Primary antifungal prophylaxis for cryptococcal disease in HIV‐positive people

Background Cryptococcal disease remains one of the main causes of death in HIV‐positive people who have low cluster of differentiation 4 (CD4) cell counts. Currently, the World Health Organization (WHO) recommends screening HIV‐positive people with low CD4 counts for cryptococcal antigenaemia (CrAg), and treating those who are CrAg‐positive. This Cochrane Review examined the effects of an approach where those with low CD4 counts received regular prophylactic antifungals, such as fluconazole. Objectives To assess the efficacy and safety of antifungal drugs for the primary prevention of cryptococcal disease in adults and children who are HIV‐positive. Search methods We searched the CENTRAL, MEDLINE PubMed, Embase OVID, CINAHL EBSCOHost, WHO International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, conference proceedings for the International AIDS Society (IAS) and Conference on Retroviruses and Opportunistic Infections (CROI), and reference lists of relevant articles up to 31 August 2017. Selection criteria Randomized controlled trials of adults and children, who are HIV‐positive with low CD4 counts, without a current or prior diagnosis of cryptococcal disease that compared any antifungal drug taken as primary prophylaxis to placebo or standard care. Data collection and analysis Two review authors independently assessed eligibility and risk of bias, and extracted and analysed data. The primary outcome was all‐cause mortality. We summarized all outcomes using risk ratios (RR) with 95% confidence intervals (CI). Where appropriate, we pooled data in meta‐analyses. We assessed the certainty of the evidence using the GRADE approach. Main results Nine trials, enrolling 5426 participants, met the inclusion criteria of this review. Six trials administered fluconazole, while three trials administered itraconazole. Antifungal prophylaxis may make little or no difference to all‐cause mortality (RR 1.07, 95% CI 0.80 to 1.43; 6 trials, 3220 participants; low‐certainty evidence). For cryptococcal specific outcomes, prophylaxis probably reduces the risk of developing cryptococcal disease (RR 0.29, 95% CI 0.17 to 0.49; 7 trials, 5000 participants; moderate‐certainty evidence), and probably reduces deaths due to cryptococcal disease (RR 0.29, 95% CI 0.11 to 0.72; 5 trials, 3813 participants; moderate‐certainty evidence). Fluconazole prophylaxis may make no clear difference to the risk of developing clinically resistant Candida disease (RR 0.93, 95% CI 0.56 to 1.56; 3 trials, 1198 participants; low‐certainty evidence); however, there may be an increased detection of fluconazole‐resistant Candida isolates from surveillance cultures (RR 1.25, 95% CI 1.00 to 1.55; 3 trials, 539 participants; low‐certainty evidence). Antifungal prophylaxis was generally well‐tolerated with probably no clear difference in the risk of discontinuation of antifungal prophylaxis compared with placebo (RR 1.01, 95% CI 0.91 to 1.13; 4 trials, 2317 participants; moderate‐certainty evidence). Antifungal prophylaxis may also make no difference to the risk of having any adverse event (RR 1.07, 95% CI 0.88 to 1.30; 4 trials, 2317 participants; low‐certainty evidence), or a serious adverse event (RR 1.08, 95% CI 0.83 to 1.41; 4 trials, 888 participants; low‐certainty evidence) when compared to placebo or standard care. Authors' conclusions Antifungal prophylaxis reduced the risk of developing and dying from cryptococcal disease. Therefore, where CrAG screening is not available, antifungal prophylaxis may be used in patients with low CD4 counts at diagnosis and who are at risk of developing cryptococcal disease

Derivation of Benefits from Dislikes in the Advancement via Individual Determination (AVID) College Readiness System

This phenomenological study employed a sequence of three interviews per student to explore the experiences of 20 students in the Advancement via Individual Determination (AVID) college readiness program.  Data from recorded interviews was analyzed using categorizing and connecting strategies.  Responses indicated that students varied most in their perceptions of the utility of various AVID strategies, but that students recognized they acquired skills that would serve them in the future.  Some participants indicated that they disliked specific strategies of the AVID program.  Nevertheless, findings showed that students benefitted from strategies, which they stated that they did not enjoy

Can village savings and loan groups be a potential tool in the malnutrition fight? Mixed method findings from Mozambique

Child malnutrition is a pervasive problem in sub-Saharan Africa that affects individual and national development. This article examines the impact of participation in village savings and loan (VSL) groups, alone and in combination with a rotating labor scheme called Ajuda Mútua (AM), on household and child nutritional outcomes in Nampula Province in Mozambique. It combines findings from an impact evaluation and a qualitative exploration of the dynamics underlying nutritional outcomes.Three pairs of districts were randomly allocated to two interventions (VSL or VSL. +. AM) or control. The impact evaluation utilized a prospective, longitudinal design. In total, 1276 households were surveyed at baseline in 2009 and three years later. Difference-in-difference propensity score matching models estimated program impacts on months of food sufficiency and household dietary diversity scores (HDDS) at the household level, and on individual dietary diversity scores (IDDS) and weight-for-age at the child level. In the qualitative study, in-depth interviews (IDIs) were completed with a subset of 36 VSL and 36 VSL. +. AM participants from two districts who had taken part in the two surveys. Transcripts were analyzed using thematic analysis.Survey data indicate that both interventions had a statistically significant, positive effect on months of food sufficiency. The HDDS increased for VSL. +. AM households and their matched controls; however, the increase was smaller for the VSL. +. AM group. The difference in increase between the two groups was statistically significant. At the child level, participation in VSL only was found to increase the IDDS. There was no significant effect for weight-for-age. Mean values for both the HDDS and the IDDS remained low. IDIs confirmed that there were improvements in seasonal and transitory food insecurity, which occur when recurring periods of extreme scarcity or sporadic crises are experienced. Due to the timing of the cycle, VSLs provided participants with an infusion of cash to purchase food during the hunger season. VSLs and AMs also offered mechanisms to cope with unexpected events through loans and social support. However, IDIs highlighted lack of money as a persistent challenge in accessing foods to supplement home-grown staples for a diversified nutritional intake. Though parents tended to be aware of the nutritional needs of children, they faced financial constraints in meeting them. There were also indications of a sex gap between control over resources by men and the role played by women in child nutrition.Findings underscore the potential of economic-strengthening activities such as VSLs for improving seasonal and transitory food security, but highlight the need for additional supporting interventions in order to overcome chronic nutritional challenges

Is this photograph taken? - The active (act of) collaboration with photography

Over more than thirty years of commercial and fine art photographic practice, I have often noticed remarkable disparities between the scenes, objects, events or moments ‘out there’ I had attempted to record – and the images within the resulting photographs. These (sometimes subtle, sometimes profound, but rarely anticipatable) disparities between what I had seen and what the photograph shows me offer the tantalising suggestion that there may be something else going on here – but something which the popular conception of photography may hinder our ability to recognise. This article explores the implications of four central assumptions implicit within the popular conception of photography which may impede new ways of thinking about photographic practice. Supported by a number of photographs that depict scenes, events and ‘moments’ which were not ‘taken’ but were created by the act of photographing them, I will suggest that new opportunities for practice may be available by ‘re-imagining’ the practice of photography as an active – or, as an act of – collaboration between medium and practitioner

Progressive, Transgenerational Changes in Offspring Phenotype and Epigenotype following Nutritional Transition

Induction of altered phenotypes during development in response to environmental input involves epigenetic changes. Phenotypic traits can be passed between generations by a variety of mechanisms, including direct transmission of epigenetic states or by induction of epigenetic marks de novo in each generation. To distinguish between these possibilities we measured epigenetic marks over four generations in rats exposed to a sustained environmental challenge. Dietary energy was increased by 25% at conception in F0 female rats and maintained at this level to generation F3. F0 dams showed higher pregnancy weight gain, but lower weight gain and food intake during lactation than F1 and F2 dams. On gestational day 8, fasting plasma glucose concentration was higher and β-hydroxybutyrate lower in F0 and F1 dams than F2 dams. This was accompanied by decreased phosphoenolpyruvate carboxykinase (PEPCK) and increased PPARα and carnitine palmitoyl transferase-1 mRNA expression. PEPCK mRNA expression was inversely related to the methylation of specific CpG dinucleotides in its promoter. DNA methyltransferase (Dnmt) 3a2, but not Dnmt1 or Dnmt3b, expression increased and methylation of its promoter decreased from F1 to F3 generations. These data suggest that the regulation of energy metabolism during pregnancy and lactation within a generation is influenced by the maternal phenotype in the preceding generation and the environment during the current pregnancy. The transgenerational effects on phenotype were associated with altered DNA methylation of specific genes in a manner consistent with induction de novo of epigenetic marks in each generation

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Polyclonality of Concurrent Natural Populations of Alteromonas macleodii

We have analyzed a natural population of the marine bacterium, Alteromonas macleodii, from a single sample of seawater to evaluate the genomic diversity present. We performed full genome sequencing of four isolates and 161 metagenomic fosmid clones, all of which were assigned to A. macleodii by sequence similarity. Out of the four strain genomes, A. macleodii deep ecotype (AltDE1) represented a different genome, whereas AltDE2 and AltDE3 were identical to the previously described AltDE. Although the core genome (∼80%) had an average nucleotide identity of 98.51%, both AltDE and AltDE1 contained flexible genomic islands (fGIs), that is, genomic islands present in both genomes in the same genomic context but having different gene content. Some of the fGIs encode cell surface receptors known to be phage recognition targets, such as the O-chain of the lipopolysaccharide, whereas others have genes involved in physiological traits (e.g., nutrient transport, degradation, and metal resistance) denoting microniche specialization. The presence in metagenomic fosmids of genomic fragments differing from the sequenced strain genomes, together with the presence of new fGIs, indicates that there are at least two more A. macleodii clones present. The availability of three or more sequences overlapping the same genomic region also allowed us to estimate the frequency and distribution of recombination events among these different clones, indicating that these clustered near the genomic islands. The results indicate that this natural A. macleodii population has multiple clones with a potential for different phage susceptibility and exploitation of resources, within a seemingly unstructured habitat

The effect of HIV on morbidity and mortality in children with severe malarial anaemia

<p>Abstract</p> <p>Background</p> <p>Malaria and HIV are common causes of mortality in sub-Saharan Africa. The effect of HIV infection on morbidity and mortality in children with severe malarial anaemia was assessed.</p> <p>Methods</p> <p>Children <5 years old were followed as part of a prospective cohort study to assess the transfusion-associated transmission of blood-borne pathogens at Mulago Hospital, Kampala, Uganda. All children were hospitalized with a diagnosis of severe malarial anaemia requiring blood transfusion. Survival to different time points post-transfusion was compared between HIV-infected and uninfected children. Generalized estimating equations were used to analyse repeated measurement outcomes of morbidity, adjusting for confounders.</p> <p>Findings</p> <p>Of 847 children, 78 (9.2%) were HIV-infected. Median follow-up time was 162 days (inter-quartile range: 111, 169). HIV-infected children were more likely to die within 7 days (Hazard ratio [HR] = 2.86, 95% Confidence interval [CI] 1.30–6.29, P = 0.009) and within 28 days (HR = 3.70, 95% CI 1.91–7.17, P < 0.001) of an episode of severe malarial anaemia, and were more likely to die in the 6 months post-transfusion (HR = 5.70, 95% CI 3.54–9.16, P < 0.001) compared to HIV-uninfected children. HIV-infected children had more frequent re-admissions due to malaria within 28 days (Incidence rate ratio (IRR) = 3.74, 95% CI 1.41–9.90, P = 0.008) and within 6 months (IRR = 2.66, 95% CI 1.17 – 6.07, P = 0.02) post-transfusion than HIV-uninfected children.</p> <p>Conclusion</p> <p>HIV-infected children with severe malarial anaemia suffered higher all-cause mortality and malaria-related mortality than HIV-uninfected children. Children with HIV and malaria should receive aggressive treatment and further evaluation of their HIV disease, particularly with regard to cotrimoxazole prophylaxis and antiretroviral therapy.</p