Category: Nevin Manimala

Epileptic Disord. 2023 Mar 20. doi: 10.1002/epd2.20021. Online ahead of print.

ABSTRACT

OBJECTIVE: Risk factors for epilepsy in meningioma patients are not yet clearly defined, however, seizure freedom is a significant factor for quality of life after surgery.

METHODS: We performed a retrospective study of the 333 adult patients who received surgery for supratentorial meningioma at our centre. Various clinical, radiological, and surgical variables were included in the multivariate regression, and the outcomes measured were the occurrence of seizure(s) pre-operatively, during the hospitalization, and during the follow-up period.

RESULTS: A total of 89 (26,7%) patients experienced pre-operative seizures, of whom 62.9% were seizure-free after the surgery. Of 244 patients without epilepsy before surgery, 11.9% had at least one seizure post-operatively. In total, 63 of our patients (18.9%) experienced seizures after the surgery, of whom 20 had refractory epilepsy. Multivariate analysis identified the following predictors of pre-operative seizures: absence of headache (OR: 0.23, CI: 2.55-8.50), the presence of significant peritumoural oedema (OR: 4.35, CI: 2.57-7.35), and younger age (OR: 0.97 per year increase, CI: 0.95-0.99). Factors associated with early post-operative seizures were: younger age (OR: 0.96 per year increase, CI: 0.93-0.99) and presence of pre-operative seizures (OR: 2.73, CI: 1.13-6.57), while the presence of pre-operative seizures (OR: 4.73, CI: 2,05-10.92), tumour progression (OR: 5.38, CI: 2.25-12.89) and neurological worsening (OR: 5.21 CI: 1.72-15.81) were significant for late post-operative seizures.

SIGNIFICANCE: Our results from a single-centre meningioma cohort confirm, in general, data from some previous studies regarding patients’ characteristics for both pre-operative and overall post-operative epilepsy. Besides previously described risk factors, younger age was important for pre-operative and early post-operative seizures. Epilepsy is common in patients with recurrence of meningioma, but the variables of significance for refractory seizures in these patients require further examination.

PMID:36939715 | DOI:10.1002/epd2.20021

Transl Vis Sci Technol. 2023 Mar 1;12(3):19. doi: 10.1167/tvst.12.3.19.

ABSTRACT

PURPOSE: Performance comparison of optical coherence tomography (OCT) and visual field (VF) summary metrics for detecting glaucomatous progression.

METHODS: Thirty healthy control eyes (mean deviation [MD], -1.25 ± 2.03; pattern standard deviation [PSD] , 1.78 ± 0.77) and 91 patient eyes comprised of 54 glaucoma patients and 37 glaucoma suspects (MD, -1.58 ± 1.96; PSD, 2.82 ± 1.92) with a follow-up of at least 1 year formed a group to evaluate progression with event analyses (P-Event). A subset of eyes with an additional criterion of a minimum of four tests was used for trend analyses (P-Trend) (30 healthy controls and 73 patients). For P-Event analysis, test-retest variability thresholds (lower 5th percentile) were estimated with repeat tests within a 4-month period. A P-Event eye was considered a “progressor” if the difference between follow-up and baseline tests exceeded the variability thresholds. For the P-Trend analysis, rates of change were calculated based on least-squares regression. Negative rates with significant (P < 0.05) values were considered progressing. For a reference standard, 17 patient eyes were classified as definitely progressing based on clear evidence of structural and corresponding functional progression.

RESULTS: Isolated OCT and VF summary metrics were either inadequately sensitive or not too specific. Combinations of OCT-OCT and OCT-VF metrics markedly improved specificity to nearly 100%. A novel combination of OCT metrics (circumpapillary retinal nerve fiber layer and ganglion cell layer) showed high precision, with 13 of the 15 statistical progressors confirmed as true positives.

CONCLUSIONS: Although relying solely on metrics is not recommended for clinical purposes, in situations requiring very high specificity and precision, combinations of OCT-OCT metrics can be used.

TRANSLATIONAL RELEVANCE: All available OCT and VF metrics can miss eyes with progressive glaucomatous damage and/or can falsely identify progression in stable eyes.

PMID:36939711 | DOI:10.1167/tvst.12.3.19

JAMA Netw Open. 2023 Mar 1;6(3):e233572. doi: 10.1001/jamanetworkopen.2023.3572.

ABSTRACT

IMPORTANCE: The 21st Century Cures Act Final Rule mandates the immediate electronic availability of test results to patients, likely empowering them to better manage their health. Concerns remain about unintended effects of releasing abnormal test results to patients.

OBJECTIVE: To assess patient and caregiver attitudes and preferences related to receiving immediately released test results through an online patient portal.

DESIGN, SETTING, AND PARTICIPANTS: This large, multisite survey study was conducted at 4 geographically distributed academic medical centers in the US using an instrument adapted from validated surveys. The survey was delivered in May 2022 to adult patients and care partners who had accessed test results via an online patient portal account between April 5, 2021, and April 4, 2022.

EXPOSURES: Access to test results via a patient portal between April 5, 2021, and April 4, 2022.

MAIN OUTCOMES AND MEASURES: Responses to questions related to demographics, test type and result, reaction to result, notification experience and future preferences, and effect on health and well-being were aggregated. To evaluate characteristics associated with patient worry, logistic regression and pooled random-effects models were used to assess level of worry as a function of whether test results were perceived by patients as normal or not normal and whether patients were precounseled.

RESULTS: Of 43 380 surveys delivered, there were 8139 respondents (18.8%). Most respondents were female (5129 [63.0%]) and spoke English as their primary language (7690 [94.5%]). The median age was 64 years (IQR, 50-72 years). Most respondents (7520 of 7859 [95.7%]), including 2337 of 2453 individuals (95.3%) who received nonnormal results, preferred to immediately receive test results through the portal. Few respondents (411 of 5473 [7.5%]) reported that reviewing results before they were contacted by a health care practitioner increased worry, though increased worry was more common among respondents who received abnormal results (403 of 2442 [16.5%]) than those whose results were normal (294 of 5918 [5.0%]). The result of the pooled model for worry as a function of test result normality was statistically significant (odds ratio [OR], 2.71; 99% CI, 1.96-3.74), suggesting an association between worry and nonnormal results. The result of the pooled model evaluating the association between worry and precounseling was not significant (OR, 0.70; 99% CI, 0.31-1.59).

CONCLUSIONS AND RELEVANCE: In this multisite survey study of patient attitudes and preferences toward receiving immediately released test results via a patient portal, most respondents preferred to receive test results via the patient portal despite viewing results prior to discussion with a health care professional. This preference persisted among patients with nonnormal results.

PMID:36939703 | DOI:10.1001/jamanetworkopen.2023.3572

JAMA Netw Open. 2023 Mar 1;6(3):e233630. doi: 10.1001/jamanetworkopen.2023.3630.

ABSTRACT

IMPORTANCE: Surgical diseases account for approximately 30% of the global burden of disease. Gender diversity in biomedical research is critical to generate innovative patient-centered research in surgery.

OBJECTIVE: To examine the distribution of biomedical research funding by the National Institutes of Health (NIH) among women and men surgeon-scientists during a 25-year period.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used publicly available data from the NIH RePORTER (Research Portfolio Online Reporting Tools: Expenditures and Results) database for research project grants awarded to women and men surgeon-scientists who were principal investigators between 1995 and 2020. Data were retrieved between January 20 and March 20, 2022. The representation of women surgeon-scientists among academic surgeons was compared with the representation of men surgeon-scientists over time.

MAIN OUTCOMES AND MEASURES: Distribution of NIH funding to women and men surgeon-scientists was examined via 2 metrics: holding a large-dollar (ie, R01-equivalent) grant and being a super principal investigator (SPI) with $750 000 or more in total annual research funding. Statistical analysis was performed between April 1 and August 31, 2022.

RESULTS: Between 1995 and 2020, 2078 principal investigator surgeons received funding from the NIH. The proportion of women academic surgeons who were surgeon-scientists remained unchanged during this same period (1995, 14 of 792 [1.8%] vs 2020, 92 of 3834 [2.4%]; P = .10). Compared with their men counterparts, women surgeon-scientists obtained their first NIH grant earlier in their career (mean [SD] years after first faculty appointment, 8.8 [6.2] vs 10.8 [7.9] years; P < .001) and were as likely to obtain large-dollar grants (aRR, 0.99 [95% CI, 0.95-1.03]) during the period 2016 to 2020. Despite this success, women surgeon-scientists remained significantly underrepresented among SPIs and were 25% less likely to be an SPI (aRR, 0.75 [95% CI, 0.60-0.95] during the period 2016 to 2020).

CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional study of NIH-funded surgeons suggest that women surgeons remained underrepresented among surgeon-scientists over a 25-year period despite early career success in receiving NIH funding. This is concerning and warrants further investigation to increase the distribution of NIH funding among women surgeon-scientists.

PMID:36939702 | DOI:10.1001/jamanetworkopen.2023.3630

JAMA Netw Open. 2023 Mar 1;6(3):e233646. doi: 10.1001/jamanetworkopen.2023.3646.

ABSTRACT

IMPORTANCE: Metformin may have a protective association against developing osteoarthritis (OA), but robust epidemiological data are lacking.

OBJECTIVE: To determine the risk of OA and joint replacement in individuals with type 2 diabetes treated with metformin compared with a sulfonylurea.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used claims data from the Optum deidentified Clinformatics Data Mart Database between December 2003 and December 2019. Participants included individuals aged 40 years or older with at least 1 year of continuous enrollment and type 2 diabetes. Individuals with type 1 diabetes or a prior diagnosis of OA, inflammatory arthritis, or joint replacement were excluded. Time-conditional propensity score matching was conducted using age, sex, race, Charlson comorbidity score, and treatment duration to create a prevalent new-user cohort. Data were analyzed from April to December 2021.

EXPOSURES: Treatment with metformin or a sulfonylurea.

MAIN OUTCOMES AND MEASURES: The outcomes of interest were incident OA and joint replacement. Cox proportional hazard models were used to calculate adjusted hazard ratios (aHRs) of incident OA and joint replacement. In a sensitivity analysis, individuals only ever treated with metformin were compared with individuals only ever treated with a sulfonylurea, allowing for longer-term follow up of the outcome (even after stopping the medication of interest).

RESULTS: After time-conditional propensity score matching, the metformin and control groups each included 20 937 individuals (mean [SD] age 62.0 [11.5] years; 24 379 [58.2%] males). In the adjusted analysis, the risk of developing OA was reduced by 24% for individuals treated with metformin compared with a sulfonylurea (aHR, 0.76; 95% CI, 0.68-0.85; P < .001), but there was no significant difference for risk of joint replacement (aHR, 0.80; 95% CI, 0.50-1.27; P = .34). In the sensitivity analysis, the risk of developing OA remained lower in individuals treated with metformin compared with a sulfonylurea (aHR, 0.77; 95% CI, 0.65-0.90; P < .001) and the risk of joint replacement remained not statistically significant (aHR, 1.04; 95% CI, 0.60-1.82; P = .89).

CONCLUSIONS AND RELEVANCE: In this cohort study of individuals with diabetes, metformin treatment was associated with a significant reduction in the risk of developing OA compared with sulfonylurea treatment. These results further support preclinical and observational data that suggest metformin may have a protective association against the development of OA; future interventional studies with metformin for the treatment or prevention of OA should be considered.

PMID:36939700 | DOI:10.1001/jamanetworkopen.2023.3646

JAMA Neurol. 2023 Mar 20. doi: 10.1001/jamaneurol.2023.0285. Online ahead of print.

ABSTRACT

IMPORTANCE: Carotid artery stenting has been limited to use in patients with high surgical risk; outcomes in patients with standard surgical risk are not well known.

OBJECTIVE: To compare stroke, death, and myocardial infarction outcomes following transcarotid artery revascularization vs carotid endarterectomy in patients with standard surgical risk.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective propensity-matched cohort study was conducted from August 2016 to August 2019 with follow-up until August 31, 2020, using data from the multicenter Vascular Quality Initiative Carotid Artery Stent and Carotid Endarterectomy registries. Patients with standard surgical risk, defined as those lacking Medicare-defined high medical or surgical risk characteristics and undergoing transcarotid artery revascularization (n = 2962) or carotid endarterectomy (n = 35 063) for atherosclerotic carotid disease. In total, 760 patients were excluded for treatment of multiple lesions or in conjunction with other procedures.

EXPOSURES: Transcarotid artery revascularization vs carotid endarterectomy.

MAIN OUTCOMES AND MEASURES: The primary outcome was a composite end point of 30-day stroke, death, or myocardial infarction or 1-year ipsilateral stroke.

RESULTS: After 1:3 matching, 2962 patients undergoing transcarotid artery revascularization (mean [SD] age, 70.4 [6.9] years; 1910 [64.5%] male) and 8886 undergoing endarterectomy (mean [SD] age, 70.0 [6.5] years; 5777 [65.0%] male) were identified. There was no statistically significant difference in the risk of the primary composite end point between the 2 cohorts (transcarotid 3.0% vs endarterectomy 2.6%; absolute difference, 0.40% [95% CI, -0.43% to 1.24%]; relative risk [RR], 1.14 [95% CI, 0.87 to 1.50]; P = .34). Transcarotid artery revascularization was associated with a higher risk of 1-year ipsilateral stroke (1.6% vs 1.1%; absolute difference, 0.52% [95% CI, 0.03 to 1.08]; RR, 1.49 [95% CI, 1.05 to 2.11%]; P = .02) but no difference in 1-year all-cause mortality (2.6% vs 2.5%; absolute difference, -0.13% [95% CI, -0.18% to 0.33%]; RR, 1.04 [95% CI, 0.78 to 1.39]; P = .67).

CONCLUSIONS AND RELEVANCE: In this study, the risk of 30-day stroke, death, or myocardial infarction or 1-year ipsilateral stroke was similar in patients undergoing transcarotid artery revascularization compared with those undergoing endarterectomy for carotid stenosis.

PMID:36939697 | DOI:10.1001/jamaneurol.2023.0285

JAMA Pediatr. 2023 Mar 20. doi: 10.1001/jamapediatrics.2023.0034. Online ahead of print.

NO ABSTRACT

PMID:36939696 | DOI:10.1001/jamapediatrics.2023.0034

Epileptic Disord. 2023 Mar 20. doi: 10.1002/epd2.20024. Online ahead of print.

ABSTRACT

BACKGROUND: The neurofilament light chain (NfL) is receiving increased attention as a biomarker of neurological diseases, as NfL concentration is elevated in the blood and cerebrospinal fluid after neuronal damage. However, few studies have addressed NfL in epilepsy. We aimed to investigate alteration of serum NfL in adult patients with epilepsy, and the association between this biomarker and cognitive impairment.

METHODS: A total of 38 consecutive epilepsy patients and 24 controls underwent cross-sectional measurement of serum NfL levels and cognitive testing using the Mini-Mental State Examination (MMSE), the Japanese version of the Montreal Cognitive Assessment (MoCA-J), the Frontal Assessment Battery (FAB), the Trail-Making Test, and the Stroop Colour-Word Test. Statistical analysis was performed with the Student’s t-test to compare serum NfL levels between the epilepsy group and the control group, and with Spearman’s correlation and age-corrected partial correlation analyses to evaluate the association between serum NfL level and cognitive impairment in epilepsy patients.

RESULTS: There was no difference in serum NfL levels between the epilepsy and control groups (epilepsy [mean ± SD]: 17.3 ± 13.9 pg/mL; control: 17.7 ± 11.5 pig/mL; p = 0.92), however, the MoCA-J scores were lower in the epilepsy group (26.6 ± 3.1 vs. 28.1 ± 1.6; p = 0.03). The age-corrected partial correlation analysis showed a correlation between serum NfL level and cognitive test scores in the epilepsy group (MMSE: r_s = -0.63, p < 0.01; MoCA-J: r_s = -0.54, p < 0.01; FAB: r_s = -0.68, p < 0.01), whereas serum NfL levels were correlated exclusively with MMSE scores in the control group (r_s = 0.44, p = 0.04).

SIGNIFICANCE: In adult epilepsy patients, the serum NfL level was not significantly elevated, but was correlated with cognitive test scores. Our findings suggest that serum NfL concentration could be an indicator of cognitive function in epilepsy patients.

PMID:36939694 | DOI:10.1002/epd2.20024

Hum Vaccin Immunother. 2023 Mar 19:2175519. doi: 10.1080/21645515.2023.2175519. Online ahead of print.

ABSTRACT

The rapid increase in antibiotic resistance presents a dire situation necessitating the need for alternative therapeutic agents. Among the current alternative therapies, phage therapy (PT) is promising. This review extensively summarizes preclinical PT approaches in various in-vivo models. PT has been evaluated in several recent clinical trials. However, there are still several unanswered concerns due to a lack of appropriate regulation and pharmacokinetic data regarding the application of phages in human therapeutic procedures. In this review, we also presented the current state of PT and considered how animal models can be used to adapt these therapies for humans. The development of realistic solutions to circumvent these constraints is critical for advancing this technology.

PMID:36935353 | DOI:10.1080/21645515.2023.2175519

Biol Psychiatry. 2023 Jan 20:S0006-3223(23)00037-9. doi: 10.1016/j.biopsych.2023.01.010. Online ahead of print.

ABSTRACT

Psychiatric disorders are complex, often emerging from multiple atypical processes within specified domains over the course of development. Characterizing the development of the neural circuits supporting these domains may help break down the components of complex disorders and reveal variations in functioning associated with psychiatric risk. This review highlights the current and potential role of infant task-based functional magnetic resonance imaging (fMRI) in elucidating the developmental neurobiology of psychiatric disorders. Task-fMRI measures evoked brain activity in response to specific stimuli through changes in the blood oxygen level-dependent signal. First, we review extant studies using task-fMRI from birth through the first few years of life and synthesize current evidence for when, where, and how different neural computations are performed across the infant brain. Neural circuits for sensory perception, the perception of abstract categories, and the detection of statistical regularities have been characterized with task-fMRI in infants, providing developmental context for identifying and interpreting variation in the functioning of neural circuits related to psychiatric risk. Next, we discuss studies that specifically examine variation in the functioning of these neural circuits during infancy in relation to risk for psychiatric disorders. These studies reveal when maturation of specific neural circuits diverges, the influence of environmental risk factors, and the potential utility for task-fMRI to facilitate early treatment or prevention of later psychiatric problems. Finally, we provide considerations for future infant task-fMRI studies with the potential to advance understanding of both functioning of neural circuits during infancy and subsequent risk for psychiatric disorders.

PMID:36935330 | DOI:10.1016/j.biopsych.2023.01.010