Category: Nevin Manimala

J Am Acad Child Adolesc Psychiatry. 2023 Oct 18:S0890-8567(23)02136-6. doi: 10.1016/j.jaac.2023.10.004. Online ahead of print.

ABSTRACT

OBJECTIVE: Adolescence is a key developmental window that may determine long-term mental health. As schools may influence students’ mental health, we examined the association of school-level characteristics with students’ mental health over time.

METHOD: We analysed longitudinal data from a cluster randomised controlled trial on 8,376 students (55% female; aged 11-14 years at baseline) across 84 schools in the United Kingdom. Data collection started in the academic years 2016/2017 (Cohort 1) and 2017/2018 (Cohort 2), with follow-up at 1, 1.5, and 2 years. We explored students’ mental health (risk for depression (Center for Epidemiologic Studies-Depression Scale), social-emotional-behavioural difficulties (Strength and Difficulties Questionnaire)) and well-being (Warwick-Edinburgh Mental Well-Being Scale), and their relationship with student- and school-level characteristics, using multilevel regression models.

RESULTS: Mental health difficulties and poorer well-being increased over time, particularly in girls. Differences among schools represented a small but statistically significant proportion of variation (95% CI) in students’ mental health at each timepoint: depression: 1.7% (0.9%-2.5%) to 2.5% (1.6%-3.4%), social-emotional-behavioural difficulties: 1.9% (1.1%-2.7%) to 2.8% (2.1%-3.5%), and well-being: 1.8% (0.9%-2.7%) to 2.2% (1.4%-3.0%). Better student-rated school climate analysed as time-varying at the student- and school-level was associated with lower risk of depression (regression coefficient (95%CI) student-level: -4.25 (-4.48,-4.01), school-level: -4.28 (-5.81,-2.75)), fewer social-emotional-behavioural difficulties (student-level: -2.46 (-2.57,-2.35), school-level: -2.36 (-3.08,-1.63)), and higher well-being (student-level: 3.88 (3.70,4.05); school-level: 4.28 (3.17,5.38)), which was a stable relationship.

CONCLUSION: Student-rated school climate predicted mental health in early adolescence. Policy and system interventions that focus on school climate may promote students’ mental health.

PMID:37866473 | DOI:10.1016/j.jaac.2023.10.004

J Heart Lung Transplant. 2023 Oct 20:S1053-2498(23)02078-8. doi: 10.1016/j.healun.2023.10.014. Online ahead of print.

ABSTRACT

OBJECTIVE: The development of modern antiviral therapy for hepatitis C virus (HCV) has allowed for the transplantation of HCV nucleic acid amplification testing positive (NAT+) donor lungs with acceptable short-term outcomes. We sought to evaluate trends and mid-term outcomes of lung transplant recipients of HCV NAT+ donor allografts.

METHODS: All adults undergoing isolated lung transplantation in the United Network for Organ Sharing database from January 2016 to December 2022 were included in the study. Lung transplant recipients were stratified based on donor HCV status (HCV NAT+ vs NAT-). Propensity-score matching was used to adjust for differences between groups. Several outcomes, including acute rejection by one year, early (30-day and in-hospital) mortality and both 1- and 3-year survival were compared between matched groups.

RESULTS: A total of 16,725 patients underwent lung transplantation during the study period, with 489 (3%) receiving HCV NAT+ donor lungs. Regions 1 (18%), and 6/8 (both 0%) had the highest and lowest proportions, respectively, of HCV NAT+ donor transplants. Utilization of HCV NAT+ donors increased throughout the study period from 2 (0.1%) in 2016 to a peak of 117 (5%) in 2019. Donors who were HCV NAT+ were younger (34 vs 36 years, P<0.001), more often female (44% vs 39%, P<0.01) and more commonly died due to drug intoxication (56% vs 15%, P<0.001). Recipients of HCV NAT+ donor lungs were similar in age (62 vs 62 years, P=0.69) and female gender (43% vs 39%, P=0.15) but had lower lung allocation scores (38 vs 41, P<0.001) compared to others. Rates of acute rejection (13% vs 17%, P=0.09), early mortality (30-day: 2% vs 1%, P=0.59, in-hospital: 3% vs 4%, P=0.38) as well as 1- (90% vs 92%, P=0.29) and 3-year survival (69% vs 75%, P=0.13) were not significantly different between matched groups.

CONCLUSIONS: Lung transplant recipients of HCV NAT+ donor allografts experience similar rates of acute rejection, early mortality and 3-year survival compared to all other lung recipients. Increased use of HCV NAT+ donor allografts may help to expand the donor pool and alleviate donor shortages.

PMID:37866469 | DOI:10.1016/j.healun.2023.10.014

J Am Acad Dermatol. 2023 Oct 20:S0190-9622(23)03029-3. doi: 10.1016/j.jaad.2023.10.026. Online ahead of print.

ABSTRACT

BACKGROUND: Eblasakimab, an interleukin (IL)-13 receptor α1 antagonist, blocks IL-4 and IL-13 signaling through the type 2 receptor.

OBJECTIVE: The safety and efficacy of eblasakimab was evaluated in adults with moderate-to-severe atopic dermatitis (AD).

METHODS: In this phase 1b randomized, double-blinded study, 52 patients with moderate-to-severe AD received weekly subcutaneous injections of eblasakimab 200, 400, or 600 mg, or placebo for 8 weeks. Primary outcome was the incidence of treatment-emergent adverse events (TEAEs). Secondary outcomes included percentage change in the Eczema Area and Severity Index (EASI) from baseline; EASI improvement of at least 50%, 75%, or 90% from baseline; and percentage change in the peak-pruritus numeric rating scale score from baseline.

RESULTS: TEAEs were reported in 47% placebo and 71% eblasakimab patients; most were considered mild or moderate and did not lead to study discontinuation. At week 8 eblasakimab 600 mg showed statistically significant improvement in mean percentage change in EASI vs. placebo (-65% vs. -27%, P=0.014). Other key secondary physician- and patient-reported end points were met.

LIMITATIONS: Longer studies are required to confirm eblasakimab safety and efficacy in AD patients.

CONCLUSIONS: Treatment of adults with moderate-to-severe AD with eblasakimab was well-tolerated and associated with significant clinical improvements vs. placebo.

PMID:37866456 | DOI:10.1016/j.jaad.2023.10.026

Photodiagnosis Photodyn Ther. 2023 Oct 20:103855. doi: 10.1016/j.pdpdt.2023.103855. Online ahead of print.

ABSTRACT

AIM: To evaluate serum vitamin D levels in sub-types of retinal vascular occlusions and compare the levels in ischemic and non-ischemic presentations.

METHODS: This study included 50 patients of retinal vascular occlusions comprising central retinal vein occlusion, branch retinal vein occlusion, central retinal artery occlusion, branch retinal artery occlusion (study group) diagnosed on basis of clinical characteristics as well as investigations and an age and gender-matched healthy control group (control group). The study group was further classified into ischemic and non-ischemic subtypes and serum vitamin D levels were analysed and compared.

RESULTS: There were 50 patients of various sub-types of retinal vascular occlusions comprising 13 cases of CRVO, 30 cases of BRVO, 05 cases of CRAO, 02 cases of BRAO and 50 age and sex-matched controls. Mean BCVA and CMT in RVO patients was +1.12 log MAR, 346.72± 27.93µm while in control group was +0.37 log MAR, 236.22 ±3.71 µm which were statistically significant (p=0.004; p=0.002). The mean serum vitamin D value in study group was 18.39 ng/dl as compared to 32.31ng/dl in control group which was statistically significant (p=0.001). The difference in the baseline vitamin D value between the ischemic and non -ischemic sub groups among total vascular occlusion was found to be statistically significant (p= 0.010). However, baseline vitamin D levels difference among ischemic and non-ischemic cases in individual sub-types of vascular occlusion was statistically insignificant.

CONCLUSION: High prevalence of low serum vitamin D levels is seen in patients of retinal vascular occlusion spectrum diseases. Moreover, ischemic types of retinal vascular occlusion have significantly lower serum vitamin D levels as compared to non – ischemic despite having fewer no of patients in arterial occlusion sub-types. Therefore, vitamin D supplements may be considered as possible future targeted therapy in optimizing the severity of disease.

PMID:37866444 | DOI:10.1016/j.pdpdt.2023.103855

Photodiagnosis Photodyn Ther. 2023 Oct 20:103840. doi: 10.1016/j.pdpdt.2023.103840. Online ahead of print.

ABSTRACT

BACKGROUND: Photodynamic therapy (PDT) is a potential treatment for port-wine stains (PWS), but its effects on intraocular pressure (IOP) have not been reported. This study evaluated the efficacy of PDT for facial PWS and analyzed the changes in IOP before and after treatment.

METHODS: Data from 32 patients with facial PWS who underwent single PDT treatment at our department were collected. The patients were divided into three groups based on the location of the PWS. Group A (15 cases) involved the eyelid of the eye being measured; Group B (10 cases) was located near the eyes but did not involve the measured eyelid; and Group C (7 cases) was situated on the face but not near the eyes. IOP measurements were taken before and after treatment, and the efficacy and changes in IOP were analyzed.

RESULTS: The overall efficacy rates of single PDT were 84.37%, demonstrating superior efficacy for the pink type, age < 6 years, and skin lesions < 10 cm² (P < 0.05). The higher IOP was observed on the side with eyelid involvement of PWS (P < 0.001). The IOP of the affected side in Group A decreased by 2.13 ± 2.10 mmHg on average after treatment, which was statistically significant compared with the other two groups (P<0.05).

CONCLUSIONS: Eyelid involvement in PWS increases the risk of elevated IOP. Hemoporfin-mediated PDT can reduce the IOP in patients with PWS involving the eyelid within a safe range. PDT for facial PWS is considered to be safe and effective.

PMID:37866443 | DOI:10.1016/j.pdpdt.2023.103840

Lancet Child Adolesc Health. 2023 Oct 19:S2352-4642(23)00216-X. doi: 10.1016/S2352-4642(23)00216-X. Online ahead of print.

ABSTRACT

BACKGROUND: Paediatric health systems across high-income countries are facing avoidable adverse outcomes and increasing demands and costs. The aim of this study was to compare the effect of an enhanced usual care model with that of an integrated health-care model that offers local health clinics for general paediatric problems and early intervention and care for children and young people with tracer conditions.

METHODS: In this pragmatic two-arm cluster randomised controlled trial, we compared the Children and Young People’s Health Partnership (CYPHP) model of care versus enhanced usual care (EUC) among children registered at general practices in south London, UK. The CYPHP trial intervention was delivered between April 1, 2018, and June 30, 2021, and children younger than 16 years during the intervention period and registered at study practices on June 30, 2021, were included in the analysis. A restricted randomisation (1:1) following a computer-generated sequence was done by a masked independent statistician at the level of general practice cluster, stratified by borough (Lambeth or Southwark). Cluster allocation and data collection were masked, with unmasking of trial statisticians before analysis. The CYPHP model comprised all elements of EUC (electronic decision support, a primary care hotline, health checks, self-management support and health promotion, and resilience building and mental health first aid) plus local child health clinics delivered by paediatricians and general practitioners, and a nurse-led early intervention service for children with tracer conditions (asthma, eczema, and constipation). Primary outcomes were non-elective admissions (NELA; admissions coded as an emergency) among the whole trial population up to June 30, 2021, and paediatric quality of life (Pediatric Quality of Life Inventory [PedsQL]) among participants with tracer conditions at 6 months after recruitment. Secondary outcomes were primary and secondary care use, child mental health, parental wellbeing, standardised symptom scores for asthma, eczema, and constipation, health-care quality, and child absences from school and parent absences from work. The trial was registered on ClinicalTrials.gov, NCT03461848, and is complete.

FINDINGS: The trial was conducted between April 1, 2018, and Dec 31, 2021. In total, 23 general practice clusters, consisting of 70 practices with 97 970 registered children, were randomised to CYPHP (n=11) or EUC (n=12). We found no effect, at the population level, of CYPHP versus EUC on non-elective admissions during the intervention period (adjusted mean incidence rate ratio [IRR] 1·00 [95% CI 0·91 to 1·10], p=0·99). Among children with tracer conditions, we found no difference in paediatric quality of life (PedsQL score) at 6 months (adjusted mean difference -0·033 [95% CI -0·122 to 0·055], p=0·46). As a secondary outcome, among children with tracer conditions and requiring care, NELA rates at 12 months did not differ between the CYPHP and EUC groups (66·1 per 1000 person-years vs 75·3 per 1000 person-years; adjusted mean IRR 0·87 [0·61-1·22], p=0·42). In children requiring care, a statistically significant improvement was observed in eczema symptoms at 6 months from baseline in the CYPHP group versus the EUC group (adjusted mean difference -1·370 [-2·630 to -0·122], p=0·032). Quality of asthma care significantly improved among children in the CYPHP group compared with children in the EUC group. No significant improvement was seen for all other secondary outcomes.

INTERPRETATION: Although the CYPHP trial found a null effect for the primary outcomes, we found clinically important improvements in some secondary outcomes including care quality. Previous research has shown that large-scale system change requires time to observe a potential positive effect.

FUNDING: Guy’s and St Thomas Charity, the Lambeth and Southwark Clinical Commissioning Groups, and Evelina London Children’s Hospital.

PMID:37866369 | DOI:10.1016/S2352-4642(23)00216-X

Int Immunopharmacol. 2023 Oct 20;125(Pt A):111041. doi: 10.1016/j.intimp.2023.111041. Online ahead of print.

ABSTRACT

MAGEA family proteins are immunogenic and can produce corresponding autoantibodies, and we aim to evaluate the diagnostic value of anti-MAGEA family protein autoantibodies in esophageal squamous cell carcinoma (ESCC). Protein chip was used to detect the expression level of anti-MAGEA autoantibodies (IgG and IgM) in 20 mixed serum samples. Enzyme linked immunosorbent assay was adopted to determine the expression level of autoantibodies in 1019 serum samples (423 ESCC, 423 healthy control (HC), 173 benign esophageal disease (BED)), and stepwise logistic regression analysis was used for developing a diagnostic model. Eight anti-MAGEA autoantibodies were screened out based on the protein chip. The levels of 7 autoantibodies (MAGEA1-IgG, MAGEA3-IgG, MAGEA3-IgM, MAGEA4-IgG, MAGEA6-IgG, MAGEA10-IgG, MAGEA12-IgG) in ESCC were significantly higher than that in HC, and the levels of anti-MAGEA1 IgG, anti-MAGEA3-IgG, anti-MAGEA4-IgG, anti-MAGEA10-IgG and anti-MAGEA12-IgG autoantibodies in ESCC group were significantly higher than those in BED group. The area under curve (AUC), sensitivity and specificity of the logistic regression model (MAGEA1-IgG, MAGEA4-IgG, MAGEA6-IgG, MAGEA12-IgG) in the training set and the validation set were 0.725 and 0.698, 55.2% and 51.8%, 80.4% and 84.5%, respectively, in distinguishing ESCC and HC. The model also could distinguish between ESCC and BED, with the AUC of 0.743, sensitivity of 55.4% and specificity of 89.0%. The positive rate of the model combined with cytokeratin 19 fragment to diagnose ESCC reached 78.0%. The study identified anti-MAGEA autoantibodies with potential diagnostic value for ESCC, which may provide new promising for the detection of the disease.

PMID:37866309 | DOI:10.1016/j.intimp.2023.111041

Talanta. 2023 Oct 9;268(Pt 1):125295. doi: 10.1016/j.talanta.2023.125295. Online ahead of print.

ABSTRACT

BACKGROUND: The COVID-19 pandemic challenged the management of technical and human resources in intensive care units (ICU) across the world. Several long-term predictors for COVID-19 disease progression have been discovered. However, predictors to support short-term planning of resources and medication that can be translated to future pandemics are still missing. A workflow was established to identify a predictor for short-term COVID-19 disease progression in the acute phase of intensive care patients to support clinical decision-making.

METHODS: Thirty-two patients with SARS-CoV-2 infection were recruited on admission to the ICU and clinical data collected. During their hospitalization, plasma samples were acquired from each patient on multiple occasions, excepting one patient for which only one time point was possible, and the proteome (Inflammation, Immune Response and Organ Damage panels from Olink® Target 96), metabolome and lipidome (flow injection analysis and liquid chromatography-mass spectrometry) analyzed for each sample. Patient visits were grouped according to changes in disease severity based on their respiratory and organ function, and evaluated using a combination of statistical analysis and machine learning. The resulting short-term predictor from this multi-omics approach was compared to the human assessment of disease progression. Furthermore, the potential markers were compared to the baseline levels of 50 healthy subjects with no known SARS-CoV-2 or other viral infections.

RESULTS: A total of 124 clinical parameters, 271 proteins and 782 unique metabolites and lipids were assessed. The dimensionality of the dataset was reduced, selecting 47 from the 1177 parameters available following down-selection, to build the machine learning model. Subsequently, two proteins (C-C motif chemokine 7 (CCL7) and carbonic anhydrase 14 (CA14)) and one lipid (hexosylceramide 18:2; O2/20:0) were linked to disease progression in the studied SARS-CoV-2 infections. Thus, a predictor delivering the prognosis of an upcoming worsening of the patient’s condition up to five days in advance with a reasonable accuracy (79 % three days prior to event, 84 % four to five days prior to event) was found. Interestingly, the predictor’s performance was complementary to the clinicians’ capabilities to foresee a worsening of a patient.

CONCLUSION: This study presents a workflow to identify omics-based biomarkers to support clinical decision-making and resource management in the ICU. This was successfully applied to develop a short-term predictor for aggravation of COVID-19 symptoms. The applied methods can be adapted for future small cohort studies.

PMID:37866305 | DOI:10.1016/j.talanta.2023.125295

Integr Zool. 2023 Oct 22. doi: 10.1111/1749-4877.12776. Online ahead of print.

ABSTRACT

There is currently limited information regarding the levels of infection and distribution of sarcoptic mange in the wombat population throughout Australia. We analyzed cases of sarcoptic mange in bare-nosed wombats reported into WomSAT, a website and mobile phone application where citizen scientists can upload sightings of wombats, burrows, and sarcoptic mange status. We used Maxent software to predict locations and the environmental factors associated with sarcoptic mange occurrence in bare-nosed wombats. A total of 1379 sarcoptic mange-infected and 3043 non-sarcoptic mange-infected wombats were reported by 674 and 841 citizen scientists, respectively. Of all the wombats reported to WomSAT from 2015 to 2019, 31.2% were infected with sarcoptic mange. Sarcoptic mange in bare-nosed wombats was reported in 502 suburbs across four states. New South Wales had the highest number of sarcoptic mange cases reported to WomSAT. There was no statistically significant seasonal variation of sarcoptic mange levels in bare-nosed wombats. The model showed that Euclidean distance to urban areas was the highest contributing factor for sarcoptic mange occurrence. As distance to urban areas decreased, the suitability for sarcoptic mange increased. Annual precipitation was the next contributing factor in the model, with higher rainfall of 400-700 mm correlating to an increase in sarcoptic mange occurrence. As the data collected to date have provided the largest-scale contemporary distribution of sarcoptic mange in wombats, data should continue to be collected by citizen scientists as it is an easy and low-cost method of collecting data over large areas. We suggest targeting the identified hotspot areas and more site-specific studies for studying and mitigating sarcoptic mange in bare-nosed wombats.

PMID:37865949 | DOI:10.1111/1749-4877.12776

Ann Surg Oncol. 2023 Oct 22. doi: 10.1245/s10434-023-14429-9. Online ahead of print.

ABSTRACT

BACKGROUND: The surveillance guidelines following treatment completion for patients with high-grade sarcomas of the extremities are based largely upon expert opinions and consensus. In the current meta-analysis, we aim to study the utility of surveillance imaging to diagnose local and metastatic pulmonary relapses among patients with extremity soft tissue sarcomas and primary bone sarcomas.

PATIENTS AND METHODS: A meta-analysis was performed to assess the sensitivity, specificity and diagnostic odds ratio (DOR) of surveillance imaging to diagnose local and metastatic pulmonary relapse among patients with sarcoma of the extremities. In addition, impact of surveillance imaging on overall survival was assessed. Heterogeneity among eligible studies was evaluated by I² statistics. Sensitivity analysis was assessed using influence plots and Baujat plots.

RESULTS: Ten studies including 2160 patients with sarcoma were found eligible. For diagnoses of local recurrence based on surveillance imaging (nine studies, 1917 patients), the estimated sensitivity, specificity, and DOR were 13.6%, 99.5%, and 78.15, respectively. Only 16.7% of local recurrences were diagnosed based on imaging. For diagnoses of metastatic pulmonary recurrence (eight studies; 1868 patients), estimated sensitivity, specificity, and DOR were 76.1%, 99.3%, and 1059.9, respectively. A sensitivity analysis showed significant heterogeneity among included studies. None of the included studies showed an overall-survival benefit with the use of surveillance imaging.

CONCLUSION: The current meta-analysis challenges the notion of routine use of imaging to detect local relapse, while favoring chest imaging, using either chest radiography or computed tomography scan, for surveillance. Further studies are required to study the ideal surveillance strategy including timing and imaging modality.

PMID:37865942 | DOI:10.1245/s10434-023-14429-9