Blood Pressure Lowering and Risk of Mortality in Chronic Kidney Disease: A Meta2 Analysis of Randomized Controlled Trials

Importance: Trials in hypertensive patients demonstrate that intensive blood pressure (BP) lowering reduces risk of cardiovascular disease (CVD) and all-cause mortality, but may increase risk of chronic kidney disease (CKD) incidence and progression. Whether intensive BP lowering is associated with a mortality benefit in patients with prevalent CKD remains unknown. Objective: We conducted a meta-analysis of Randomized controlled trials (RCTs) to determine if more intensive, compared with a less intensive, BP control is associated with reduced mortality risk in persons with CKD stages 3-5. Data Sources: Ovid Medline, Cochrane Library, Embase, Pubmed, Science Citation Index, Google Scholar, and ClinicalTrials.gov electronic databases. Study Selection: All RCTs that compared two defined BP targets (either active treatment vs.placebo or no treatment, or intensive vs. less intensive BP control) and enrolled adult (≥18years) persons with CKD stages 3-5 (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2) exclusively or that included a CKD subgroup between January 1950 and June 2016 were included. Data extraction and synthesis: Two reviewers independently evaluated study quality and extracted characteristics and mortality events among persons with CKD within the intervention phase for each trial. When outcomes within the CKD group had not previously been published, we contacted trial investigators and requested data within the CKD subset of their original trials. Main outcomes and measures: All-cause mortality during the active treatment phase of each trial. Results: We identified 30 RCTs that potentially met inclusion criteria, among which we were able to extract the CKD subset mortality data in 18 trials. Among these, there were 1293 deaths among 15,924 participants with CKD. The mean baseline systolic blood pressure (SBP) was 148±16 mm hg in both intensive and less-intensive arms. The mean SBP dropped by 16 mm Hg to 132 mm Hg in the intensive arm and by 8 mm Hg to 140 mm Hg in the less-intensive arm. More vs. less-intensive BP control resulted in 14% lower risk of all-cause mortality (Odds Ratio (OR) 0.86; 95% CI 0.76 to 0.97, p = 0.01); a finding that was without significant heterogeneity and appeared consistent across multiple subgroups including type of treatment in the comparator arm (placebo vs. less intensive BP target), length of follow-up, presence of diabetes, CKD severity, baseline systolic blood pressure (SBP), achieved SBP during the trial and degree of SBP differences across the treatment arms. Conclusion and Relevance: Randomization to more intensive BP control is associated with lower mortality risk among trial participants with hypertension and CKD. Further studies are required to define absolute BP targets for maximal benefit and minimal harm

The prevalence of pelvic organ prolapse symptoms and signs and their relation with bladder and bowel disorders in a general female population

Contains fulltext : 81191.pdf (publisher's version ) (Closed access)INTRODUCTION AND HYPOTHESIS: In selected populations, pelvic organ prolapse (POP) was associated with bladder/bowel symptoms, but data on the general female population are lacking. Our aim was to obtain normative data on the prevalence of POP and pelvic floor dysfunction (PFD) symptoms and signs and to identify associations. METHODS: Validated questionnaires on POP and PFD (urogenital distress inventory, (UDI) and defaecation distress inventory (DDI)) were sent to a general population of 2,979 women (aged 45-85 years). Data were analysed using the Kruskal-Wallis test, chi square test and Spearman's rank correlation coefficient. RESULTS: Response rate was 62.7%. Associations between POP stage and parity (0.002) and vaginal bulging (<0.001) are significant. Anatomical locations of POP and PFD symptoms correlated significantly with incontinence of flatus, feeling anal prolapse, manual evacuation of stool, vaginal bulging, constipation and pain during faecal urge (p < or = 0.005). CONCLUSIONS: Strategies should be developed to alleviate obstructive bowel disorders associated with POP

Development of paediatric quality of inpatient care indicators for low-income countries - A Delphi study

BACKGROUND: Indicators of quality of care for children in hospitals in low-income countries have been proposed, but information on their perceived validity and acceptability is lacking. METHODS: Potential indicators representing structural and process aspects of care for six common conditions were selected from existing, largely qualitative WHO assessment tools and guidelines. We employed the Delphi technique, which combines expert opinion and existing scientific information, to assess their perceived validity and acceptability. Panels of experts, one representing an international panel and one a national (Kenyan) panel, were asked to rate the indicators over 3 rounds and 2 rounds respectively according to a variety of attributes. RESULTS: Based on a pre-specified consensus criteria most of the indicators presented to the experts were accepted: 112/137(82%) and 94/133(71%) for the international and local panels respectively. For the other indicators there was no consensus; none were rejected. Most indicators were rated highly on link to outcomes, reliability, relevance, actionability and priority but rated more poorly on feasibility of data collection under routine conditions. There was moderate to substantial agreement between the two panels of experts. CONCLUSIONS: This Delphi study provided evidence for the perceived usefulness of most of a set of measures of quality of hospital care for children proposed for use in low-income countries. However, both international and local experts expressed concerns that data for many process-based indicators may not currently be available. The feasibility of widespread quality assessment and responsiveness of indicators to intervention should be examined as part of continued efforts to improve approaches to informative hospital quality assessment

Molecular and Electrophysiological Characterization of a Novel Cation Channel of Trypanosoma cruzi

We report the identification, functional expression, purification, reconstitution and electrophysiological characterization of a novel cation channel (TcCat) from Trypanosoma cruzi, the etiologic agent of Chagas disease. This channel is potassium permeable and shows inward rectification in the presence of magnesium. Western blot analyses with specific antibodies indicated that the protein is expressed in the three main life cycle stages of the parasite. Surprisingly, the parasites have the unprecedented ability to rapidly change the localization of the channel when they are exposed to different environmental stresses. TcCat rapidly translocates to the tip of the flagellum when trypomastigotes are submitted to acidic pH, to the plasma membrane when epimastigotes are submitted to hyperosmotic stress, and to the cell surface when amastigotes are released to the extracellular medium. Pharmacological block of TcCat activity also resulted in alterations in the trypomastigotes ability to respond to hyperosmotic stress. We also demonstrate the feasibility of purifying and reconstituting a functional ion channel from T. cruzi after recombinant expression in bacteria. The peculiar characteristics of TcCat could be important for the development of specific inhibitors with therapeutic potential against trypanosomes

Fatal hypothermia : an analysis from a sub-arctic region

Objectives. To determine the incidence as well as contributing factors to fatal hypothermia. Study design. Retrospective, registry-based analysis. Methods. Cases of fatal hypothermia were identified in the database of the National Board of Forensic Medicine for the 4 northernmost counties of Sweden and for the study period 1992-2008. Police reports, medical records and autopsy protocols were studied. Results. A total of 207 cases of fatal hypothermia were noted during the study period, giving an annual incidence of 1.35 per 100,000 inhabitants. Seventy-two percent occurred in rural areas, and 93% outdoors. Many (40%) were found within approximately 100 meters of a building. The majority (75%) occurred during the colder season (October to March). Some degree of paradoxical undressing was documented in 30%. Ethanol was detected in femoral vein blood in 43% of the victims. Contributing co-morbidity was common and included heart disease, earlier stroke, dementia, psychiatric disease, alcoholism, and recent trauma. Conclusions. With the identification of groups at high risk for fatal hypothermia, it should be possible to reduce risk through thoughtful interventions, particularly related to the highest risk subjects (rural, living alone, alcohol-imbibing, and psychiatric diagnosis-carrying) citizens

Development and initial validation of a simple clinical decision tool to predict the presence of heart failure in primary care: the MICE (Male, Infarction, Crepitations, Edema) rule.

AIMS: Diagnosis of heart failure in primary care is often inaccurate, and access to and use of echocardiography is suboptimal. This study aimed to develop and provisionally validate a clinical prediction rule to optimize referral for echocardiography of people identified in primary care with suspected heart failure. METHODS AND RESULTS: A systematic review identified studies of diagnosis of heart failure set in primary care. The individual patient data for five of these studies were obtained. Logistic regression models to predict heart failure were developed on one of the data sets and validated on the others using area under the receiver operating characteristic curve (AUROC), and goodness-of-fit calibration plots. A model based upon four simple clinical features (Male, history of myocardial Infarction, Crepitations, Edema: MICE) and natriuretic peptide had good validity when applied to other data sets, with AUROCs between 0.84 and 0.93, and reasonable calibration. The rule performed well across the data sets, with sensitivity between 81% and 96% and specificity between 57% and 74%. CONCLUSIONS: A simple clinical rule based upon gender, history of myocardial infarction, presence of ankle oedema, and presence of basal lung crepitations can discriminate between people with suspected heart failure who should be referred straight for echocardiography and people for whom referral should depend upon the result of a natriuretic peptide test. Prospective validation and an implementation evaluation of the rule is now warranted