Nevin Manimala

Cancer Chemother Pharmacol. 2022 Nov 21. doi: 10.1007/s00280-022-04489-1. Online ahead of print.

ABSTRACT

PURPOSE: Pemetrexed is a chemotherapeutic drug in the treatment of non-small cell lung cancer and mesothelioma. Optimized dosing of pemetrexed based on renal function instead of body surface area (BSA) is hypothesized to reduce pharmacokinetic variability in systemic exposure and could therefore improve treatment outcomes. The aim of this study is to compare optimized dosing to standard BSA-based dosing.

METHODS: A multicenter randomized (1:1) controlled trial was performed to assess superiority of optimized dosing versus BSA-based dosing in patients who were eligible for pemetrexed-based chemotherapy. The individual exposure to pemetrexed in terms of area under the concentration-time curve (AUC) was determined. The fraction of patients attaining to a predefined typical target AUC (164 mg × h/L ± 25%) was calculated.

RESULTS: A total of 81 patients were included. Target attainment was not statistically significant different between both arms (89% vs. 84% (p = 0.505)). The AUC of pemetrexed was similar between the optimized dosing arm (n = 37) and the standard of care arm (n = 44) (155 mg × h/L vs 160 mg × h/L (p = 0.436).

CONCLUSION: We could not show superiority of optimized dosing of pemetrexed in patients with an adequate renal function does not show added value on the attainment of a pharmacokinetic endpoint, safety, nor QoL compared to standard of care dosing.

CLINICAL TRIAL NUMBER: Clinicaltrials.gov identifier: NCT03655821.

PMID:36413252 | DOI:10.1007/s00280-022-04489-1

Sleep. 2022 Nov 22:zsac278. doi: 10.1093/sleep/zsac278. Online ahead of print.

ABSTRACT

STUDY OBJECTIVES: International guidelines recommend using benzodiazepine receptor agonists (BZRA) for maximally four weeks. Nevertheless, long-term use for chronic insomnia disorder remains a common practice. This study aimed to test the effectiveness of blended care for discontinuing long-term BZRA use in general practice.

METHODS: A pragmatic cluster randomized controlled superiority trial compared blended care to usual care through urine toxicology screening. In the intervention, care by the general practitioner (GP) was complemented by an interactive e-learning program, based on cognitive behavioral therapy for insomnia. Adults using BZRA daily for minimally six months were eligible. Participants were clustered at the level of the GP surgery for allocation (1:1). Effectiveness was measured as the proportion of patients who had discontinued at one-year follow-up. Data analysis followed intention-to-treat principles.

RESULTS: In total, 916 patients in 86 clusters, represented by 99 GPs, were randomized. Primary outcome data was obtained from 727 patients (79%). At one-year follow-up, 82 patients (18%) in blended care, compared to 91 patients (20%) in usual care, had discontinued. There was no statistically significant effect for the intervention (OR: 0·924; 95% CI: 0·60, 1·43). No adverse events were reported to the research team.

CONCLUSIONS: The findings did not support the superiority of blended care over usual care. Both strategies showed clinical effectiveness, with an average of 19% of patients having discontinued at one-year follow-up. Further research is important to study the effect of structurally implementing digital interventions in general practice.

PMID:36413221 | DOI:10.1093/sleep/zsac278

Eur J Transl Myol. 2022 Nov 22. doi: 10.4081/ejtm.2022.10847. Online ahead of print.

ABSTRACT

Mutations in tumor suppressor p53 protein can occur at different phases of malignant transformation and affect the patient’s prognosis. This study aimed to evaluate the expression of mutant p53 protein in Iranian patients with the primary and recurrence oral squamous cell carcinoma (OSCC). This retrospective cross-sectional study conducted on a group of patients with the primary OSCC (n=122) and the control subjects with oral noncancerous reactive lesions (n=80). Immunohistochemistry was performed with the DO-7 monoclonal antibody against p53 protein, and samples with ≥10% immunostaining were considered positive. Statistical analyses were carried out using SPSS. Positive staining for p53 was observed in none of the control subjects and 57.4% (70 of 122) of the primary OSCC patients (p<0.0001, OR=107.69, 95%CI=6.49-179.0). The p53 immunopositivity had no significant differences between males and females (54.2% vs. 62%, p=0.390), but significantly different between those aged below and over 50 years (p<0.0001, OR=4.52, 95%CI=1.07-12.05). During follow-up, OSCC recurrence occurred in 104 patients, but the phenotype of the mutant p53 protein in patients who relapsed was the same as in matched primary tumors (p=0.763). Risk of recurrence had no significant differences between p53-positive and p53-negative cases (p=0.953), males and females (p=0.263), and age below and over 50 years (p=0.223). Despite its confirmed diagnostic value, the immunoexpression of the p53 mutant protein in OSCC in cancer recurrence was the same as in the primary tumor. However, further studies with a larger sample size and longer follow-up are needed to confirm or change our conclusions.

PMID:36413207 | DOI:10.4081/ejtm.2022.10847

AANA J. 2022 Dec;90(6):439-445.

ABSTRACT

Patients undergoing one-lung ventilation (OLV) are at risk for lung injury leading to postoperative pulmonary complications (PPCs). Lung protective ventilation (LPV) challenges traditional anesthetic management by using lower tidal volumes, individualized positive end-expiratory pressure (PEEP), and recruitment maneuvers (RMs). LPV reduces driving pressure when properly applied, which reduces the incidence of PPCs. An LPV protocol was developed and implemented for this study for patients undergoing one-lung ventilation. Knowledge and confidence were measured prior to, immediately following, and 12 weeks after an educational offering and distribution of cognitive aids. Clinical data were collected 12 weeks prior to implementation, immediately after implementation, and again at 12 weeks post-implementation. There was a significant increase in provider knowledge regarding LPV (P = .015). A significant adherence to monitoring driving pressures (P < .05) was observed at 12 weeks post-implementation. There were increases in adherence to each component (tidal volume, PEEP, RM, and FiO₂) as well as overall adherence (P = .356). Implementation of the protocol resulted in increased adherence to lung protective strategies, including a statistically significant decrease (P < 0.05) in driving pressure which has been shown to reduce complications in patients having thoracic surgery with OLV.

PMID:36413189

Transplantation. 2022 Oct 27. doi: 10.1097/TP.0000000000004372. Online ahead of print.

ABSTRACT

BACKGROUND: Transcriptome analysis could be an additional diagnostic parameter in diagnosing kidney transplant (KTx) rejection. Here, we assessed feasibility and potential of NanoString nCounter analysis of KTx biopsies to aid the classification of rejection in clinical practice using both the Banff-Human Organ Transplant (B-HOT) panel and a customized antibody-mediated rejection (AMR)-specific NanoString nCounter Elements (Elements) panel. Additionally, we explored the potential for the classification of KTx rejection building and testing a classifier within our dataset.

METHODS: Ninety-six formalin-fixed paraffin-embedded KTx biopsies were retrieved from the archives of the ErasmusMC Rotterdam and the University Hospital Cologne. Biopsies with AMR, borderline or T cell-mediated rejections (BLorTCMR), and no rejection were compared using the B-HOT and Elements panels.

RESULTS: High correlation between gene expression levels was found when comparing the 2 chemistries pairwise (r = 0.76-0.88). Differential gene expression (false discovery rate; P < 0.05) was identified in biopsies diagnosed with AMR (B-HOT: 294; Elements: 76) and BLorTCMR (B-HOT: 353; Elements: 57) compared with no rejection. Using the most predictive genes from the B-HOT analysis and the Element analysis, 2 least absolute shrinkage and selection operators-based regression models to classify biopsies as AMR versus no AMR (BLorTCMR or no rejection) were developed achieving an receiver-operating-characteristic curve of 0.994 and 0.894, sensitivity of 0.821 and 0.480, and specificity of 1.00 and 0.979, respectively, during cross-validation.

CONCLUSIONS: Transcriptomic analysis is feasible on KTx biopsies previously used for diagnostic purposes. The B-HOT panel has the potential to differentiate AMR from BLorTCMR or no rejection and could prove valuable in aiding kidney transplant rejection classification.

PMID:36413151 | DOI:10.1097/TP.0000000000004372

Arch Argent Pediatr. 2022 Nov 24:e202202598. doi: 10.5546/aap.2022-02598.eng. Online ahead of print.

ABSTRACT

Introduction. Usually, during anorectal manometry, only the presence or absence of rectoanal inhibitory reflex (RAIR) is investigated. Studies have reported that a detailed analysis may provide data of interest. Our hypothesis is that RAIR measurement may provide information to detect organic causes (tethered cord, lipoma, etc.) in patients in whom a functional cause had been previously considered. Objectives. To compare RAIR duration in anorectal manometry between patients with refractory functional constipation (RFC) and myelomeningocele (MMC). Population and methods. Observational, analytical, cross-sectional study (2004-2019). Patients with chronic constipation and functional and organic fecal incontinence (myelomeningocele). The anorectal manometry was performed with a water-perfused system, and the duration of RAIR was measured with different volumes (20, 40, and 60 cc). Group 1 (G1): 81 RFC. Group 2 (G2): 54 MMC. Patients with developmental delay, compliant anal sphincter, sacral agenesis and non-cooperative patients were excluded. Results. A total of 135 individuals were included (62 were male). Their median age was 9.57 years in G1 and 9.63 years in G2. Average duration in G1 versus G2 with 20 cc: 8.89 versus 15.21 seconds; 40 cc: 11.41 versus 21.12 seconds; 60 cc: 14.15 versus 26.02 seconds. The difference in RAIR duration with the varying volumes was statistically significant (p = 0.0001). Conclusion. RAIR duration was longer with increasing balloon inflation volumes in both populations. RAIR duration was longer in patients with MMC than in those with RFC. Spinal injury should be ruled out in patients with prolonged RAIR.

PMID:36413143 | DOI:10.5546/aap.2022-02598.eng

J Am Med Inform Assoc. 2022 Nov 22:ocac216. doi: 10.1093/jamia/ocac216. Online ahead of print.

ABSTRACT

OBJECTIVE: Accurate and rapid phenotyping is a prerequisite to leveraging electronic health records for biomedical research. While early phenotyping relied on rule-based algorithms curated by experts, machine learning (ML) approaches have emerged as an alternative to improve scalability across phenotypes and healthcare settings. This study evaluates ML-based phenotyping with respect to (1) the data sources used, (2) the phenotypes considered, (3) the methods applied, and (4) the reporting and evaluation methods used.

MATERIALS AND METHODS: We searched PubMed and Web of Science for articles published between 2018 and 2022. After screening 850 articles, we recorded 37 variables on 100 studies.

RESULTS: Most studies utilized data from a single institution and included information in clinical notes. Although chronic conditions were most commonly considered, ML also enabled the characterization of nuanced phenotypes such as social determinants of health. Supervised deep learning was the most popular ML paradigm, while semi-supervised and weakly supervised learning were applied to expedite algorithm development and unsupervised learning to facilitate phenotype discovery. ML approaches did not uniformly outperform rule-based algorithms, but deep learning offered a marginal improvement over traditional ML for many conditions.

DISCUSSION: Despite the progress in ML-based phenotyping, most articles focused on binary phenotypes and few articles evaluated external validity or used multi-institution data. Study settings were infrequently reported and analytic code was rarely released.

CONCLUSION: Continued research in ML-based phenotyping is warranted, with emphasis on characterizing nuanced phenotypes, establishing reporting and evaluation standards, and developing methods to accommodate misclassified phenotypes due to algorithm errors in downstream applications.

PMID:36413056 | DOI:10.1093/jamia/ocac216

Phys Sportsmed. 2022 Nov 22:1-6. doi: 10.1080/00913847.2022.2148492. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of the study was to evaluate the effect of Osgood-Schlatter disease (OSD) on knee joint function in elite young soccer players. Our hypothesis was that knee joint function in elite young soccer players was impaired following OSD compared with soccer players with no history of OSD.

METHOD: In young male soccer players (n = 36) from elite academies (mean ±SD, age: age: 15,3 ± 1,7 years; height: 1,7 ± 0,06 m; weight: 63,5 ± 8 kg; BMI: 20,7 ± 2). The duration between the completion of treatment or the last complaint to the study commencement was 31 ± 19 months.

RESULTS: The average treatment duration of OSD among study participants was 18,5 ± 12 days (95%, 14-23), and the disease most often manifested in winter and spring, 33% and 31% of cases, respectively. Soccer players with a history of OSD were statistically different in IKDC and KOOS scores when compared with soccer players with no previously reported OSD (Mann-Whitney, p < 0,0001). The soccer players with a history of OSD also use NSAIDs more frequently compared with soccer players with no history of OSD (36% vs 3% respectively).

CONCLUSIONS: OSD among young soccer players, when symptoms resolve, continue about one month and they can return to regular training and participation in games. Wherein, the negative effects in knee joint function were significantly more likely in soccer players with previous OSD history when compared with their peers with no history of OSD. While oral non-steroidal anti-inflammatory drugs was also more widely employed in soccer players with previous OSD history. Potentially this may lead to performance deficits and disadvantages for their future careers and coaches and physicians should be informed.

PMID:36413052 | DOI:10.1080/00913847.2022.2148492

J Int Med Res. 2022 Nov;50(11):3000605221135147. doi: 10.1177/03000605221135147.

ABSTRACT

OBJECTIVE: To apply deep learning to a data set of dental panoramic radiographs to detect the mental foramen for automatic assessment of the mandibular cortical width.

METHODS: Data from the seventh survey of the Tromsø Study (Tromsø7) were used. The data set contained 5197 randomly chosen dental panoramic radiographs. Four pretrained object detectors were tested. We randomly chose 80% of the data for training and 20% for testing. Models were trained using GeForce RTX 2080 Ti with 11 GB GPU memory (NVIDIA Corporation, Santa Clara, CA, USA). Python programming language version 3.7 was used for analysis.

RESULTS: The EfficientDet-D0 model showed the highest average precision of 0.30. When the threshold to regard a prediction as correct (intersection over union) was set to 0.5, the average precision was 0.79. The RetinaNet model achieved the lowest average precision of 0.23, and the precision was 0.64 when the intersection over union was set to 0.5. The procedure to estimate mandibular cortical width showed acceptable results. Of 100 random images, the algorithm produced an output 93 times, 20 of which were not visually satisfactory.

CONCLUSIONS: EfficientDet-D0 effectively detected the mental foramen. Methods for estimating bone quality are important in radiology and require further development.

PMID:36412242 | DOI:10.1177/03000605221135147

Suicide Life Threat Behav. 2022 Nov 22. doi: 10.1111/sltb.12929. Online ahead of print.

ABSTRACT

INTRODUCTION: Suicide is a leading cause of death for men in the United States. Men traditionally have been hesitant to seek help, based on masculine norms of stoicism and self-reliance, among other factors. Man Therapy (MT) is an online suicide prevention and mental health initiative that provides promise for facilitating male help-seeking.

METHODS: This study draws on data from a randomized controlled trial which examined effects of MT on a sample of men residing in Michigan aged 25-64. The current study utilized logistic regression to test MT’s effect on nonprofessional and professional help-seeking, controlling for marital status, education, and sexual orientation.

RESULTS: A statistically significant positive association was found between MT and professional help-seeking (OR = 1.55, p = 0.049). A significant inverse association was also found with marital status, with partnered men less likely to seek professional help (OR = 0.53, p = 0.007). There was no significant association between MT and nonprofessional help-seeking.

CONCLUSION: Man Therapy demonstrates the promise of web-based suicide prevention efforts to reach men who typically do not engage in help-seeking, providing a gateway to vital professional support. As technology continues to emerge, further suicide research is needed on use of this modality with working-age men from diverse backgrounds.

PMID:36412229 | DOI:10.1111/sltb.12929