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Nevin Manimala Statistics

Bacterial Persistence in Urinary Tract Infection Among Postmenopausal Population

Urogynecology (Phila). 2024 Mar 1;30(3):205-213. doi: 10.1097/SPV.0000000000001452. Epub 2024 Jan 15.

ABSTRACT

IMPORTANCE: Urinary tract infections (UTIs) are common in older-aged women. Our study examined bacterial persistence with commonly prescribed antibiotics. Bacterial growth was demonstrated despite antibiotic treatment.

OBJECTIVES: The aims of this study were to quantify the bacterial persister phenotype in urine collected from postmenopausal women with acute and recurrent UTI and to determine the capabilities of first-line antibiotics to effectively treat persister cells.

STUDY DESIGN: This was an institutional review board-approved cross-sectional analysis within a large academic referral center. Uropathogens were cultured from postmenopausal women with acute or recurrent UTI and screened for persister cells using persistence assays. Demographic and clinical variables were collected and analyzed. The entire experimental process was repeated in triplicate. Data were analyzed for significance (P < 0.05) between the persister culture and antibiotic treatments using a 1-way analysis of variance with multiple comparisons in Prism 9.3.0.

RESULTS: Forty participants were included: 62.5% White, 22.5% Black, 3% Asian, and 2% Hispanic with a mean age of 72.3 ± 11.62 years. The persister phenotype was demonstrated in all of Escherichia coli isolates. Treatment with fosfomycin demonstrated reduced colony-forming units per milliliter compared with control (P < 0.01). Among recurrent isolates, there was a statistically significant decrease in colony-forming units per milliliter after antibiotic treatment with all 4 antibiotics (P < 0.05).

CONCLUSIONS: This study demonstrated in vitro bacterial persistence in uropathogens from urogynecology patients despite treatment with commonly prescribed antibiotics. Fosfomycin generated the least amount of persister cells. Results suggest that persistence may be one bacterial defense mechanism involved in UTIs. Further research is needed to understand the clinical implications.

PMID:38484233 | DOI:10.1097/SPV.0000000000001452

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Biomarker Inference and the Timing of Next-Generation Sequencing in a Multi-Institutional, Cross-Cancer Clinicogenomic Data Set

JCO Precis Oncol. 2024 Mar;8:e2300489. doi: 10.1200/PO.23.00489.

ABSTRACT

PURPOSE: Observational clinicogenomic data sets, consisting of tumor next-generation sequencing (NGS) data linked to clinical records, are commonly used for cancer research. However, in real-world practice, oncologists frequently request NGS in search of treatment options for progressive cancer. The extent and impact of this dynamic on analysis of clinicogenomic research data are not well understood.

METHODS: We analyzed clinicogenomic data for patients with non-small cell lung, colorectal, breast, prostate, pancreatic, or urothelial cancers in the American Association for Cancer Research Biopharmaceutical Consortium cohort. Associations between baseline and time-varying clinical characteristics and time from diagnosis to NGS were measured. To explore the impact of informative cohort entry on biomarker inference, statistical interactions between selected biomarkers and time to NGS with respect to overall survival were calculated.

RESULTS: Among 7,182 patients, time from diagnosis to NGS varied significantly by clinical factors, including cancer type, calendar year of sequencing, institution, and age and stage at diagnosis. NGS rates also varied significantly by dynamic clinical status variables; in an adjusted model, compared with patients with stable disease at any given time after diagnosis, patients with progressive disease by imaging or oncologist assessment had higher NGS rates (hazard ratio for NGS, 1.61 [95% CI, 1.45 to 1.78] and 2.32 [95% CI, 2.01 to 2.67], respectively). Statistical interactions between selected biomarkers and time to NGS with respect to survival, potentially indicating biased biomarker inference results, were explored.

CONCLUSION: To evaluate the appropriateness of a data set for a particular research question, it is crucial to measure associations between dynamic cancer status and the timing of NGS, as well as to evaluate interactions involving biomarkers of interest and NGS timing with respect to survival outcomes.

PMID:38484212 | DOI:10.1200/PO.23.00489

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Comprehensive Analysis Identifies Variability in PI3K Pathway Alterations in Triple-Negative Breast Cancer Subtypes

JCO Precis Oncol. 2024 Mar;8:e2300124. doi: 10.1200/PO.23.00124.

ABSTRACT

PURPOSE: The PI3K pathway is frequently altered in triple-negative breast cancer (TNBC). Limited cell line and human data suggest that TNBC tumors characterized as mesenchymal (M) and luminal androgen receptor (LAR) subtypes have increased incidence of alterations in the PI3K pathway. The impact of PI3K pathway alterations across TNBC subtypes is poorly understood.

METHODS: Pretreatment tumor was evaluated from operable TNBC patients enrolled on a clinical trial of neoadjuvant therapy (NAT; A Robust TNBC Evaluation fraMework to Improve Survival [ClinicalTrials.gov identifier: NCT02276443]). Tumors were characterized into seven TNBC subtypes per Pietenpol criteria (basal-like 1, basal-like 2, immunomodulatory, M, mesenchymal stem-like, LAR, and unstable). Using whole-exome sequencing, RNA sequencing, and immunohistochemistry for PTEN, alterations were identified in 32 genes known to activate the PI3K pathway. Alterations in each subtype were associated with pathologic response to NAT.

RESULTS: In evaluated patients (N = 177), there was a significant difference in the incidence of PI3K pathway alterations across TNBC subtypes (P < .01). The highest incidence of alterations was seen in LAR (81%), BL2 (79%), and M (62%) subtypes. The odds ratio for pathologic complete response (pCR) in the presence of PIK3CA mutation, PTEN mutation, and/or PTEN loss was highest in the LAR subtype and lowest in the M subtype, but these findings did not reach statistical significance. Presence of PIK3CA mutation was associated with pCR in the LAR subtype (P = .02).

CONCLUSION: PI3K pathway alteration can affect response to NAT in TNBC, and targeted agents may improve outcomes, particularly in patients with M and LAR TNBC.

PMID:38484209 | DOI:10.1200/PO.23.00124

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Successful Management of Neutropenic Sepsis Is Key to Better Survival of Patients With Blood Cancer in Sri Lanka: Real-World Data From the Resource-Limited Setting

JCO Glob Oncol. 2024 Mar;10:e2300412. doi: 10.1200/GO.23.00412.

ABSTRACT

PURPOSE: Sepsis is the main cause of nonrelapse mortality, and there are no published data on applicability of supportive care protocols from high-income countries such as Sri Lanka. The aim of the study was to investigate management and mortality of neutropenic episodes among Hemato-Oncology patients.

MATERIALS AND METHODS: Retrospective analysis of clinical characteristics, management, morbidity, and mortality of neutropenic Hemato-Oncology patients presented to the Lanka Hospital Blood Cancer Centre from January 1, 2019 to December 31, 2019 was performed.

RESULTS: A total of 169 neutropenic episodes were identified; 115 (68%) of such episodes were related to chemotherapy. Acute leukemia, lymphoproliferative disorders, and plasma cell disorders accounted for 23%, 69%, and 8% of patients, respectively. The median age of patients who had sepsis was 56 years, whereas that of those who had no sepsis was 53 years (P = .49). The median time to neutropenia was 9 days for those in the sepsis group compared with 8 days in the group that had no sepsis (0.64). The median neutrophil count in the group that had sepsis was 0.06, whereas it was 0.69 in the group that had no sepsis (P ≤ .05). The median time to commencement of antibiotics was 20 minutes.

CONCLUSION: To our knowledge, this is the only documented study related to outcome and successful applicability of western supportive care protocols to Sri Lankan patients with neutropenia. In this study, we have shown that neutropenic sepsis can be successfully managed in the setting of limited resources with service development, following guidelines and staff training.

PMID:38484192 | DOI:10.1200/GO.23.00412

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Biochar from co-pyrolysis of biological sludge and sawdust in comparison with the conventional filling media of vertical-flow constructed wetlands for the treatment of domestic-textile wastewater

Water Sci Technol. 2024 Mar;89(5):1252-1263. doi: 10.2166/wst.2024.056.

ABSTRACT

A biochar from co-pyrolysis of a mixture of sawdust and biological sludge (70/30, w/w), providing a high environmental compatibility in terms of water leachable polycyclic aromatic hydrocarbons and inorganic elements, together with a remarkable surface area (389 m2/g), was integrated into laboratory-scale vertical-flow constructed wetlands (VF-CWs), planted with Phragmites australis and unplanted. Biochar-filled VF-CWs have been tested for 8 months for the refining of effluents from the tertiary clariflocculation stage of a wastewater treatment plant operating in a mixed domestic-industrial textile context, in comparison with systems filled with gravel. VF-CW influents and effluents were monitored for chemical oxygen demand (COD), nitrogen and phosphorus cycles, and absorbance values at 254 and 420 nm, the latter as rapid and reliable screening parameters of the removal of organic micropollutants containing aromatic moieties and/or chromophores. Biochar-based systems provided a statistically significant improvement in COD (Δ = 22%) and ammonia (Δ = 35%) removal, as well as in the reduction of UV-Vis absorbance values (Δ = 32-34% and Δ = 28% for 254 and 420 nm, respectively), compared to gravel-filled microcosms. The higher removal of organic was mainly attributed to the well-known adsorption properties of biochars, while for nitrogen the biological mechanisms seem to play a predominant role.

PMID:38483496 | DOI:10.2166/wst.2024.056

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Statistical evaluation of trends of water quality monitoring parameters relevant to cyanobacterial blooms in the urban tropical reservoir

Water Sci Technol. 2024 Mar;89(5):1240-1251. doi: 10.2166/wst.2024.039.

ABSTRACT

The accelerated growth of cyanobacteria in water bodies is a global critical environmental issue caused by continuous discharges of effluents into the environment that are rich in phosphorus and nitrogen. So, cyanobacteria have found propitious conditions for proliferation, provoking significant ecological imbalances. Cyanobacteria produce cyanotoxins, which are harmful to life, and compounds like 2-methylisoborneol and geosmin that affect water’s taste and odor. This study analyzed a long-term database of important environmental parameters from a tropical reservoir in São Paulo State, Brazil. The statistical methods of correlation matrices and principal component analysis were used. Data analysis revealed a significant relationship between cyanobacteria growth and high levels of phosphate and nitrogen. Furthermore, positive correlations were found among concentrations of biocidal elements like antimony, arsenic, and selenium related to cyanobacterial bloomings. These correlations can be attributed to agricultural wastewaters and/or possible algicide used to control these microorganisms.

PMID:38483495 | DOI:10.2166/wst.2024.039

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Implementing patient-reported outcome measures on an adolescent inpatient psychiatry unit: A feasibility study

Psychol Serv. 2024 Mar 14. doi: 10.1037/ser0000851. Online ahead of print.

ABSTRACT

This article examines the feasibility of implementing patient-reported outcome (PRO) measures with adolescents on an inpatient psychiatry service. During the study period (March 8, 2021, to June 7, 2022), a total of 154 patient encounters were recorded for adolescents between 12 and 17 years of age. PROs were piloted during the first 3 months of the study period, with a focus on technical implementation. In the 12 months from June 8, 2021, through June 7, 2022, the PRO project moved to full implementation across all patient encounters. Fisher’s exact test and independent t tests were conducted to examine the differences between patients who completed the PROs and patients who did not complete them to determine the representativeness of the sample receiving them. During the 3-month pilot period, 31.8% of patients completed the PROs at admission and discharge, while during the 12-month full implementation, 74.5% of patients completed them at both time points. Statistical tests showed no significant diagnostic, sex, or race/ethnicity differences between patients who received and did not receive the outcome measures. Even without funding, small inpatient psychiatry services for adolescents can feasibly implement PROs with completion rates similar to other published studies and capture the majority of the patients served. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

PMID:38483486 | DOI:10.1037/ser0000851

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Unlocking the mechanism of action: a cost-effective flow cytometry approach for accelerating antimicrobial drug development

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

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Patients’ Perspectives on Plans Generated During Primary Care Visits and Self-Reported Adherence at 3 Months: Data From a Randomized Trial

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

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Latino Parents’ Reactions to and Engagement With a Facebook Group-Based COVID-19 Vaccine Promotion Intervention: Mixed Methods Pilot Study

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