Category: Nevin Manimala

Diabetes Care. 2023 Jul 17:dc222426. doi: 10.2337/dc22-2426. Online ahead of print.

ABSTRACT

OBJECTIVE: In participants with type 2 diabetes (T2D) and HbA1c >9.0-10.0%, guidelines recommend treatment with basal-bolus insulin.

RESEARCH DESIGN AND METHODS: This randomized trial compared the efficacy and safety of insulin degludec and liraglutide (IDegLira) and basal-bolus among participants with high HbA1c ≥9.0-15.0%, previously treated with 2 or 3 oral agents and/or basal insulin, allocated (1:1) to basal-bolus (n = 73) or IDegLira (n = 72). The primary end point was noninferiority (0.4%) in HbA1c reduction between groups.

RESULTS: Among 145 participants (HbA1c 10.8% ± 1.3), there was no statistically significant difference in HbA1c reduction (3.18% ± 2.29 vs. 3.00% ± 1.79, P = 0.65; estimated treatment difference (ETD) 0.18%, 95% CI -0.59, 0.94) between the IDegLira and basal-bolus groups. IDegLira resulted in significantly lower rates of hypoglycemia <70 mg/dL (26% vs. 48%, P = 0.008; odds ratio 0.39, 95% CI 0.19, 0.78), and less weight gain (1.24 ± 8.33 vs. 5.84 ± 6.18 kg, P = 0.001; ETD -4.60, 95% CI -7.33, -1.87).

CONCLUSIONS: In participants with T2D and HbA1c ≥9.0-15.0%, IDegLira resulted in similar HbA1c reduction, less hypoglycemia, and less weight gain compared with the basal-bolus regimen.

PMID:37459574 | DOI:10.2337/dc22-2426

J Clin Oncol. 2023 Jul 17:JCO2202705. doi: 10.1200/JCO.22.02705. Online ahead of print.

ABSTRACT

PURPOSE: The ALL10 protocol improved outcomes for children with ALL by stratifying and adapting therapy into three minimal residual disease-defined risk groups: standard risk, medium risk (MR), and high risk. IKZF1-deleted (IKZF1del) ALL in the largest MR group still showed poor outcome, in line with protocols worldwide, accounting for a high number of overall relapses. ALL10 showed high toxicity in Down syndrome (DS) and excellent outcome in ETV6::RUNX1 ALL. Poor prednisone responders (PPRs) were treated as high risk in ALL10. In ALL11, we prolonged therapy for IKZF1del from 2 to 3 years. We reduced therapy for DS by omitting anthracyclines completely, for ETV6::RUNX1 in intensification, and for PPR by treatment as MR.

METHODS: Eight hundred nineteen patients with ALL (age, 1-18 years) were enrolled on ALL11 and stratified as in ALL10. Results were compared with those in ALL10.

RESULTS: The five-year overall survival (OS), event-free survival (EFS), cumulative risk of relapse (CIR), and death in complete remission on ALL11 were 94.2% (SE, 0.9%), 89.0% (1.2), 8.2% (1.1), and 2.3% (0.6), respectively. Prolonged maintenance for IKZF1del MR improved 5-year CIR by 2.2-fold (10.8% v 23.4%; P = .035) and EFS (87.1% v 72.3%; P = .019). Landmark analysis at 2 years from diagnosis showed a 2.9-fold reduction of CIR (25.6%-8.8%; P = .008) and EFS improvement (74.4%-91.2%; P = .007). Reduced therapy did not abrogate 5-year outcome for ETV6::RUNX1 (EFS, 98.3%; OS, 99.4%), DS (EFS, 87.0%; OS, 87.0%), and PPR (EFS, 81.1%; OS, 94.9%).

CONCLUSION: Children with IKZF1del ALL seem to benefit from prolonged maintenance therapy. Chemotherapy was successfully reduced for patients with ETV6::RUNX1, DS, and PPR ALL. It has to be noted that these results were obtained in a nonrandomized study using a historical control group.

PMID:37459571 | DOI:10.1200/JCO.22.02705

Pediatr Blood Cancer. 2023 Jul 17:e30572. doi: 10.1002/pbc.30572. Online ahead of print.

ABSTRACT

Neuroblastoma is the most common extra-cranial solid tumor in children and is known for its clinical heterogeneity. A greater understanding of the biology of this disease has led to both improved risk stratification and new approaches to therapy. Outcomes for children with low and intermediate risk disease are excellent overall, and efforts to decrease therapy for such patients have been largely successful. Although survival has improved over time for patients with high-risk disease and treatments evaluated in the relapse setting are now being moved into earlier phases of treatment, much work remains to improve survival and decrease therapy-related toxicities. Studies of highly annotated biobanked samples continue to lead to important insights regarding neuroblastoma biology. Such studies, along with correlative biology studies incorporated into therapeutic trials, are expected to continue to provide insights that lead to new and more effective therapies. A focus on translational science is accompanied by an emphasis on new agent development, optimized risk stratification, and international collaboration to address questions relevant to molecularly defined subsets of patients. In addition, the COG Neuroblastoma Committee is committed to addressing the patient/family experience, mitigating late effects of therapy, and studying social determinants of health in patients with neuroblastoma.

PMID:37458162 | DOI:10.1002/pbc.30572

Pediatr Obes. 2023 Jul 17:e13066. doi: 10.1111/ijpo.13066. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVES: Electronic phenotyping is a method of using electronic-health-record (EHR) data to automate identifying a patient/population with a characteristic of interest. This study determines validity of using EHR data of children with overweight/obesity to electronically phenotype evidence of clinician ‘attention’ to high body mass index (BMI) and each of four distinct comorbidities.

METHODS: We built five electronic phenotypes classifying 2-18-year-old children with overweight/obesity (n = 17,397) by electronic/health-record evidence of distinct attention to high body mass index, hypertension, lipid disorders, fatty liver, and prediabetes/diabetes. We reviewed, selected and cross-checked random charts to define items clinicians select in EHRs to build problem lists, and to order medications, laboratory tests and referrals to electronically classify attention to overweight/obesity and each comorbidity. Operating characteristics of each clinician-attention phenotype were determined by comparing comprehensive chart review by reviewers masked to electronic classification who adjudicated evidence of clinician attention to high BMI and each comorbidity.

RESULTS: In a random sample of 817 visit-records reviewed/coded, specificity of each electronic phenotype is 99%-100% (with PPVs ranging from 96.8% for prediabetes/diabetes to 100% for dyslipidemia and hypertension). Sensitivities of the attention classifications range from 69% for hypertension (NPV, 98.9%) to 84.7% for high-BMI attention (NPV, 92.3%).

CONCLUSIONS: Electronic phenotypes for clinician attention to overweight/obesity and distinct comorbidities are highly specific, with moderate (BMI) to modest (each comorbidity) sensitivity. The high specificity supports using phenotypes to identify children with prior high-BMI/comorbidity attention.

PMID:37458161 | DOI:10.1111/ijpo.13066

Vet Pathol. 2023 Jul 17:3009858231186189. doi: 10.1177/03009858231186189. Online ahead of print.

ABSTRACT

Phocine distemper virus (PDV) is a significant cause of mortality for phocid seals; however, the susceptibility of otariids to this virus is poorly understood. The authors used a lymph-node explant culture system from California sea lions (Zalophus californianus, CSL) to investigate: (1) the role of signaling lymphocyte activation molecule (SLAM) and nectin-4 in PDV infection and their cellular expression patterns, (2) if PDV induces transcriptional regulation of cell-entry receptors, and (3) the involvement of apoptosis in PDV infection. PDV replicated in the lymph-node explants with peak replication 3 days post-infection (dpi), but the replication was not sustained 4 to 5 dpi. The PDV+ cells co-localized SLAM and nectin-4. These cells expressed IBA1, indicating a histiocytic lineage. Comparison of receptor expression between infected and mock-infected lymph nodes suggested transcriptional downregulation of both receptors during the initial stage of infection and upregulation during the late stage of infection, but the values lack of statistical significance. Cleaved caspase-3+ cells were slightly increased in the infected lymph nodes compared with the mock-infected lymph node from 1 to 4 dpi, but without statistical significance, and a few apoptotic cells co-expressed PDV. The results suggest that lymph-node explants might be an important model to study PDV pathogenesis. CSLs have the potential to be infected with PDV, as they express both cell-entry receptors in histiocytes. The lack of statistical significance in the PDV replication, transcriptional regulation of viral receptors, and changes in apoptosis suggest that although CSL might be infected by PDV, they might be less susceptible than phocid species.

PMID:37458158 | DOI:10.1177/03009858231186189

Health Psychol Rev. 2023 Jul 17:1-107. doi: 10.1080/17437199.2023.2236180. Online ahead of print.

ABSTRACT

AbstractConsiderable research has examined how involvement in gay-affiliated communities is associated with sexual health behaviors in sexual minority men (i.e., gay, bisexual, and other men who have sex with men), yet findings in this domain are often contradictory and inconclusive. This systematic review aimed to (a) synthesize the related empirical literature, and (b) identify potential factors driving inconsistent findings. Peer-reviewed publications were included if they contained quantitative data and at least one measure of the statistical association between gay community involvement and sexual health behavior. The search strategy was implemented in six databases and returned 6,409 articles, of which 86 met the inclusion criteria. There was considerable heterogeneity in how gay community involvement was assessed across studies. Although gay community involvement was consistently associated with greater engagement in protective behaviors across studies, the association between gay community involvement and risk behaviors appeared to depend on how gay community involvement was conceptualized and measured (e.g., nightlife involvement vs. political activism). Findings emphasize a need for studies that employ validated measures that reflect the multidimensional nature of gay community involvement, as well as research designs better suited to address the causal effects of community involvement on HIV/STI transmission and prevention.

PMID:37458157 | DOI:10.1080/17437199.2023.2236180

Allergy. 2023 Jul 17. doi: 10.1111/all.15815. Online ahead of print.

ABSTRACT

BACKGROUND: The urban ambient air quality has been largely improved in the past decade. It is unknown whether childhood asthma prevalence is still increasing in ever top-ranking city of Shanghai, whether the improved air quality is beneficial for children’s asthma and what time window of exposure plays critical roles.

METHODS: Using a repeat cross-sectional design, we analyzed the association between early life exposure to particles and wheezing/asthma in each individual and combined surveys in 2011 and 2019, respectively, in 11,825 preschool children in Shanghai.

RESULTS: A significantly lower prevalence of doctor-diagnosed asthma (DDA) (6.6% vs. 10.5%, p < 0.001) and wheezing (10.5% vs. 23.2%, p < 0.001) was observed in 2019 compared to 2011. Exposure to fine particulate matter (PM_2.5 ), coarse particles (PM_2.5-10 ) and inhalable particles (PM₁₀ ) was decreased in 2019 by 6.3%, 35.4%, and 44.7% in uterus and 24.3%, 20.2%, and 31.8% in infancy, respectively. Multilevel log-binomial regression analysis showed exposure in infancy had independent association with wheezing/DDA adjusting for exposure in uterus. For each interquartile range (IQR) increase of infancy PM_2.5 , PM_2.5-10 and PM₁₀ exposure, the odds ratios were 1.39 (95% confidence interval (CI): 1.24-1.56), 1.51 (95% CI:1.15-1.98) and 1.53 (95% CI:1.27-1.85) for DDA, respectively. The distributed lag non-linear model showed the sensitive exposure window (SEW) was 5.5-11 months after birth. Stratified analysis showed the SEWs were at or shortly after weaning, but only in those with <6 months of exclusive breastfeeding.

CONCLUSIONS: Improved ambient PM benefits in decreasing childhood asthma prevalence. We firstly reported the finding of SEW to PM at or closely after weaning on childhood asthma.

PMID:37458141 | DOI:10.1111/all.15815

Stat Med. 2023 Aug 15;42(18):3145-3163. doi: 10.1002/sim.9769. Epub 2023 May 15.

ABSTRACT

Expression quantitative trait loci (eQTL) studies utilize regression models to explain the variance of gene expressions with genetic loci or single nucleotide polymorphisms (SNPs). However, regression models for eQTL are challenged by the presence of high dimensional non-sparse and correlated SNPs with small effects, and nonlinear relationships between responses and SNPs. Principal component analyses are commonly conducted for dimension reduction without considering responses. Because of that, this non-supervised learning method often does not work well when the focus is on discovery of the response-covariate relationship. We propose a new supervised structural dimensional reduction method for semiparametric regression models with high dimensional and correlated covariates; we extract low-dimensional latent features from a vast number of correlated SNPs while accounting for their relationships, possibly nonlinear, with gene expressions. Our model identifies important SNPs associated with gene expressions and estimates the association parameters via a likelihood-based algorithm. A GTEx data application on a cancer related gene is presented with 18 novel eQTLs detected by our method. In addition, extensive simulations show that our method outperforms the other competing methods in bias, efficiency, and computational cost.

PMID:37458069 | DOI:10.1002/sim.9769

J Xray Sci Technol. 2023 Jul 13. doi: 10.3233/XST-230095. Online ahead of print.

ABSTRACT

BACKGROUND: By providing both functional and anatomical information from a single scan, digital imaging technologies like PET/CT and PET/MRI hybrids are gaining popularity in medical imaging industry. In clinical practice, the median value (SUVmed) receives less attention owing to disagreements surrounding what defines a lesion, but the SUVmax value, which is a semi-quantitative statistic used to analyse PET and PET/CT images, is commonly used to evaluate lesions.

OBJECTIVE: This study aims to build an image processing technique with the purpose of automatically detecting and isolating lesions in PET/CT images, as well as measuring and assessing the SUVmed.

METHODS: The pictures are separated into their respective lesions using mathematical morphology and the crescent region, which are both part of the image processing method. In this research, a total of 18 different pictures of lesions were evaluated.

RESULTS: The findings of the study reveal that the threshold is satisfied by both the SUVmax and the SUVmed for most of the lesion types. However, in six instances, the SUVmax and SUVmed values are found to be in different courts.

CONCLUSION: The new information revealed by this study needs to be further investigated to determine if it has any practical value in diagnosing and monitoring lesions. However, results of this study suggest that SUVmed should receive more attention in the evaluation of lesions in PET and CT images.

PMID:37458060 | DOI:10.3233/XST-230095

Int J Risk Saf Med. 2023 Jun 21. doi: 10.3233/JRS-220066. Online ahead of print.

ABSTRACT

BACKGROUND: Healthcare organizations are among high-risk organizations due to the nature of their work as well as structural, physical and technological complexities. Accordingly, it is very important to use risk management and control programs in all departments of these organizations.

OBJECTIVE: The present study was conducted for the first time to evaluate the risk management status of the operating room and laboratory departments of Hamadan hospitals in 2022.

METHODS: In this descriptive-observational cross-sectional study, laboratory and operating room departments were selected as the research environment. To conduct this research, a valid and reliable questionnaire was used to collect data, and the data were analyzed using the SPSS 22 statistical software.

RESULTS: The findings of the present study showed that the overall mean score of risk management status for the laboratory and operating room departments was 2.66 ± 0.15 and 2.89 ± 0.13, respectively. Furthermore, there was no statistically significant difference in the mean scores of the research components based on work experience, education level, and gender.

CONCLUSION: It is suggested that the laboratory and operating room departments should focus more on adopting policies and solutions to improve the position of risk management, training and budget allocation for risk management.

PMID:37458049 | DOI:10.3233/JRS-220066