Category: Nevin Manimala

Health Rep. 2024 Jul 17;35(7):3-13. doi: 10.25318/82-003-x202400700001-eng.

ABSTRACT

BACKGROUND: Most individuals prefer to spend their final moments of life outside a hospital setting. This study compares the places of care and death of long-term care (LTC) home residents in Ontario in the last 90 days of life, according to LTC home rurality.

DATA AND METHODS: This retrospective cohort study was conducted using health administrative data from ICES (formerly known as the Institute for Clinical Evaluative Sciences). The study population, which was identified through algorithms, included all Ontario LTC home residents with a dementia diagnosis who died between April 1, 2014, and March 31, 2019. The location of death was categorized as in an acute care hospital, an LTC home, a subacute care facility, or the community. Places of care included emergency department visits and hospitalizations in the last 90 days of life. Statistical tests were used to evaluate differences in location of death and places of care by rurality.

RESULTS: Of the 65,375 LTC home residents with dementia, 49,432 (75.6%) died in an LTC home. Residents of LTC homes in the most urban areas were less likely to die in an LTC home than those in more rural homes (adjusted relative risk: 0.84; 95% confidence interval: 0.83 to 0.85). A higher proportion of residents of the most urban LTC homes had at least one hospitalization in the last 90 days of life compared with rural residents (23.7% versus 9.9% palliative hospitalizations and 28.3% versus 15.9% non-palliative hospitalizations [p ⟨ 0.001]).

INTERPRETATION: Individuals with dementia residing in urban LTC homes are more likely to receive care in the hospital and to die outside a LTC home than their counterparts living in rural LTC homes. The findings of this work will inform efforts to improve end-of-life care for older adults with dementia living in LTC homes.

PMID:39018523 | DOI:10.25318/82-003-x202400700001-eng

J Clin Oncol. 2024 Jul 17:JCO2400178. doi: 10.1200/JCO.24.00178. Online ahead of print.

ABSTRACT

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Although dose-dense adjuvant chemotherapy administered once every 2 weeks leads to superior outcomes compared with standard regimens once every 3 weeks, the observed improvement is largely limited to studies using the suboptimal paclitaxel schedule once every 3 weeks as control. PANTHER is an international phase III trial which compared sequential epirubicin/cyclophosphamide and docetaxel administered either once every 2 or once every 3 weeks, with tailored dosing at the dose-dense schedule according to hematologic toxicity. In this end-of-study analysis, the median follow-up was 10.3 years. Compared with standard adjuvant chemotherapy, dose-dense treatment improved breast cancer recurrence-free survival (hazard ratio [HR], 0.80 [95% CI, 0.65 to 0.98]; P = .030), event-free survival (HR, 0.78 [95% CI, 0.65 to 0.94]; P = .009), and distant disease-free survival (HR, 0.79 [95% CI, 0.64 to 0.98]; P = .030) while the improvement in overall survival was not statistically significant (HR, 0.82 [95% CI, 0.65 to 1.04]; P = .109). To our knowledge, this is the first trial that confirms the benefit of a dose-dense regimen over a control regimen containing docetaxel once every 3 weeks.

PMID:39018515 | DOI:10.1200/JCO.24.00178

JCO Clin Cancer Inform. 2024 Jul;8:e2400037. doi: 10.1200/CCI.24.00037.

ABSTRACT

PURPOSE: Patient outcomes may differ from randomized trial averages. We aimed to predict benefit from FOLFOXIRI versus infusional fluorouracil, leucovorin, and oxaliplatin/fluorouracil, leucovorin, and irinotecan (FOLFOX/FOLFIRI), both plus bevacizumab, in patients with metastatic colorectal cancer (mCRC).

METHODS: A Cox model with prespecified clinical, molecular, and laboratory variables was developed in 639 patients from the TRIBE2 trial for predicting 2-year mortality. Data from the CHARTA (n = 232), TRIBE1 (n = 504), and CAIRO5 (liver-only mCRC, n = 287) trials were used for external validation and heterogeneity of treatment effects (HTE) analysis. This involves categorizing patients into risk groups and assessing treatment effects across these groups. Performance was assessed by the C-index and calibration plots. The C-for-benefit was calculated to assess evidence for HTE. The c-for-benefit is specifically designed for HTE analysis. Like the commonly known c-statistic, it summarizes the discrimination of a model. Values over 0.5 indicate evidence for HTE.

RESULTS: In TRIBE2, the overoptimism-corrected C-index was 0.66 (95% CI, 0.63 to 0.69). At external validation, the C-index was 0.69 (95% CI, 0.64 to 0.75), 0.68 (95% CI, 0.64 to 0.72), and 0.65 (95% CI, 0.65 to 0.66), in CHARTA, TRIBE1, and CAIRO5, respectively. Calibration plots indicated slight underestimation of mortality. The c-for-benefit indicated evidence for HTE in CHARTA (0.56, 95% CI, 0.48 to 0.65), but not in TRIBE1 (0.49, 95% CI, 0.44 to 0.55) and CAIRO5 (0.40, 95% CI, 0.32 to 0.48).

CONCLUSION: Although 2-year mortality could be reasonably estimated, the HTE analysis showed that clinically available variables did not reliably identify which patients with mCRC benefit from FOLFOXIRI versus FOLFOX/FOLFIRI, both plus bevacizumab, across the three studies.

PMID:39018510 | DOI:10.1200/CCI.24.00037

J Am Med Inform Assoc. 2024 Jul 17:ocae194. doi: 10.1093/jamia/ocae194. Online ahead of print.

ABSTRACT

OBJECTIVES: This work presents the development and evaluation of coordn8, a web-based application that streamlines fax processing in outpatient clinics using a “human-in-the-loop” machine learning framework. We demonstrate the effectiveness of the platform at reducing fax processing time and producing accurate machine learning inferences across the tasks of patient identification, document classification, spam classification, and duplicate document detection.

METHODS: We deployed coordn8 in 11 outpatient clinics and conducted a time savings analysis by observing users and measuring fax processing event logs. We used statistical methods to evaluate the machine learning components across different datasets to show generalizability. We conducted a time series analysis to show variations in model performance as new clinics were onboarded and to demonstrate our approach to mitigating model drift.

RESULTS: Our observation analysis showed a mean reduction in individual fax processing time by 147.5 s, while our event log analysis of over 7000 faxes reinforced this finding. Document classification produced an accuracy of 81.6%, patient identification produced an accuracy of 83.7%, spam classification produced an accuracy of 98.4%, and duplicate document detection produced a precision of 81.0%. Retraining document classification increased accuracy by 10.2%.

DISCUSSION: coordn8 significantly decreased fax-processing time and produced accurate machine learning inferences. Our human-in-the-loop framework facilitated the collection of high-quality data necessary for model training. Expanding to new clinics correlated with performance decline, which was mitigated through model retraining.

CONCLUSION: Our framework for automating clinical tasks with machine learning offers a template for health systems looking to implement similar technologies.

PMID:39018499 | DOI:10.1093/jamia/ocae194

Cutan Ocul Toxicol. 2024 Jul 17:1-10. doi: 10.1080/15569527.2024.2380310. Online ahead of print.

ABSTRACT

AIM: There is no marker that can predict whether there is resistance to treatment in patients with psoriasis. In this study, we investigated the relationship between the staining rates of TNF-α, IL-1, IL-12, IL-17, IL-23, and IL-36 markers immunohistochemically from cutaneous biopsy and the treatment success.

METHODS: The patients who were followed up in the dermatology clinic with the diagnosis of plaque-type psoriasis vulgaris and received biological treatment and previously had cutaneous biopsy were included in the study. The cutaneous biopsies of the cases that met the conditions were re-sectioned and subjected to immunohistochemical examination for TNF-α, IL-1, IL-12, IL-17, IL-23, and IL-36.

RESULTS: Comparing the staining scores with psoriasis area severity index (PASI); A statistically significant positive correlation was found between PASI and TNF-α staining score(p = 0.034). A statistically significant positive correlation was found between PASI and IL-17 staining score(p = 0.004).When the staining scores and PASI response rates of psoriasis treatment were evaluated in terms of correlation; there was a positive correlation between TNF-α, IL-17, and IL-23 immunohistochemical staining rates and PASI response rates.

CONCLUSIONS: In line with the data obtained from our study, we think that making immunohistochemical scoring before the biological treatment decision in psoriasis patients will be beneficial in treatment selection. In this respect, our study may open a new era in the selection of biological treatments for psoriasis.

PMID:39018470 | DOI:10.1080/15569527.2024.2380310

Urogynecology (Phila). 2024 Jul 16. doi: 10.1097/SPV.0000000000001556. Online ahead of print.

ABSTRACT

IMPORTANCE: Although parturients report few postpartum symptoms, birth is clearly associated with future symptom development. The ability to identify asymptomatic at-risk women would facilitate prevention.

OBJECTIVE: The aim of the study was to develop a model predicting abnormal recovery in women at risk for childbirth-associated pelvic floor injury.

STUDY DESIGN: Women undergoing first vaginal birth at high risk of pelvic floor injury underwent examinations and ultrasound imaging and completed 6-week and 6-month postpartum questionnaires. We defined “abnormal” recovery as having ≥1 of the following 3 findings: (1) levator ani injury, (2) decreased objective pelvic floor strength, and (3) Pelvic Organ Prolapse Quantification point Bp ≥0. Descriptive statistics and bivariate analyses compared “normal” and “abnormal” recovery. Birth characteristics, 6-week examinations, and questionnaires potentially predicted abnormal recovery at 6 months. Significant variables were included as candidates in the multivariable logistic regression predicting “abnormal” recovery after birth.

RESULTS: Fifty-four women (63.5%) had normal and 31 (36.5%) had abnormal recovery at 6 months. At 6 weeks, women with abnormal recovery had decreased pelvic floor strength by Oxford scores (3 [2-5], 6 [2-8]; P = 0.002), lower point Bp (-1 [-3 to 0], -2 [-3 to -1]; P = 0.02), larger genital hiatus (4 [3 to 4], 3 [3 to 3.5]; P = 0.02), and higher levator ani injury rate (76.7%, 22.4%; P < 0.001). Between-group questionnaire differences were not clinically significant. Our final model included postpartum examination findings or birth characteristics: Oxford Scale, 6-week Pelvic Organ Prolapse Quantification GH strain, infant head circumference, and second stage ≥120 minutes. The area under the curve for predicting abnormal recovery at 6 months was 0.84, indicating a good sensitivity and specificity balance.

CONCLUSION: The model identifies women at risk for an abnormal recovery trajectory.

PMID:39018453 | DOI:10.1097/SPV.0000000000001556

J Med Chem. 2024 Jul 17. doi: 10.1021/acs.jmedchem.4c00776. Online ahead of print.

ABSTRACT

30 covalent drugs were used to assess clearance (CL) prediction reliability in animals and humans. In animals, marked CL underprediction was observed using cryopreserved hepatocytes or liver microsomes (LMs) supplemented for cytochrome P450 activity. Improved quantitative performance was observed by combining metabolic stability data from LMs and liver S9 fractions, the latter supplemented with reduced glutathione for glutathione transferase activity. While human LMs provided reliable human CL predictions, prediction statistics were improved further by incorporating S9 stability data. CL predictions with allometric scaling were less robust compared to in vitro drug metabolism methods; the best results were obtained using the fu-corrected intercept model. Human volume of distribution (V_d) was well predicted using allometric scaling of animal pharmacokinetic data; the most reliable results were achieved using simple allometric scaling of unbound V_d values. These results provide a quantitative framework to guide appropriate method selection for human PK prediction with covalent drugs.

PMID:39018425 | DOI:10.1021/acs.jmedchem.4c00776

PLoS One. 2024 Jul 17;19(7):e0305600. doi: 10.1371/journal.pone.0305600. eCollection 2024.

ABSTRACT

Plants intimately coexist with diverse taxonomically structured microbial communities that influence host health and productivity. The coexistence of plant microbes in the phyllosphere benefits biodiversity maintenance, ecosystem function, and community stability. However, differences in community composition and network structures of phyllosphere epiphytic and endophytic fungi are widely unknown. Using Illumina Miseq sequencing of internal transcribed spacer (ITS) and 28S rRNA gene amplicons, we characterised the epiphytic and endophytic fungal communities associated with cashew phyllosphere (leaf, flower and fruit) from Kwale, Kilifi and Lamu counties in Kenya. The ITS and 28S rRNA gene sequences were clustered into 267 and 108 operational taxonomic units (OTUs) at 97% sequence similarity for both the epiphytes and endophytes. Phylum Ascomycota was abundant followed by Basidiomycota, while class Saccharomycetes was most dominant followed by Dothideomycetes. The major non-ascomycete fungi were associated only with class Tremellales. The fungal communities detected had notable ecological functions as saprotrophs and pathotrophs in class Saccharomyectes and Dothideomycetes. The community composition of epiphytic and endophytic fungi significantly differed between the phyllosphere organs which was statistically confirmed by the Analysis of Similarity test (ANOSIM Statistic R: 0.3273, for 28S rRNA gene and ANOSIM Statistic R: 0.3034 for ITS). The network analysis revealed that epiphytic and endophytic structures were more specialized, modular and had less connectance. Our results comprehensively describe the phyllosphere cashew-associated fungal community and serve as a foundation for understanding the host-specific microbial community structures among cashew trees.

PMID:39018319 | DOI:10.1371/journal.pone.0305600

PLOS Glob Public Health. 2024 Jul 17;4(7):e0003194. doi: 10.1371/journal.pgph.0003194. eCollection 2024.

ABSTRACT

The Covid-19 pandemic and associated restrictions have the potential to alter sexual risk behaviours for HIV acquisition with important implications for HIV prevention programmes in sub-Saharan Africa. To date, no large-scale data have been published to substantiate hypothesised changes in sexual risk behaviours. We used longitudinal survey data to assess the impact of Covid-19 on sexual risk behaviours in east Zimbabwe. Data on sexual behaviours in HIV-negative adults aged 15-54 years were collected in two rounds of a general population open-cohort survey conducted in Manicaland, Zimbabwe shortly before (July 2018 to December 2019; N = 7316) and several months into the Covid-19 epidemic (February to July 2021; N = 6356). Descriptive statistics and logistic regression models of serial cross-sectional and prospective cohort data were used to assess changes in sexual risk behaviours. The proportion of females aged 15-19 years reporting sexual debut declined from 29.7% before Covid-19 to 20.3% during Covid-19 (adjusted odds ratio (AOR) = 0.49, 95% confidence interval (95% CI), 0.38-0.63). Fewer sexually-active females reported multiple sexual partners during Covid-19 (3.35% versus 6.07%; AOR = 0.55, 95% CI, 0.43-0.72). No population-level changes in male behaviour between survey rounds were recorded but the cohort analysis revealed a complex pattern of behaviour change with HIV risk behaviours increasing for some individuals and decreasing for others. Overall HIV risk behaviours remained high in a sub-Saharan African population with a generalised HIV epidemic over a period of Covid-19 lockdowns when movements and social contacts were restricted.

PMID:39018312 | DOI:10.1371/journal.pgph.0003194

PLoS One. 2024 Jul 17;19(7):e0307284. doi: 10.1371/journal.pone.0307284. eCollection 2024.

ABSTRACT

With the overall objective of providing implication for clinical and research practices regarding the identification and measurement of modifiable predicting factors for return to work (RTW) in people with musculoskeletal disorders (MSDs) and common mental disorders (CMDs), this study 1) systematically examined and synthetized the research evidence available in the literature on the topic, and 2) critically evaluated the tools used to measure each identified factor. A systematic search of prognostic studies was conducted, considering four groups of keywords: 1) population (i.e., MSDs or CMDs), 2) study design (prospective), 3) modifiable factors, 4) outcomes of interest (i.e., RTW). Studies showing high risk of bias were eliminated. Tools used to measure prognostic factors were assessed using psychometric and usability criteria. From the 78 studies that met inclusion criteria, 19 (for MSDs) and 5 (for CMDs) factors reaching moderate or strong evidence were extracted. These factors included work accommodations, RTW expectations, job demands (physical), job demands (psychological), job strain, work ability, RTW self-efficacy, expectations of recovery, locus of control, referred pain (back pain), activities as assessed with disability questionnaires, pain catastrophizing, coping strategies, fears, illness behaviours, mental vitality, a positive health change, sleep quality, and participation. Measurement tools ranged from single-item tools to multi-item standardized questionnaires or subscales. The former generally showed low psychometric properties but excellent usability, whereas the later showed good to excellent psychometric properties and variable usability. The rigorous approach to the selection of eligible studies allowed the identification of a relatively small set of prognostic factors, but with a higher level of certainty. For each factor, the present tool assessment allows an informed choice to balance psychometric and usability criteria.

PMID:39018306 | DOI:10.1371/journal.pone.0307284