Cryptococcus neoformans is a ubiquitous environmental fungus that can cause life-threatening meningitis and fungemia, often in the presence of acquired immunodeficiency syndrome (AIDS), liver ...cirrhosis, diabetes mellitus, or other medical conditions. To distinguish risk factors from comorbidities, we performed a hospital-based, density-sampled, matched case-control study.
All new-onset cryptococcal meningitis cases and cryptococcemia cases at a university hospital in Taiwan from 2002-2010 were retrospectively identified from the computerized inpatient registry and were included in this study. Controls were selected from those hospitalized patients not experiencing cryptococcal meningitis or cryptococcemia. Controls and cases were matched by admission date, age, and gender. Conditional logistic regression was used to analyze the risk factors.
A total of 101 patients with cryptococcal meningitis (266 controls) and 47 patients with cryptococcemia (188 controls), of whom 32 patients had both cryptococcal meningitis and cryptococcemia, were included in this study. Multivariate regression analysis showed that AIDS (adjusted odds ratio aOR = 181.4; p < 0.001), decompensated liver cirrhosis (aOR = 8.5; p = 0.008), and cell-mediated immunity (CMI)-suppressive regimens without calcineurin inhibitors (CAs) (aOR = 15.9; p < 0.001) were independent risk factors for cryptococcal meningitis. Moreover, AIDS (aOR = 216.3, p < 0.001), decompensated liver cirrhosis (aOR = 23.8; p < 0.001), CMI-suppressive regimens without CAs (aOR = 7.3; p = 0.034), and autoimmune diseases (aOR = 9.3; p = 0.038) were independent risk factors for developing cryptococcemia. On the other hand, diabetes mellitus and other medical conditions were not found to be risk factors for cryptococcal meningitis or cryptococcemia.
The findings confirm AIDS, decompensated liver cirrhosis, CMI-suppressive regimens without CAs, and autoimmune diseases are risk factors for invasive C. neoformans diseases.
Background: We investigated the association between prenatal GDM exposure and offspring DNA methylation (DNAm) age at 3-10 years of age in the Tianjin GDM Observational Study.
Methods: This study ...included 578 GDM and 578 non-GDM mother-child pairs. Children underwent an exam with anthropometric measurements and blood draw for DNAm analysis (Illumina 850 K array) at a median age of 5.9 years (range 3.1-10.2). DNAm age was calculated using two epigenetic clock algorithms (Horvath and Hannum). The residual resulting from regressing DNAm age on chronological age was used as a metric for age acceleration.
Results: Chronological age was positively correlated with Horvath DNAm age (r = 0.53, p < 0.0001) and Hannum DNAm age (r = 0.38, p < 0.0001). Offspring age acceleration was higher in the GDM group than non-GDM group after adjustment for potential confounders (Horvath: 4.96 months higher, adjusted for sex, pre-pregnancy BMI, cell-type proportions, and technical bias, p = 0.0002; Hannum: 11.2 months higher, adjusted for cell-type proportions and technical bias, p < 0.0001). Increased offspring DNAm age acceleration was associated with increased offspring weight-for-age Z-score, BMI-for-age-Z-score, waist circumference, body fat percentage, subscapular skinfold, suprailiac skinfold, upper-arm circumference, and blood pressure; findings were stronger in the GDM group.
Conclusions: We found that offspring of women with GDM exhibit accelerated epigenetic age compared to control participants, independent of other maternal factors. Epigenetic age in offspring was associated with cardiometabolic risk factors, suggesting that GDM and GDM-associated factors may have long-term effects on offspring epigenetic age and contribute to health outcomes.
Children living with HIV (CLHIV) have decreased bone mineral content (BMC) and density (BMD), increasing risk for fracture and future osteoporosis. While DXA is the gold-standard for bone ...assessments, it lacks availability in resource-constrained settings (RCS). Quantitative ultrasound (QUS) offers an alternative owing to its portability, low cost, ease of handling, and lack of ionizing radiation. While QUS has detected reduced bone quality in CLHIV, the relationship between QUS and DXA in this population remains unexplored. At baseline and 12 months, BMC and BMD of the whole body, lumbar spine, and radius were measured by DXA in a longitudinal cohort of CLHIV in Johannesburg, South Africa. Calcaneal speed of sound (SOS) and broadband ultrasound attenuation (BUA) and radius SOS were obtained by QUS, and calcaneal stiffness index (SI) was calculated. Spearman correlations, with and without HIV stratification, were performed between QUS and DXA measurements at each visit and for absolute difference in measurements between visits. At baseline and 12-months, calcaneal BUA and SI displayed strong positive correlations with DXA, with only modest correlations between radial QUS and DXA at baseline. Longitudinal measures of QUS did not correlate with DXA. At both baseline and 12-months, individuals with DXA whole-body BMD z-score < -1 displayed significantly lower calcaneal BUA and SI. Cross-sectionally, calcaneal QUS correlates strongly with whole body DXA and may represent a viable diagnostic alternative in RCS. Longitudinally, the two methods do not correlate well, possibly reflecting that each method assesses distinct aspects of bone architecture.
COVID-19 is a multi-system infection with emerging evidence-based antiviral and anti-inflammatory therapies to improve disease prognosis. However, a subset of patients with COVID-19 signs and ...symptoms have repeatedly negative RT-PCR tests, leading to treatment hesitancy. We used comparative serology early in the COVID-19 pandemic when background seroprevalence was low to estimate the likelihood of COVID-19 infection among RT-PCR negative patients with clinical signs and/or symptoms compatible with COVID-19.
Between April and October 2020, we conducted serologic testing of patients with (i) signs and symptoms of COVID-19 who were repeatedly negative by RT-PCR ('Probables'; N = 20), (ii) signs and symptoms of COVID-19 but with a potential alternative diagnosis ('Suspects'; N = 15), (iii) no signs and symptoms of COVID-19 ('Non-suspects'; N = 43), (iv) RT-PCR confirmed COVID-19 patients (N = 40), and (v) pre-pandemic samples (N = 55).
Probables had similar seropositivity and levels of IgG and IgM antibodies as propensity-score matched RT-PCR confirmed COVID-19 patients (60.0% vs 80.0% for IgG, p-value = 0.13; 50.0% vs 72.5% for IgM, p-value = 0.10), but multi-fold higher seropositivity rates than Suspects and matched Non-suspects (60.0% vs 13.3% and 11.6% for IgG; 50.0% vs 0% and 4.7% for IgM respectively; p-values < 0.01). However, Probables were half as likely to receive COVID-19 treatment than the RT-PCR confirmed COVID-19 patients with similar disease severity.
Findings from this study indicate a high likelihood of acute COVID-19 among RT-PCR negative with typical signs/symptoms, but a common omission of COVID-19 therapies among these patients. Clinically diagnosed COVID-19, independent of RT-PCR positivity, thus has a potential vital role in guiding treatment decisions.
In 2019 there were 490,000 children under five living with HIV. Understanding the dynamics of HIV suppression and rebound in this age group is crucial to optimizing treatment strategies and ...increasing the likelihood of infants achieving and sustaining viral suppression. Here we studied data from a cohort of 122 perinatally-infected infants who initiated antiretroviral treatment (ART) early after birth and were followed for up to four years. These data included longitudinal measurements of viral load (VL) and CD4 T cell numbers, together with information regarding treatment adherence. We previously showed that the dynamics of HIV decline in 53 of these infants who suppressed VL within one year were similar to those in adults. However, in extending our analysis to all 122 infants, we find that a deterministic model of HIV infection in adults cannot explain the full diversity in infant trajectories. We therefore adapt this model to include imperfect ART adherence and natural CD4 T cell decline and reconstitution processes in infants. We find that individual variation in both processes must be included to obtain the best fits. We also find that infants with faster rates of CD4 reconstitution on ART were more likely to experience resurgences in VL. Overall, our findings highlight the importance of combining mathematical modeling with clinical data to disentangle the role of natural immune processes and viral dynamics during HIV infection.
The latent viral reservoir is the major obstacle to achieving HIV remission and necessitates life-long antiretroviral therapy (ART) for HIV-infected individuals. Studies in adults and children have ...found that initiating ART soon after infection is associated with a reduction in the size of the HIV-1 reservoir. Here we quantified cell-associated HIV-1 DNA in early-treated but currently older HIV-infected children suppressed on ART.
The study participants comprised of a cohort of 146 early-treated children with HIV-1 RNA <50 copies/ml enrolled as part of a clinical trial in Johannesburg, South Africa. A stored buffy coat sample collected after a median 4.3 years on ART and where HIV-1 RNA was <50 copies/ml was tested for cell-associated HIV-1 DNA levels. An in-house, semi-nested real-time quantitative hydrolysis probe PCR assay to detect total HIV-1 subtype C proviral DNA was used. Children were followed prospectively for up to 3 years after this measurement to investigate subsequent HIV-1 RNA rebound/failure while remaining on ART. Age at ART initiation, HIV-1 RNA decline prior to HIV-1 DNA measurement and other factors were investigated.
A gradient between age at ART initiation and later HIV-1 DNA levels was observed. When ART was started <2 months of age, the lowest levels of cell-associated HIV-1 DNA (median 1.4 log10copies/106 cells, interquartile range IQR 0.95-1.55) were observed compared to ART started at 2-4 months (median 1.68, IQR 1.26-1.97) or 5-14 months of age (median1.98, IQR 1.69-2.25). A low CD4 T-cell count pre-treatment predicted higher levels of HIV-1 DNA on later testing. The probability of HIV-1 RNA rebound >50 copies/ml whilst on ART within 3 years after the DNA measurement was 2.07 (95% CI: 1.352-3.167) times greater if the HIV-1 DNA level was above the median of 55 copies/106 cells.
Cell-associated HIV-1 DNA levels measured after more than 4 years on ART were lower the younger the age of the child when ART was initiated. This marker of the size of the viral reservoir also predicted subsequent viral rebound/treatment failure while ART was sustained. The results provide additional evidence of the benefits of prompt diagnosis and early ART initiation in newborns and infants.
Although the flipped classroom model has been widely adopted in medical education, reports on its use in graduate-level public health programs are limited. This study describes the design, ...implementation, and evaluation of a flipped classroom redesign of an introductory epidemiology course and compares it to a traditional model.
One hundred fifty Masters-level students enrolled in an introductory epidemiology course with a traditional format (in-person lecture and discussion section, at-home assignment; 2015, N = 72) and a flipped classroom format (at-home lecture, in-person discussion section and assignment; 2016, N = 78). Using mixed methods, we compared student characteristics, examination scores, and end-of-course evaluations of the 2016 flipped classroom format and the 2015 traditional format. Data on the flipped classroom format, including pre- and post-course surveys, open-ended questions, self-reports of section leader teaching practices, and classroom observations, were evaluated.
There were no statistically significant differences in examination scores or students' assessment of the course between 2015 (traditional) and 2016 (flipped). In 2016, 57.1% (36) of respondents to the end-of-course evaluation found watching video lectures at home to have a positive impact on their time management. Open-ended survey responses indicated a number of strengths of the flipped classroom approach, including the freedom to watch pre-recorded lectures at any time and the ability of section leaders to clarify targeted concepts. Suggestions for improvement focused on ways to increase regular interaction with lecturers.
There was no significant difference in students' performance on quantitative assessments comparing the traditional format to the flipped classroom format. The flipped format did allow for greater flexibility and applied learning opportunities at home and during discussion sections.
Repeat HAIs among frequently hospitalized patients may be contributing to the high rates of antibiotic resistance seen in gram-negative bacteria (GNB) in hospital settings. This systematic review ...examines the state of the literature assessing the association between repeat GNB HAIs and changes in antibiotic susceptibility patterns. A systematic search of English language published literature was conducted to identify studies in peer-reviewed journals from 2000 to 2015. Studies must have assessed drug resistance in repeat GNB infections longitudinally at the patient level. Two researchers independently reviewed search results for papers meeting inclusion criteria and extracted data. Risk of bias was assessed using a modified quality assessment tool based on the Checklist for Measuring Study Quality and the Quality Assessment Checklist for Cases Series. From 3385 articles identified in the search, seven met inclusion criteria. Five reported lower antibiotic susceptibility in repeated infections, one found a change but did not specify in which direction, and one reported no change. All studies were of low to average quality. Despite the dearth of studies examining repeat GNB infections, evidence suggests that repeat infections result in lower antibiotic susceptibility among hospitalized patients. Larger scale studies with strong methodology are warranted.
Background: Vaccine hesitancy remains a societal problem, including during the COVID-19 pandemic. New Jersey (NJ) Safe Schools Program provides work-based learning training to supervisory-level ...career–technical–vocational education teachers and administrators who have to consider varied state and local mandates concerning COVID-19 vaccination and exemptions. Methods: In early 2022, we distributed an online survey via PsychData to individuals trained between 2014 and 2022 to understand NJ teachers’ practices and concerns regarding COVID-19 vaccines. Overall, 269 completed the survey. We stratified data by vaccination status, number of doses, booster status, age, teaching experience, gender, race, county of work, and COVID-19 diagnosis status. Results: Overall, results suggested differences in COVID-19-related concerns, including access to, perceptions of, and confidence in COVID-19 vaccines and COVID-19-related practices. About 90.7% received the initial vaccine; 77.7% received the booster. About half the participants had received a positive COVID-19 diagnosis by the time of the survey; they were less likely to get the vaccine or booster if they had received the initial vaccine. Conclusions: Data suggested differences in levels of COVID-19-related concerns and confidence in, or importance of, vaccines when comparing different demographic factors and vaccination practices. The data informs efforts to understand factors affecting vaccine hesitancy among educational professionals.
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