Tag: nevin manimala

J Clin Psychiatry. 2023 May 31;84(3):23f14933. doi: 10.4088/JCP.23f14933.

ABSTRACT

Statistics such as the mean difference (MD), standardized mean difference (SMD), relative risk (RR), odds ratio (OR), hazard ratio (HR), and others are meant to be examined along with their 95% confidence intervals (CIs), and their significance can be understood by viewing these CIs as compatibility intervals. The 95% CIs around the MD and SMD are easily understood because they are expressed along a linear scale. The 95% CIs around the RR, OR, and HR are harder to understand because they are expressed along an exponential scale; however, when the numbers are log-transformed, they are linearized, and understanding becomes easy. Another approach to understanding the CIs around the RR, OR, or HR is to examine the reciprocal of the lower limit of the CI; however, because the reciprocal also lies along an exponential scale, this method is inferior to the log-transformation method. These approaches may seem daunting, but the difficulty is an illusion because log transformation or reciprocal transformation takes only a few seconds when a statistical calculator is opened. All terms and concepts are explained with extreme simplification and with the help of examples.

PMID:37256636 | DOI:10.4088/JCP.23f14933

JAMA Netw Open. 2023 May 1;6(5):e2314934. doi: 10.1001/jamanetworkopen.2023.14934.

ABSTRACT

IMPORTANCE: Prenatal perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been linked to adverse birth outcomes. Previous research showed that higher folate concentrations are associated with lower blood PFAS concentrations in adolescents and adults. Further studies are needed to explore whether prenatal folate status mitigates PFAS-related adverse birth outcomes.

OBJECTIVE: To examine whether prenatal folate status modifies the negative associations between pregnancy PFAS concentrations, birth weight, and gestational age previously observed in a US cohort.

DESIGN, SETTING, AND PARTICIPANTS: In a prospective design, a prebirth cohort of mothers or pregnant women was recruited between April 1999 and November 2002, in Project Viva, a study conducted in eastern Massachusetts. Statistical analyses were performed from May 24 and October 25, 2022.

EXPOSURE: Plasma concentrations of 6 PFAS compounds were measured in early pregnancy (median gestational week, 9.6). Folate status was assessed through a food frequency questionnaire and measured in plasma samples collected in early pregnancy.

MAIN OUTCOMES AND MEASURES: Birth weight and gestational age, abstracted from delivery records; birth weight z score, standardized by gestational age and infant sex; low birth weight, defined as birth weight less than 2500 g; and preterm birth, defined as birth at less than 37 completed gestational weeks.

RESULTS: The cohort included a total of 1400 mother-singleton pairs. The mean (SD) age of the mothers was 32.21 (4.89) years. Most of the mothers were White (73.2%) and had a college degree or higher (69.1%). Early pregnancy plasma perfluorooctanoic acid concentration was associated with lower birth weight and birth weight z score only among mothers whose dietary folate intake (birth weight: β, -89.13 g; 95% CI, -166.84 to -11.42 g; birth weight z score: -0.13; 95% CI, -0.26 to -0.003) or plasma folate concentration (birth weight: -87.03 g; 95% CI, -180.11 to 6.05 g; birth weight z score: -0.14; 95% CI, -0.30 to 0.02) were below the 25th percentile (dietary: 660 μg/d, plasma: 14 ng/mL). No associations were found among mothers in the higher folate level groups, although the tests for heterogeneity did not reject the null. Associations between plasma perfluorooctane sulfonic acid and perfluorononanoate (PFNA) concentrations and lower birth weight, and between PFNA and earlier gestational age were noted only among mothers whose prenatal dietary folate intake or plasma folate concentration was in the lowest quartile range. No associations were found among mothers in higher folate status quartile groups.

CONCLUSIONS AND RELEVANCE: In this large, US prebirth cohort, early pregnancy exposure to select PFAS compounds was associated with adverse birth outcomes only among mothers below the 25th percentile of prenatal dietary or plasma folate levels.

PMID:37256622 | DOI:10.1001/jamanetworkopen.2023.14934

JAMA Netw Open. 2023 May 1;6(5):e2315315. doi: 10.1001/jamanetworkopen.2023.15315.

ABSTRACT

IMPORTANCE: Extremely preterm infants who develop bronchopulmonary dysplasia (BPD) are at a higher risk for adverse pulmonary and neurodevelopmental outcomes. In the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) Hydrocortisone Trial, hydrocortisone neither reduced rates of BPD or death nor increased rates of neurodevelopmental impairment (NDI) or death.

OBJECTIVE: To determine whether estimated risk for grades 2 to 3 BPD or death is associated with the effect of hydrocortisone on the composite outcomes of (1) grades 2 to 3 BPD or death and (2) moderate or severe NDI or death.

DESIGN, SETTING, AND PARTICIPANTS: This secondary post hoc analysis used data from the NICHD NRN Hydrocortisone Trial, which was a double-masked, placebo-controlled, randomized clinical trial conducted in 19 US academic centers. The NICHD HRN Hydrocortisone Trial enrolled infants born at a gestational age of less than 30 weeks who received mechanical ventilation for at least 7 days, including at the time of enrollment, and who were aged 14 to 28 postnatal days. Infants were enrolled between August 22, 2011, and February 4, 2018, with follow-up between 22 and 26 months of corrected age completed on March 29, 2020. Data were analyzed from September 13, 2021, to March 25, 2023.

INTERVENTION: Infants were randomized to 10 days of hydrocortisone or placebo treatment.

MAIN OUTCOMES AND MEASURES: Infants’ baseline risk of grades 2 to 3 BPD or death was estimated using the NICHD Neonatal BPD Outcome Estimator. Differences in absolute and relative treatment effects by baseline risk were evaluated using interaction terms in models fitted to the efficacy outcome of grades 2 to 3 BPD or death and the safety outcome of moderate or severe NDI or death by follow-up.

RESULTS: Among the 799 infants included in the analysis (421 boys [52.7%]), the mean (SD) gestational age was 24.9 (1.5) weeks, and the mean (SD) birth weight was 715 (167) g. The mean estimated baseline risk for grades 2 to 3 BPD or death was 54% (range, 18%-84%) in the study population. The interaction between treatment group and baseline risk was not statistically significant on a relative or absolute scale for grades 2 to 3 BPD or death; the size of the effect ranged from a relative risk of 1.13 (95% CI, 0.82-1.55) in quartile 1 to 0.94 (95% CI, 0.81-1.09) in quartile 4. Similarly, the interaction between treatment group and baseline risk was not significant on a relative or absolute scale for moderate or severe NDI or death; the size of the effect ranged from a relative risk of 1.04 (95% CI, 0.80-1.36) in quartile 1 to 0.99 (95% CI, 0.80-1.22) in quartile 4.

CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial, the effect of hydrocortisone vs placebo was not appreciably modified by baseline risk for grades 2 to 3 BPD or death.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01353313.

PMID:37256621 | DOI:10.1001/jamanetworkopen.2023.15315

JAMA Netw Open. 2023 May 1;6(5):e2316060. doi: 10.1001/jamanetworkopen.2023.16060.

ABSTRACT

IMPORTANCE: Rates of pediatric hospitalizations following an injury while riding an all-terrain vehicle (ATV) are increasing. Few studies have compared the rates of severe injuries among children, adolescents, and adults.

OBJECTIVES: To investigate whether younger ATV riders are at risk for more severe ATV-related injuries.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted using administrative data from hospitals in 9 provinces in Canada. Participants included patients admitted to hospitals with ATV-related injuries between 2002 and 2019. Statistical analysis was performed from June 2020 to September 2021.

EXPOSURES: The primary exposure was age younger than 16 years. Comparison groups were youths aged 16 to 20 years and adults aged 21 years and older.

MAIN OUTCOMES AND MEASURES: The main outcomes of interest were death, spinal cord injury, and an Injury Severity Score (ISS) greater than 25. Secondary outcomes were less severe injuries, including head injuries, crush type injuries, and fractures.

RESULTS: Among 52 745 patients with complete data, 15% were youths younger than 16 years, 13% were youths aged 16 to 20 years, 82% were male, and 47% lived in rural areas. After adjusting for covariates, the odds of dying were higher among youths aged 16 to 20 years (adjusted odds ratio [aOR], 1.64; 95% CI, 1.04-2.60) compared with those younger than 16 years. Youths aged 16 to 20 years also had higher odds of spinal cord injury (aOR, 2.72; 95% CI, 1.80-4.20) and an injury severity score greater than 25 (aOR, 1.63; 95% CI, 1.36-1.96) compared with youths 16 years of age or less. Sex-specific analyses revealed these associations were greater for male youths aged 16 to 20 years (spinal cord injury: aOR, 3.81; 95% CI, 1.38-11.10, and dying in a hospital: aOR, 4.37; 95% CI, 1.19-21.02) than female youths aged 16 to 20 years.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of patients hospitalized for ATV injuries in Canada, youths aged 16 to 20 years and adults aged 21 years and older were at an increased risk of death and severe injuries compared with youths younger than 16 years. The increased risk of death and severe injuries was most evident among male patients.

PMID:37256619 | DOI:10.1001/jamanetworkopen.2023.16060

JAMA Dermatol. 2023 May 31. doi: 10.1001/jamadermatol.2023.1338. Online ahead of print.

ABSTRACT

IMPORTANCE: Biosimilars have the potential to reduce costs for the management of moderate-to-severe psoriasis compared with originators. However, the extrapolation of evidence enables the approval of a biosimilar for use in indications held by the originator without directly being studied in clinical trials. Thus, biosimilars can be approved for psoriasis based on extrapolated evidence from other diseases. The availability of evidence for the effectiveness and safety of biosimilars for the treatment of psoriasis is therefore unclear.

OBJECTIVE: To compare the efficacy/effectiveness and safety of biosimilars with originator biologics for the treatment of patients with psoriasis.

EVIDENCE REVIEW: MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov, and The European Union Clinical Trials Register were searched in August 2022. Eligible studies were appraised using the Cochrane Risk of Bias 2 and ROBINS-I tools. All analyses were conducted from September 2022 to November 2022.

FINDINGS: Fourteen trials (10 adalimumab, 2 etanercept, 1 infliximab, and 1 ustekinumab) and 3 cohort studies (1 adalimumab, 1 etanercept, 1 infliximab and etanercept) were included. Twelve trials compared biosimilars with originators in originator-naive patients (starters), and 11 trials compared switching from originator to biosimilar (switchers) with continuous originator treatments. There was no clinically or statistically significant difference in rates of achieving 75% improvement in Psoriasis Area and Severity Index scores and risks of adverse events (AEs) at week 16 and week 52 between the comparators. Two cohort studies showed no difference in effectiveness and safety outcomes between originators and biosimilars, whereas 1 study reported more AEs in patients who switched to biosimilars of adalimumab at 12 months. Three trials showed low risk of bias, whereas 11 trials had moderate risk of bias. All cohort studies had moderate to high risk of bias.

CONCLUSIONS AND RELEVANCE: In this systematic review, there was no clinically or statistically significant difference in the efficacy and safety between biosimilars and originators for the treatment of patients with psoriasis. Most of the available evidence was based on randomized clinical trials, although high-quality real-world evidence was lacking. Future studies are needed to examine the long-term effectiveness and safety of biosimilars for the treatment of patients with psoriasis.

PMID:37256582 | DOI:10.1001/jamadermatol.2023.1338

Zoolog Sci. 2023 Jun;40(3):175-188. doi: 10.2108/zs220093.

ABSTRACT

The cheilostome bryozoan Cauloramphus magnus is common in the rocky intertidal habitat from southeastern Alaska to northern Japan. We examined its phylogeography by analyzing 576 bp of the mitochondrial COI (cox1) gene sequenced for 298 colonies from 16 localities in northern Japan. A maximum-likelihood phylogeny detected three main clades (A, B, C). Clades A and B occurred throughout the study area but differed in frequency, haplotype diversity, and haplotype distribution; each resolved into three divergent subclades (AI-III, BI-III). Clade A shared none among 15 haplotypes between the Pacific and Sea of Japan sides of Hokkaido. In contrast, Clade B (29 haplotypes) was thrice as common as Clade A among samples, with haplotype B28 common on both sides. Divergent Clade C (nine haplotypes) was detected only at Rumoi. K2P divergences of 12.3-28.3% among Clades A-C suggest these are distinct biological species, a conclusion supported by different inferred evolutionary histories. A bPTP species delimitation analysis indicated nine phylogenetic species among the sequences included in our phylogeny (AI-III, BI-III, C, and one specimen each from Alaska and the Commander Islands), with K2P divergences of 3.9-6.5% among subclades in A or B. Statistical and principal components analyses suggested weak morphological differentiation between Clades A + B and C, although overlapping ranges of measurements preclude identification to clade; these three clades are morphologically cryptic. For taxonomy, we suggest retaining the name C. magnus for lineages within this species complex across its range, followed by a clade designation, if known.

PMID:37256564 | DOI:10.2108/zs220093

Phys Chem Chem Phys. 2023 May 31. doi: 10.1039/d3cp01404e. Online ahead of print.

ABSTRACT

This study comprehensively investigates the efficiency of the formulation of tetraethoxysilane (TEOS) and 3-aminopropyltriethoxysilane (APTES) copolymer in sol-gel syntheses as part of a multivariate experiment. A methodology-based response surface was used to estimate the influence of independent variables such as polymerization time and temperature, as well as the ratio of TEOS and APTES components on the surface charge response function and product yield, and in order to predict the best response values. Analysis of variance showed that when assessing the value of the zeta potential, the polymerization temperature and the ratio of components are statistically significant factors, but on the other hand, when assessing the yield of the finished product, only the ratio of components is significant. The combination of various options for temperature, time and ratio of components allows one to obtain a zeta potential in the range from +61.2 mV to -48.8 mV and a product yield of up to 4.7 g. Evaluation of the data with TGA-DTA, FTIR-ATR, and ELS methods showed an unexpected result, according to which the highest degree of polymerization and the highest surface charge were inherent in an amino-deficient system. Thus, the smaller the amino component in the system (the APTES-TEOS molar ratio is 0.25), the more efficient the polycondensation is over the absorption area of the Si-O-Si band, and the higher the zeta potential.

PMID:37256559 | DOI:10.1039/d3cp01404e

Int J Clin Oncol. 2023 May 31. doi: 10.1007/s10147-023-02356-4. Online ahead of print.

ABSTRACT

BACKGROUND: Advances in whole-slide image capture and computer image analyses using deep learning technologies have enabled the development of computer-assisted diagnostics in pathology. Herein, we built a deep learning algorithm to detect lymph node (LN) metastasis on whole-slide images of LNs retrieved from patients with gastric adenocarcinoma and evaluated its performance in clinical settings.

METHODS: We randomly selected 18 patients with gastric adenocarcinoma who underwent surgery with curative intent and were positive for LN metastasis at Chiba University Hospital. A ResNet-152-based assistance system was established to detect LN metastases and to outline regions that are highly probable for metastasis in LN images. Reference standards comprising 70 LN images from two different institutions were reviewed by six pathologists with or without algorithm assistance, and their diagnostic performances were compared between the two settings.

RESULTS: No statistically significant differences were observed between these two settings regarding sensitivity, review time, or confidence levels in classifying macrometastases, isolated tumor cells, and metastasis-negative. Meanwhile, the sensitivity for detecting micrometastases significantly improved with algorithm assistance, although the review time was significantly longer than that without assistance. Analysis of the algorithm’s sensitivity in detecting metastasis in the reference standard indicated an area under the curve of 0.869, whereas that for the detection of micrometastases was 0.785.

CONCLUSIONS: A wide variety of histological types in gastric adenocarcinoma could account for these relatively low performances; however, this level of algorithm performance could suffice to help pathologists improve diagnostic accuracy.

PMID:37256523 | DOI:10.1007/s10147-023-02356-4

Alzheimers Dement. 2023 May 31. doi: 10.1002/alz.13160. Online ahead of print.

ABSTRACT

OBJECTIVE: The Longitudinal Early-Onset Alzheimer’s Disease Study (LEADS) seeks to provide comprehensive understanding of early-onset Alzheimer’s disease (EOAD; onset <65 years), with the current study profiling baseline clinical, cognitive, biomarker, and genetic characteristics of the cohort nearing the data-collection mid-point.

METHODS: Data from 371 LEADS participants were compared based on diagnostic group classification (cognitively normal [n = 89], amyloid-positive EOAD [n = 212], and amyloid-negative early-onset non-Alzheimer’s disease [EOnonAD; n = 70]).

RESULTS: Cognitive performance was worse for EOAD than other groups, and EOAD participants were apolipoprotein E (APOE) ε4 homozygotes at higher rates. An amnestic presentation was common among impaired participants (81%), with several clinical phenotypes present. LEADS participants generally consented at high rates to optional trial procedures.

CONCLUSIONS: We present the most comprehensive baseline characterization of sporadic EOAD in the United States to date. EOAD presents with widespread cognitive impairment within and across clinical phenotypes, with differences in APOE ε4 allele carrier status appearing to be relevant.

HIGHLIGHTS: Findings represent the most comprehensive baseline characterization of sporadic early-onset Alzheimer’s disease (EOAD) to date. Cognitive impairment was widespread for EOAD participants and more severe than other groups. EOAD participants were homozygous apolipoprotein E (APOE) ε4 carriers at higher rates than the EOnonAD group. Amnestic presentation predominated in EOAD and EOnonAD participants, but other clinical phenotypes were present.

PMID:37256497 | DOI:10.1002/alz.13160

Appl Biochem Biotechnol. 2023 May 31. doi: 10.1007/s12010-023-04573-z. Online ahead of print.

ABSTRACT

Gentamicin (GM) is an aminoglycoside antibiotic used to treat bacterial infections. Nephrotoxicity refers to the impairments of the kidneys caused by the use of GM and can result in decreased kidney function and in severe cases, kidney failure. Aronia melanocarpa extract (AME), also known as the black chokeberry, has been used for its protective effects on the kidneys. AME concentration of 3.38 mg/kg (max antioxidant activity in vitro) was used to determine its effectiveness against induced nephropathy during 30 days. GM treatment caused significant hypoalbuminemia and high values of globulins, creatinine, and urea compared to the control group. GM application lead to hemolysis occurrence, echinocytosis, and platelets aggregation. Significantly high values of segmented neutrophils and low values of non-segmented neutrophils were recorded in the blood of rats treated with chokeberry extract (AME). In the pre-treatment (AME + GM), severe hypochromic anemia and a significant improvement in hematological parameters, as well as a reduction of anemia in the post-treatment (GM + AME), were noted. Post-treatment AME also significantly regulates urea and creatinine values. Statistically significantly low hemoglobin values were found in all groups treated with AME. Current study suggests that compounds in the AME have a moderate beneficial effect against renal injury and anti-inflammatory properties that may help protect the kidneys from injury caused by GM.

PMID:37256488 | DOI:10.1007/s12010-023-04573-z