Nevin Manimala

Epilepsia. 2023 Apr 14. doi: 10.1111/epi.17607. Online ahead of print.

ABSTRACT

OBJECTIVES: The factors that influence seizure timing are poorly understood, and seizure unpredictability remains a major cause of disability. Work in chronobiology has shown that cyclical physiological phenomena are ubiquitous, with daily and multiday cycles evident in immune, endocrine, metabolic, neurological, and cardiovascular function. Additionally, work with chronic brain recordings has identified that seizure risk is linked to daily and multiday cycles in brain activity. Here, we provide the first characterization of the relationships between the cyclical modulation of a diverse set of physiological signals, brain activity, and seizure timing.

METHODS: In this cohort study, fourteen subjects underwent chronic ambulatory monitoring with a multimodal wrist worn sensor (recording heart rate, accelerometry, electrodermal activity, temperature) and an implanted responsive neurostimulation system (recording interictal epileptiform abnormalities (IEA) and electrographic seizures). Wavelet and filter-Hilbert spectral analyses characterized circadian and multiday cycles in brain and wearable recordings. Circular statistics assessed electrographic seizure timing and cycles in physiology.

RESULTS: Ten subjects met inclusion criteria. The mean recording duration was 232 days. Seven subjects had reliable EEG seizure detections (mean 76 seizures). Multiday cycles were present in all wearable device signals across all subjects. Seizure timing was phase locked to multiday cycles in five (temperature), four (heart rate, phasic electrodermal activity), and three (accelerometry, heart rate variability, tonic electrodermal activity) subjects. Notably, after regression of behavioral covariates from heart rate, six of seven subjects had seizure phase locking to the residual heart rate signal.

SIGNIFICANCE: Seizure timing is associated with daily and multiday cycles in multiple physiological processes. Chronic multimodal wearable device recordings can situate rare paroxysmal events, like seizures, within a broader chronobiology context of the individual. Wearable devices may advance the understanding of factors that influence seizure risk and enable personalized time-varying approaches to epilepsy care.

PMID:37060170 | DOI:10.1111/epi.17607

BMC Pediatr. 2023 Apr 14;23(1):174. doi: 10.1186/s12887-023-03981-8.

ABSTRACT

BACKGROUND: Several previous studies have identified a potential role that the gut microbiome can play in autism spectrum disorder (ASD) in children, but little is known about how variations in the virome may be involved in ASD. We aimed to understand the changes in the gut DNA virome of children with ASD.

METHODS: A case-control study was presented, in which 13 two-children families were observed while considering the age, mode of birth, history of antibiotic use, and vaccination history to minimize the influence of confounding factors. DNA viral metagenomic sequencing was successfully performed on stool samples from 11 children with ASD and 12 healthy non-ASD children. The basic composition and gene function of the participants’ fecal DNA virome were detected and analyzed. Finally, the abundance and diversity of the DNA virome of children with ASD and their healthy siblings were compared.

RESULTS: The gut DNA virome in children aged 3-11 years was found to be dominated by the Siphoviridae family of Caudovirales. The proteins encoded by the DNA genes mainly carry out the functions of genetic information transmission and metabolism. Compared the gut DNA virome of ASD and healthy non-ASD children, their abundance of Caudovirales and Petitvirales both showed a significant negative correlation (r = -0.902, P < 0.01), there was no statistically significant difference in the relative abundance of viruses at the order and family levels, and a difference in the relative abundance at the genus level for Skunavirus (Ζ = -2.157, P = 0.031). Viral α diversity was reduced in children with ASD, but α diversity and β diversity did not differ statistically between groups.

CONCLUSIONS: This study indicates that elevated Skunavirus abundance and decreased α diversity in the gut DNA virulence group of children with ASD, but no statistically significant difference in the change in alpha and beta diversity. This provides preliminary cumulative information on virological aspects of the relationship between the microbiome and ASD, and should benefit future multi-omics and large sample studies on the gut microbes in children with ASD.

PMID:37060094 | DOI:10.1186/s12887-023-03981-8

BMC Infect Dis. 2023 Apr 14;23(1):228. doi: 10.1186/s12879-023-08162-7.

ABSTRACT

BACKGROUND: Taste or smell disorders have been reported as strongly associated with COVID-19 diagnosis. We aimed to identify subject characteristics, symptom associations, and antibody response intensity associated with taste or smell disorders.

METHODS: We used data from SAPRIS, a study based on a consortium of five prospective cohorts gathering 279,478 participants in the French general population. In the analysis, we selected participants who were presumably infected by SARS-CoV-2 during the first epidemic wave.

RESULTS: The analysis included 3,439 patients with a positive ELISA-Spike. Sex (OR = 1.28 [95% CI 1.05-1.58] for women), smoking (OR = 1.54 [95% CI 1.13-2.07]), consumption of more than 2 drinks of alcohol a day (OR = 1.37 [95% CI 1.06-1.76]) were associated with a higher probability of taste or smell disorders. The relationship between age and taste or smell disorders was non-linear. Serological titers were associated with taste or smell disorders: OR = 1.31 [95% CI 1.26-1.36], OR = 1.37 [95% CI 1.33-1.42] and OR = 1.34 [95% CI 1.29-1.39] for ELISA-Spike, ELISA-Nucleocapsid and seroneutralization, respectively. Among participants with taste or smell disorders, 90% reported a wide variety of other symptoms whereas 10% reported no other symptom or only rhinorrhea.

CONCLUSIONS: Among patients with a positive ELISA-Spike test, women, smokers and people drinking more than 2 drinks a day were more likely to develop taste or smell disorders. This symptom was strongly associated with an antibody response. The overwhelming majority of patients with taste or smell disorders experienced a wide variety of symptoms.

PMID:37060075 | DOI:10.1186/s12879-023-08162-7

BMC Musculoskelet Disord. 2023 Apr 14;24(1):297. doi: 10.1186/s12891-023-06415-9.

ABSTRACT

BACKGROUND: Although disease-modifying properties of nonsteroidal anti-inflammatory drugs (NSAIDs) for osteoarthritis (OA) have been reported, the effects of NSAIDs on OA progression remain controversial. The purpose of this study was to investigate the effect of early initiation of oral NSAID therapy on the progression of knee OA.

METHODS: In this retrospective cohort study, we extracted data of patients newly diagnosed with knee OA between November 2007 and October 2018 from a Japanese claims database. The primary outcome was the time to knee replacement (KR), and the secondary outcome was the time to composite event including joint lavage and debridement, osteotomy, or arthrodesis in addition to KR. Weighted Cox regression analysis with standardized mortality/morbidity ratio (SMR) weight was performed to compare the outcomes between patients prescribed oral NSAID (NSAID group) and those prescribed oral acetaminophen (APAP) (APAP group) early after a diagnosis of knee OA. Propensity scores were calculated using logistic regression conditioned on potential confounding factors, and SMR weights were calculated using the propensity scores.

RESULTS: The study population comprised 14,261 patients, who were divided into two groups as follows: 13,994 in the NSAID group and 267 in the APAP group. The mean ages of patients in the NSAID and APAP groups were 56.9 and 56.1 years, respectively. Furthermore, 62.01% and 68.16% patients in the NSAID and APAP groups, respectively, were female. The NSAID group had a reduced risk of KR compared with the APAP group in the analysis using SMR weighting (SMR-weighted hazard ratio, 0.19; 95% confidence interval, 0.05-0.78). While no statistically significant difference was found for the risk of composite event between the two groups (SMR-weighted hazard ratio, 0.56; 95% confidence interval, 0.16-1.91).

CONCLUSIONS: The risk of KR in the NSAID group was significantly lower than that in the APAP group after accounting for residual confounding using SMR weighting. This finding suggests that oral NSAID therapy early after the initial diagnosis is associated with a reduced risk of KR in patients with symptomatic knee OA.

PMID:37060072 | DOI:10.1186/s12891-023-06415-9

Int J Equity Health. 2023 Apr 14;22(1):68. doi: 10.1186/s12939-023-01883-w.

ABSTRACT

BACKGROUND: Colorectal cancer is a leading cause of morbidity and mortality across U.S. racial/ethnic groups. Existing studies often focus on a particular race/ethnicity or single domain within the care continuum. Granular exploration of disparities among different racial/ethnic groups across the entire colon cancer care continuum is needed. We aimed to characterize differences in colon cancer outcomes by race/ethnicity across each stage of the care continuum.

METHODS: We used the 2010-2017 National Cancer Database to examine differences in outcomes by race/ethnicity across six domains: clinical stage at presentation; timing of surgery; access to minimally invasive surgery; post-operative outcomes; utilization of chemotherapy; and cumulative incidence of death. Analysis was via multivariable logistic or median regression, with select demographics, hospital factors, and treatment details as covariates.

RESULTS: 326,003 patients (49.6% female, 24.0% non-White, including 12.7% Black, 6.1% Hispanic/Spanish, 1.3% East Asian, 0.9% Southeast Asian, 0.4% South Asian, 0.3% AIAE, and 0.2% NHOPI) met inclusion criteria. Relative to non-Hispanic White patients: Southeast Asian (OR 1.39, p < 0.01), Hispanic/Spanish (OR 1.11 p < 0.01), and Black (OR 1.09, p < 0.01) patients had increased odds of presenting with advanced clinical stage. Southeast Asian (OR 1.37, p < 0.01), East Asian (OR 1.27, p = 0.05), Hispanic/Spanish (OR 1.05 p = 0.02), and Black (OR 1.05, p < 0.01) patients had increased odds of advanced pathologic stage. Black patients had increased odds of experiencing a surgical delay (OR 1.33, p < 0.01); receiving non-robotic surgery (OR 1.12, p < 0.01); having post-surgical complications (OR 1.29, p < 0.01); initiating chemotherapy more than 90 days post-surgery (OR 1.24, p < 0.01); and omitting chemotherapy altogether (OR 1.12, p = 0.05). Black patients had significantly higher cumulative incidence of death at every pathologic stage relative to non-Hispanic White patients when adjusting for non-modifiable patient factors (p < 0.05, all stages), but these differences were no longer statistically significant when also adjusting for modifiable factors such as insurance status and income.

CONCLUSIONS: Non-White patients disproportionately experience advanced stage at presentation. Disparities for Black patients are seen across the entire colon cancer care continuum. Targeted interventions may be appropriate for some groups; however, major system-level transformation is needed to address disparities experienced by Black patients.

PMID:37060065 | DOI:10.1186/s12939-023-01883-w

BMC Med Educ. 2023 Apr 14;23(1):243. doi: 10.1186/s12909-023-04170-y.

ABSTRACT

BACKGROUND: Currently, 75-80% of the medical workforce worldwide consists of women. Yet, women comprise 21% of full professors and less than 20% of department chairs and medical school deans. Identified causes of gender disparities are multifactorial including work-life responsibilities, gender discrimination, sexual harassment, bias, lack of confidence, gender differences in negotiation and leadership emergence, and lack of mentorship, networking, and/or sponsorship. A promising intervention for the advancement of women faculty is the implementation of Career Development Programs (CDPs). Women physician CDP participants were shown to be promoted in rank at the same rate as men by year five, and more likely to remain in academics after eight years compared to both men and women counterparts. The objective of this pilot study is to investigate the effectiveness of a novel, simulation-based, single-day CDP curriculum for upper-level women physician trainees to teach communication skills identified as contributing to medicine’s gender advancement gap.

METHODS: This was a pilot, pre/post study performed in a simulation center implementing a curriculum developed to educate women physicians on 5 identified communication skills recognized to potentially reduce the gender gap. Pre- and post-intervention assessments included confidence surveys, cognitive questionnaires, and performance action checklists for five workplace scenarios. Assessment data were analyzed using scored medians and descriptive statistics, applying Wilcoxon test estimation to compare pre- versus post-curriculum intervention scores, with p < 0.05 considered statistically significant.

RESULTS: Eleven residents and fellows participated in the curriculum. Confidence, knowledge, and performance improved significantly after completion of the program. Pre-confidence: 28 (19.0-31.0); Post-confidence: 41 (35.0-47.0); p < 0.0001. Pre-knowledge: 9.0 (6.0-11.00); Post knowledge: 13.0 (11.0-15.0); p < 0.0001. Pre-performance: 35.0 (16.0-52.0); Post-performance: 46.0 (37-53.00); p < 0.0001.

CONCLUSION: Overall, this study demonstrated the successful creation of a novel, condensed CDP curriculum based on 5 identified communication skills needed for women physician trainees. The post-curriculum assessment demonstrated improved confidence, knowledge, and performance. Ideally, all women medical trainees would have access to convenient, accessible, and affordable courses teaching these crucial communication skills to prepare them for careers in medicine to strive to reduce the gender gap.

PMID:37060057 | DOI:10.1186/s12909-023-04170-y

BMC Microbiol. 2023 Apr 15;23(1):102. doi: 10.1186/s12866-023-02852-7.

ABSTRACT

BACKGROUND: Many studies reported the association between gut microbiota and type 2 diabetes mellitus (T2D), but it is still unclear which bacterial genus plays a key role and how the metabolic function of gut microbiota changes in the occurrence and development of T2D. Besides, there is a high diabetic prevalence in Mongolian population, which may be partly affected by their high calorie diet. This study identified the main bacterial genus influencing T2D in Mongolian population, and analyzed the changes of metabolic function of gut microbiome. The association between dietary factors and the relative abundance of main bacterial genus and its metabolic function was also studied.

METHODS: Dietary surveys and gut microbiota test were performed on 24 Mongolian volunteers that were divided into T2D (6 cases), PRET2D (6 cases) and Control group (12 cases) according to fasting plasma glucose (FPG) values. The relative abundance and metabolic function of gut microbiome from their fecal samples were measured by metagenomic analysis. Statistic method was used to evaluate the association between dietary factors and the relative abundance of the main bacterial genus or its metabolic function.

RESULTS: This study found that the Clostridium genus may be one of the key bacterial genera affecting the process of T2D. First, the relative abundance of Clostridium genus was significantly different among the three groups. Second, there was a higher relative abundance of metabolic enzymes of gut bacteria in PRET2D and T2D group than that in Control group. Third, a strong correlation between Clostridium genus and many metabolic enzymes was uncovered, many of which may be produced by the Clostridium. Last, carotene intake daily was negatively correlated with the Clostridium but positively correlated with tagaturonate reductase catalyzing interconversions of pentose and glucuronate.

CONCLUSIONS: The gut Clostridium genus may play an important role in the development of T2D and it could be a potential biomarker for T2D in Mongolian population. Meanwhile, the metabolic function of gut bacteria has changed during the early stage of T2D and the changes in carbohydrate, amino acid, lipid or energy metabolism of Clostridium genus may play a critical role. In addition, the carotene intake may affect reproduction and metabolic function of Clostridium genus.

PMID:37060052 | DOI:10.1186/s12866-023-02852-7

BMC Oral Health. 2023 Apr 14;23(1):215. doi: 10.1186/s12903-023-02931-1.

ABSTRACT

OBJECTIVE: To study the airway changes of edentulous patients with a magnitude of long centric (MLC) ≥ 1.5 mm during occlusal reconstruction at the centric relation position (CRP) and muscular position (MP).

METHODS: The CRP and MP were determined by Gothic arch. The cephalometric analysis was taken at the two occlusal positions. The sagittal distance of each part of the upper airway was measured. The differences between two occlusal positions were compared. The difference values were calculated by subtracting the two. The correlation between the MLC and the difference value was analyzed.

RESULTS: The sagittal diameters of palatopharynx and glossopharynx airway at MP were statistically larger than those at CRP (P < 0.05). The MLC had a strong correlation with the ANB angle (r = 0.745, P < 0.001).

CONCLUSION: Compared with the occlusal position of CRP, occlusion reconstruction at MP can provide better airway condition for edentulous patients with large MLC.

PMID:37060039 | DOI:10.1186/s12903-023-02931-1

BMC Med Inform Decis Mak. 2023 Apr 14;23(1):68. doi: 10.1186/s12911-023-02148-w.

ABSTRACT

BACKGROUND: The incidence of diagnostic delays is unknown for many diseases and specific healthcare settings. Many existing methods to identify diagnostic delays are resource intensive or difficult to apply to different diseases or settings. Administrative and other real-world data sources may offer the ability to better identify and study diagnostic delays for a range of diseases.

METHODS: We propose a comprehensive framework to estimate the frequency of missed diagnostic opportunities for a given disease using real-world longitudinal data sources. We provide a conceptual model of the disease-diagnostic, data-generating process. We then propose a bootstrapping method to estimate measures of the frequency of missed diagnostic opportunities and duration of delays. This approach identifies diagnostic opportunities based on signs and symptoms occurring prior to an initial diagnosis, while accounting for expected patterns of healthcare that may appear as coincidental symptoms. Three different bootstrapping algorithms are described along with estimation procedures to implement the resampling. Finally, we apply our approach to the diseases of tuberculosis, acute myocardial infarction, and stroke to estimate the frequency and duration of diagnostic delays for these diseases.

RESULTS: Using the IBM MarketScan Research databases from 2001 to 2017, we identified 2,073 cases of tuberculosis, 359,625 cases of AMI, and 367,768 cases of stroke. Depending on the simulation approach that was used, we estimated that 6.9-8.3% of patients with stroke, 16.0-21.3% of patients with AMI and 63.9-82.3% of patients with tuberculosis experienced a missed diagnostic opportunity. Similarly, we estimated that, on average, diagnostic delays lasted 6.7-7.6 days for stroke, 6.7-8.2 days for AMI, and 34.3-44.5 days for tuberculosis. Estimates for each of these measures was consistent with prior literature; however, specific estimates varied across the different simulation algorithms considered.

CONCLUSIONS: Our approach can be easily applied to study diagnostic delays using longitudinal administrative data sources. Moreover, this general approach can be customized to fit a range of diseases to account for specific clinical characteristics of a given disease. We summarize how the choice of simulation algorithm may impact the resulting estimates and provide guidance on the statistical considerations for applying our approach to future studies.

PMID:37060037 | DOI:10.1186/s12911-023-02148-w

Breast Cancer Res. 2023 Apr 14;25(1):40. doi: 10.1186/s13058-023-01643-2.

ABSTRACT

BACKGROUND: Hormone receptor (HR)-positive, HER2/neu-negative breast cancers have a sustained risk of recurrence up to 20 years from diagnosis. TEAM (Tamoxifen, Exemestane Adjuvant Multinational) is a large, multi-country, phase III trial that randomized 9776 women for the use of hormonal therapy. Of these 2754 were Dutch patients. The current study aims for the first time to correlate the ten-year clinical outcomes with predictions by CanAssist Breast (CAB)-a prognostic test developed in South East Asia, on a Dutch sub-cohort that participated in the TEAM. The total Dutch TEAM cohort and the current Dutch sub-cohort were almost similar with respect to patient age and tumor anatomical features.

METHODS: Of the 2754 patients from the Netherlands, which are part of the original TEAM trial, 592 patients’ samples were available with Leiden University Medical Center (LUMC). The risk stratification of CAB was correlated with outcomes of patients using logistic regression approaches entailing Kaplan-Meier survival curves, univariate and multivariate cox-regression hazards model. We used hazard ratios (HRs), the cumulative incidence of distant metastasis/death due to breast cancer (DM), and distant recurrence-free interval (DRFi) for assessment.

RESULTS: Out of 433 patients finally included, the majority, 68.4% had lymph node-positive disease, while only a minority received chemotherapy (20.8%) in addition to endocrine therapy. CAB stratified 67.5% of the total cohort as low-risk [DM = 11.5% (95% CI, 7.6-15.2)] and 32.5% as high-risk [DM = 30.2% (95% CI, 21.9-37.6)] with an HR of 2.90 (95% CI, 1.75-4.80; P < 0.001) at ten years. CAB risk score was an independent prognostic factor in the consideration of clinical parameters in multivariate analysis. At ten years, CAB high-risk had the worst DRFi of 69.8%, CAB low-risk in the exemestane monotherapy arm had the best DRFi of 92.7% [vs CAB high-risk, HR, 0.21 (95% CI, 0.11-0.43), P < 0.001], and CAB low-risk in the sequential arm had a DRFi of 84.2% [vs CAB high-risk, HR, 0.48 (95% CI, 0.28-0.82), P = 0.009].

CONCLUSIONS: Cost-effective CAB is a statistically robust prognostic and predictive tool for ten-year DM for postmenopausal women with HR+/HER2-, early breast cancer. CAB low-risk patients who received exemestane monotherapy had an excellent ten-year DRFi.

PMID:37060036 | DOI:10.1186/s13058-023-01643-2