Prevalence and factors associated with cryptococcal antigenemia among severely immunosuppressed HIV-infected adults in Uganda: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Cryptococcal infection is a common opportunistic infection among severely immunosuppressed HIV patients and is associated with high mortality. Positive cryptococcal antigenemia is an independent predictor of cryptococcal meningitis and death in patients with severe immunosuppression. We evaluated the prevalence and factors associated with cryptococcal antigenemia among patients with CD4 counts of 100 cells/mm³or less in Mulago Hospital, Kampala, Uganda. Screening of a targeted group of HIV patients may enable early detection of cryptococcal infection and intervention before initiating antiretroviral therapy. Factors associated with cryptococcal antigenemia may be used subsequently in resource-limited settings in screening for cryptococcal infection, and this data may also inform policy for HIV care.</p> <p>Methods</p> <p>In this cross-sectional study, HIV-infected patients aged 18 years and older with CD4 counts of up to 100 cells/mm³were enrolled between December 2009 and March 2010. Data on socio-demographics, physical examinations and laboratory tests were collected. Factors associated with cryptococcal antigenemia were analyzed using multiple logistic regression.</p> <p>Results</p> <p>We enrolled 367 participants and the median CD4 count was 23 (IQR 9-51) cells/mm³. Sixty-nine (19%) of the 367 participants had cryptococcal antigenemia. Twenty-four patients (6.5%) had cryptococcal meningitis on cerebrospinal fluid analysis and three had isolated cryptococcal antigenemia. Factors associated with cryptococcal antigenemia included: low body mass index of 15.4 kg/m²or less (adjusted odds ratio, AOR = 0.5; 95% CI 0.3-1.0), a CD4+ T cell count of less than 50 cells/mm³(AOR = 2.7; 95% CI1.2-6.1), neck pain (AOR = 2.3; 95% CI 1.2-4.6), recent diagnosis of HIV infection (AOR = 1.9; 95% CI 1.1-3.6), and meningeal signs (AOR = 7.9; 95% CI 2.9-22.1). However, at sub-analysis of asymptomatic patients, absence of neck pain (AOR = 0.5), photophobia (AOR = 0.5) and meningeal signs (AOR = 0.1) were protective against cryptococcal infection.</p> <p>Conclusions</p> <p>Cryptococcal antigenemia is common among severely immunosuppressed HIV patients in Mulago Hospital, Kampala, Uganda. Independent predictors of positive serum cryptococcal antigenemia were CD4⁺T cell counts of less than 50 cells/mm, low body mass index, neck pain, signs of meningeal irritation, and a recent diagnosis of HIV infection. Routine screening of this category of patients may detect cryptococcosis, and hence provide an opportunity for early intervention. Absence of neck pain, photophobia and meningeal signs were protective against cryptococcal infection compared with symptomatic patients.</p

‘It’s all about context’: Building school capacity to implement a whole-school approach to bullying

Student bullying behaviours are a significant social issue in schools worldwide. Whilst school staff have access to quality bullying prevention interventions, schools can face significant challenges implementing the whole-school approach required to address the complexity of these behaviours. This study aimed to understand how schools’ capacity to implement whole-school bullying prevention interventions could be strengthened to promote sustainability and improve student outcomes. Qualitative methods were used to observe schools over time to gain insight into their implementation capacity to improve student social and emotional wellbeing and prevent and ameliorate harm from bullying. A four-year longitudinal, multi-site case study intensively followed eight schools’ implementation of Friendly Schools, an Australian evidenced-based whole-school bullying prevention intervention. Regular in-depth interviews with school leaders and implementation teams over four years led to the refinement of a staged-implementation process and capacity building tools and revealed four common drivers of implementation quality: (1) strong, committed leadership; (2) organisational structures, processes and resources; (3) staff competencies and commitment; and (4) translating evidence into local school policy and practice. This paper considers the strengths of qualitative data in understanding how and why bullying prevention interventions work as well as actions schools can take to enhance their implementation and sustainability of complex social interventions

Ability to Taste 6‐ n ‐Propylthiouracil and BMI in Low‐income Preschool‐aged Children

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93763/1/oby.2008.227.pd

Safety and immunogenicity of pneumococcal conjugate vaccines in a high-risk population : A randomized controlled trial of 10-valent and 13-valent pneumococcal conjugate vaccine in Papua New Guinean infants

Background. There are little data on the immunogenicity of PCV10 and PCV13 in the same high-risk population. Methods. PCV10 and PCV13 were studied head-to-head in a randomized controlled trial in Papua New Guinea in which 262 infants received 3 doses of PCV10 or PCV13 at 1, 2, and 3 months of age. Serotype-specific immunoglobulin G (IgG) concentrations, and pneumococcal and nontypeable Haemophilus influenzae (NTHi) carriage were assessed prevaccination and at 4 and 9 months of age. Infants were followed up for safety until 9 months of age. Results. One month after the third dose of PCV10 or PCV13, 80% of infants had IgG concentrations ≥0.35µg/mL for vaccine serotypes, and 6 months postvaccination IgG concentrations ≥0.35 µg/mL were maintained for 8/10 shared PCV serotypes in > 75% of children vaccinated with either PCV10 or PCV13. Children carried a total of 65 different pneumococcal serotypes (plus nonserotypeable). At 4 months of age, 92% (95% confidence interval [CI] 85–96) of children vaccinated with PCV10 and 81% (95% CI 72–88) vaccinated with PCV13 were pneumococcal carriers (P = .023), whereas no differences were seen at 9 months of age, or for NTHi carriage. Both vaccines were well tolerated and not associated with serious adverse events. Conclusions. Infant vaccination with 3 doses of PCV10 or PCV13 is safe and immunogenic in a highly endemic setting; however, to significantly reduce pneumococcal disease in these settings, PCVs with broader serotype coverage and potency to reduce pneumococcal carriage are needed. Clinical Trials Registration. NCT01619462

Escherichia coli and Community-acquired Gastroenteritis, Melbourne, Australia

Atypical strains of enteropathogenic E. coli are a leading cause of gastroenteritis in Melbourne

Safety and Immunogenicity of Neonatal Pneumococcal Conjugate Vaccination in Papua New Guinean Children: A Randomised Controlled Trial

Background: Approximately 826,000 children, mostly young infants, die annually from invasive pneumococcal disease. A 6-10-14-week schedule of pneumococcal conjugate vaccine (PCV) is efficacious but neonatal PCV may provide earlier protection and better coverage. We conducted an open randomized controlled trial in Papua New Guinea to compare safety, immunogenicity and priming for memory of 7-valent PCV (PCV7) given in a 0-1-2-month (neonatal) schedule with that of the routine 1-2-3-month (infant) schedule. Methods: We randomized 318 infants at birth to receive PCV7 in the neonatal or infant schedule or no PCV7. All infants received 23-valent pneumococcal polysaccharide vaccine (PPV) at age 9 months. Serotype-specific serum IgG for PCV7 (VT) serotypes and non-VT serotypes 2, 5 and 7F were measured at birth and 2, 3, 4, 9, 10 and 18 months of age. Primary outcomes were geometric mean concentrations (GMCs) and proportions with concentration ≥0.35 µg/ml of VT serotype-specific pneumococcal IgG at age 2 months and one month post-PPV.Results: We enrolled 101, 105 and 106 infants, respectively, into neonatal, infant and control groups. Despite high background levels of maternally derived antibody, both PCV7 groups had higher GMCs than controls at age 2 months for serotypes 4 (p<0.001) and 9V (p<0.05) and at age 3 months for all VTs except 6B. GMCs for serotypes 4, 9V, 18C and 19F were significantly higher (p<0.001) at age 2 months in the neonatal (one month post-dose2 PCV7) than in the infant group (one month post-dose1 PCV7). PPV induced significantly higher VT antibody responses in PCV7-primed than unprimed infants, with neonatal and infant groups equivalent. High VT and non-VT antibody concentrations generally persisted to age 18 months. Conclusions: PCV7 is well-tolerated and immunogenic in PNG neonates and young infants and induces immunologic memory to PPV booster at age 9 months with antibody levels maintained to age 18 months

Examining the generalizability of research findings from archival data

This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability—for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570