Tag: nevin manimala

J Clin Oncol. 2023 Sep 5:JCO2202906. doi: 10.1200/JCO.22.02906. Online ahead of print.

ABSTRACT

PURPOSE: Selinexor inhibits exportin-1 (XPO1) resulting in nuclear accumulation of tumor suppressor proteins including p53 and has clinical activity in endometrial cancer (EC). The primary end point was to assess progression-free survival (PFS) with once-weekly oral selinexor in patients with advanced or recurrent EC.

PATIENTS AND METHODS: ENGOT-EN5/GOG-3055/SIENDO was a randomized, prospective, multicenter, double-blind, placebo-controlled, phase III study at 107 sites in 10 countries. Patients 18 years or older with histologically confirmed EC were enrolled. All had completed a single line of at least 12 weeks of taxane-platinum combination chemotherapy and achieved partial or complete response. Patients were assigned to receive 80 mg oral selinexor once weekly or placebo with 2:1 random assignment (ClinicalTrials.gov identifier: NCT03555422).

RESULTS: Between January 2018 and December 2021, 263 patients were randomly assigned, with 174 allocated to selinexor and 89 to placebo. The median PFS was 5.7 months (95% CI, 3.81 to 9.20) with selinexor versus 3.8 months (95% CI, 3.68 to 7.39) with placebo (hazard ratio [HR], 0.76 [95% CI, 0.54 to 1.08]; two-sided P = .126), which did not meet the criteria for statistical significance in the intent-to-treat population. Incorrect chemotherapy response stratification data for 7 (2.7%) patients were identified. In a prespecified exploratory analysis of PFS in audited stratification data, PFS for selinexor met the threshold for statistical significance (HR, 0.71; 95% CI, 0.499 to 0.996; two-sided P = .049). Furthermore, patients with the TP53 wild-type (wt) EC had a median PFS of 13.7 and 3.7 months with selinexor and placebo. The most common grade 3 treatment-related adverse events were nausea (9%), neutropenia (9%), and thrombocytopenia (7%).

CONCLUSION: The significance level for PFS was only met in the audited analysis. However, a preliminary analysis of a prespecified exploratory subgroup of patients with TP53wt EC showed promising results with selinexor maintenance therapy.

PMID:37669480 | DOI:10.1200/JCO.22.02906

J Craniofac Surg. 2023 Sep 4. doi: 10.1097/SCS.0000000000009728. Online ahead of print.

ABSTRACT

This study aims to compare the effects of osteoplastic craniotomy on temporalis muscle and bone graft atrophy in patients operated on with a pterional approach to the standard technique. Patients operated on for an intracranial aneurysm with a pterional approach between 2014 and 2018 were studied. Following the exclusion criteria, 36 patients were included in this retrospective study. Temporalis muscle volume and bone graft volume were calculated. The volumes were compared from preoperative and postoperative computed tomography images for temporalis muscle and from early and late postoperative computed tomography images for the bone graft. The osteoplastic craniotomy group (group I) had 17 patients, and the standard craniotomy group had 19 patients (group II). Temporalis muscle volume and bone graft volume decreased statistically significantly in group II after surgery. However, no significant volume difference was found in group I measurements. When compared with the standard technique, osteoplastic craniotomy reduces the likelihood of postoperative temporalis muscle and bone graft atrophy in patients undergoing pterional craniotomy. As a result, the patients’ cosmetic and functional well-being is improved.

PMID:37669471 | DOI:10.1097/SCS.0000000000009728

J Craniofac Surg. 2023 Sep 4. doi: 10.1097/SCS.0000000000009709. Online ahead of print.

ABSTRACT

BACKGROUND: Up to 17.4 in every 10,000 births are affected by microtia, but no consensus exists on a gold standard technique for autogenous repair. In this study, the authors compare 2 common methods-the Brent and Nagata autogenous costal cartilage ear reconstruction techniques. A systematic review of the literature and a quantitative meta-analysis to compare the outcomes of these 2 approaches were performed. The outcomes analyzed included rates of infection, necrosis, cartilage exposure, cartilage resorption, hematoma, wire extrusion, and hypertrophic scar.

METHODS: A MEDLINE database systematic review with the following keywords: microtia, Brent, and Nagata was performed. Case reports and articles without original data or patient outcomes were excluded. Inclusion methods for study selection are outlined in Supplemental Digital Content 1, http://links.lww.com/SCS/F461, below. The prevalence of outcomes for each study was analyzed through meta-analysis of proportions using Stata.

RESULTS: A total of 536 potential studies were retrieved for review. Twelve of these studies met inclusion criteria. Four studies utilized the Brent method of repair with the inclusion of 563 ear reconstructions. Nine studies implemented the Nagata technique in 2304 reconstructions. Two studies directly compared the Brent (327 ears) and Nagata (471 ears) techniques. The calculated rate and 95% confidence intervals are summarized in Supplemental Digital Content 2, http://links.lww.com/SCS/F461. There were no statistically significant differences in complication rates between the Brent and Nagata microtic reconstruction techniques identified in this study.

CONCLUSIONS: The Brent and Nagata microtia reconstruction techniques have no difference in the risk of infection, necrosis, cartilage exposure, cartilage resorption, hematoma, wire extrusion, or hypertrophic scars.

PMID:37669467 | DOI:10.1097/SCS.0000000000009709

Cornea. 2023 Oct 1;42(10):1309-1319. doi: 10.1097/ICO.0000000000003319. Epub 2023 Jul 7.

ABSTRACT

PURPOSE: The aim of this study was to perform automated segmentation of corneal nerves and other structures in corneal confocal microscopy (CCM) images of the subbasal nerve plexus (SNP) in eyes with ocular surface diseases (OSDs).

METHODS: A deep learning-based 2-stage algorithm was designed to perform segmentation of SNP features. In the first stage, to address applanation artifacts, a generative adversarial network-enabled deep network was constructed to identify 3 neighboring corneal layers on each CCM image: epithelium, SNP, and stroma. This network was trained/validated on 470 images of each layer from 73 individuals. The segmented SNP regions were further classified in the second stage by another deep network as follows: background, nerve, neuroma, and immune cells. Twenty-one-fold cross-validation was used to assess the performance of the overall algorithm on a separate data set of 207 manually segmented SNP images from 43 patients with OSD.

RESULTS: For the background, nerve, neuroma, and immune cell classes, the Dice similarity coefficients of the proposed automatic method were 0.992, 0.814, 0.748, and 0.736, respectively. The performance metrics for automatic segmentations were statistically better or equal as compared to human segmentation. In addition, the resulting clinical metrics had good to excellent intraclass correlation coefficients between automatic and human segmentations.

CONCLUSIONS: The proposed automatic method can reliably segment potential CCM biomarkers of OSD onset and progression with accuracy on par with human gradings in real clinical data, which frequently exhibited image acquisition artifacts. To facilitate future studies on OSD, we made our data set and algorithms freely available online as an open-source software package.

PMID:37669422 | DOI:10.1097/ICO.0000000000003319

Proc Natl Acad Sci U S A. 2023 Sep 12;120(37):e2217144120. doi: 10.1073/pnas.2217144120. Epub 2023 Sep 5.

ABSTRACT

Multiple ecological forces act together to shape the composition of microbial communities. Phyloecology approaches-which combine phylogenetic relationships between species with community ecology-have the potential to disentangle such forces but are often hard to connect with quantitative predictions from theoretical models. On the other hand, macroecology, which focuses on statistical patterns of abundance and diversity, provides natural connections with theoretical models but often neglects interspecific correlations and interactions. Here, we propose a unified framework combining both such approaches to analyze microbial communities. In particular, by using both cross-sectional and longitudinal metagenomic data for species abundances, we reveal the existence of an empirical macroecological law establishing that correlations in species-abundance fluctuations across communities decay from positive to null values as a function of phylogenetic dissimilarity in a consistent manner across ecologically distinct microbiomes. We formulate three variants of a mechanistic model-each relying on alternative ecological forces-that lead to radically different predictions. From these analyses, we conclude that the empirically observed macroecological pattern can be quantitatively explained as a result of shared population-independent fluctuating resources, i.e., environmental filtering and not as a consequence of, e.g., species competition. Finally, we show that the macroecological law is also valid for temporal data of a single community and that the properties of delayed temporal correlations can be reproduced as well by the model with environmental filtering.

PMID:37669363 | DOI:10.1073/pnas.2217144120

J Addict Nurs. 2023 Jul-Sep 01;34(3):E53-E64. doi: 10.1097/JAN.0000000000000538.

ABSTRACT

Emergency departments (EDs) serve as the front line when patients encounter the hospital system. Limited data are available of patients’ alcohol habits collected during Danish ED visits, and no studies have, to our knowledge, examined frontline staffs’ (registered nurses and medical secretaries) acceptability to deliver anonymous alcohol surveys to patients. We aimed at examining the proportion of survey respondents and the prevalence of patients’ alcohol habits and also exploring frontline staff acceptability of the distribution of an anonymous survey regarding patients’ alcohol habits in EDs. Intendedly, all eligible patients ≥18 years old entering two EDs in March 2019 should receive a survey based on the Alcohol Use Disorder Identification Test. The study was an explanatory, sequential, mixed methods design, and results were analyzed with descriptive statistics and a deductive content analysis based on the theoretical framework of acceptability. In total, 15% (n = 1,305) of the total 8,679 patients in the EDs returned the survey. Qualitative analysis of interviews (n = 31) with staff showed that they had been reluctant to distribute the survey primarily because of ethical concerns of anonymity, freedom of choice, and being nonjudgmental toward patients. Hence, patients with no obvious alcohol problems were more likely to receive the survey. Still, we found that 23% of the respondents had an Alcohol Use Disorder Identification Test score ≥ 8. Results indicate that frontline staffs’ recognition of patients’ alcohol use is inadequate, and findings show a low degree of acceptability among staff to deliver an anonymous survey, which is in line with earlier described barriers toward screening activities in EDs.

PMID:37669345 | DOI:10.1097/JAN.0000000000000538

J Addict Nurs. 2023 Jul-Sep 01;34(3):173-177. doi: 10.1097/JAN.0000000000000537.

ABSTRACT

BACKGROUND: Addiction to opioids, a well-known public health crisis, is now more prevalent in pregnant women as evidenced by the parallel rise with pregnant women in the epidemic with the general population. Evidence is now available that substantiates the need for global awareness to increase efforts in the treatment of pregnant women with opioid use disorder (OUD) as this vulnerable population lacks equal access to opioid abuse treatment across the United States.

AIM: The overarching aim and purpose of this quality improvement project was to increase access to treatment for pregnant women with OUD who are currently underserved in a community located in Florida.

METHODS: Between January and April 2022, the 4Ps (parents, partners, past, and pregnancy), a validated screening tool, was implemented in an organization that accepts individuals with substance abuse. Each positive screen was referred for assessment for buprenorphine induction and medication-assisted treatment follow-up. Descriptive statistics were collected counting the number of screens completed, the number of positive screens, the number of referrals, and the number of patients remaining in treatment for 30 and 60 days.

RESULTS: Twenty-two screens were completed. The results yielded an increase in referrals, a 75% increase in treatment of pregnant women, and an average of 83% of participants remained in treatment.

CONCLUSION: The implementation of a validated screening tool assisted in increasing access to treatment for pregnant women with OUD. Once implemented, the screening tool forges a pathway for referrals and evidence-based treatment for pregnant women with OUD.

PMID:37669336 | DOI:10.1097/JAN.0000000000000537

JAMA Intern Med. 2023 Sep 5. doi: 10.1001/jamainternmed.2023.4192. Online ahead of print.

ABSTRACT

IMPORTANCE: An estimated 1.5% to nearly 5% of medications are dispensed after discontinuation in the electronic health record (EHR), with 34% meeting criteria for high risk of potential harm.

OBJECTIVE: To evaluate the association of the implementation of e-prescription cancellation messaging (CancelRx) with medication dispensing after discontinuation of e-prescriptions in the EHR.

DESIGN, SETTING, AND PARTICIPANTS: This case series with interrupted time series analysis included patients who had at least 1 medication e-prescribed in ambulatory care to a health system pharmacy and discontinued in the 2-year study period from 1 year prior to approximately 1 year after CancelRx implementation (January 15, 2018, to December 7, 2019). Prior to CancelRx implementation, changes to e-prescribed medications within the EHR were not electronically communicated to health system pharmacies, which used separate pharmacy management software. Statistical analysis was performed from November 2020 to June 2023 (primary analysis from March 2021 to May 2022).

EXPOSURE: Implementation of CancelRx.

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of e-prescribed medications dispensed and sold to patients by pharmacies within 6 months after discontinuation in the EHR. A medication was defined as dispensed after discontinuation if the timestamp of dispensing was at least 1 minute and less than 6 months after the timestamp of discontinuation in the EHR. A secondary outcome was the proportion of discontinued medications that was reordered within 120 days.

RESULTS: A total of 53 298 qualifying e-prescriptions that were discontinued were identified for 17 451 unique patients (mean [SD] age, 50.6 [18.2] years; 9332 women [53.5%]). After CancelRx implementation, 22 443 (85.9%) of the 26 127 discontinued e-prescriptions resulted in a CancelRx transaction. In interrupted time series analysis, the proportion of prescriptions dispensed after discontinuation decreased from a baseline of 8.0% (2162 of 27 171) to 1.4% (369 of 26 127; P < .001), without a significant week-to-week trend (β = 0.000158; P = .37).

CONCLUSIONS AND RELEVANCE: In this case series with interrupted time series analysis, findings suggest that CancelRx implementation was associated with an immediate and persistent reduction in the proportion of e-prescriptions sold after discontinuation in the EHR. Widespread implementation of CancelRx may significantly improve medication safety through the reduction of medication dispensing after discontinuation by prescribers.

PMID:37669071 | DOI:10.1001/jamainternmed.2023.4192

Invest Ophthalmol Vis Sci. 2023 Sep 1;64(12):5. doi: 10.1167/iovs.64.12.5.

ABSTRACT

PURPOSE: To determine the pointwise relationships of central visual field (VF) defects with macular ganglion cell loss and macular vessel density (VD) loss during various stages of glaucoma.

METHODS: Eyes with primary open-angle glaucoma (POAG) were subjected to optical coherence tomography (OCT) and OCT angiography (OCTA) to evaluate macular ganglion cell layer (GCL) thickness and macular VD in the superficial and deep vascular complexes (SVC and DVC). OCT, OCTA, and VF locations were matched after correcting for retinal ganglion cell (RGC) displacement. Pointwise correlations of GCL thickness and VDs of the SVC and DVC with central VF sensitivity (VFS) were evaluated by Pearson’s correlation analysis and compared in eyes with early and advanced POAG by Meng’s test.

RESULTS: Of the 100 eyes, 52 and 48 were classified as early and advanced POAG. Macular VD showed overall better correlation with central VFS than GCL thickness in both the early and advanced groups. SVC density showed the strongest correlation with central VFS in all groups (R = 0.327 in early group, R = 0.325 in advanced group, all P < 0.001). Although DVC density showed better correlation with VFS (R = 0.311) than GCL thickness (R = 0.212) in the early group (P < 0.001), the correlation was comparable in the advanced group (R = 0.199 and 0.176, respectively, P = 0.254).

CONCLUSIONS: After adjustment for RGC displacement, macular SVC density was better correlated with central VFS than macular GCL thickness in both early and advanced POAG. Macular DVC density showed better correlation with VFS than GCL thickness in early but not in advanced POAG, indicating that DVC loss may be involved in early central VF loss.

PMID:37669065 | DOI:10.1167/iovs.64.12.5

JAMA Intern Med. 2023 Sep 5. doi: 10.1001/jamainternmed.2023.4291. Online ahead of print.

ABSTRACT

IMPORTANCE: Although oral temperature is commonly assessed in medical examinations, the range of usual or “normal” temperature is poorly defined.

OBJECTIVE: To determine normal oral temperature ranges by age, sex, height, weight, and time of day.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used clinical visit information from the divisions of Internal Medicine and Family Medicine in a single large medical care system. All adult outpatient encounters that included temperature measurements from April 28, 2008, through June 4, 2017, were eligible for inclusion. The LIMIT (Laboratory Information Mining for Individualized Thresholds) filtering algorithm was applied to iteratively remove encounters with primary diagnoses overrepresented in the tails of the temperature distribution, leaving only those diagnoses unrelated to temperature. Mixed-effects modeling was applied to the remaining temperature measurements to identify independent factors associated with normal oral temperature and to generate individualized normal temperature ranges. Data were analyzed from July 5, 2017, to June 23, 2023.

EXPOSURES: Primary diagnoses and medications, age, sex, height, weight, time of day, and month, abstracted from each outpatient encounter.

MAIN OUTCOMES AND MEASURES: Normal temperature ranges by age, sex, height, weight, and time of day.

RESULTS: Of 618 306 patient encounters, 35.92% were removed by LIMIT because they included diagnoses or medications that fell disproportionately in the tails of the temperature distribution. The encounters removed due to overrepresentation in the upper tail were primarily linked to infectious diseases (76.81% of all removed encounters); type 2 diabetes was the only diagnosis removed for overrepresentation in the lower tail (15.71% of all removed encounters). The 396 195 encounters included in the analysis set consisted of 126 705 patients (57.35% women; mean [SD] age, 52.7 [15.9] years). Prior to running LIMIT, the mean (SD) overall oral temperature was 36.71 °C (0.43 °C); following LIMIT, the mean (SD) temperature was 36.64 °C (0.35 °C). Using mixed-effects modeling, age, sex, height, weight, and time of day accounted for 6.86% (overall) and up to 25.52% (per patient) of the observed variability in temperature. Mean normal oral temperature did not reach 37 °C for any subgroup; the upper 99th percentile ranged from 36.81 °C (a tall man with underweight aged 80 years at 8:00 am) to 37.88 °C (a short woman with obesity aged 20 years at 2:00 pm).

CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study suggest that normal oral temperature varies in an expected manner based on sex, age, height, weight, and time of day, allowing individualized normal temperature ranges to be established. The clinical significance of a value outside of the usual range is an area for future study.

PMID:37669046 | DOI:10.1001/jamainternmed.2023.4291