Prognostic factors of a lower CD4/CD8 ratio in long term viral suppression HIV infected children

Background Combination antiretroviral therapy (cART) is associated with marked immune reconstitution. Although a long term viral suppression is achievable, not all children however, attain complete immunological recovery due to persistent immune activation. We use CD4/CD8 ratio like a marker of immune reconstitution. Methods Perinatal HIV-infected children who underwent a first-line cART, achieved viral suppression in the first year and maintained it for more than 5 years, with no viral rebound were included. Logistic models were applied to estimate the prognostic factors, clinical characteristics at cART start, of a lower CD4/CD8 ratio at the last visit. Results 146 HIV-infected children were included: 77% Caucasian, 45% male and 28% CDC C. Median age at cART initiation was 2.3 years (IQR: 0.5-6.2). 42 (30%) children received mono-dual therapy previously to cART. Time of undetectable viral load was 9.5 years (IQR: 7.8, 12.5). 33% of the children not achieved CD4/CD8 ratio >1. Univariate analysis showed an association between CD4/CD8 <1 with lower CD4 nadir and baseline CD4; older age at diagnosis and at cART initiation; and a previous exposure to mono-dual therapy. Multivariate analysis also revealed relationship between CD4/CD8 <1 and lower CD4 nadir (OR: 1.002, CI 95% 1.000-1.004) as well as previous exposure to mono-dual therapy (OR: 0.16, CI 95% 0.003-0.720). Conclusions CD4/CD8 > 1 was not achieved in 33% of the children. Lower CD4 nadir and previous exposure to suboptimal therapy, before initiating cART, are factors showing independently association with a worse immune recovery (CD4/CD8 < 1)

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

A cost-effectiveness study of the management of intractable urinary incontinence by urinary catheterisation or incontinence pads.

STUDY OBJECTIVE--The aim was to compare the costs and effects of management of intractable urinary incontinence by urinary catheterisation or incontinence pads. DESIGN--This was a prospective, randomised study comparing catheterisation with pads, supplemented by additional data collected from patients with chronic indwelling catheters. Main outcome measures were costs of equipment, nursing time, patient preference, nursing preference, and clinical and bacteriological assessment of urinary infection. SUBJECTS--78 intractably incontinent elderly female patients were randomly allocated to management by urinary catheter or pads and toileting. Supplementary data on equipment costs and nursing time were collected from 27 patients, of whom 22 were already catheterised at the time of the randomisation and five were catheterised by the nursing staff after the last date for entry into the randomisation. MAIN RESULTS--Of the 38 patients randomised to catheterisation, 14 refused consent so only 24 were catheterised on day 1 of the study. There was a rapid removal of catheters, especially in the first six weeks of the study and only four of the randomised catheter patients completed the full 26 weeks of the study. However, eight of the pads patients were catheterised between the 7th and 22nd week because of deteriorating general condition and all retained their catheters for the remainder of the study period. Of 35 patients who had experienced catheters and pads, 12 expressed a clear preference for catheters, 12 for pads, and 11 were undecided. Nurses were in favour of the use of pads, mainly because of concerns about urinary infection with catheters. Comparing costs for patients managed with catheters (532 patient weeks) or pads (903 patient weeks), catheter patients required less nursing time (15.4 v 29.0 h per patient per week) but equipment costs were higher (19.20-24.65 pounds v 8.79-11.35 pounds per patient per week), mainly because of the cost of catheter care (12.75 pounds per patient per week). Asymptomatic bacteriuria was prevalent in both groups but 73% of catheterised patients received treatment for clinical signs of infection compared with 40% of pads patients. Only 30% of patients who were treated had any generalised symptoms of infection. CONCLUSIONS--Use of catheters reduces nursing time but may increase weekly equipment costs depending on the cost of laundry. Despite the high dropout rate among patients randomised to catheters a minority of patients (12/35) expressed a clear preference for catheters and we believe that more patients with intractable incontinence should be given a trial of catheterisation to assess acceptability. Bacteriuria was prevalent in pads or catheter patients but no major episodes of invasive infection were noted in either group