Category: Nevin Manimala

J Child Adolesc Psychopharmacol. 2023 May 17. doi: 10.1089/cap.2023.0006. Online ahead of print.

ABSTRACT

Objectives: (1) To examine psychiatric and developmental comorbidities in school-age children and adolescents with Autism in a university-affiliated urban developmental center that serves children with developmental disabilities, and (2) to compare comorbidities by age groups. Methods: Review of all school-age children and adolescents evaluated and diagnosed with autism from 1/2019 to 1/2022. Data included: Demographics (age, gender, race/ethnic group, bilingual English/Spanish households) and other developmental and psychiatric diagnoses besides autism, including language disorder, specific learning disorders (LD), attention-deficit/hyperactivity disorder (ADHD), intellectual disabilities (ID), anxiety disorders (i.e., generalized anxiety disorder, anxiety disorder, unspecified, social anxiety disorder), and depressive disorders (i.e., major depressive disorder, depressive disorder, unspecified). Statistics included chi-square, and nonparametric tests, comorbidities were compared between school-age children and adolescents. Results: Of all children evaluated in that period (n = 599), 119 (20%) were diagnosed with autism, 97 (81%) boys, age 11.8 ± 3 years old, 46 (39%) bilingual English/Spanish households; 65 (55%) were school-age children and 54 (45%) were adolescents (age = 12-18). Of the 119, 115 (96%) presented with one or more co-occurring conditions, including language disorder in 101 (85%), LD in 23 (19%), ADHD in 50 (42%), and ID in 30 (25%). Psychiatric co-occurring conditions included anxiety disorders in 24 (20%) and depressive disorders in 8 (6%). School-age children with autism were more likely to be diagnosed with ADHD combined type (42% vs. 22%, p = 0.04) and language disorders (91% vs. 73%, p = 0.04), whereas adolescents with autism were more likely to be diagnosed with depressive disorders (13% vs. 1%, p = 0.03), with no other differences between the groups. Conclusion: In this urban, ethnically diverse group of children with autism, the vast majority presented with one or more comorbid diagnoses. School-age children were more likely to be diagnosed with language disorder and ADHD, while adolescents were more likely to be diagnosed with depression. Early detection and treatment of co-occurring conditions in autism are necessary.

PMID:37196211 | DOI:10.1089/cap.2023.0006

Health Aff (Millwood). 2023 May 17:101377hlthaff202201502. doi: 10.1377/hlthaff.2022.01502. Online ahead of print.

ABSTRACT

Social determinants of health can adversely affect health and therefore lead to poor health care outcomes. When it launched in 2017, the Accountable Health Communities (AHC) Model was at the forefront of US health policy initiatives seeking to address social determinants of health. The AHC Model, sponsored by the Centers for Medicare and Medicaid Services, screened Medicare and Medicaid beneficiaries for health-related social needs and offered eligible beneficiaries assistance in connecting with community services. This study used data from the period 2015-21 to test whether the model had impacts on health care spending and use. Findings show statistically significant reductions in emergency department visits for both Medicaid and fee-for-service Medicare beneficiaries. Impacts on other outcomes were not statistically significant, but low statistical power may have limited our ability to detect model effects. Interviews with AHC Model participants who were offered navigation services to help them find community-based resources suggested that navigation services could have directly affected the way in which beneficiaries engage with the health care system, leading them to be more proactive in seeking appropriate care. Collectively, findings provide mixed evidence that engaging with beneficiaries who have health-related social needs can affect health care outcomes.

PMID:37196210 | DOI:10.1377/hlthaff.2022.01502

J Phys Chem B. 2023 May 17. doi: 10.1021/acs.jpcb.3c00117. Online ahead of print.

ABSTRACT

Atomistic simulations with reliable models are extremely useful in providing exquisitely detailed pictures of biomolecular phenomena that are not always accessible to experiments. One such biomolecular phenomenon is RNA folding, which often requires exhaustive simulations with combined advanced sampling techniques. In this work, we employed the multithermal-multiumbrella on-the-fly probability enhanced sampling (MM-OPES) technique and compared it against combined parallel tempering and metadynamics simulations. We found that MM-OPES simulations were successful in reproducing the free energy surfaces from combined parallel tempering and metadynamics simulations. Importantly, we also investigated a wide range of temperature sets (minimum and maximum temperatures) for MM-OPES simulations in order to identify some guidelines for deciding the temperature limits for an accurate and efficient exploration of the free energy landscapes. We found that most temperature sets yielded almost the same accuracy in reproducing the free energy surface at the ambient conditions as long as (i) the maximum temperature is reasonably high, (ii) the temperature at which we run the simulation is reasonably high (in our simulations, running temperature is defined as [minimum temperature + maximum temperature]/2), and (iii) the effective sample size at the temperature of interest is statistically reasonable. In terms of the computational cost, all MM-OPES simulations were nearly 4 times less costly than the combined parallel tempering and metadynamics simulations. We concluded that the demanding combined parallel tempering and metadynamics simulations can safely be replaced with approximately 4 times less costly MM-OPES simulations (with carefully selected temperature limits) to obtain the same information.

PMID:37196167 | DOI:10.1021/acs.jpcb.3c00117

Br J Surg. 2023 May 17:znad123. doi: 10.1093/bjs/znad123. Online ahead of print.

ABSTRACT

BACKGROUND: Anastomotic leak is a severe complication after oesophagectomy. Anastomotic leak has diverse clinical manifestations and the optimal treatment strategy is unknown. The aim of this study was to assess the efficacy of treatment strategies for different manifestations of anastomotic leak after oesophagectomy.

METHODS: A retrospective cohort study was performed in 71 centres worldwide and included patients with anastomotic leak after oesophagectomy (2011-2019). Different primary treatment strategies were compared for three different anastomotic leak manifestations: interventional versus supportive-only treatment for local manifestations (that is no intrathoracic collections; well perfused conduit); drainage and defect closure versus drainage only for intrathoracic manifestations; and oesophageal diversion versus continuity-preserving treatment for conduit ischaemia/necrosis. The primary outcome was 90-day mortality. Propensity score matching was performed to adjust for confounders.

RESULTS: Of 1508 patients with anastomotic leak, 28.2 per cent (425 patients) had local manifestations, 36.3 per cent (548 patients) had intrathoracic manifestations, 9.6 per cent (145 patients) had conduit ischaemia/necrosis, 17.5 per cent (264 patients) were allocated after multiple imputation, and 8.4 per cent (126 patients) were excluded. After propensity score matching, no statistically significant differences in 90-day mortality were found regarding interventional versus supportive-only treatment for local manifestations (risk difference 3.2 per cent, 95 per cent c.i. -1.8 to 8.2 per cent), drainage and defect closure versus drainage only for intrathoracic manifestations (risk difference 5.8 per cent, 95 per cent c.i. -1.2 to 12.8 per cent), and oesophageal diversion versus continuity-preserving treatment for conduit ischaemia/necrosis (risk difference 0.1 per cent, 95 per cent c.i. -21.4 to 1.6 per cent). In general, less morbidity was found after less extensive primary treatment strategies.

CONCLUSION: Less extensive primary treatment of anastomotic leak was associated with less morbidity. A less extensive primary treatment approach may potentially be considered for anastomotic leak. Future studies are needed to confirm current findings and guide optimal treatment of anastomotic leak after oesophagectomy.

PMID:37196149 | DOI:10.1093/bjs/znad123

Sci Adv. 2023 May 19;9(20):eade7172. doi: 10.1126/sciadv.ade7172. Epub 2023 May 17.

ABSTRACT

Adverse conditions in early life can have negative consequences for adult health and survival in humans and other animals. What variables mediate the relationship between early adversity and adult survival? Adult social environments represent one candidate: Early life adversity is linked to social adversity in adulthood, and social adversity in adulthood predicts survival outcomes. However, no study has prospectively linked early life adversity, adult social behavior, and adult survival to measure the extent to which adult social behavior mediates this relationship. We do so in a wild baboon population in Amboseli, Kenya. We find weak mediation and largely independent effects of early adversity and adult sociality on survival. Furthermore, strong social bonds and high social status in adulthood can buffer some negative effects of early adversity. These results support the idea that affiliative social behavior is subject to natural selection through its positive relationship with survival, and they highlight possible targets for intervention to improve human health and well-being.

PMID:37196090 | DOI:10.1126/sciadv.ade7172

Sci Adv. 2023 May 19;9(20):eadg3254. doi: 10.1126/sciadv.adg3254. Epub 2023 May 17.

ABSTRACT

Knowledge of drug concentrations in the brains of behaving subjects remains constrained on a number of dimensions, including poor temporal resolution and lack of real-time data. Here, however, we demonstrate the ability of electrochemical aptamer-based sensors to support seconds-resolved, real-time measurements of drug concentrations in the brains of freely moving rats. Specifically, using such sensors, we achieve <4 μM limits of detection and 10-s resolution in the measurement of procaine in the brains of freely moving rats, permitting the determination of the pharmacokinetics and concentration-behavior relations of the drug with high precision for individual subjects. In parallel, we have used closed-loop feedback-controlled drug delivery to hold intracranial procaine levels constant (±10%) for >1.5 hours. These results demonstrate the utility of such sensors in (i) the determination of the site-specific, seconds-resolved neuropharmacokinetics, (ii) enabling the study of individual subject neuropharmacokinetics and concentration-response relations, and (iii) performing high-precision control over intracranial drug levels.

PMID:37196087 | DOI:10.1126/sciadv.adg3254

Oncologist. 2023 May 17:oyad095. doi: 10.1093/oncolo/oyad095. Online ahead of print.

ABSTRACT

BACKGROUND: Hypofractionated stereotactic radiotherapy (hFSRT) is a salvage option for recurrent glioblastoma (GB) which may synergize anti-PDL1 treatment. This phase I study evaluated the safety and the recommended phase II dose of anti-PDL1 durvalumab combined with hFSRT in patients with recurrent GB.

METHODS: Patients were treated with 24 Gy, 8 Gy per fraction on days 1, 3, and 5 combined with the first 1500 mg Durvalumab dose on day 5, followed by infusions q4weeks until progression or for a maximum of 12 months. A standard 3 + 3 Durvalumab dose de-escalation design was used. Longitudinal lymphocytes count, cytokines analyses on plasma samples, and magnetic resonance imaging (MRI) were collected.

RESULTS: Six patients were included. One dose limiting toxicity, an immune-related grade 3 vestibular neuritis related to Durvalumab, was reported. Median progression-free interval (PFI) and overall survival (OS) were 2.3 and 16.7 months, respectively. Multi-modal deep learning-based analysis including MRI, cytokines, and lymphocytes/neutrophil ratio isolated the patients presenting pseudoprogression, the longest PFI and those with the longest OS, but statistical significance cannot be established considering phase I data only.

CONCLUSION: Combination of hFSRT and Durvalumab in recurrent GB was well tolerated in this phase I study. These encouraging results led to an ongoing randomized phase II. (ClinicalTrials.gov Identifier: NCT02866747).

PMID:37196069 | DOI:10.1093/oncolo/oyad095

Int J Prosthodont. 2023 May 17. doi: 10.11607/ijp.8295. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate relevant material properties (flexural strength (σf), elastic modulus (E), water sorption (Wsp) and solubility (Wsl), and biocompatibility) of a 3D-printed resin (3D) and a heat cured acrylic resin (AR-control) used for complete denture manufacturing, testing the hypothesis that constructs from both materials would present acceptable material properties for clinical use.

MATERIALS AND METHODS: The σf, E, Wsp and Wsl were evaluated according to the ISO 20795-1:2013 standard, and the biocompatibility was evaluated using 3-4,5-dimethyl-thiazol-2-yl-2.5-diphenyltetrazolium bromide (MTT) and sulforhodamine B (SRB) assays. Disk-shaped specimens were fabricated and used for Wsp (n = 5), Wsl (n = 5), and biocompatibility (n = 3). Bar-shaped specimens (n = 30) were fabricated and stored in 37⁰ C distilled water for 48 hours and 6 months before flexural testing in a universal testing machine with constant displacement rate (5 ± 1 mm/min) until fracture. Data from σf, E, Wsp, Wsl and biocompatibility were statistically analyzed using Student t test (α= 0.05), Weibull analysis was also used for σf and E data.

RESULTS: Significant differences between the two polymers were found for the evaluated material properties. Water storage for 6 months did not affect the flexural strength of 3D. Yet, the additive manufactured polymer showed inadequate flexural strength and water solubility values.

CONCLUSION: Despite adequate biocompatibility and strength stability after 6 months of water storage, the additive manufactured polymer recommended for complete denture needs further development to improve the remaining material properties evaluated in this study.

PMID:37196039 | DOI:10.11607/ijp.8295

Int J Surg. 2023 May 17. doi: 10.1097/JS9.0000000000000437. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with relatively poor survival. Surgery is the first choice for treating patients with early pancreatic cancer. However, the surgical approach and the extent of resection for patients with pancreatic cancer are currently controversial.

METHODS: We optimized the procedure of standard pancreaticoduodenectomy to selective extended dissection (SED), which is based on the extra-pancreatic nerve plexus (PLX) potentially invaded by the tumor. We retrospectively analyzed the clinicopathological data of patients with pancreatic adenocarcinoma who underwent radical surgery in our center from 2011 to 2020. Patients who underwent standard dissection (SD) were matched 2:1 to those who underwent SED using propensity score matching (PSM). The log-rank test and cox regression model were used to analyze survival data. In addition, statistical analyses were performed for the perioperative complications, postoperative pathology and recurrence pattern.

RESULTS: A total of 520 patients were included in the analysis. Among patients with extra-pancreatic perineural invasion (EPNI), disease-free survival (DFS) was significantly longer in those who received SED than in those who received SD (14.5 mo vs. 10 mo, P<0.05). The incidence of metastasis in No.9 and No.14 lymph nodes was significantly higher in patients with EPNI. In addition, there was no significant difference in the incidence rate of perioperative complications between the two surgical procedures.

CONCLUSION: Compared with SD, SED exhibits significant prognostic benefit for patients with EPNI. The SED procedure aiming at specific nerve plexus dissection displayed particular efficacy and safety in resectable PDAC patients.

PMID:37195787 | DOI:10.1097/JS9.0000000000000437

J Med Internet Res. 2023 May 17;25:e39933. doi: 10.2196/39933.

ABSTRACT

BACKGROUND: People living with chronic conditions and disabilities experience harassment both offline and on the web. Cybervictimization is an umbrella term for negative web-based experiences. It has distressing consequences on physical health, mental well-being, and social relationships. These experiences have mostly been documented among children and adolescents. However, the scope of such experiences is not well documented among adults with long-term conditions, and the potential impact has not been examined from a public health perspective.

OBJECTIVE: This study aimed to examine the scope of cybervictimization among adults living with long-term conditions in the United Kingdom and the perceived impact on self-management of chronic conditions.

METHODS: This paper reports the findings of the quantitative phase of a mixed methods study in the United Kingdom. This cross-sectional study targeted adults aged ≥18 years with long-term conditions. Using a web-based link, the survey was shared on the web via 55 victim support groups, health support organizations, and social media accounts of nongovernmental organizations and activists such as journalists and disability campaigners. People with long-term conditions were asked about their health conditions, comorbidities, self-management, negative web-based experiences, their impact on them, and support sought to mitigate the experiences. The perceived impact of cybervictimization was measured using a set of questions on a Likert scale, frequency tables, and the Stanford Self-Efficacy for Managing Chronic Diseases Scale. Demographic data and the impact on self-management were cross-tabulated to identify the demographic characteristics of the targeted individuals and potential conditions with complications and highlight directions for future research.

RESULTS: Data from 152 participants showed that almost 1 in every 2 adults with chronic conditions was cybervictimized (69/152, 45.4%). Most victims (53/69, 77%) had disabilities; the relationship between cybervictimization and disability was statistically significant (P=.03). The most common means of contacting the victims was Facebook (43/68, 63%), followed by personal email or SMS text messaging, each accounting for 40% (27/68). Some participants (9/68, 13%) were victimized in web-based health forums. Furthermore, 61% (33/54) of victims reported that experiencing cybervictimization had affected their health condition self-management plan. The highest impact was on lifestyle changes such as exercise, diet, avoiding triggers, and avoiding excessive smoking and alcohol consumption. This was followed by changes to medications and follow-ups with health care professionals. Most victims (38/55, 69%) perceived a worsened self-efficacy on the Self-Efficacy for Managing Chronic Diseases Scale. Formal support was generally rated as poor, with only 25% (13/53) of victims having disclosed this experience to their physicians.

CONCLUSIONS: Cybervictimization of people with chronic conditions is a public health issue with worrying consequences. This triggered considerable fear and negatively influenced the self-management of different health conditions. Further context- and condition-specific research is needed. Global collaborations to address inconsistencies in research are recommended.

PMID:37195761 | DOI:10.2196/39933