A disintegrin and metalloprotease (ADAM) 33 protein in patients with pulmonary sarcoidosis

Background and objective: A disintegrin and metalloproteinase (ADAM) 33 is a susceptibility gene associated with inflammatory lung and skin diseases. It is selectively expressed in mesenchymal cells, and its metalloprotease activity has been linked to angiogenesis and tissue remodelling. A soluble form of ADAM33 (sADAM33) has been identified in the bronchoalveolar lavage fluid (BALF) of asthmatic patients, and its levels inversely correlate with lung function. Because of its association with inflammatory lung diseases, it was hypothesized that sADAM33 is elevated in BALF of patients with pulmonary sarcoidosis. Methods: After removal of Ig using Protein A/G and enrichment using Concanavalin A beads, sADAM33 was identified in BALF by Western blotting. A fluorescence resonance energy transfer peptide cleavage assay was used to assess ADAM33‐like activity in BALF. Results: sADAM33 protein in BALF was detected as a 25 kDa fragment, and levels were significantly increased in samples from sarcoid patients when compared to healthy controls (P < 0.05). Levels of sADAM33 were inversely correlated with lung function (FVC%) (P < 0.05) and DL_CO % predicted (P < 0.01). No difference in sADAM33 enzymatic activity was observed between healthy and sarcoid BALF samples. Conclusions: Release of sADAM33 is increased in sarcoid and may be associated with abnormal lung function. sADAM33 may be a biomarker of lung tissue inflammation and remodelling in sarcoid.     

不同置管方式用于股神经阻滞术后镇痛的效果

目的 采用连续刺激导管进行股神经置管,比较膝关节镜术后不同置管方法的镇痛效果.方法 选择择期行膝关节镜手术患者80例,随机均分为股神经刺激器引导置管组(RA组)和传统经验置管组(RT组).两组均采用1.73％碳酸利多卡因连续硬膜外维持术中麻醉,麻醉后置入连续股神经阻滞导管.两组术后经导管持续输注0.2％罗哌卡因5 ml/h.观察并记录术后2、6、24、48 h静息VAS评分、患者满意度、不良反应及伍用镇痛药情况.结果 术后2、6hRA组静息VAS评分明显低于RT组(P＜0.01).术后24 h和48 h两组静息VAS评分均低于3分,差异无统计学意义.两组患者术后均未出现头痛、恶心、呕吐、尿潴留等不良反应.结论 膝关节镜术后2、6 h神经刺激器引导置管较传统经验置管静息镇痛效果明显改善,但术后24、48 h镇痛效果无显著差别.     

The role of duloxetine in stress urinary incontinence: a systematic review and meta-analysis

Objectives

This systematic review determined whether the duloxetine can get more benefits versus placebo in managing women with stress urinary incontinence (SUI) all over the world.

Methods

We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing duloxetine with placebo in these patients. The eligible RCTs were identified from the following electronic databases: Cochrane CENTRAL, Medline and EMBASE. We treated the incontinence episode frequency (IEF) as the main outcome, and the secondary outcomes were cured, average voiding interval, incontinence quality of life (I-QOL), treatment-emergent adverse events (TEAEs) and discontinuation.

Results

The review contained ten trials including 5,738 women who were randomized to take duloxetine or placebo. All arms in individual trials were comparable for various baseline characteristics. Individual studies showed a significantly greater decrease in IEF than placebo group. The total IEF responders (defined as a woman who had at least a 50 % decrease in IEF with treatment) within the duloxetine-treated women were more than the placebo-treated women (52.5 vs. 33.7 %; RR = 1.56; 95 %CI, 1.46–1.66; p < 0.00001). TEAEs were commonly experienced by both two groups (62.7 vs. 45.3 %) though they were not critical.

Authors’ conclusions

Our meta-analysis showed that significant efficacy can be found in women treated with a certain dose of duloxetine. The adverse events like nausea, constipation, dry mouth, fatigue etc. are common.     

Associations of Frequency and Duration of Patient-Doctor Contact in Hemodialysis Facilities with Mortality

It is unknown whether regular patient-doctor contact (PDC) contributes to better outcomes for patients undergoing hemodialysis. Here, we analyzed the associations between frequency and duration of PDC during hemodialysis treatments with clinical outcomes among 24,498 patients from 778 facilities in the international Dialysis Outcomes and Practice Patterns Study (DOPPS). The typical facility PDC frequency, estimated by facility personnel, was high (more than once per week) for 55% of facilities, intermediate (once per week) for 24%, and low (less than once per week) for 21%. The mean ± SD estimated duration of a typical interaction between patient and physician was 7.7±5.6 minutes. PDC frequency and duration varied across DOPPS phases and countries; the proportion of facilities with high PDC frequency was 17% in the United States and 73% across the other countries. Compared with high PDC frequency, the adjusted hazard ratio (HR) for all-cause mortality was 1.06 (95% confidence interval [CI], 0.96 to 1.17) for intermediate PDC frequency and 1.11 (95% CI, 1.01 to 1.23) for low PDC frequency (P=0.03 for trend). Furthermore, each 5-minutes-shorter duration of PDC was associated with a 5% higher risk for death, on average (HR, 1.05; 95% CI, 1.01 to 1.09), adjusted for PDC frequency and other covariates. Multivariable analyses also suggested modest inverse associations between both PDC frequency and duration with hospitalization but not with kidney transplantation. Taken together, these results suggest that policies supporting more frequent and longer duration of PDC may improve patient outcomes in hemodialysis.Although maintenance hemodialysis (HD) saves lives, survival of patients with ESRD remains poor and is much worse than for the general population.¹ HD facilities differ with respect to provision of important clinical practices;^2,3 among these, differences in patterns of dialysis unit staffing might influence mortality.^4,5 HD patients usually receive thrice-weekly dialysis provided by a multidisciplinary team of health care professionals (doctors, nurses, technicians, dietitians, and social workers). As part of this team, the physician’s role in improving the quality of chronic disease care is considered crucial.^6,7Many health care providers and researchers believe that more frequent and longer patient-doctor contact (PDC) in HD care may improve patient outcomes because it provides physicians with greater opportunity to monitor treatments; enhance communication and build trust with the patient; and detect, prevent, and treat new medical problems.^2,5,8 However, the actual frequency and duration of PDC for HD care have not been reported in many countries, and there is little direct evidence that more frequent and longer PDC contributes to better patient health outcomes. Previous studies from the United States showed that less frequent PDC was associated with lower patient satisfaction, lower patient adherence, lower patient achievement of clinical performance targets, and higher hospitalization, but more frequent PDC was not necessarily related to longer patient survival.^8–10 A recent study based on data from the U.S. Renal Data System (USRDS) also reported no difference in survival for PDC frequency of <4 times per month compared with 4 times per month.¹⁰ However, the study was limited to one country and was unable to evaluate differences in outcomes between 4 times per month and >4 times per month because of limitations of the billing codes and relatively low proportion of high PDC frequency in the United States.This study examined the estimated typical frequency and duration of PDC that occurs at the time of HD treatments and its associations with all-cause mortality as a primary outcome among participants in the Dialysis Outcomes and Practice Patterns Study (DOPPS), an international prospective cohort study of HD patients and facilities. PDC was studied at the facility level, reducing the opportunity for patient-level confounding by indication in this international cohort. Among such patients, a high PDC frequency (>4 times per month) is much more common outside of than in the United States. We also examined the associations of PDC frequency and duration with first hospitalization and kidney transplantation as secondary outcomes. A better understanding of the effect of PDC intensity could have implications for health policy in addition to improving health care delivery and HD patient outcomes.