Category: Nevin Manimala

Microbiol Spectr. 2024 Mar 14:e0393123. doi: 10.1128/spectrum.03931-23. Online ahead of print.

ABSTRACT

Antimicrobial resistance is one of the greatest challenges to global health. While the development of new antimicrobials can combat resistance, low profitability reduces the number of new compounds brought to market. Elucidating the mechanism of action is crucial for developing new antimicrobials. This can become expensive as there are no universally applicable pipelines. Phenotypic heterogeneity of microbial populations resulting from antimicrobial treatment can be captured through flow cytometric fingerprinting. Since antimicrobials are classified into limited groups, the mechanism of action of known compounds can be used for predictive modeling. We demonstrate a cost-effective flow cytometry approach for determining the mechanism of action of new compounds. Cultures of Actinomyces viscosus and Fusobacterium nucleatum were treated with different antimicrobials and measured by flow cytometry. A Gaussian mixture mask was applied over the data to construct phenotypic fingerprints. Fingerprints were used to assess statistical differences between mechanism of action groups and to train random forest classifiers. Classifiers were then used to predict the mechanism of action of cephalothin. Statistical differences were found among the different mechanisms of action groups. Pairwise comparison showed statistical differences for 35 out of 45 pairs for A. viscosus and for 32 out of 45 pairs for F. nucleatum after 3.5 h of treatment. The best-performing random forest classifier yielded a Matthews correlation coefficient of 0.92 and the mechanism of action of cephalothin could be successfully predicted. These findings suggest that flow cytometry can be a cheap and fast alternative for determining the mechanism of action of new antimicrobials.IMPORTANCEIn the context of the emerging threat of antimicrobial resistance, the development of novel antimicrobials is a commonly employed strategy to combat resistance. Elucidating the mechanism of action of novel compounds is crucial in this development but can become expensive, as no universally applicable pipelines currently exist. We present a novel flow cytometry-based approach capable of determining the mechanism of action swiftly and cost-effectively. The workflow aims to accelerate drug discovery and could help facilitate a more targeted approach for antimicrobial treatment of patients.

PMID:38483479 | DOI:10.1128/spectrum.03931-23

J Particip Med. 2024 Mar 14;16:e50242. doi: 10.2196/50242.

ABSTRACT

BACKGROUND: Effective primary care necessitates follow-up actions by the patient beyond the visit. Prior research suggests room for improvement in patient adherence.

OBJECTIVE: This study sought to understand patients’ views on their primary care visits, the plans generated therein, and their self-reported adherence after 3 months.

METHODS: As part of a large multisite cluster randomized pragmatic trial in 3 health care organizations, patients completed 2 surveys-the first within 7 days after the index primary care visit and another 3 months later. For this analysis of secondary outcomes, we combined the results across all study participants to understand patient adherence to care plans. We recorded patient characteristics and survey responses. Cross-tabulation and chi-square statistics were used to examine bivariate associations, adjusting for multiple comparisons when appropriate. We used multivariable logistic regression to assess how patients’ intention to follow, agreement, and understanding of their plans impacted their plan adherence, allowing for differences in individual characteristics. Qualitative content analysis was conducted to characterize the patient’s self-reported plans and reasons for adhering (or not) to the plan 3 months later.

RESULTS: Of 2555 patients, most selected the top box option (9=definitely agree) that they felt they had a clear plan (n=2011, 78%), agreed with the plan (n=2049, 80%), and intended to follow the plan (n=2108, 83%) discussed with their provider at the primary care visit. The most common elements of the plans reported included reference to exercise (n=359, 14.1%), testing (laboratory, imaging, etc; n=328, 12.8%), diet (n=296, 11.6%), and initiation or adjustment of medications; (n=284, 11.1%). Patients who strongly agreed that they had a clear plan, agreed with the plan, and intended to follow the plan were all more likely to report plan completion 3 months later (P<.001) than those providing less positive ratings. Patients who reported plans related to following up with the primary care provider (P=.008) to initiate or adjust medications (P≤.001) and to have a specialist visit were more likely to report that they had completely followed the plan (P=.003). Adjusting for demographic variables, patients who indicated intent to follow their plan were more likely to follow-through 3 months later (P<.001). Patients’ reasons for completely following the plan were mainly that the plan was clear (n=1114, 69.5%), consistent with what mattered (n=1060, 66.1%), and they were determined to carry through with the plan (n=887, 53.3%). The most common reasons for not following the plan were lack of time (n=217, 22.8%), having decided to try a different approach (n=105, 11%), and the COVID-19 pandemic impacted the plan (n=105, 11%).

CONCLUSIONS: Patients’ initial assessment of their plan as clear, their agreement with the plan, and their initial willingness to follow the plan were all strongly related to their self-reported completion of the plan 3 months later. Patients whose plans involved lifestyle changes were less likely to report that they had “completely” followed their plan.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03385512; https://clinicaltrials.gov/study/NCT03385512.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/30431.

PMID:38483458 | DOI:10.2196/50242

JMIR Form Res. 2024 Mar 14;8:e51331. doi: 10.2196/51331.

ABSTRACT

BACKGROUND: Misinformation in Spanish on social media platforms has contributed to COVID-19 vaccine hesitancy among Latino parents. Brigada Digital de Salud was established to disseminate credible, science-based information about COVID-19 in Spanish on social media.

OBJECTIVE: This study aims to assess participants’ reactions to and engagement with Brigada Digital content that sought to increase COVID-19 vaccine uptake among US Latino parents and their children.

METHODS: We conducted a 5-week intervention in a private, moderator-led Facebook (Meta Platforms, Inc) group with Spanish-speaking Latino parents of children aged ≤18 years (N=55). The intervention participants received 3 to 4 daily Brigada Digital posts and were encouraged to discuss the covered topics through comments and polls. To assess participants’ exposure, reactions, and engagement, we used participants’ responses to a web-based survey administered at 2 time points (baseline and after 5 weeks) and Facebook analytics to calculate the average number of participant views, reactions, and comments. Descriptive statistics were assessed for quantitative survey items, qualitative responses were thematically analyzed, and quotes were selected to illustrate the themes.

RESULTS: Overall, 101 posts were published. Most participants reported visiting the group 1 to 3 times (22/55, 40%) or 4 to 6 (18/55, 33%) times per week and viewing 1 to 2 (23/55, 42%) or 3 to 4 (16/55, 29%) posts per day. Facebook analytics validated this exposure, with 36 views per participant on average. The participants reacted positively to the intervention. Most participants found the content informative and trustworthy (49/55, 89%), easy to understand, and presented in an interesting manner. The participants thought that the moderators were well informed (51/55, 93%) and helpful (50/55, 91%) and praised them for being empathic and responsive. The participants viewed the group environment as welcoming and group members as friendly (45/55, 82%) and supportive (19/55, 35%). The 3 most useful topics for participants were the safety and efficacy of adult COVID-19 vaccines (29/55, 53%), understanding child risk levels (29/55, 53%), and the science behind COVID-19 (24/55, 44%). The preferred formats were educational posts that could be read (38/55, 69%) and videos, including expert (28/55, 51%) and instructional (26/55, 47%) interviews. Regarding engagement, most participants self-reported reacting to posts 1 to 2 (16/55, 29%) or 3 to 4 (15/55, 27%) times per week and commenting on posts 1 to 2 (16/55, 29%) or <1 (20/55, 36%) time per week. This engagement level was validated by analytics, with 10.6 reactions and 3 comments per participant, on average, during the 5 weeks. Participants recommended more opportunities for engagement, such as interacting with the moderators in real time.

CONCLUSIONS: With adequate intervention exposure and engagement and overall positive participant reactions, the findings highlight the promise of this digital approach for COVID-19 vaccine-related health promotion.

PMID:38483457 | DOI:10.2196/51331

J Med Internet Res. 2024 Mar 14;26:e50882. doi: 10.2196/50882.

ABSTRACT

BACKGROUND: The widespread use of artificial intelligence, such as ChatGPT (OpenAI), is transforming sectors, including health care, while separate advancements of the internet have enabled platforms such as China’s DingXiangYuan to offer remote medical services.

OBJECTIVE: This study evaluates ChatGPT-4’s responses against those of professional health care providers in telemedicine, assessing artificial intelligence’s capability to support the surge in remote medical consultations and its impact on health care delivery.

METHODS: We sourced remote orthopedic consultations from “Doctor DingXiang,” with responses from its certified physicians as the control and ChatGPT’s responses as the experimental group. In all, 3 blindfolded, experienced orthopedic surgeons assessed responses against 7 criteria: “logical reasoning,” “internal information,” “external information,” “guiding function,” “therapeutic effect,” “medical knowledge popularization education,” and “overall satisfaction.” We used Fleiss κ to measure agreement among multiple raters.

RESULTS: Initially, consultation records for a cumulative count of 8 maladies (equivalent to 800 cases) were gathered. We ultimately included 73 consultation records by May 2023, following primary and rescreening, in which no communication records containing private information, images, or voice messages were transmitted. After statistical scoring, we discovered that ChatGPT’s “internal information” score (mean 4.61, SD 0.52 points vs mean 4.66, SD 0.49 points; P=.43) and “therapeutic effect” score (mean 4.43, SD 0.75 points vs mean 4.55, SD 0.62 points; P=.32) were lower than those of the control group, but the differences were not statistically significant. ChatGPT showed better performance with a higher “logical reasoning” score (mean 4.81, SD 0.36 points vs mean 4.75, SD 0.39 points; P=.38), “external information” score (mean 4.06, SD 0.72 points vs mean 3.92, SD 0.77 points; P=.25), and “guiding function” score (mean 4.73, SD 0.51 points vs mean 4.72, SD 0.54 points; P=.96), although the differences were not statistically significant. Meanwhile, the “medical knowledge popularization education” score of ChatGPT was better than that of the control group (mean 4.49, SD 0.67 points vs mean 3.87, SD 1.01 points; P<.001), and the difference was statistically significant. In terms of “overall satisfaction,” the difference was not statistically significant between the groups (mean 8.35, SD 1.38 points vs mean 8.37, SD 1.24 points; P=.92). According to how Fleiss κ values were interpreted, 6 of the control group’s score points were classified as displaying “fair agreement” (P<.001), and 1 was classified as showing “substantial agreement” (P<.001). In the experimental group, 3 points were classified as indicating “fair agreement,” while 4 suggested “moderate agreement” (P<.001).

CONCLUSIONS: ChatGPT-4 matches the expertise found in DingXiangYuan forums’ paid consultations, excelling particularly in scientific education. It presents a promising alternative for remote health advice. For health care professionals, it could act as an aid in patient education, while patients may use it as a convenient tool for health inquiries.

PMID:38483451 | DOI:10.2196/50882

J Chem Inf Model. 2024 Mar 14. doi: 10.1021/acs.jcim.3c01925. Online ahead of print.

ABSTRACT

The lengthy and expensive process of developing new drugs from scratch, coupled with a high failure rate, has prompted the emergence of drug repurposing/repositioning as a more efficient and cost-effective approach. This approach involves identifying new therapeutic applications for existing approved drugs, leveraging the extensive drug-related data already gathered. However, the diversity and heterogeneity of data, along with the limited availability of known drug-disease interactions, pose significant challenges to computational drug design. To address these challenges, this study introduces EKGDR, an end-to-end knowledge graph-based approach for computational drug repurposing. EKGDR utilizes the power of a drug knowledge graph, a comprehensive repository of drug-related information that encompasses known drug interactions and various categorization information, as well as structural molecular descriptors of drugs. EKGDR employs graph neural networks, a cutting-edge graph representation learning technique, to embed the drug knowledge graph (nodes and relations) in an end-to-end manner. By doing so, EKGDR can effectively learn the underlying causes (intents) behind drug-disease interactions and recursively aggregate and combine relational messages between nodes along different multihop neighborhood paths (relational paths). This process generates representations of disease and drug nodes, enabling EKGDR to predict the interaction probability for each drug-disease pair in an end-to-end manner. The obtained results demonstrate that EKGDR outperforms previous models in all three evaluation metrics: area under the receiver operating characteristic curve (AUROC = 0.9475), area under the precision-recall curve (AUPRC = 0.9490), and recall at the top-200 recommendations (Recall@200 = 0.8315). To further validate EKGDR’s effectiveness, we evaluated the top-20 candidate drugs suggested for each of Alzheimer’s and Parkinson’s diseases.

PMID:38483449 | DOI:10.1021/acs.jcim.3c01925

J Emerg Nurs. 2024 Mar 13:S0099-1767(24)00021-7. doi: 10.1016/j.jen.2024.01.006. Online ahead of print.

ABSTRACT

INTRODUCTION: Pediatric convulsive status epilepticus is one of the most common neurologic emergencies and should be managed by health care professionals as soon as possible based on current guidelines. This study aimed to determine the nursing approaches and management of pediatric convulsive status epilepticus from the perspective of emergency nurses in Turkey.

METHODS: A cross-sectional, multicenter study was conducted with 162 emergency nurses working in emergency departments in 35 different provinces in Turkey. The data were collected via an online form. Descriptive statistical methods were used in data analysis.

RESULTS: Most emergency nurses (72.2%) attempted an intravenous access immediately to administer antiseizure medications during the stabilization phase. Approximately half the emergency nurses stated that rectal diazePAM was frequently administered in the initial therapy phase and intravenous diazePAM was administered in the second therapy phase. The emergency nurses had most difficulties attempting intravenous access, determining status epilepticus types, and calming the parents.

DISCUSSION: As health care professionals and important members of the health team, emergency nurses have the responsibility to manage pediatric convulsive status epilepticus in the fastest and the most appropriate way based on current practice guidelines in emergency departments. When intravenous access is not available, nonintravenous benzodiazepines should be considered in the first-line treatment of pediatric convulsive status epilepticus, followed by immediate intravenous access.

PMID:38483423 | DOI:10.1016/j.jen.2024.01.006

J Allergy Clin Immunol. 2024 Feb 28:S0091-6749(24)00126-X. doi: 10.1016/j.jaci.2024.01.023. Online ahead of print.

ABSTRACT

BACKGROUND: Long-standing health inequalities in Australian society that were exposed by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were described as “fault lines” in a recent call to action by a consortium of philanthropic organizations. With asthma a major contributor to childhood disease burden, studies of its spatial epidemiology can provide valuable insights into the emergence of health inequalities early in life.

OBJECTIVE: The aims of this study were to characterize the spatial variation of asthma prevalence among children living within Australia’s 4 largest cities and quantify the relative contributions of climatic and environmental factors, outdoor air pollution, and socioeconomic status in determining this variation.

METHODS: A Bayesian model with spatial smoothing was developed to regress ecologic health status data from the 2021 Australian Census against groups of explanatory covariates intended to represent mechanistic pathways.

RESULTS: The prevalence of asthma in children aged 5 to 14 years averages 7.9%, 8.2%, 8.5%, and 7.6% in Sydney, Melbourne, Brisbane, and Perth, respectively. This small inter-city variation contrasts against marked intracity variation at the small-area level, which ranges from 6% to 12% between the least and most affected locations in each. Statistical variance decomposition on a subsample of Australian-born, nonindigenous children attributes 66% of the intracity spatial variation to the assembled covariates. Of these covariates, climatic and environmental factors contribute 30%, outdoor air pollution contributes 19%, and areal socioeconomic status contributes the remaining 51%.

CONCLUSION: Geographic health inequalities in the prevalence of childhood asthma within Australia’s largest cities reflect a complex interplay of factors, among which socioeconomic status is a principal determinant.

PMID:38483422 | DOI:10.1016/j.jaci.2024.01.023

J Manipulative Physiol Ther. 2024 Mar 13:S0161-4754(24)00001-0. doi: 10.1016/j.jmpt.2024.02.003. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to determine whether seated cervical manipulation produced changes in autonomic nervous system activity, as measured by heart rate variability and plasma norepinephrine levels.

METHODS: Ninety-five healthy young adults (ages 20-48 years) were recruited into a single-blinded physiological study, with 47 randomized to a seated cervical manipulation and 44 randomized to a sham procedure. Heart rate variability in the frequency domain, and plasma norepinephrine levels were measured prior to, immediately following, and 5 minutes following the intervention.

RESULTS: Electrocardiograms were obtained from 39 subjects in the sham group and 43 subjects in the manipulation group. No statistically significant changes were found in measures of heart rate variability in the frequency domain in either the manipulation or sham groups. Blood samples were obtained from 22 subjects in the sham group and 27 subjects in the manipulation group. Plasma norepinephrine levels, as measured by spectrophotometry, declined in both groups from pre- to immediately postintervention, and they remained at decreased levels 5 minutes after the interventions. There were no statistically significant differences between groups in pre- or postintervention norepinephrine levels.

CONCLUSIONS: Measures of heart rate variability and plasma norepinephrine levels did not show that seated cervical manipulation produced short-term changes in autonomic nervous system activity compared to a sham procedure in healthy young adults.

PMID:38483415 | DOI:10.1016/j.jmpt.2024.02.003

JAMA Oncol. 2024 Mar 14. doi: 10.1001/jamaoncol.2023.7291. Online ahead of print.

ABSTRACT

IMPORTANCE: No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy.

OBJECTIVE: To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years.

DESIGN, SETTING, AND PARTICIPANTS: In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (<0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed.

INTERVENTION: Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT).

MAIN OUTCOMES AND MEASURES: The coprimary end points were the 2-year change in score from baseline for the bowel and urinary domains of the Expanded Prostate Cancer Composite Index questionnaire. Secondary objectives were to compare between arms freedom from biochemical failure, time to progression, local failure, regional failure, salvage therapy, distant metastasis, prostate cancer-specific survival, overall survival, and adverse events.

RESULTS: Of the 296 patients randomized (median [range] age, 65 [44-81] years; 100% male), 144 received HYPORT and 152 received COPORT. At the end of RT, the mean GU change scores among those in the HYPORT and COPORT arms were neither clinically significant nor different in statistical significance and remained so at 6 and 12 months. The mean (SD) GI change scores for HYPORT and COPORT were both clinically significant and different in statistical significance at the end of RT (-15.52 [18.43] and -7.06 [12.78], respectively; P < .001). However, the clinically and statistically significant differences in HYPORT and COPORT mean GI change scores were resolved at 6 and 12 months. The 24-month differences in mean GU and GI change scores for HYPORT were noninferior to COPORT using noninferiority margins of -5 and -6, respectively, rejecting the null hypothesis of inferiority (mean [SD] GU score: HYPORT, -5.01 [15.10] and COPORT, -4.07 [14.67]; P = .005; mean [SD] GI score: HYPORT, -4.17 [10.97] and COPORT, -1.41 [8.32]; P = .02). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT vs COPORT for biochemical failure, defined as a PSA of 0.4 ng/mL or higher and rising (2-year rate, 12% vs 8%; P = .28).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, HYPORT was associated with greater patient-reported GI toxic effects compared with COPORT at the completion of RT, but both groups recovered to baseline levels within 6 months. At 2 years, HYPORT was noninferior to COPORT in terms of patient-reported GU or GI toxic effects. HYPORT is a new acceptable practice standard for patients receiving postprostatectomy radiotherapy.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03274687.

PMID:38483412 | DOI:10.1001/jamaoncol.2023.7291

JAMA Ophthalmol. 2024 Mar 14. doi: 10.1001/jamaophthalmol.2024.0151. Online ahead of print.

ABSTRACT

IMPORTANCE: Primary open-angle glaucoma (POAG) is a highly heritable disease, with 127 identified risk loci to date. Polygenic risk score (PRS) may provide a clinically useful measure of aggregate genetic burden and improve patient risk stratification.

OBJECTIVE: To assess whether a PRS improves prediction of POAG onset in patients with ocular hypertension.

DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc analysis of the Ocular Hypertension Treatment Study. Data were collected from 22 US sites with a mean (SD) follow-up of 14.0 (6.9) years. A total of 1636 participants were followed up from February 1994 to December 2008; 1077 participants were enrolled in an ancillary genetics study, of which 1009 met criteria for this analysis. PRS was calculated using summary statistics from the largest cross-ancestry POAG meta-analysis, with weights trained using 8 813 496 variants from 449 186 cross-ancestry participants in the UK Biobank. Data were analyzed from July 2022 to December 2023.

EXPOSURES: From February 1994 to June 2002, participants were randomized to either topical intraocular pressure-lowering medication or close observation. After June 2002, both groups received medication.

MAIN OUTCOMES AND MEASURES: Outcome measures were hazard ratios for POAG onset. Concordance index and time-dependent areas under the receiver operating characteristic curve were used to compare the predictive performance of multivariable Cox proportional hazards models.

RESULTS: Of 1009 included participants, 562 (55.7%) were female, and the mean (SD) age was 55.9 (9.3) years. The mean (SD) PRS was significantly higher for 350 POAG converters (0.24 [0.95]) compared with 659 nonconverters (-0.12 [1.00]) (P < .001). POAG risk increased 1.36% (95% CI, 1.08-1.64) with each higher PRS decile, with conversion ranging from 9.52% (95% CI, 7.09-11.95) in the lowest PRS decile to 21.81% (95% CI, 19.37-24.25) in the highest decile. Comparison of low-risk and high-risk PRS tertiles showed a 2.0-fold increase in 20-year POAG risk for participants of European and African ancestries. In the subgroup randomized to delayed treatment, each increase in PRS decile was associated with a 0.52-year (95% CI, 0.01-1.03) decrease in age at diagnosis (P = .047). No significant linear association between PRS and age at POAG diagnosis was present in the early treatment group. Prediction models significantly improved with the addition of PRS as a covariate (C index = 0.77) compared with the Ocular Hypertension Treatment Study baseline model (C index = 0.75) (P < .001). Each 1-SD higher PRS conferred a mean hazard ratio of 1.25 (95% CI, 1.13-1.44) for POAG onset.

CONCLUSIONS AND RELEVANCE: Higher PRS was associated with increased risk for POAG in patients with ocular hypertension. The inclusion of a PRS improved the prediction of POAG onset.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00000125.

PMID:38483402 | DOI:10.1001/jamaophthalmol.2024.0151