A clinician-nurse model to reduce early mortality and increase clinic retention among high-risk HIV-infected patients initiating combination antiretroviral treatment

<p>Abstract</p> <p>Background</p> <p>In resource-poor settings, mortality is at its highest during the first 3 months after combination antiretroviral treatment (cART) initiation. A clear predictor of mortality during this period is having a low CD4 count at the time of treatment initiation. The objective of this study was to evaluate the effect on survival and clinic retention of a nurse-based rapid assessment clinic for high-risk individuals initiating cART in a resource-constrained setting.</p> <p>Methods</p> <p>The USAID-AMPATH Partnership has enrolled more than 140,000 patients at 25 clinics throughout western Kenya. High Risk Express Care (HREC) provides weekly or bi-weekly rapid contacts with nurses for individuals initiating cART with CD4 counts of ≤100 cells/mm³. All HIV-infected individuals aged 14 years or older initiating cART with CD4 counts of ≤100 cells/mm³were eligible for enrolment into HREC and for analysis. Adjusted hazard ratios (AHRs) control for potential confounding using propensity score methods.</p> <p>Results</p> <p>Between March 2007 and March 2009, 4,958 patients initiated cART with CD4 counts of ≤100 cells/mm³. After adjusting for age, sex, CD4 count, use of cotrimoxazole, treatment for tuberculosis, travel time to clinic and type of clinic, individuals in HREC had reduced mortality (AHR: 0.59; 95% confidence interval: 0.45-0.77), and reduced loss to follow up (AHR: 0.62; 95% CI: 0.55-0.70) compared with individuals in routine care. Overall, patients in HREC were much more likely to be alive and in care after a median of nearly 11 months of follow up (AHR: 0.62; 95% CI: 0.57-0.67).</p> <p>Conclusions</p> <p>Frequent monitoring by dedicated nurses in the early months of cART can significantly reduce mortality and loss to follow up among high-risk patients initiating treatment in resource-constrained settings.</p

Evaluating the structure and magnitude of the ash plume during the initial phase of the 2010 Eyjafjallajökull eruption using lidar observations and NAME simulations

The Eyjafjallajökull volcano in Iceland erupted explosively on 14 April 2010, emitting a plume of ash into the atmosphere. The ash was transported from Iceland toward Europe where mostly cloud-free skies allowed ground-based lidars at Chilbolton in England and Leipzig in Germany to estimate the mass concentration in the ash cloud as it passed overhead. The UK Met Office's Numerical Atmospheric-dispersion Modeling Environment (NAME) has been used to simulate the evolution of the ash cloud from the Eyjafjallajökull volcano during the initial phase of the ash emissions, 14–16 April 2010. NAME captures the timing and sloped structure of the ash layer observed over Leipzig, close to the central axis of the ash cloud. Relatively small errors in the ash cloud position, probably caused by the cumulative effect of errors in the driving meteorology en route, result in a timing error at distances far from the central axis of the ash cloud. Taking the timing error into account, NAME is able to capture the sloped ash layer over the UK. Comparison of the lidar observations and NAME simulations has allowed an estimation of the plume height time series to be made. It is necessary to include in the model input the large variations in plume height in order to accurately predict the ash cloud structure at long range. Quantitative comparison with the mass concentrations at Leipzig and Chilbolton suggest that around 3% of the total emitted mass is transported as far as these sites by small (<100 μm diameter) ash particles

RNA-Seq identifies SPGs as a ventral skeletal patterning cue in sea urchins

The sea urchin larval skeleton offers a simple model for formation of developmental patterns. The calcium carbonate skeleton is secreted by primary mesenchyme cells (PMCs) in response to largely unknown patterning cues expressed by the ectoderm. To discover novel ectodermal cues, we performed an unbiased RNA-Seq-based screen and functionally tested candidates; we thereby identified several novel skeletal patterning cues. Among these, we show that SLC26a2/7 is a ventrally expressed sulfate transporter that promotes a ventral accumulation of sulfated proteoglycans, which is required for ventral PMC positioning and skeletal patterning. We show that the effects of SLC perturbation are mimicked by manipulation of either external sulfate levels or proteoglycan sulfation. These results identify novel skeletal patterning genes and demonstrate that ventral proteoglycan sulfation serves as a positional cue for sea urchin skeletal patterning

Identifying positively deviant elderly medical wards using routinely collected NHS Safety Thermometer data: an observational study.

Objective The positive deviance approach seeks to identify and learn from exceptional performers. Although a framework exists to apply positive deviance within healthcare organisations, there is limited guidance to support its implementation. The approach has also rarely explored exceptional performance on broad outcomes, been implemented at ward level, or applied within the UK. This study develops and critically appraises a pragmatic method for identifying positively deviant wards using a routinely collected, broad measure of patient safety. Design A two-phased observational study was conducted. During phase 1, cross-sectional and temporal analyses of Safety Thermometer data were conducted to identify a discrete group of positively deviant wards that consistently demonstrated exceptional levels of safety. A group of matched comparison wards with above average performances were also identified. During phase 2, multidisciplinary staff and patients on the positively deviant and comparison wards completed surveys to explore whether their perceptions of safety supported the identification of positively deviant wards. Setting 34 elderly medical wards within a northern region of England, UK. Participants Multidisciplinary staff (n=161) and patients (n=188) clustered within nine positively deviant and comparison wards. Results Phase 1: A combination of analyses identified five positively deviant wards that performed best in the region, outperformed their organisation and performed consistently well over 12 months. Five above average matched comparator wards were also identified. Phase 2: Staff and patient perceptions of safety generally supported the identification of positively deviant wards using Safety Thermometer data, although patient perceptions of safety were less concordant with the routinely collected data. Conclusions This study tentatively supports a pragmatic method of using routinely collected data to identify positively deviant elderly medical wards; however, it also highlights the various challenges that are faced when conducting the first stage of the positive deviance approach. Trial registration number UK Clinical Research Network Portfolio (reference-18050)

REFINE (reduced frequency ImmuNE checkpoint inhibition in cancers): A multi-arm phase II basket trial testing reduced intensity immunotherapy across different cancers

Background Immune checkpoint inhibitors (ICI) have revolutionised treating advanced cancers. ICI are administered intravenously every 2–6 weeks for up to 2 years, until cancer progression/unacceptable toxicity. Physiological efficacy is observed at lower doses than those used as standard of care (SOC). Pharmacodynamic studies indicate sustained target occupancy, despite a pharmacological half-life of 2–3 weeks. Reducing frequency of administration may be possible without compromising outcomes. The REFINE trial aims to limit individual patient exposure to ICI whilst maintaining efficacy, with potential benefits in quality of life and reduced drug treatment/attendance costs. Methods/Design REFINE is a randomised phase II, multi-arm, multi-stage (MAMS) adaptive basket trial investigating extended interval administration of ICIs. Eligible patients are those responding to conventionally dosed ICI at 12 weeks. In stage I, patients (n = 160 per tumour-specific cohort) will be randomly allocated (1:1) to receive maintenance ICI at SOC vs extended dose interval. REFINE is currently recruiting UK patients with locally advanced or metastatic renal cell carcinoma (RCC) who have tolerated and responded to initial nivolumab/ipilimumab, randomised to receive maintenance nivolumab SOC (480 mg 4 weekly) vs extended interval (480 mg 8 weekly). Additional tumour cohorts are planned. Subject to satisfactory outcomes (progression-free survival) stage II will investigate up to 5 different treatment intervals. Secondary outcome measures include overall survival, quality-of-life, treatment-related toxicity, mean incremental pathway costs and quality-adjusted life-years per patient. REFINE is funded by the Jon Moulton Charity Trust and Medical Research Council, sponsored by University College London (UCL), and coordinated by the MRC CTU at UCL

Localizing chronic disease management: Information work and health translations

Based on interviews with people who had diabetes, high blood pressure, and kidney disease in Flint, Michigan, we found people actively doing information work to manage their health in the face of poverty, potentially violent conditions, high stress, and a distrust of institutionalized medicine. More specifically, we observed people translating information into the context of their everyday lives. We present various translations of health information in the form of local strategies for chronic illness management. Study findings highlight initial implications to support health information services on a community level.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106960/1/14505001090_ftp.pd

Developmental expression of non-coding RNAs in Chlamydia trachomatis during normal and persistent growth

Chlamydia trachomatis is an obligate intracellular bacterium that exhibits a unique biphasic developmental cycle that can be disrupted by growth in the presence of IFN-γ and β-lactams, giving rise to an abnormal growth state termed persistence. Here we have examined the expression of a family of non-coding RNAs (ncRNAs) that are differentially expressed during the developmental cycle and the induction of persistence and reactivation. ncRNAs were initially identified using an intergenic tiling microarray and were confirmed by northern blotting. ncRNAs were mapped, characterized and compared with the previously described chlamydial ncRNAs. The 5′- and 3′-ends of the ncRNAs were determined using an RNA circularization procedure. Promoter predictions indicated that all ncRNAs were expressed from σ66 promoters and eight ncRNAs contained non-templated 3′-poly-A or poly-AG additions. Expression of ncRNAs was studied by northern blotting during (i) the normal developmental cycle, (ii) IFN-γ-induced persistence and (iii) carbenicillin-induced persistence. Differential temporal expression during the developmental cycle was seen for all ncRNAs and distinct differences in expression were seen during IFN-γ and carbenicillin-induced persistence and reactivation. A heterologous co-expression system was used to demonstrate that one of the identified ncRNAs regulated the expression of FtsI by inducing degradation of ftsI mRNA