects. We compared a biomarker strategy to adjust corticosteroid dose using a composite score of T2 biomarkers (fractional exhaled nitric oxide FENO, blood eosinophils, and serum periostin) with a standardised symptom–risk-based algorithm (control).
We did a single-blind, parallel group, randomised controlled trial in adults (18–80 years of age) with severe asthma (at treatment steps 4 and 5 of the Global Initiative for Asthma) and FENO of less than 45 parts per billion at 12 specialist severe asthma centres across England, Scotland, and Northern Ireland. Patients were randomly assigned (4:1) to either the biomarker strategy group or the control group by an online electronic case-report form, in blocks of ten, stratified by asthma control and use of rescue systemic steroids in the previous year. Patients were masked to study group allocation throughout the entirety of the study. Patients attended clinic every 8 weeks, with treatment adjustment following automated treatment-group-specific algorithms: those in the biomarker strategy group received a default advisory to maintain treatment and those in the control group had their treatment adjusted according to the steps indicated by the trial algorithm. The primary outcome was the proportion of patients with corticosteroid dose reduction at week 48, in the intention-to-treat (ITT) population. Secondary outcomes were inhaled corticosteroid (ICS) dose at the end of the study; cumulative dose of ICS during the study; proportion of patients on maintenance oral corticosteroids (OCS) at study end; rate of protocol-defined severe exacerbations per patient year; time to first severe exacerbation; number of hospital admissions for asthma; changes in lung function, Asthma Control Questionnaire-7 score, Asthma Quality of Life Questionnaire score, and T2 biomarkers from baseline to week 48; and whether patients declined to progress to OCS. A secondary aim of our study was to establish the proportion of patients with severe asthma in whom T2 biomarkers remained low when corticosteroid therapy was decreased to a minimum ICS dose. This study is registered with ClinicalTrials.gov, NCT02717689 and has been completed.
Patients were recruited from Jan 8, 2016, to July 12, 2018. Of 549 patients assessed, 301 patients were included in the ITT population and were randomly assigned to the biomarker strategy group (n=240) or to the control group (n=61). 28·4% of patients in the biomarker strategy group were on a lower corticosteroid dose at week 48 compared with 18·5% of patients in the control group (adjusted odds ratio aOR 1·71 95% CI 0·80–3·63; p=0·17). In the per-protocol (PP) population (n=121), a significantly greater proportion of patients were on a lower corticosteroid dose at week 48 in the biomarker strategy group (30·7% of patients) compared with the control group (5·0% of patients; aOR 11·48 95% CI 1·35–97·83; p=0·026). Patient choice to not follow treatment advice was the principle reason for loss to PP analysis. There was no difference in secondary outcomes between study groups and no loss of asthma control among patients in the biomarker strategy group who reduced their corticosteroid dose.
Biomarker-based corticosteroid adjustment did not result in a greater proportion of patients reducing corticosteroid dose versus control. Understanding the reasons for patients not following treatment advice in both treatment strategies is an important area for future research. The prevalence of T2 biomarker-low severe asthma was low.
This study was funded, in part, by the Medical Research Council UK.
PDF
