Category: Nevin Manimala

Nat Microbiol. 2021 Dec 31. doi: 10.1038/s41564-021-01029-0. Online ahead of print.

ABSTRACT

Global and national surveillance of SARS-CoV-2 epidemiology is mostly based on targeted schemes focused on testing individuals with symptoms. These tested groups are often unrepresentative of the wider population and exhibit test positivity rates that are biased upwards compared with the true population prevalence. Such data are routinely used to infer infection prevalence and the effective reproduction number, R_t, which affects public health policy. Here, we describe a causal framework that provides debiased fine-scale spatiotemporal estimates by combining targeted test counts with data from a randomized surveillance study in the United Kingdom called REACT. Our probabilistic model includes a bias parameter that captures the increased probability of an infected individual being tested, relative to a non-infected individual, and transforms observed test counts to debiased estimates of the true underlying local prevalence and R_t. We validated our approach on held-out REACT data over a 7-month period. Furthermore, our local estimates of R_t are indicative of 1-week- and 2-week-ahead changes in SARS-CoV-2-positive case numbers. We also observed increases in estimated local prevalence and R_t that reflect the spread of the Alpha and Delta variants. Our results illustrate how randomized surveys can augment targeted testing to improve statistical accuracy in monitoring the spread of emerging and ongoing infectious disease.

PMID:34972825 | DOI:10.1038/s41564-021-01029-0

Am J Crit Care. 2022 Jan 1;31(1):65-72. doi: 10.4037/ajcc2022732.

ABSTRACT

BACKGROUND: The Barthel Index, originally developed and validated to assess activities of daily living in patients with neuromuscular disorders, is commonly used in research and clinical practice involving critically ill patients.

OBJECTIVES: To evaluate the internal consistency, reliability, measurement error, and construct validity of the Barthel Index used at intensive care unit discharge.

METHODS: In this observational study, 2 physiotherapists measured the physical functioning of 122 patients at intensive care unit discharge, using the Barthel Index and other measurement instruments.

RESULTS: The patients had a median (IQR) age of 56 (47-66) years, and 62 patients (51%) were male. The primary reason for intensive care unit admission was sepsis (28 patients [23%]), and 83 patients (68%) were receiving mechanical ventilation. The Cronbach α value indicating internal consistency was 0.81. For interrater reliability, the intraclass correlation coefficient for the total score was 0.98 (95% CI, 0.97-0.98; P < .001) and the κ statistic for the individual items was 0.54 to 0.94. The standard error of measurement was 7.22, the smallest detectable change was 20.01, and the 95% limits of agreement were -10.3 and 11.8. The Barthel Index showed moderate to high correlations with the other physical functioning measurement instruments (ρ = 0.57 to 0.88; P < .001 for all).

CONCLUSION: The Barthel Index is a reliable and valid instrument for assessing physical functioning at intensive care unit discharge.

PMID:34972844 | DOI:10.4037/ajcc2022732

Addiction. 2021 Dec 31. doi: 10.1111/add.15786. Online ahead of print.

ABSTRACT

AIMS: To compare quantitatively the efficacy and tolerability of pharmacologically active interventions in the treatment and prevention of alcohol-induced hangover.

METHODS: Systematic review of placebo-controlled randomised trials in healthy adults that evaluated any pharmacologically active intervention in the treatment or prevention of hangover. We searched Medline, Embase, PsycINFO and CENTRAL from database inception until 1^st August 2021. The primary efficacy outcome was any continuous measure of overall hangover symptoms and the primary tolerability outcome the number of people dropping out due to adverse events (AEs). Quality was assessed using the Grading of Recommendations Assessment Development and Evaluation (GRADE) framework.

RESULTS: 21 studies were included reporting on 386 participants. No two studies reported on the same intervention; as such, meta-analysis could not be undertaken. Methodological concerns and imprecision resulted in all studied efficacy outcomes being rated as very low quality. When compared with placebo, individual studies reported a statistically significant reduction in the mean percentage overall hangover symptom score for clove extract (42.5% vs. 19.0%, p<0.001), tolfenamic acid (84.0% vs. 50.0%, p<0.001), pyritinol (34.1% vs. 16.2%, p<0.01), Hovenia dulcis fruit extract (p=0.029), L-cysteine (p=0.043), red ginseng (21.1% vs. 14.0%, p<0.05) and Korean pear juice (41.5% vs 33.3%, p<0.05). All studied tolerability outcomes were of low or very low quality with no studies reporting any drop-outs due to AEs.

CONCLUSIONS: Only very low quality evidence of efficacy is available to recommend any pharmacologically active intervention for the treatment or prevention of alcohol-induced hangover. Of the limited interventions studied, all had favourable tolerability profiles and very low quality evidence suggests clove extract, tolfenamic acid, and pyritinol may most warrant further study.

PMID:34972259 | DOI:10.1111/add.15786

FASEB J. 2022 Feb;36(2):e22124. doi: 10.1096/fj.202101332R.

ABSTRACT

Nerve growth factor-induced gene B (Nur77) has been shown to ameliorate several biological processes in chronic diseases, including inflammatory response, cellular proliferation, and metabolism. Chronic kidney disease (CKD) is characterized by tubulointerstitial fibrosis for which no targeted therapies are available as yet. In this study, we performed in vivo and in vitro experiments to demonstrate that Nur77 targets fibrosis signals and attenuates renal tubulointerstitial fibrosis during the aging process. We observed that the TGF-β/Smads signal pathway was significantly suppressed by Nur77, suggesting that Nur77 controlled the activation of key steps in TGF-β/Smads signaling. We further showed that Nur77 interacted with Smad7, the main repressor of nuclear translocation of Smad2/3, and stabilized Smad7 protein homeostasis. Nur77 deficiency resulted in Smad7 degradation, aggravating Smad2/3 phosphorylation, and promoting transcription of its downstream target genes, ACTA2 and collagen I. Our findings demonstrate that Nur77 is a potential therapeutic target for age-related kidney diseases including CKD. Maintenance of Nur77 may be an effective strategy for blocking renal tubulointerstitial fibrosis and improving renal function in the elderly.

PMID:34972249 | DOI:10.1096/fj.202101332R

Chem Senses. 2022 Jan 1;47:bjab052. doi: 10.1093/chemse/bjab052.

ABSTRACT

CD36 and GNAT3 mediate taste responses, with CD36 acting as a lipid detector and GNAT3 acting as the α subunit of gustducin, a G protein governing sweet, savory, and bitter transduction. Strikingly, the genes encoding CD36 and GNAT3 are genomically superimposed, with CD36 completely encompassing GNAT3. To characterize genetic variation across the CD36-GNAT3 region, its implications for phenotypic diversity, and its recent evolution, we analyzed from ~2,500 worldwide subjects sequenced by the 1000 Genomes Project (1000GP). CD36-GNAT3 harbored extensive diversity including 8,688 single-nucleotide polymorphisms (SNPs), 414 indels, and other complex variants. Sliding window analyses revealed that nucleotide diversity and population differentiation across CD36-GNAT3 were consistent with genome-wide trends in the 1000GP (π = 0.10%, P = 0.64; FST = 9.0%, P = 0.57). In addition, functional predictions using SIFT and PolyPhen-2 identified 60 variants likely to alter protein function, and they were in weak linkage disequilibrium (r2 < 0.17), suggesting their effects are largely independent. However, the frequencies of predicted functional variants were low (P¯ = 0.0013), indicating their contributions to phenotypic variance on population scales are limited. Tests using Tajima’s D statistic revealed that pressures from natural selection have been relaxed across most of CD36-GNAT3 during its recent history (0.39 < P < 0.67). However, CD36 exons showed signs of local adaptation consistent with prior reports (P < 0.035). Thus, CD36 and GNAT3 harbor numerous variants predicted to affect taste sensitivity, but most are rare and phenotypic variance on a population level is likely mediated by a small number of sites.

PMID:34972209 | DOI:10.1093/chemse/bjab052

Thorac Cardiovasc Surg. 2021 Dec 31. doi: 10.1055/s-0041-1740539. Online ahead of print.

ABSTRACT

BACKGROUND: Decellularized pulmonary homografts are being increasingly adopted for right ventricular outflow tract reconstruction in adult patients undergoing the Ross procedure. Few reports presented Matrix PplusN xenograft (Matrix) in a negative light. The objective of this study was to compare our midterm outcomes of Matrix xenograft versus standard cryopreserved pulmonary homograft (CPHG).

METHODS: Eighteen patients received Matrix xenograft between January 2012 and June 2016, whereas 66 patients received CPHG. Using nonparametric statistical tests and survival analysis, we compared midterm echocardiographic and clinical outcomes between the groups.

RESULTS: Except for significant age difference (the Matrix group was significantly older with 57 ± 8 years than the CPHG group, 48 ± 9 years, p = 0.02), the groups were similar in all other baseline characteristics. There were no significant differences in cardiopulmonary bypass times (208.3 ± 32.1 vs. 202.8 ± 34.8) or in cross-clamp times (174 ± 33.9 vs. 184.4 ± 31.1) for Matrix and CPHG, respectively. The Matrix group had significantly inferior freedom from reintervention than the CPHG group with 77.8 versus 98.5% (p = 0.02). Freedom from pulmonary valve regurgitation ≥ 2 was not significantly different between the groups with 82.4 versus 90.5% for Matrix versus CPHG, respectively. After median follow-up of 4.9 years, Matrix xenograft developed significantly higher peak pressure gradients compared with CPHG (20.4 ± 15.5 vs. 12.2 ± 9.0 mm Hg; p = 0.04).

CONCLUSION: After 5 years of clinical and echocardiographic follow-up, the decellularized Matrix xenograft had inferior freedom from reintervention compared with the standard CPHG. Closer follow-up is necessary to avoid progression of valve failure into right ventricular deterioration.

PMID:34972237 | DOI:10.1055/s-0041-1740539

PLoS One. 2021 Dec 31;16(12):e0262145. doi: 10.1371/journal.pone.0262145. eCollection 2021.

ABSTRACT

User-friendly interfaces have been increasingly used to facilitate the learning of advanced statistical methodology, especially for students with only minimal statistical training. In this paper, we illustrate the use of MBGapp for teaching geostatistical analysis to population health scientists. Using a case-study on Loa loa infections, we show how MBGapp can be used to teach the different stages of a geostatistical analysis in a more interactive fashion. For wider accessibility and usability, MBGapp is available as an R package and as a Shiny web-application that can be freely accessed on any web browser. In addition to MBGapp, we also present an auxiliary Shiny app, called VariagramApp, that can be used to aid the teaching of Gaussian processes in one and two dimensions using simulations.

PMID:34972193 | DOI:10.1371/journal.pone.0262145

PLoS One. 2021 Dec 31;16(12):e0262171. doi: 10.1371/journal.pone.0262171. eCollection 2021.

ABSTRACT

OBJECTIVE: The Childhood Diabetes Registry of Saxony has been existing since 1999. The aim of this study was to investigate the incidence rates, cohort and point prevalence, and the trends of type 1 diabetes among children and adolescents based on the registry data over the past 21 years.

METHODS: A completeness check of the Childhood Diabetes Registry of Saxony for the observation period 2012-2019 was performed using the capture-recapture method. The age-standardized incidence rates per 100,000 person years (PY) were estimated for the observation period 1999-2019. Prevalence was estimated per 100,000 children and adolescents as the point prevalence of five consecutive years, and as a cohort prevalence for the birth cohorts, which result from the difference of age and year at diagnosis. Trend analyses were executed using join point regression.

RESULTS: A completeness of 98% (95% CI 89-100) was determined for the period from 2012 to 2019. The standardized incidence rate of type 1 diabetes among children and adolescents increased from 17.1 per 100,000 PY in 1999 to 24.7 per 100,000 PY in 2019. If this trend continues, the incidence rate will increase to 34.8 (95% CI 24.4-49.6) per 100,000 PY in 2030. The point prevalence of 5 consecutive years did not show a continuous trend over time. According to this method, the prevalence reached a plateau in the last segment (2013-2019). The calculation of cohort prevalence indicated a continuous increase from 2013 to 2019 with no significant statistical difference in terms of sex.

CONCLUSION: The point prevalence and the last incidence rates indicate that type 1 diabetes of children and adolescents is slowing down or has reached a plateau in Saxony. Nevertheless, the cohort prevalence predicts a steady increase. Future studies should continue investigating these trends in a longer observation period and consider including possible correlating environmental factors.

PMID:34972197 | DOI:10.1371/journal.pone.0262171

PLoS One. 2021 Dec 31;16(12):e0261951. doi: 10.1371/journal.pone.0261951. eCollection 2021.

ABSTRACT

PURPOSE: Maternal surgical site infection after cesarean delivery is a clinical problem which contributes to significant morbidity and mortality. In Ethiopia admissions following cesarean section due to surgical site infection have been routine activities of health care institutions but there is limited scientific evidence on both the magnitude of the problem and factors associated with it making prevention mechanisms less effective. Therefore, this study aimed to assess magnitude and risk factors of post-cesarean section surgical site infection at primary hospitals of East Gojjam Zone, Northwest Ethiopia.

METHODS: Institution-based cross sectional study with retrospective chart review was conducted from September 10-30 /2020 at 3 randomly selected primary hospitals of east Gojjam zone. The data were entered in Epi data version 3.1 and exported to Statistical Package for Social Science Software version 26. Post-cesarean section surgical site infection was measured based on disease classification and definition of the term by Center for Disease Control and Prevention. After checking for presence of multicollinarity, presence and degree of association of factors with outcome variable were computed through logistic regression analysis. Factors with P value ≤ 0.2 in bi-variable logistic regression analysis were included in the multivariable logistic regression analysis and those variables with P-value of <0.05 in multivariable analysis were considered statistically significant.

RESULT: From 622 medical records of women who underwent cesarean section, 77 (12.4%) of them developed surgical site infection. Rural residence [(AOR = 2.30, 95%CI: (1.29, 4.09)], duration of labor greater than 24hrs [(AOR = 3.48, 95%CI: (1.49, 8.09)], rupture of membrane>12hrs[(AOR = 4.61,95%CI:(2.34,9.09)], hypertension[(AOR = 3.14,95%CI:(1.29,7.59)] and preoperative Hematocrit ≤30%[(AOR = 3.22,95%CI:(1.25,8.31)] were factors significantly associated with post-cesarean section surgical site infections.

CONCLUSION: Magnitude of post-cesarean section surgical site infection was a significant problem in primary hospitals. Minimizing prolonged labor; minimize early rupture of membrane, properly managing patients with comorbidities like hypertension, strengthen prophylaxis and treatment for anemia during antenatal care and raising awareness for rural residents can reduce the problem. Zonal police makers should give emphasis to reduce its burden.

PMID:34972176 | DOI:10.1371/journal.pone.0261951

PLoS One. 2021 Dec 31;16(12):e0261974. doi: 10.1371/journal.pone.0261974. eCollection 2021.

ABSTRACT

INTRODUCTION: Obstetric intensive care unit admission (ICU) suggests severe morbidity. However, there is no available data on the subject in Ghana. This retrospective review was conducted to determine the indications for obstetric ICU admission, their outcomes and factors influencing these outcomes to aid continuous quality improvement in obstetric care.

METHODS: This was a retrospective review conducted in a tertiary hospital in Ghana. Data on participant characteristics including age and whether participant was intubated were collected from patient records for all obstetric ICU admissions from 1st January 2010 to 31st December 2019. Descriptive statistics were presented as frequencies, proportions and charts. Hazard ratios were generated for relations between obstetric ICU admission outcome and participant characteristics. A p-value <0.05 was deemed statistically significant.

RESULTS: There were 443 obstetric ICU admissions over the review period making up 25.7% of all ICU admissions. The commonest indications for obstetric ICU admissions were hypertensive disorders of pregnancy (70.4%, n = 312/443), hemorrhage (14.4%, n = 64/443) and sepsis (9.3%, n = 41/443). The case fatality rates for hypertension, hemorrhage, and sepsis were 17.6%, 37.5%, and 63.4% respectively. The obstetric ICU mortality rate was 26% (115/443) over the review period. Age ≥25 years and a need for mechanical ventilation carried increased mortality risks following ICU admission while surgery in the index pregnancy was associated with a reduced risk of death.

CONCLUSION: Hypertension, haemorrhage and sepsis are the leading indications for obstetric ICU admissions. Thus, preeclampsia screening and prevention, as well as intensifying antenatal education on the danger signs of pregnancy can minimize obstetric complications. The establishment of an obstetric HDU in CCTH and the strengthening of communication between specialists and the healthcare providers in the lower facilities, are also essential for improved pregnancy outcomes. Further studies are needed to better appreciate the wider issues underlying obstetric ICU admission outcomes.

PLAIN LANGUAGE SUMMARY: This was a review of the reasons for admitting severely-ill pregnant women and women who had delivered within the past 42 days to the intensive care unit (ICU), the admission outcomes and risk factors associated with ICU mortality in a tertiary hospital in a low-resource country. High blood pressure and its complications, bleeding and severe infections were observed as the three most significant reasons for ICU admissions in decreasing order of significance. Pre-existing medical conditions and those arising as a result of, or aggravated by pregnancy; obstructed labour and post-operative monitoring were the other reasons for ICU admission over the study period. Overall, 26% of the admitted patients died at the ICU and maternal age of at least 25 years and the need for intubation were identified as risk factors for ICU deaths. Attention must be paid to high blood pressure during pregnancy.

PMID:34972184 | DOI:10.1371/journal.pone.0261974