Making co-enrolment feasible for randomised controlled trials in paediatric intensive care.

Enrolling children into several trials could increase recruitment and lead to quicker delivery of optimal care in paediatric intensive care units (PICU). We evaluated decisions taken by clinicians and parents in PICU on co-enrolment for two large pragmatic trials: the CATCH trial (CATheters in CHildren) comparing impregnated with standard central venous catheters (CVCs) for reducing bloodstream infection in PICU and the CHIP trial comparing tight versus standard control of hyperglycaemia

Effectiveness of VIA, Pap, and HPV DNA Testing in a Cervical Cancer Screening Program in a Peri-Urban Community in Andhra Pradesh, India

BACKGROUND: While many studies have compared the efficacy of Pap cytology, visual inspection with acetic acid (VIA) and human papillomavirus (HPV) DNA assays for the detection cervical intraepithelial neoplasia and cancer, few have evaluated the program effectiveness. METHODS AND FINDINGS: A population-based sample of 5603 women from Medchal Mandal in Andhra Pradesh, India were invited to participate in a study comparing Pap cytology, VIA, and HPV DNA screening for the detection of CIN3+. Participation in primary screening and all subsequent follow-up visits was rigorously tracked. A 20% random sample of all women screened, in addition to all women with a positive screening test result underwent colposcopy with directed biopsy for final diagnosis. Sensitivity, specificity, positive and negative predictive values were adjusted for verification bias. HPV testing had a higher sensitivity (100%) and specificity (90.6%) compared to Pap cytology (sensitivity  =  78.2%; specificity = 86.0%) and VIA (sensitivity = 31.6%; specificity = 87.5%). Since 58% of the sample refused involvement and another 28% refused colposcopy or biopsy, we estimated that potentially 87.6% of the total underlying cases of CIN3 and cancer may have been missed due to program failures. CONCLUSIONS: We conclude that despite our use of available resources, infrastructure, and guidelines for cervical cancer screening implementation in resource limited areas, community participation and non-compliance remain the major obstacles to successful reduction in cervical cancer mortality in this Indian population. HPV DNA testing was both more sensitive and specific than Pap cytology and VIA. The use of a less invasive and more user-friendly primary screening strategy (such as self-collected swabs for HPV DNA testing) may be required to achieve the coverage necessary for effective reduction in cervical cancer mortality

Consistency between guidelines and reported practice for reducing the risk of catheter-related infection in British paediatric intensive care units.

PURPOSE: Optimal strategies for reducing catheter-related blood stream infection (CR-BSI) differ for adults and children. National guidelines do not make child-specific recommendations. We determined whether evidence explained the inconsistencies between guidelines and reported practice in paediatric intensive care units (PICUs). METHODS: We conducted a survey of eight interventions for reducing CR-BSI in all 25 British PICUs in 2009. Interventions were categorised as requiring child-specific evidence, generalisable to adults and children, or organisational recommendations. RESULTS: Twenty-four of the 25 PICUs responded. For child-specific interventions, practice diverged from guidelines for "Insert into subclavian/jugular veins" (18 PICUs frequently used femoral veins, supported by observational evidence for increased safety in children). Practice reflected guidelines for "Use standard but consider antimicrobial-impregnated central venous catheters (CVCs) for high-risk patients" (14 used standard only, 3 used standard and antimicrobial-impregnated despite no randomised controlled trial (RCT) evidence for antimicrobial-impregnated CVCs in children, 7 used heparin-bonded for some or all children); "Use 2% chlorhexidine for skin preparation" (20 PICUs); "Avoid routine CVC replacement" (20 PICUs). For generalisable interventions, practice was consistent with guidelines for "Administration set replacement" (21 PICUs) but deviated for "Maintenance of CVC asepsis" (11 PICUs used alcohol due to inconclusive evidence for chlorhexidine). Practice diverged from guidelines for organisational interventions: "Train healthcare workers in CVC care" (9 PICUs); "Monitor blood stream infection (BSI) rates" (8 PICUs). CONCLUSIONS: Guidelines should explicitly address paediatric practice and report the quality of evidence and strength of recommendations. Organisations should ensure doctors are trained in CVC insertion and invest in BSI monitoring, especially in PICUs. The type of CVC and insertion site are important gaps in evidence for children

Seroepidemiology of Human Papillomavirus 16 (HPV16) L2 and Generation of L2-Specific Human Chimeric Monoclonal Antibodies.

Presently, the seroprevalence of human papillomavirus (HPV) minor capsid antigen L2-reactive antibody is not well understood, and no serologic standard exists for L2-specific neutralizing antibodies. Therefore, we screened a total of 1,078 serum samples for HPV16 L2 reactivity, and these were obtained from four prior clinical studies: a population-based (n = 880) surveillance study with a high-risk HPV DNA prevalence of 10.8%, a cohort study of women (n = 160) with high-grade cervical intraepithelial neoplasia (CIN), and two phase II trials in women with high-grade vulvar intraepithelial neoplasia (VIN) receiving imiquimod therapy combined with either photodynamic therapy (PDT) (n = 19) or vaccination with a fusion protein comprising HPV16 L2, E7, and E6 (TA-CIN) (n = 19). Sera were screened sequentially by HPV16 L2 enzyme-linked immunosorbent assay (ELISA) and then Western blot. Seven of the 1,078 serum samples tested had L2-specific antibodies, but none were detectably neutralizing for HPV16. To develop a standard, we substituted human IgG1 sequences into conserved regions of two rodent monoclonal antibodies (MAbs) specific for neutralizing epitopes at HPV16 L2 residues 17 to 36 and 58 to 64, creating JWW-1 and JWW-2, respectively. These chimeric MAbs retained neutralizing activity and together reacted with 33/34 clinically relevant HPV types tested. In conclusion, our inability to identify an HPV16 L2-specific neutralizing antibody response even in the sera of patients with active genital HPV disease suggests the subdominance of L2 protective epitopes and the value of the chimeric MAbs JWW-1 and JWW-2 as standards for immunoassays to measure L2-specific human antibodies