Nevin Manimala

STAR Protoc. 2023 Jan 25;4(1):102069. doi: 10.1016/j.xpro.2023.102069. Online ahead of print.

ABSTRACT

Understanding cellular metabolism is important across biotechnology and biomedical research and has critical implications in a broad range of normal and pathological conditions. Here, we introduce the user-friendly web-based platform ImmCellFie, which allows the comprehensive analysis of metabolic functions inferred from transcriptomic or proteomic data. We explain how to set up a run using publicly available omics data and how to visualize the results. The ImmCellFie algorithm pushes beyond conventional statistical enrichment and incorporates complex biological mechanisms to quantify cell activity. For complete details on the use and execution of this protocol, please refer to Richelle et al. (2021).¹.

PMID:36853701 | DOI:10.1016/j.xpro.2023.102069

Hosp Top. 2023 Feb 28:1-8. doi: 10.1080/00185868.2023.2185172. Online ahead of print.

ABSTRACT

The significant and apparent variance in hospital charges and inpatient care in the U.S. has perplexed the general public including many stakeholders such as the healthcare regulators and insurers. While the clinical side of inpatient care has been undergoing tremendous progress and standardization, the overall cost of healthcare has been ballooning. The purpose of this research is to conduct statistical analyses that reveal the sources of variance in hospital charges and inpatient care using the annual data from the AHRQ’s (Agency for Healthcare Research and Quality) HCUP’s (Hospital Cost and Utilization Project) NIS (National Inpatient Sample) database. Our focus is on non-clinical factors such as patient age, gender, income and race and hospital location data as independent variables to investigate their impact on hospital charges and inpatient care. Our research sample is the liver transplant cases in 2019 sampled in the NIS 2019 database. Our regression results show patient age and gender as well as payer affect the number of diagnoses; and hospital charges are affected by age, payer and hospital location. Number of procedures was not affected by any of these non-clinical factors except the hospital location. Implications suggest that there is more room for standardization of the number of diagnoses and procedures across regions in the US. Results also reveal that race and income do not have any effect on hospital charges and inpatient care. Our study contributes to an empirical understanding of non-clinical factors in the explanation of variance in hospital charges and inpatient care.

PMID:36853649 | DOI:10.1080/00185868.2023.2185172

JAMA Netw Open. 2023 Feb 1;6(2):e230380. doi: 10.1001/jamanetworkopen.2023.0380.

ABSTRACT

IMPORTANCE: Sepsis is associated with long-term cognitive impairment and worse psychological and functional outcomes. Potential mechanisms include intracerebral oxidative stress and inflammation, yet little is known about the effects of early antioxidant and anti-inflammatory therapy on cognitive, psychological, and functional outcomes in sepsis survivors.

OBJECTIVE: To describe observed differences in long-term cognitive, psychological, and functional outcomes of vitamin C, thiamine, and hydrocortisone between the intervention and control groups in the Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) randomized clinical trial.

DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary analysis reports the 6-month outcomes of the multicenter, double-blind, placebo-controlled VICTAS randomized clinical trial, which was conducted between August 2018 and July 2019. Adult patients with sepsis-induced respiratory and/or cardiovascular dysfunction who survived to discharge or day 30 were recruited from 43 intensive care units in the US. Participants were randomized 1:1 to either the intervention or control group. Cognitive, psychological, and functional outcomes at 6 months after randomization were assessed via telephone through January 2020. Data analyses were conducted between February 2021 and December 2022.

INTERVENTIONS: The intervention group received intravenous vitamin C (1.5 g), thiamine hydrochloride (100 mg), and hydrocortisone sodium succinate (50 mg) every 6 hours for 96 hours or until death or intensive care unit discharge. The control group received matching placebo.

MAIN OUTCOMES AND MEASURES: Cognitive performance, risk of posttraumatic stress disorder and depression, and functional status were assessed using a battery of standardized instruments that were administered during a 1-hour telephone call 6 months after randomization.

RESULTS: After exclusions, withdrawals, and deaths, the final sample included 213 participants (median [IQR] age, 57 [47-67] years; 112 males [52.6%]) who underwent long-term outcomes assessment and had been randomized to either the intervention group (n = 108) or control group (n = 105). The intervention group had lower immediate memory scores (adjusted OR [aOR], 0.49; 95% CI, 0.26-0.89), higher odds of posttraumatic stress disorder (aOR, 3.51; 95% CI, 1.18-10.40), and lower odds of receiving mental health care (aOR, 0.38; 95% CI, 0.16-0.89). No other statistically significant differences in cognitive, psychological, and functional outcomes were found between the 2 groups.

CONCLUSIONS AND RELEVANCE: In survivors of sepsis, treatment with vitamin C, thiamine, and hydrocortisone did not improve or had worse cognitive, psychological, and functional outcomes at 6 months compared with patients who received placebo. These findings challenge the hypothesis that antioxidant and anti-inflammatory therapy during critical illness mitigates the development of long-term cognitive, psychological, and functional impairment in sepsis survivors.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03509350.

PMID:36853612 | DOI:10.1001/jamanetworkopen.2023.0380

JAMA Netw Open. 2023 Feb 1;6(2):e230819. doi: 10.1001/jamanetworkopen.2023.0819.

ABSTRACT

IMPORTANCE: In a porcine model of liver transplant, a combined drug approach that targeted the donor graft and graft recipient reduced ischemia-reperfusion injury, a major hurdle to the success of liver transplant.

OBJECTIVE: To assess the effect of a clinical form of a perioperative combined drug approach delivered immediately before implantation to the procured liver and to the liver recipient on the degree of ischemia-reperfusion injury.

DESIGN, SETTING, AND PARTICIPANTS: This unicentric, investigator-driven, open-label randomized clinical trial with 2 parallel arms was conducted in Belgium from September 2013 through February 2018, with 1-year follow-up. Adults wait-listed for a first solitary full-size liver transplant were screened for eligibility. Exclusion criteria were acute liver failure, kidney failure, contraindication to treatment, participation in another trial, refusal, technical issues, and death while awaiting transplant. Included patients were enrolled and randomized at the time of liver offer. Data were analyzed from May 20, 2019, to May 27, 2020.

INTERVENTIONS: Participants were randomized to a combined drug approach with standard of care (static cold storage) or standard of care only (control group). In the combined drug approach group, following static cold preservation, donor livers were infused with epoprostenol (ex situ, portal vein); recipients were given oral α-tocopherol and melatonin prior to anesthesia and intravenous antithrombin III, infliximab, apotransferrin, recombinant erythropoietin-β, C1-inhibitor, and glutathione during the anhepatic and reperfusion phase.

MAIN OUTCOMES AND MEASURES: The primary outcome was the posttransplant peak serum aspartate aminotransferase (AST) level within the first 72 hours. Secondary end points were the frequencies of postreperfusion syndrome, ischemia-reperfusion injury score, early allograft dysfunction, surgical complications, ischemic cholangiopathy, acute kidney injury, acute cellular rejection, and graft and patient survival.

RESULTS: Of 93 randomized patients, 21 were excluded, resulting in 72 patients (36 per study arm) in the per protocol analysis (median recipient age, 60 years [IQR, 51.7-66.2 years]; 52 [72.2%] men). Peak AST serum levels were not different in the combined drug approach and control groups (geometric mean, 1262.9 U/L [95% CI, 946.3-1685.4 U/L] vs 1451.2 U/L [95% CI, 1087.4-1936.7 U/L]; geometric mean ratio, 0.87 [95% CI, 0.58-1.31]; P = .49) (to convert AST to μkat/L, multiply by 0.0167). There also were no significant differences in the secondary end points between the groups.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the combined drug approach targeting the post-cold storage graft and the recipient did not decrease ischemic-reperfusion injury. The findings suggest that in addition to a downstream strategy that targets the preimplantation liver graft and the graft recipient, a clinically effective combined drug approach may need to include an upstream strategy that targets the donor graft during preservation. Dynamic preservation strategies may provide an appropriate delivery platform.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02251041.

PMID:36853611 | DOI:10.1001/jamanetworkopen.2023.0819

JAMA Netw Open. 2023 Feb 1;6(2):e230999. doi: 10.1001/jamanetworkopen.2023.0999.

ABSTRACT

IMPORTANCE: Children with special health care needs (CSHCN) are recognized to be at increased risk of developing dental caries (decay). Evidence is mixed regarding the association of preventive oral health care delivered by pediatric primary care clinicians with caries experience among CSHCN.

OBJECTIVE: To investigate caries experience, including untreated decay, among Medicaid-enrolled preschoolers with or without special health care needs.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from the Pediatric Providers Against Cavities in Children’s Teeth study, a cluster-randomized hybrid effectiveness-implementation trial conducted among 1022 Medicaid-enrolled preschoolers aged 3 to 6 years attending well-child visits at 18 participating community pediatric primary care practices in northeast Ohio. Baseline data were collected from November 1, 2017, to August 31, 2019, with statistical analyses conducted from April to August 2022.

EXPOSURES: Presence of special health care needs, as assessed by applying the Pediatric Medical Complexity Algorithm to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes, was abstracted from electronic medical records. CSHCN were defined as having either noncomplex chronic disease (presence of only 1 nonprogressive chronic condition, or multiple nonprogressive chronic conditions in a single body system) or complex chronic disease (presence of any progressive chronic condition, malignant neoplasm, or significant chronic conditions involving multiple body systems).

MAIN OUTCOMES AND MEASURES: Untreated dental decay and caries experience as assessed through clinical dental examinations using International Caries Detection and Assessment System criteria.

RESULTS: A total of 1022 children aged 3 to 6 years from 18 practices were enrolled in the study. The mean (SD) age of the study population was 4.3 (1.1) years, 554 (54.2%) were boys, and of 988 with data on race and ethnicity, 451 (45.6%) were Black. Of these, 301 of 1019 (29.5%) had a likely special health care need (225 with noncomplex chronic conditions and 76 with complex chronic conditions). The most frequent chronic conditions included asthma (n = 209) and mental or behavioral health disorders (n = 146), including attention-deficit/hyperactivity disorder, autism, and developmental delays. Overall, 296 children (29.0%) had untreated decay, and 378 (37.0%) had caries experience (decayed and filled teeth). Accounting for sociodemographic characteristics, CSHCN had 34% reduced odds of untreated decay (adjusted odds ratio [AOR], 0.66 [95% CI, 0.48-0.92]) compared with those with without chronic disease. In addition, caries experience was lower among CSHCN (AOR, 0.79 [95% CI, 0.60-1.04]).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of Medicaid-enrolled children who attended well-child visits as preschoolers, untreated dental decay was lower among CSHCN compared with those without chronic conditions. This study suggests that CSHCN may have had better access to the various types of dental care facilitated in medical settings.

PMID:36853605 | DOI:10.1001/jamanetworkopen.2023.0999

Ann Surg Oncol. 2023 Feb 28. doi: 10.1245/s10434-023-13226-8. Online ahead of print.

ABSTRACT

BACKGROUND: Carbon ion radiotherapy (CIRT) is an evolving treatment option for malignant pelvic tumors in patients with poor surgical indications. However, the difference in complications and functional outcomes between CIRT and surgery is poorly understood. This study compares the complications and functional outcomes of CIRT and surgery to facilitate treatment selection.

METHODS: A total of 28 patients who underwent CIRT for pelvic bone tumors while theoretically meeting the surgical resection criteria were included. Sixty-nine patients who underwent surgery for pelvic bone tumors were included as controls. Major complication rates and functional outcomes (ambulatory, pain, urination, constipation) were evaluated and compared at several time points (pretreatment, discharge, and final follow-up) between the groups.

RESULTS: Early (within 90 days) major complications were not observed in the CIRT group but occurred in 30% of the surgery group, which was statistically significant (P < 0.001). In contrast, late (after 90 days) major complications occurred more often in the CIRT group than in the surgery group (18% and 4%, respectively; P = 0.042). From pretreatment until discharge, all functional outcomes in the surgery group deteriorated (P < 0.001 for all) but did not change in the CIRT group (P = 0.77-1.00). At the final follow-up, all functional outcomes showed no significant intergroup difference (P = 0.28-0.92) due to the recovery trend in the surgery group and the deterioration trend in the CIRT group.

CONCLUSIONS: Compared with surgery, CIRT may have favorable safety and stable functional outcomes in the short-term but more late complications. Mid-term functional outcomes were similar between the groups.

PMID:36853566 | DOI:10.1245/s10434-023-13226-8

Appl Health Econ Health Policy. 2023 Feb 28. doi: 10.1007/s40258-022-00782-5. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Economic evaluations, a decision-support tool for policy makers, will be crucial in planning and tailoring HIV prevention and treatment strategies especially in the wake of stalled and decreasing funding for the global HIV response. As HIV testing and treatment coverage increase, case identification becomes increasingly difficult and costly. Determining which subset of the population these strategies should be targeted to becomes of vital importance as well. Generating quality economic evidence begins with the validity of the modelling approach and the model structure employed. This study synthesises and critiques the reporting around modelling methodology of economic models in the evaluation of HIV testing strategies in sub-Saharan Africa.

METHODS: The following databases were searched from January 2000 to September 2020: MEDLINE, Embase, Scopus, EconLit and Global Health. Any model-based economic evaluation of a unique HIV testing strategy conducted in sub-Saharan Africa presenting a cost-effectiveness measure published from 2013 onwards was eligible. Data were extracted around three components: general study characteristics; economic evaluation design; and quality of model reporting using a novel tool developed for the purposes of this study.

RESULTS: A total of 21 studies were included; 10 cost-effectiveness analyses, 11 cost-utility analyses. All but one study was conducted in Eastern and Southern Africa. Modelling approaches for HIV testing strategies can be broadly characterised as static aggregate models (3/21), static individual models (6/21), dynamic aggregate models (5/21) and dynamic individual models (7/21). Adequate reporting around data handling was the highest of the three categories assessed (74%), and model validation, the lowest (45%). Limitations to model structure, justification of chosen time horizon and cycle length, and description of external model validation process were all adequately reported in less than 40% of studies. The predominant limitation of this review relates to the potential implications of the narrow inclusion criteria.

CONCLUSIONS: This review is the first to synthesise economic evaluations of HIV testing strategies in sub-Saharan Africa. The majority of models exhibited dynamic, stochastic and individual properties. Model reporting against the 13 criteria in our novel tool was mixed. Future model-based economic evaluations of HIV testing strategies would benefit from transparency around the choice of modelling approach, model structure, data handling procedures and model validation techniques.

PMID:36853553 | DOI:10.1007/s40258-022-00782-5

Eur Child Adolesc Psychiatry. 2023 Feb 28. doi: 10.1007/s00787-023-02173-0. Online ahead of print.

ABSTRACT

Adolescence is a critical phase for the development of substance use disorders (SUDs). For Europe and Germany, there are limited data on problematic substance use from representative youth samples. Trait mindfulness is relevant in buffering against substance use-related problems and associated deficits in self-regulatory control. The objective of this study is to estimate 12-month prevalence rates for SUDs in a representative sample of adolescents in Germany and to examine associations with mindfulness and related factors such as stress, impulsivity, sensation seeking and symptoms of psychopathology. A sample of 4001 adolescents aged 12-18 years from Germany was surveyed based on DSM-IV diagnostic criteria for SUDs. Logistic regression analyses were used to examine associations with mindfulness-related variables. Criteria of at least one of the assessed SUDs were endorsed by 11.2% of the adolescents. Alcohol use disorders had the highest prevalence rate (10.1%) followed by cannabis use disorders (2.6%). For both substances, the criteria for abuse were met about twice as often as those for dependence. The prevalence of cigarette dependence was 1.7%, while the prevalence for e-cigarette dependence was only 0.1%. Prevalence rates were higher for male youth and increasing with age. SUD prevalence was also related to mindfulness, impulsivity and sensation seeking and externalizing symptoms of psychopathology. The statistically significant associations varied across different SUDs. SUDs appear highly prevalent among German adolescents. The results have public health implications with regard to treatment needs and prevention measures in the youth population in Germany.

PMID:36853515 | DOI:10.1007/s00787-023-02173-0

Forensic Sci Med Pathol. 2023 Feb 28. doi: 10.1007/s12024-023-00594-6. Online ahead of print.

ABSTRACT

The purpose of this study is to estimate chronological age and determine whether individuals were aged under or over 18 years using root pulp visibility (RPV) in cone-beam computed tomography (CBCT) images. The study included CBCT images of 699 individuals aged between 15 and 75 years. One thousand twenty-three mandibular second molar (2M) teeth were evaluated using Olze’s RPV method in four stages. Descriptive statistics of the stages and the relationship between the stages and the chronological age were assessed. The distribution of the stages was analyzed according to the 18-year age threshold. There was a positive correlation between RPV stages and chronological ages in both sexes. For females and males, the mean ages of stage 0, stage 1, and stage 2, for females and males, were found as 27.21, 28.93, and 33.68 years, and 37.69, 40.9, and 44.88 years, respectively. Stage 0 and stage 1 were found both in individuals aged under and over 18 years, and stage 2 and stage 3 were not observed in individuals aged under 18 years. The presence of stage 2 and stage 3 may be an indication that an individual is aged over 18 years according to Olze’s RPV age estimation method. For more reliable results, 2M teeth should be examined bilaterally in forensic science.

PMID:36853501 | DOI:10.1007/s12024-023-00594-6

Paediatr Drugs. 2023 Feb 28. doi: 10.1007/s40272-023-00561-2. Online ahead of print.

ABSTRACT

BACKGROUND: The prescription of antidepressant drugs during pregnancy has been steadily increasing for several decades. Meta-analyses (MAs), which increase the statistical power and precision of results, have gained interest for assessing the safety of antidepressant drugs during pregnancy.

OBJECTIVE: We aimed to provide a meta-review of MAs assessing the benefits and risks of antidepressant drug use during pregnancy.

METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search on PubMed and Web of Science databases was conducted on 25 October, 2021, on MAs assessing the association between antidepressant drug use during pregnancy and health outcomes for the pregnant women, embryo, fetus, newborn, and developing child. Study selection and data extraction were carried out independently and in duplicate by two authors. The methodological quality of included studies was evaluated with the AMSTAR-2 tool. Overlap among MAs was assessed by calculating the corrected covered area. Data were presented in a narrative synthesis, using four levels of evidence.

RESULTS: Fifty-one MAs were included, all but one assessing risks. These provided evidence for a significant increase in the risks for major congenital malformations (selective serotonin reuptake inhibitors, paroxetine, fluoxetine, no evidence for sertraline; eight MAs), congenital heart defects (paroxetine, fluoxetine, sertraline; 11 MAs), preterm birth (eight MAs), neonatal adaptation symptoms (eight MAs), and persistent pulmonary hypertension of the newborn (three MAs). There was limited evidence (only one MA for each outcome) for a significant increase in the risks for postpartum hemorrhage, and with a high risk of bias, for stillbirth, impaired motor development, and intellectual disability. There was inconclusive evidence, i.e., discrepant results, for an increase in the risks for spontaneous abortion, small for gestational age and low birthweight, respiratory distress, convulsions, feeding problems, and for a subsequent risk for autism with an early antidepressant drug exposure. Finally, MAs provided no evidence for an increase in the risks for gestational hypertension, preeclampsia, and for a subsequent risk for attention-deficit/hyperactivity disorder. Only one MA assessed benefits, providing limited evidence for preventing relapse in severe or recurrent depression. Effect sizes were small, except for neonatal symptoms (small to large). Results were based on MAs in which overall methodological quality was low (AMSTAR-2 score = 54.8% ± 12.9%, [19-81%]), with a high risk of bias, notably indication bias. The corrected covered area was 3.27%, which corresponds to a slight overlap.

CONCLUSIONS: This meta-review has implications for clinical practice and future research. First, these results suggest that antidepressant drugs should be used as a second-line treatment during pregnancy (after first-line psychotherapy, according to the guidelines). The risk of major congenital malformations could be prevented by observing guidelines that discourage the use of paroxetine and fluoxetine. Second, to decrease heterogeneity and bias, future MAs should adjust for maternal psychiatric disorders and antidepressant drug dosage, and perform analyses by timing of exposure.

PMID:36853497 | DOI:10.1007/s40272-023-00561-2