Constipation is the most common GI symptom in patients with diabetes mellitus (DM). Importantly, patients with constipation have lower health-related quality of life than those without constipation. ...Effective therapies for constipation are limited and there is a paucity of data evaluating the treatment of constipation in diabetics.
Diabetic patients with chronic idiopathic constipation (CIC) as defined by Rome III criteria were recruited from outpatient clinics at a tertiary-care center and a Veterans Administration Hospital. Demographic data, baseline stool patterns, and a constipation-specific quality of life survey (Patient Assessment of Constipation Quality of Life (PAC-QOL)) were obtained. Baseline colonic transit time (CTT) was evaluated utilizing the wireless motility capsule. Patients were randomized in a double-blind fashion to 48 mcg per day lubiprostone or placebo for 8 weeks. The primary end point measured was the difference in number of spontaneous bowel movements (SBMs) per week vs. baseline for each group at each week after initiation of therapy. Secondary end points included changes in CTT after 4 weeks of therapy, PAC-QOL after 8 weeks of therapy, and changes from baseline in associated gastrointestinal (GI) symptoms as well as need for rescue medication at 2, 4, and 8 weeks.
Seventy-six patients (mean age, 56.9±9.1 years, 62% females) were randomized. There were no significant differences between the two groups' baseline data or demographics. During the 8-week treatment period, patients in the lubiprostone group experienced an average of 1.83±0.80 (P=0.02) more SBMs per week than those in the placebo group as compared with baseline. The duration of CTT at Week 4 was shorter by an average of 13 h compared with baseline in the lubiprostone group, and was prolonged by an average of 7 h compared with baseline in the placebo group, leading to a treatment effect of 20.3±7.3 h (P=0.006). PAC-QOL improved in both the groups; however, there was no significant difference between the groups. There was no difference in associated GI symptoms and need for rescue medication between the two groups after 8 weeks. There were no serious adverse events reported during the study.
This study suggests that lubiprostone is a safe and effective treatment for increasing weekly SBMs and decreasing CTT in patients with DM and CIC.
Objective
To estimate the relative risk of incident cancer diagnosis among patients with juvenile idiopathic arthritis (JIA) compared to patients without JIA.
Methods
A cohort of biologics‐naive ...patients diagnosed with JIA between 1998 and 2007 and a matched cohort of comparators without JIA were assembled from the PharMetrics Patient‐Centric Database. The primary outcome was any incident malignancy, excluding nonmelanoma skin cancer and carcinoma in situ. Claims profiles of patients with any cancer‐related diagnosis codes were reviewed to determine outcomes. Incidence rates and 95% confidence intervals (95% CIs) of cancer were calculated and compared between cohorts using Cox proportional hazards regression. Standardized incidence ratios (SIRs) for each cohort compared to the general population were calculated using reference rates from the US Surveillance, Epidemiology, and End‐Results (SEER) program.
Results
The JIA and non‐JIA cohorts included 3,605 and 37,689 patients, respectively, with a mean age of 11 years. The incidence rates of cancer were 67.0 (95% CI 1.3–132.5) cases/100,000 person‐years (PY) for JIA and 23.2 (95% CI 12.2–34.2) cases/100,000 PY for non‐JIA. The risk of cancer associated with biologics‐naive JIA was elevated (hazard ratio 2.8, 95% CI 0.9–8.3). The JIA cohort had a significantly elevated SIR of 4.0 (95% CI 2.6–6.0); the non‐JIA cohort SIR was not significantly above SEER rates (SIR 1.4, 95% CI 0.6–2.6).
Conclusion
We found a nearly 3‐fold increased risk of cancer in biologics‐naive JIA patients, which approached significance despite the small number of outcomes. This finding suggests an elevated underlying risk of cancer in this disease population.
Immune checkpoint inhibitors (ICIs) have shown significant efficacy in patients with various malignancies, however, they are associated with a wide range of immune-related toxicities affecting many ...organs, including the liver. Immune-mediated liver injury caused by checkpoint inhibitors (ILICI) is a distinctive form of drug induced liver injury (DILI), that differs from most DILI types in presumed underlying mechanism, incidence, and response to therapeutic interventions. Despite increased awareness of ILICI and other immune-related adverse effects of ICIs reflected by recent guidelines for their management in post marketing clinical practice, there is lack of uniform best practices to address ILICI risk during drug development. As efforts to develop safer and more effective ICIs for additional indications grow, and as combination therapies including ICIs are increasingly investigated, there is a growing need for consistent practices for ILICI in drug development. This publication summarizes current best practices to optimize the monitoring, diagnosis, assessment, and management of suspected ILICI in clinical trials using ICI as a single agent and in combination with other ICIs or other oncological agents. It is one of several publications developed by the IQ DILI Initiative in collaboration with DILI experts from academia and regulatory agencies. Recommended best practices are outlined pertaining to hepatic inclusion and exclusion criteria, monitoring of liver tests, ILICI detection, approach to a suspected ILICI signal, causality assessment, hepatic discontinuation rules and additional medical treatment.
•Immune-mediated liver injury caused by checkpoint inhibitors is a distinctive type of drug induced liver injury.•There is lack of uniform recommendations regarding the approach to this type of liver injury during drug development.•There is a growing need for consistent practices for immune-mediated liver injury in drug development.•This paper offers recommendations based on published data and consensus among experts from academia, FDA and drug industry.•These best practices optimize the detection, monitoring, and management of immune-mediated liver injury in clinical trials.
Denitrification in Alluvial Wetlands in an Urban Landscape Harrison, Melanie D.; Groffman, Peter M.; Mayer, Paul M. ...
Journal of environmental quality,
March 2011, 2011 Mar-Apr, 2011-03-00, 20110301, Letnik:
40, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Riparian wetlands have been shown to be effective “sinks” for nitrate N (NO3−), minimizing the downstream export of N to streams and coastal water bodies. However, the vast majority of riparian ...denitrification research has been in agricultural and forested watersheds, with relatively little work on riparian wetland function in urban watersheds. We investigated the variation and magnitude of denitrification in three constructed and two relict oxbow urban wetlands, and in two forested reference wetlands in the Baltimore metropolitan area. Denitrification rates in wetland sediments were measured with a 15N‐enriched NO3− “push–pull” groundwater tracer method during the summer and winter of 2008. Mean denitrification rates did not differ among the wetland types and ranged from 147 ± 29 μg N kg soil−1 d−1 in constructed stormwater wetlands to 100 ± 11 μg N kg soil−1 d−1 in relict oxbows to 106 ± 32 μg N kg soil−1 d−1 in forested reference wetlands. High denitrification rates were observed in both summer and winter, suggesting that these wetlands are sinks for NO3− year round. Comparison of denitrification rates with NO3− standing stocks in the wetland water column and stream NO3− loads indicated that mass removal of NO3− in urban wetland sediments by denitrification could be substantial. Our results suggest that urban wetlands have the potential to reduce NO3− in urban landscapes and should be considered as a means to manage N in urban watersheds.
Objective
The Effects of Youngsters’ Eyesight on Quality of Life (EYE‐Q) is a novel measure of vision‐related quality of life (QOL) and function in children. We aim to determine the validity of the ...EYE‐Q in childhood uveitis.
Methods
We ed medical record data on arthritis and uveitis in a convenience sample of children with juvenile idiopathic arthritis (JIA) and/or uveitis. In addition to the EYE‐Q, parents and patients completed questionnaires on overall QOL (Pediatric Quality of Life Inventory PedsQL), and physical functioning (Childhood Health Assessment Questionnaire C‐HAQ).
Results
Among 57 children (8 JIA, 24 JIA and uveitis, 25 uveitis alone), 102 ocular examinations were performed within 1 month of completing questionnaires. Uveitis patients had bilateral disease (69%), anterior involvement (78%), synechiae (51%), and cataracts (49%). Children with vision loss in their better eye (visual acuity VA 20/50 or worse) had worse EYE‐Q (P = 0.006) and PedsQL (P = 0.028) scores, but not C‐HAQ scores. The EYE‐Q moderately correlated with logMAR VA (rs = −0.43), PedsQL (rs = 0.43), and C‐HAQ (rs = −0.45), but was not correlated with anterior chamber cells or intraocular pressure. The PedsQL and C‐HAQ did not correlate with VA or cells. There were strong correlations between the parent and child EYE‐Q (rs = 0.62). Cronbach's α for the child report was 0.91. The EYE‐Q had strong test–retest reliability (rs = 0.75).
Conclusion
The EYE‐Q may be an important tool in the assessment of visual outcomes in childhood uveitis and an improvement over general measures in detecting changes in vision‐related function.
Geomorphic spatial heterogeneity affects sediment denitrification, an anaerobic microbial process that results in the loss of nitrogen (N), and other anaerobic microbial processes such as ...methanogenesis in urban streams. We measured sediment denitrification potential (DEA), net nitrification, methanogenesis, and a suite of ancillary microbial variables in geomorphic stream features (organic debris dams, pools, riffles, and sloughs) in forested, urban degraded and urban restored streams in the Baltimore, MD, USA metropolitan area, between June 2005 and November 2006. DEA was higher in organic debris dams (2783
±
1405
ng
N
g
−1
h
−1, mean
±
standard error) than in pools (505
±
144), riffles (360
±
78), and sloughs (270
±
106), and was higher in forest (1439
±
613) than in urban degraded (442
±
98) and restored sites (391
±
116), but the differences were not statistically significant. DEA was positively related to microbial biomass N (MBN) (
p
<
0.0001) and percent sediment organic matter (SOM) (
p
=
0.006). DEA and MBN were significantly higher in June 2005 and August 2006 than in November 2006, a temporal pattern that may have been driven by changes in microbial biomass. Methanogenesis was active in all stream geomorphic features across all study sites. Reach scale estimates of nitrification ranged from 157 to 344
mg
N
m
−2
d
−1 and were similar to reach scale DEA rates (97–230
mg
N
m
−2
d
−1), with no significant differences between restored and unrestored reaches. These results suggest that in-stream geomorphic features in urban restored and degraded sites have the potential to function as N sinks by maintaining anaerobic conditions and microbial biomass and activity that stimulate denitrification.
A ¹⁵N-tracer method was used to quantify nitrogen (N) removal processes in two relict oxbow wetlands located adjacent to the Minebank Run restored stream reach in Baltimore County (Maryland, USA) ...during summer 2009 and early spring 2010. A mass-balance approach was used to directly determine the flow of ¹⁵NO₃ ⁻ to plants, algae, and sediments, with unaccounted for ¹⁵N assumed to be denitrified. During the summer, plant and algal uptake accounted for 42%, of the added ¹⁵NO₃ ⁻ in oxbow 1, less than 1% remained in the water column and 57% was unaccounted for. In oxbow 2 during the summer, plant and algal uptake accounted for 63% of the added ¹⁵NO₃ ⁻, with <1% remaining in the water column and 38% unaccounted for. During the early spring, plant and algal uptake were much lower in both oxbows, ranging from 0.05 to 13.3% of the ¹⁵N added, with 97 and 87% was unaccounted for in oxbow 1 and 2, respectively. The amount of unaccounted for ¹⁵N was equivalent to estimated areal denitrification rates of 12 and 6 mg N m⁻² d⁻¹ in the summer and 78 and 15 mg N m⁻² d⁻¹ in the spring, in oxbow 1 and oxbow 2, respectively. However, the uncertainty of these estimates is high as it was difficult to detect accumulation of ¹⁵N in the sediments which could have accounted for a very large percentage of the added ¹⁵N. Our results suggest that the two relict oxbow wetlands are sinks for NO₃ ⁻ during both summer and spring but that the pathways of removal vary with plants and algae playing a major role in summer but not in spring.
Objective
To determine the validity and reliability of a novel questionnaire to measure vision‐related quality of life (VRQOL) in children ages 8–18 years for use in juvenile idiopathic arthritis ...(JIA)–associated uveitis: the Effects of Youngsters' Eyesight on Quality of Life (EYE‐Q).
Methods
Several steps validated the EYE‐Q. We interviewed experts and children on how vision affects a child's activities. We developed new items and selected relevant items from existing instruments. We administered initial versions of the EYE‐Q to normal‐sighted children and those with JIA‐associated uveitis. For this study, children with various (or no) ocular conditions were recruited from a clinical population. Visual acuity and contrast sensitivity were performed, and the EYE‐Q and Pediatric Quality of Life Inventory (PedsQL) were administered. The EYE‐Q was repeated 10 days later. Patients, parents, and physicians rated vision severity.
Results
Of 120 patients, 48% were female, 46.7% had no visual impairment, and 53.3% had bilateral eye involvement. The mean age was 11.3 years. There were significant differences in the measures based on visual acuity (P < 0.001). Children with more severe visual acuity and bilateral eye involvement had worse EYE‐Q scores (P < 0.001). There were significant associations between the EYE‐Q and PedsQL (r = 0.375), repeat EYE‐Q (r = 0.864), and clinical measures of ocular disease (r = −0.620).
Conclusions
Our study provides evidence of the validity and reliability of the EYE‐Q in the measurement of VRQOL. The EYE‐Q may complement clinical measures of visual impairment and overall QOL and become an important tool in the assessment of QOL in JIA‐associated uveitis.
Management of neuropsychiatric lupus Hanly, John G.; Harrison, Melanie J.
Best practice & research. Clinical rheumatology,
10/2005, Letnik:
19, Številka:
5
Journal Article
Recenzirano
Nervous system disease in systemic lupus erythematosus (SLE) is manifested by a wide variety of clinical manifestations. Despite the development of a universal classification for neuropsychiatric ...(NP) lupus in 1999, there continues to be considerable variability in the reported prevalence of NP syndromes between different lupus cohorts. Due to the lack of specificity of individual NP manifestations, non-SLE causes such as complications of therapy and co-morbidities must be considered in advance of attributing the event to one or more primary immunopathogenic mechanisms. These include intracranial microangiopathy, autoantibodies to neuronal and non-neuronal antigens, and the generation of proinflammatory cytokines and mediators. The diagnosis of NP-SLE remains largely one of exclusion and is approached in individual patients by thorough clinical evaluation, supported when necessary by autoantibody profiles, diagnostic imaging, electrophysiologic studies and objective assessment of cognitive performance. Given the diversity in clinical manifestations, the management is tailored to the specific needs of individual patients. In the absence of controlled studies, the use of symptomatic therapies, immunosuppressives, anticoagulants and non-pharmacologic interventions is supported by case series and clinical experience.
PDF
