Category: Nevin Manimala

Inflamm Bowel Dis. 2023 Feb 8:izad013. doi: 10.1093/ibd/izad013. Online ahead of print.

ABSTRACT

BACKGROUND: High histologic remission rates have been reported with placebos in randomized controlled trials (RCTs) evaluating ulcerative colitis (UC) therapies and have varied based on trial designs. We performed a systematic review and meta-analysis to quantify placebo histological remission rates and identify factors influencing those rates.

METHODS: MEDLINE, EMBASE, and the Cochrane library were searched from inception of the databases until December 2021. We included placebo-controlled RCTs of adult patients with UC treated with aminosalicylates, corticosteroids, immunosuppressives, biologics, and small molecules. We pooled estimates using a random-effects model and performed subgroup analysis and meta-regression to evaluate the effect of different covariates on placebo rates.

RESULTS: Thirty-three studies (30 induction and 3 maintenance) were included. The overall placebo histological remission rate was 15.7% (95% confidence interval, 12.9%-19%) across all 33 studies. High heterogeneity was observed among studies with I2 = 62.10%. The pooled estimate of histological remission was 15.8% in induction studies and 14.5% in maintenance studies. Subgroup analysis revealed statistically significant differences in placebo rates when accounting for background medications, the intervention drug class, and disease severity (P = .041, .025, and .025, respectively). There was no statistical difference between induction vs maintenance studies or between different histological scales (P = .771, and .075, respectively).

CONCLUSIONS: Placebo histological remission rates range from 13% to 19% in UC RCTs, but studies are highly heterogeneous. Factors found to influence placebo rates include presence of background medications, the drug used, and the disease severity. These observations inform future trial designs to minimize placebo rates and reduce heterogeneity.

PMID:36753516 | DOI:10.1093/ibd/izad013

PLoS Negl Trop Dis. 2023 Feb 8;17(2):e0011072. doi: 10.1371/journal.pntd.0011072. eCollection 2023 Feb.

ABSTRACT

Burkholderia pseudomallei, the causative agent of melioidosis, is a gram-negative soil bacterium well recognized in Southeast Asia and northern Australia. However, wider and expanding global distribution of B. pseudomallei has been elucidated. Early diagnosis is critical for commencing the specific therapy required to optimize outcome. Serological testing using the indirect hemagglutination (IHA) antibody assay has long been used to augment diagnosis of melioidosis and to monitor progress. However, cross reactivity and prior exposure may complicate the diagnosis of current clinical disease (melioidosis). The goal of our study was to develop and initially evaluate a serology assay (BurkPx) that capitalized upon host response to multiple antigens. Antigens were selected from previous studies for expression/purification and conjugation to microspheres for multiantigen analysis. Selected serum samples from non-melioidosis controls and serial samples from culture-confirmed melioidosis patients were used to characterize the diagnostic power of individual and combined antigens at two times post admission. Multiple variable models were developed to evaluate multivariate antigen reactivity, identify important antigens, and determine sensitivity and specificity for the diagnosis of melioidosis. The final multiplex assay had a diagnostic sensitivity of 90% and specificity of 93%, which was superior to any single antigen in side-by-side comparisons. The sensitivity of the assay started at >85% for the initial serum sample after admission and increased to 94% 21 days later. Weighting antigen contribution to each model indicated that certain antigen contributed to diagnosis more than others, which suggests that the number of antigens in the assay can be decreased. In summation, the BurkPx assay can facilitate the diagnosis of melioidosis and potentially improve on currently available serology assays. Further evaluation is now required in both melioidosis-endemic and non-endemic settings.

PMID:36753506 | DOI:10.1371/journal.pntd.0011072

PLoS One. 2023 Feb 8;18(2):e0281474. doi: 10.1371/journal.pone.0281474. eCollection 2023.

ABSTRACT

In this paper, we introduced a novel general two-parameter statistical distribution which can be presented as a mix of both exponential and gamma distributions. Some statistical properties of the general model were derived mathematically. Many estimation methods studied the estimation of the proposed model parameters. A new statistical model was presented as a particular case of the general two-parameter model, which is used to study the performance of the different estimation methods with the randomly generated data sets. Finally, the COVID-19 data set was used to show the superiority of the particular case for fitting real-world data sets over other compared well-known models.

PMID:36753497 | DOI:10.1371/journal.pone.0281474

PLoS One. 2023 Feb 8;18(2):e0281466. doi: 10.1371/journal.pone.0281466. eCollection 2023.

ABSTRACT

BACKGROUND: Polypharmacy can be a consequence of overprescribing that is prevalent in older adults with multimorbidity. Polypharmacy can cause adverse reactions and result in hospital admission. This study predicted risks of adverse drug reaction (ADR)-related and emergency hospital admissions by medicine classes.

METHODS: We used electronic health record data from general practices of Clinical Practice Research Datalink (CPRD GOLD) and Aurum. Older patients who received at least five medicines were included. Medicines were classified using the British National Formulary sections. Hospital admission cases were propensity-matched to controls by age, sex, and propensity for specific diseases. The matched data were used to develop and validate random forest (RF) models to predict the risk of ADR-related and emergency hospital admissions. Shapley Additive eXplanation (SHAP) values were calculated to explain the predictions.

RESULTS: In total, 89,235 cases with polypharmacy and hospitalised with an ADR-related admission were matched to 443,497 controls. There were over 112,000 different combinations of the 50 medicine classes most implicated in ADR-related hospital admission in the RF models, with the most important medicine classes being loop diuretics, domperidone and/or metoclopramide, medicines for iron-deficiency anaemias and for hypoplastic/haemolytic/renal anaemias, and sulfonamides and/or trimethoprim. The RF models strongly predicted risks of ADR-related and emergency hospital admission. The observed Odds Ratio in the highest RF decile was 7.16 (95% CI 6.65-7.72) in the validation dataset. The C-statistics for ADR-related hospital admissions were 0.58 for age and sex and 0.66 for RF probabilities.

CONCLUSIONS: Polypharmacy involves a very large number of different combinations of medicines, with substantial differences in risks of ADR-related and emergency hospital admissions. Although the medicines may not be causally related to increased risks, RF model predictions may be useful in prioritising medication reviews. Simple tools based on few medicine classes may not be effective in identifying high risk patients.

PMID:36753492 | DOI:10.1371/journal.pone.0281466

PLoS One. 2023 Feb 8;18(2):e0276827. doi: 10.1371/journal.pone.0276827. eCollection 2023.

ABSTRACT

BACKGROUND: Mobile-linked point-of-care diagnostics forms an integral part of diagnostic health services for efficient communication between patients and healthcare professionals despite geographical location and time of diagnosis. The efficiency of this technology lies in the user experience which means that the interaction of the user with the implemented technology needs to be simple, convenient, and consistent. Having a well-structured user experience of these devices in community-based healthcare will aid in sustainable implementation. Herein, we propose to conduct a literature search to systematically map out evidence based on mobile-linked POC diagnostics user experience at a community level in resource-limited settings.

METHODOLOGY: The proposed scoping review will be guided by the advanced Arksey and O’Malley methodological framework and further advanced by Levac et al. A comprehensive search will be conducted to find relevant published literature from the following electronic databases: Scopus, Web of Science, EBSCOhost (Medline, CINAHL, Africa-wide, Academic Search Complete). Grey literature will also be searched, including reports from government and international organizations such as World Health Organization (WHO), Foundation for Innovative New Diagnostics (FIND), and the Food and Drug Administration (FDA). Two independent reviewers will screen the relevant studies and the degree of the agreement will be determined by calculating Cohen’s kappa statistic. The quality of eligible data will also be appraised using the mixed method appraisal tool version 2018.

DISCUSSION: We anticipate that the planned scoping review will present useful evidence to inform stakeholders on the integration of mobile-linked diagnostic devices in community-based healthcare which will guide further research on the subject.

PMID:36753489 | DOI:10.1371/journal.pone.0276827

PLoS One. 2023 Feb 8;18(2):e0278555. doi: 10.1371/journal.pone.0278555. eCollection 2023.

ABSTRACT

The Theory of Evolution (TE) is the backbone of biology and is the best way to explain the diversity of species that exist on the planet. However, despite all the supporting evidence, TE remains poorly understood and accepted. In this study, the levels of acceptance and understanding of TE were measured, respectively, using the Inventory of Student Evolution Acceptance (I-SEA) and Knowledge of Evolution Exam (KEE) questionnaires, in high school students in Monterrey, Mexico (N = 370). The results show that the acceptance of TE ranges from moderate (90.3 out of 120) to high (3.7 out of 5), depending on the scale with which it is measured, while the level of comprehension is low (4.5 out of 10). Statistical analysis of the data collected reveals that there is a positive relationship between acceptance and understanding of TE (r = 0.34). In addition, the proportions of I-SEA and KEE were evaluated based on several factors, such as religion and educational level of the parents, among others. It was found that the level of education of the parents positively affects the understanding of the basic concepts of TE, while religion is the main factor of negative influence on both acceptance and understanding. Finally, the low comprehension shown in this study suggests a revision and readjustment of the contents that are taught in the upper secondary education curriculum.

PMID:36753485 | DOI:10.1371/journal.pone.0278555

JMIR Med Educ. 2023 Feb 8;9:e45312. doi: 10.2196/45312.

ABSTRACT

BACKGROUND: Chat Generative Pre-trained Transformer (ChatGPT) is a 175-billion-parameter natural language processing model that can generate conversation-style responses to user input.

OBJECTIVE: This study aimed to evaluate the performance of ChatGPT on questions within the scope of the United States Medical Licensing Examination Step 1 and Step 2 exams, as well as to analyze responses for user interpretability.

METHODS: We used 2 sets of multiple-choice questions to evaluate ChatGPT’s performance, each with questions pertaining to Step 1 and Step 2. The first set was derived from AMBOSS, a commonly used question bank for medical students, which also provides statistics on question difficulty and the performance on an exam relative to the user base. The second set was the National Board of Medical Examiners (NBME) free 120 questions. ChatGPT’s performance was compared to 2 other large language models, GPT-3 and InstructGPT. The text output of each ChatGPT response was evaluated across 3 qualitative metrics: logical justification of the answer selected, presence of information internal to the question, and presence of information external to the question.

RESULTS: Of the 4 data sets, AMBOSS-Step1, AMBOSS-Step2, NBME-Free-Step1, and NBME-Free-Step2, ChatGPT achieved accuracies of 44% (44/100), 42% (42/100), 64.4% (56/87), and 57.8% (59/102), respectively. ChatGPT outperformed InstructGPT by 8.15% on average across all data sets, and GPT-3 performed similarly to random chance. The model demonstrated a significant decrease in performance as question difficulty increased (P=.01) within the AMBOSS-Step1 data set. We found that logical justification for ChatGPT’s answer selection was present in 100% of outputs of the NBME data sets. Internal information to the question was present in 96.8% (183/189) of all questions. The presence of information external to the question was 44.5% and 27% lower for incorrect answers relative to correct answers on the NBME-Free-Step1 (P<.001) and NBME-Free-Step2 (P=.001) data sets, respectively.

CONCLUSIONS: ChatGPT marks a significant improvement in natural language processing models on the tasks of medical question answering. By performing at a greater than 60% threshold on the NBME-Free-Step-1 data set, we show that the model achieves the equivalent of a passing score for a third-year medical student. Additionally, we highlight ChatGPT’s capacity to provide logic and informational context across the majority of answers. These facts taken together make a compelling case for the potential applications of ChatGPT as an interactive medical education tool to support learning.

PMID:36753318 | DOI:10.2196/45312

JAMA Psychiatry. 2023 Feb 8. doi: 10.1001/jamapsychiatry.2022.4974. Online ahead of print.

ABSTRACT

IMPORTANCE: Comorbidities and genetic correlations between gastrointestinal tract diseases and psychiatric disorders have been widely reported, with the gut-brain axis (GBA) hypothesized as a potential biological basis. However, the degree to which the shared genetic determinants are involved in these associations underlying the GBA is unclear.

OBJECTIVE: To investigate the shared genetic etiology between gastrointestinal tract diseases and psychiatric disorders and to identify shared genomic loci, genes, and pathways.

DESIGN, SETTING, AND PARTICIPANTS: This genome-wide pleiotropic association study using genome-wide association summary statistics from publicly available data sources was performed with various statistical genetic approaches to sequentially investigate the pleiotropic associations from genome-wide single-nucleotide variation (SNV; formerly single-nucleotide polymorphism [SNP]), and gene levels and biological pathways to disentangle the underlying shared genetic etiology between 4 gastrointestinal tract diseases (inflammatory bowel disease, irritable bowel syndrome, peptic ulcer disease, and gastroesophageal reflux disease) and 6 psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, attention-deficit/hyperactivity disorder, posttraumatic stress disorder, and anorexia nervosa). Data were collected from March 10, 2021, to August 25, 2021, and analysis was performed from January 8 through May 30, 2022.

MAIN OUTCOMES AND MEASURES: The primary outcomes consisted of a list of genetic loci, genes, and pathways shared between gastrointestinal tract diseases and psychiatric disorders.

RESULTS: Extensive genetic correlations and genetic overlaps were found among 22 of 24 trait pairs. Pleiotropic analysis under a composite null hypothesis identified 2910 significant potential pleiotropic SNVs in 19 trait pairs, with 83 pleiotropic loci and 24 colocalized loci detected. Gene-based analysis found 158 unique candidate pleiotropic genes, which were highly enriched in certain GBA-related phenotypes and tissues, whereas pathway enrichment analysis further highlighted biological pathways primarily involving cell adhesion, synaptic structure and function, and immune cell differentiation. Several identified pleiotropic loci also shared causal variants with gut microbiomes. Mendelian randomization analysis further illustrated vertical pleiotropy across 8 pairwise traits. Notably, many pleiotropic loci were identified for multiple pairwise traits, such as 1q32.1 (INAVA), 19q13.33 (FUT2), 11q23.2 (NCAM1), and 1p32.3 (LRP8).

CONCLUSIONS AND RELEVANCE: These findings suggest that the pleiotropic genetic determinants between gastrointestinal tract diseases and psychiatric disorders are extensively distributed across the genome. These findings not only support the shared genetic basis underlying the GBA but also have important implications for intervention and treatment targets of these diseases simultaneously.

PMID:36753304 | DOI:10.1001/jamapsychiatry.2022.4974

JAMA Netw Open. 2023 Feb 1;6(2):e2255050. doi: 10.1001/jamanetworkopen.2022.55050.

ABSTRACT

IMPORTANCE: Use of tyrosine kinase inhibitors (TKIs) is the standard therapy for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with brain metastases. Several studies have shown that adding chemotherapy to EGFR-TKIs could improve progression-free survival (PFS) in patients with EGFR-mutant advanced NSCLC; however, the efficacy of these agents in patients with brain metastases remains unclear.

OBJECTIVE: To investigate the efficacy and safety of gefitinib plus chemotherapy (pemetrexed with platinum) compared with gefitinib alone in patients with untreated EGFR-mutant NSCLC brain metastases.

DESIGN, SETTING, AND PARTICIPANTS: This open-label prospective, multicenter, phase 3 randomized clinical trial was conducted in 6 centers in China from January 13, 2016, to August 27, 2021. The median follow-up time was 21.1 months (IQR, 13.5-31.8 months). Patients with untreated confirmed brain metastases and EGFR-sensitive mutated NSCLC were enrolled.

INTERVENTIONS: The eligible patients were randomly assigned (1:1) to receive gefitinib plus chemotherapy or gefitinib alone.

MAIN OUTCOMES AND MEASURES: The primary end point was intracranial PFS; secondary end points included PFS, overall survival (OS), intracranial objective response rate, overall objective response rate, and safety. Intention-to-treat analysis was performed.

RESULTS: A total of 161 patients (87 [54.0%] women; mean [SD] age, 55 [9.8] years; range, 26-80 years) were enrolled and randomized to receive gefitinib (n = 81) or gefitinib plus chemotherapy (n = 80). The median intracranial PFS was 15.6 months (95% CI, 14.3-16.9 months) in the gefitinib plus chemotherapy group vs 9.1 months (95% CI, 8.0-10.2 months) in the gefitinib group (hazard ratio, 0.36; 95% CI, 0.25-0.53; P < .001). Similarly, the median PFS was significantly longer with gefitinib plus chemotherapy than gefitinib alone (16.3; 95% CI, 14.4-18.2 months vs 9.5; 95% CI, 8.3-10.8 months; P < .001). Gefitinib plus chemotherapy had a better intracranial objective response rate (85.0%; 95% CI, 77.0%-93.0% vs 63.0%; 95% CI, 52.2%-73.7%; P = .002) and overall objective response rate (80.0%; 95% CI, 71.0%-89.0% vs 64.2%; 95% CI, 53.5%-74.9%; P = .03) than gefitinib alone. At data cutoff, the median OS was also significantly longer in the gefitinib plus chemotherapy group vs the gefitinib group (35.0 vs 28.9 months; hazard ratio, 0.65; 95% CI, 0.43-0.99; P = .04). Grade 3 or worse adverse events were more common with gefitinib plus chemotherapy, most of which were manageable.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, gefitinib plus chemotherapy significantly improved intracranial PFS, PFS, and OS compared with gefitinib alone in patients with untreated EGFR-mutant NSCLC brain metastases and could be an optional first-line treatment for these patients.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01951469.

PMID:36753281 | DOI:10.1001/jamanetworkopen.2022.55050

JAMA Netw Open. 2023 Feb 1;6(2):e2255107. doi: 10.1001/jamanetworkopen.2022.55107.

ABSTRACT

IMPORTANCE: Rights and access for transgender individuals, including the participation of transgender athletes in sports, have long been debated. These discussions often center around fairness and mental health impacts on youths associated with identity-based inclusion in sports.

OBJECTIVE: To assess the experiences and perspectives of adolescents and young adults on the inclusion of transgender individuals in competitive sports.

DESIGN, SETTING, AND PARTICIPANTS: In this qualitative study, 5 open-ended survey questions were sent to the MyVoice cohort from December 10 to 17, 2021. MyVoice is a nationwide text-message polling platform of US youths aged 14 to 24 years. All coding and subsequent analysis was completed between January 10 and December 11, 2022.

MAIN OUTCOMES AND MEASURES: Qualitative perspectives of youths regarding transgender athlete participation in sports as measured by survey responses. Responses were reviewed using an inductive approach to qualitative thematic analysis to develop a codebook. The codes were independently applied to all responses by 2 investigators; discrepancies were resolved with discussion. Summary statistics were calculated for demographic characteristics and code frequencies, and χ2 tests (α = .05, 2-tailed) were used to evaluate differences in opinion based on gender identity and participation in competitive sports.

RESULTS: A total of 905 of 1199 youths (75%) responded to the survey. Respondents had a mean (SD) age of 20 (2) years; 482 (53%) identified as male, 29 (3%) identified as transgender, and 306 (34%) reported having participated in high school and/or collegiate athletics. Three themes emerged: (1) youths differed regarding the inclusion of transgender athletes based on gender identity vs sex assigned at birth, (2) many youths did not have personal experience related to the inclusion of transgender athletes, and (3) youths were uncertain about the impacts of gender identity-based participation on cisgender individuals but perceived positive impacts for transgender individuals. Nearly half of respondents (327 of 691 [47%]) thought that transgender athletes should participate based on their gender identity or personal preference, whereas 240 (35%) favored participation based on sex assigned at birth or in a transgender-only category. Respondents mentioned concern about the fairness of identity-based participation, specifically for cisgender women, but many (410 of 697 [59%]) also reported that it would be affirming for transgender athletes to participate based on gender identity.

CONCLUSIONS AND RELEVANCE: The youths in our study differed in their opinions regarding sports participation of transgender youths, but many felt that inclusive policies would affirm and support the mental health of transgender individuals. Negative impacts on fairness were noted by some respondents. These findings suggest that nuanced policies are needed to address the participation of transgender athletes in competitive sports and should consider the impacts on and perspectives of youths most affected.

PMID:36753280 | DOI:10.1001/jamanetworkopen.2022.55107