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Evidence based review of type 2 diabetes prevention and management in low and middle income countriesAim: To identify the newest approaches to type 2 diabetes (T2DM) prevention and control in the developing world context. Methods: We conducted a systematic review of published studies of diabetes prevention and control programs in low and middle-income countries, as defined by the World Bank. We searched PubMed using Medical Subject Headings terms. Studies needed to satisfy four criteria: (1) Must be experimental; (2) Must include patients with T2DM or focusing on prevention of T2DM; (3) Must have a lifestyle intervention component; (4) Must be written in English; and (5) Must have measurable outcomes related to diabetes. Results: A total of 66 studies from 20 developing countries were gathered with publication dates through September 2014. India contributed the largest number of trials (11/66). Of the total 66 studies reviewed, all but 3 studies reported evidence of favorable outcomes in the prevention and control of type 2 diabetes. The overwhelming majority of studies reported on diabetes management (56/66), and among these more than half were structured lifestyle education programs. The evidence suggests that lifestyle education led by allied health professionals (nurses, pharmacists) were as effective as those led by physicians or a team of clinicians. The remaining diabetes management interventions focused on diet or exercise, but the evidence to recommend one approach over another was weak. Conclusion: Large experimental diabetes prevention/control studies of dietary and exercise interventions are lacking particularly those that consider quality rather than quantity of carbohydrates and alternative exercise.
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A real-world evaluation of a tertiary care childhood obesity intervention to reduce metabolic risk in a hard-to-reach urban populationBackground: Research on outcomes associated with lifestyle interventions serving pediatric populations in urban settings, where a majority have severe obesity, is scarce. This study assessed whether participation in a lifestyle intervention improved body mass index (BMI) percentile, BMI z-score, blood pressure, and lipid levels for children and adolescents. Methods: The Live Light Live Right program is a lifestyle intervention that uses medical assessment, nutritional education, access to physical fitness classes, and behavioral modification to improve health outcomes. Data was analyzed for 144 subjects aged 2-19 who participated for a minimum of 12 consecutive months between 2002 and 2016. McNemar tests were used to determine differences in the proportion of participants who moved from abnormal values at baseline to normal at follow-up for a given clinical measure. Paired sample t-tests assessed differences in blood pressure and lipid levels. Multiple linear regression assessed the change in blood pressure or lipid levels associated with improvement in BMI%95 and BMI z-score. Results: The majority were female (62.5%), mean age was 9.6, and 71% were Black. At baseline, 70.1% had severe obesity, systolic hypertension was present in 44, and 13.9% had diastolic hypertension. One-third had abnormally low high-density lipoprotein (HDL) at baseline, 35% had elevated low-density lipoprotein (LDL), and 47% had abnormal total cholesterol (TC). The average difference in percentage points of BMI%95 at follow-up compared was - 3.0 (95% CI: - 5.0, - 1.1; p < 0.003). The mean difference in BMI z-score units at follow-up was - 0.15 (95% CI: - 0.2, - 0.1; p < 0.0001). Participants with systolic or diastolic hypertension had an average improvement in blood pressure of - 15.3 mmHg (p < 0.0001) and - 9.6 mmHg (p < 0.0001), respectively. There was a mean improvement of 4.4 mg/dL for participants with abnormal HDL (p < 0.001) and - 7.8 mg/dL for those with abnormal LDL at baseline (p = 0.036). For those with abnormal baseline TC, a one-unit improvement in BMI%95 was associated with a 0.61 mg/dL improvement in TC while holding constant age, contact hours, and months since enrollment (p = 0.043).
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Implementation of a Case Investigation and Contact Tracing Program at an Academic Medical Center in New York CityProblem: In the spring of 2020, New York City was an epicenter of COVID-19 infections, hospitalizations, and mortality. One of the hardest hit areas in New York City was central Brooklyn, where State University of New York (SUNY) Downstate is located. As the severity of the initial wave of the COVID-19 pandemic waned in New York City, SUNY Downstate Health Sciences University planned to institute COVID-19 surveillance on campus to limit its spread among employees and students. Approach: In collaboration with university leadership and students across schools, the SUNY Downstate Contact Tracing Corps was established in July 2020. Using guidance from the Centers for Disease Control and Prevention and the New York State Department of Health, protocols for case and contact investigations, including scripts, were developed. Students were recruited and trained in remote and confidential case and contact investigations. Outcomes: From August 1, 2020, to March 23, 2021, there were 185 COVID-19 cases referred to the contact tracing program; of these, 180 were successfully investigated and isolated (97%). Case investigations identified 111 Downstate close contacts; 105 were investigated and quarantined (94.5%). There were 122 exposure-only investigations referred to the program, and 121 were successfully investigated and quarantined (99%). Next steps: The SUNY Downstate Contact Tracing Corps transitioned to a core group of tracers in January 2021 and has been maintained at 4 to 6 tracers since that time. With the emergence of COVID-19 variants, the threat of new variants, and variable COVID-19 vaccination rates across Brooklyn, Downstate employees and students remain vulnerable to COVID-19 transmission. Given this, the SUNY Downstate Contact Tracing Corps will continue to conduct case and contact investigations.
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Insights into the challenges and facilitators to physical activity among brooklyn teens enroled in a weight management programmePurpose: A qualitative study was carried out to explore obese adolescents' understanding of physical activity, perceptions of the ideal body type and to identify facilitators of and barriers to physical activity. Methods: Twenty-two adolescents 12-18 years of age and 14 of their parents were recruited from an obesity intervention programme in Brooklyn, New York, from June to November 2017. Data were collected using focus groups and individual semi-structured interviews, followed by interpretative phenomenological analysis of the transcripts. Results: The adolescents wanted to 'lose some weight', but not to be 'thin' or 'look hungry'. Most females desired a 'slim-thick' figure, which was 'a flat stomach with big thighs, and curvy'. Fun and support from parents, peers and programme staff facilitated achieving their physical activity goals. Barriers included low self-efficacy, inactive families, fear of neighbourhood gangs and crime and perceptions that the parks were small and overcrowded, with limited physical activity options for adolescents. Conclusion: These findings highlight the need to consider local norms concerning body image when designing obesity interventions. To effectively reduce childhood obesity in New York City, policy should prioritize the promotion of public safety, improvement of neighbourhood parks and increase options for physical activity. Patient or public contribution: The voices and narratives of patients and their families informed this study.
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Evaluation of a Childhood Obesity Program Serving a High-Need Population in Brooklyn, New York Using Survival AnalysisIn this study, we used survival analysis to evaluate whether contact hours intensity was associated with a reduction in time to improvement of various BMI metrics over a 5-year follow-up period at the Live Light Live Right pediatric obesity program in Brooklyn, New York. This was a single-center retrospective longitudinal study of 406 patients during 2010-2016. Participants were categorized based on hours of exposure to Live Light Live Right's interventions; high contact hours (≥50 h) vs. low contact hours (<50 h). At baseline, 88% of patients in the high contact hour group had severe obesity and the mean age for this group was 10.0 ± 2.66. High contact hours were independently associated with a shorter time to BMI improvement in the sample. There was also a significant association between high contact hours and a longer duration in the improved state. Survival analysis was successful in evaluating the efficacy of the Live Light Live Right Program and demonstrated a positive association between greater intervention intensity and a healthier metabolic profile. Patients' active engagement in a robust treatment model exemplified by Live Light Live Right is recommended to address the childhood obesity crisis in central Brooklyn.
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Community Perceptions of Health Equity: A Qualitative StudyIntroduction: Notable inequities in patient experiences exist in the healthcare system. Communities with a large concentration of blacks and immigrants are often marginalized rather than centralized in the healthcare system. These inequities may fuel distrust and exacerbate adverse outcomes, thereby widening the health gap. Addressing differences in patients' experiences of care is paramount for reducing health inequities. Methods: In this qualitative study, we used a purposive sampling method to recruit 62 participants to conduct 10 FGs (44 participants total) and 18 key informant interviews with stakeholders across Central Brooklyn. Results: The data revealed three primary themes: Trust, Discrimination, and Social Determinants of Health (SDOHs). Each theme comprised subthemes as follows: For Trust, the subthemes included (1) confidence in the healthcare professional, (2) provider empathy, and (3) active participation in healthcare decisions. Regarding Discrimination, the subthemes involved (1) racism and identity, as well as (2) stigma related to diagnosis, disease state, and pain management. Lastly, for Social Determinants of Health, the key subtheme was the acknowledgment by providers that patients encounter competing priorities acting as barriers to care, such as housing instability and food insecurity. For the first theme, participants' interactions with the healthcare system were prompted by a necessity for medical attention, and not by trust. The participants reported that experiences of discrimination resulting from identity and stigma associated with diagnosis, disease state, and pain management amplified the disconnect between the community, the patients, and the healthcare system. This also exacerbated the poor healthcare experiences suffered by many people of color. For SDOHs, the participants identified housing, food security, and other various social factors that may undermine the effectiveness of the healthcare that patients receive. Conclusions: Improvements in the health system, based on feedback from patients of color regarding their unique care experiences, are important initiatives in combating inequities in healthcare.
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Do digital health interventions hold promise for stroke prevention and care in Black and Latinx populations in the United States? A scoping reviewBackground: Black and Latinx populations are disproportionately affected by stroke and are likely to experience gaps in health care. Within fragmented care systems, remote digital solutions hold promise in reversing this pattern. However, there is a digital divide that follows historical disparities in health. Without deliberate attempts to address this digital divide, rapid advances in digital health will only perpetuate systemic biases. This study aimed to characterize the range of digital health interventions for stroke care, summarize their efficacy, and examine the inclusion of Black and Latinx populations in the evidence base. Methods: We searched PubMed, the Web of Science, and EMBASE for publications between 2015 and 2021. Inclusion criteria include peer-reviewed systematic reviews or meta-analyses of experimental studies focusing on the impact of digital health interventions on stroke risk factors and outcomes in adults. Detailed information was extracted on intervention modality and functionality, clinical/behavioral outcome, study location, sample demographics, and intervention results. Results: Thirty-eight systematic reviews met inclusion criteria and yielded 519 individual studies. We identified six functional categories and eight digital health modalities. Case management (63%) and health monitoring (50%) were the most common intervention functionalities. Mobile apps and web-based interventions were the two most commonly studied modalities. Evidence of efficacy was strongest for web-based, text-messaging, and phone-based approaches. Although mobile applications have been widely studied, the evidence on efficacy is mixed. Blood pressure and medication adherence were the most commonly studied outcomes. However, evidence on the efficacy of the various intervention modalities on these outcomes was variable. Among all individual studies, only 38.0% were conducted in the United States (n = 197). Of these U.S. studies, 54.8% adequately reported racial or ethnic group distribution. On average, samples were 27.0% Black, 17.1% Latinx, and 63.4% White. Conclusion: While evidence of the efficacy of selected digital health interventions, particularly those designed to improve blood pressure management and medication adherence, show promise, evidence of how these interventions can be generalized to historically underrepresented groups is insufficient. Including these underrepresented populations in both digital health experimental and feasibility studies is critical to advancing digital health science and achieving health equity.
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Community design of the Brooklyn Health Equity IndexHealth equity drives quality care. Few reliable metrics that capture patients' perceptions of health equity exist. We report on the development of a patient-centered metric for health systems change in central Brooklyn, which stands out as an outlier in New York City with a disproportionate burden of poverty, disease, and death. A community-engaged, sequential, mixed-methods research design was used. Qualitative interviews were conducted with 80 community and health care stakeholders across central Brooklyn. Candidate items were derived from qualitative themes and examined for face, interpretive validity, and language. Interitem reliability and confirmatory factor analysis was assessed using data collected via text and automated discharge calls among 368 patients from a local hospital. Qualitative data analysis informed the content of 11 draft questions covering 3 broad domains: trust-building, provider appreciation of social determinants of health, and experiences of discrimination. Psychometric testing resulted in a Cronbach's alpha of 0.774 and led to deletion of 1 item, resulting in a 10-item Brooklyn Health Equity Index (BKHI). The 10-item BKHI is a novel, brief, and reliable measure that captures patients' perceptions of inequities and offers a real-time measure for health systems and payors to monitor progress toward advancing health equity.
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Diabetes and Hypertension Risk Across Acculturation and Education Levels in Hispanic/Latino AdultsImportance: Acculturation among Hispanic/Latino populations, defined as adaptation to US lifestyle and culture, is often assumed to lead to adverse health outcomes that will reduce the immigrant health advantage. Objective: To evaluate the risks for incident diabetes and hypertension by levels of acculturation and educational attainment. Design, setting, and participants: This study used data from the Hispanic Community Health Study/Study of Latinos, a population-based cohort study of men and women aged 18 to 74 years who identified as Central American, Cuban, Dominican, Mexican, Puerto Rican, or South American living in 4 urban locales in the US. Visit 1 spanned March 2008 to June 2011; visit 2 spanned October 2014 to December 2017. Main outcomes and measures: Multivariable logistic regression was used to evaluate the association between language acculturation level defined by the Short Acculturation Scale for Hispanics (SASH) and educational attainment (less than high school graduate vs more than high school) and incident diabetes and hypertension by heritage group. Results: Of 11 623 adult participants, 1207 (10.4%) were of Central American heritage, 1645 (14.2%) of Cuban heritage, 1021 (8.8%) of Dominican heritage, 11 623 (41.3%) of Mexican heritage, 1801 (15.5%) of Puerto Rican heritage, and 795 (6.8%) of South American heritage. The mean (SE) age of all participants was 43.1 (0.3) years, and 7345 (56.3%) were female. A total of 8697 (71.4%) were born outside the US, 4358 (32.5%) had less than a high school education, and 7475 (58.3%) were less acculturated (SASH score less than 2). Incident rates of diabetes (total cohort, 14.6% [95% CI, 13.6%-15.6%]) and hypertension (total cohort, 20.4% [95% CI, 19.0%-21.9%]) varied across heritages; Mexican individuals (17.2% [95% CI, 15.5%-19.0%]) had the highest diabetes incidence and Dominican individuals the highest hypertension incidence (27.1% [95% CI, 22.7%-31.4%]). Persons with more educational attainment were at lower risk for diabetes and hypertension independent of acculturation, and more acculturated participants had a lower risk for incident diabetes. Less acculturated with lower socioeconomic status (SES) were more likely to have incident diabetes (weighted predicted probability [WPP], 0.17 [95% CI, 0.14-0.19]), and more acculturated with lower SES had the highest predicted probability of hypertension (WPP, 0.19 [95% CI, 0.15-0.23]). More acculturated with higher SES were at lower risk of diabetes (WPP, 0.11 [95% CI, 0.09-0.13]) and had a lower predicted probability of hypertension (WPP, 0.10 [95% CI, 0.08-0.12]). Conclusions and relevance: In this cohort study, the association of acculturation with health outcomes is not unidirectional and interacts with educational attainment in determining incident diabetes and hypertension. The Hispanic and Latino paradox, in which immigrants have a health advantage, is influenced by more factors than acculturation and may persist with higher educational attainment. These observations may inform prevention and treatment strategies associated with cardiometabolic health in Hispanic/Latino populations.
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Efficacy of a Novel BCL-xL Degrader, DT2216, in Preclinical Models of JAK2-mutated Post-MPN AMLAcute myeloid leukemia (AML) that evolves from myeloproliferative neoplasm (MPN) is known as post-MPN AML. Current treatments don't significantly extend survival beyond 12 months. BCL-xL has been found to be overexpressed in leucocytes from MPN patients, making it a potential therapeutic target. We investigated the role of BCL-xL in post-MPN AML and tested the efficacy of DT2216, a platelet-sparing BCL-xL proteolysis-targeting chimera (PROTAC), in preclinical models of post-MPN AML. We found that BCL2L1, the gene encoding BCL-xL, is expressed at higher levels in post-MPN AML patients compared to those with de novo AML. Single-cell multi-omics analysis revealed that leukemia cells harboring both MPN-driver and TP53 mutations exhibited higher BCL2L1 expression, elevated scores for leukemia stem cell, megakaryocyte development, and erythroid progenitor than wild-type cells. BH3 profiling confirmed a strong dependence on BCL-xL in post-MPN AML cells. DT2216 alone, or in combination with standard AML/MPN therapies, effectively degraded BCL-xL, reduced the apoptotic threshold, and induced apoptosis in post-MPN AML cells. DT2216 effectively eliminated viable cells in JAK2-mutant AML cell lines, induced pluripotent stem cell-derived hematopoietic progenitor cells (iPSC-HPCs), primary samples, and reduced tumor burden in cell line-derived xenograft model in vivo by degrading BCL-xL. DT2216, either as a single agent or in combination with azacytidine, effectively inhibited the clonogenic potential of CD34+ leukemia cells from post-MPN AML patients. In summary, our data indicate that the survival of post-MPN AML is BCL-xL dependent, and DT2216 may offer therapeutic advantage in this high-risk leukemia subset with limited treatment options.
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BH3 mimetics augment cytotoxic T cell killing of acute myeloid leukemia via mitochondrial apoptotic mechanismAdoptive cell therapy (ACT) can address an unmet clinical need for patients with relapsed/refractory acute myeloid leukemia (AML), but its effect is often modest in the setting of high tumor burden. In this study, we postulated that strategies to lower the AML apoptotic threshold will augment T cell killing of AML cells. BH3 mimetics, such as venetoclax, are a clinically approved class of compounds that predispose cells to intrinsic apoptosis by inhibiting anti-apoptotic mitochondrial proteins. We explored the anti-leukemic efficacy of BH3 mimetics combined with WT1-specific CD8+ T cells on AML cell lines and primary samples from patients with a diverse array of disease characteristics to evaluate if lowering the cellular apoptotic threshold via inhibition of anti-apoptotic mitochondrial proteins can increase leukemic cell sensitivity to T cell therapy. We found that the combination approach of BH3 mimetic and CD8+ T cells led to significantly increased killing of established AML lines as well as of adverse-risk primary AML leukemic blast cells. In contrast to the hypothesis that enhanced killing would be due to combined activation of the intrinsic and extrinsic apoptotic pathways, our data suggests that CTL-mediated killing of AML cells was accomplished primarily through activation of the intrinsic/mitochondrial apoptotic pathway. This highly effective combinatorial activity due to convergence on the mitochondrial apoptotic pathway was conserved across multiple AML cell lines and primary samples, suggesting that mitochondrial priming may represent a novel mechanism of optimizing adoptive cell therapy for AML patients.
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Obstructive Sleep Apnea is Associated With Increased Rates of Acute Respiratory Failure, Length of Stay, and Hospital Costs in Patients Undergoing Elective Single-Level Anterior Cervical Discectomy and FusionStudy designRetrospective cohort study.ObjectivesTo examine differences in postoperative complications, recovery course, and costs between patients with and without obstructive sleep apnea (OSA) undergoing single-level anterior cervical discectomy and fusion (ACDF).MethodsThe National Inpatient Sample (NIS) database was queried to identify patients undergoing single-level ACDF between 2016 and 2022. After exclusions, patients were divided into OSA and control groups. Propensity score matching (1:2) controlled for age, sex, obesity, and year of surgery to balance characteristics. Postoperative outcomes, including complications, length of stay (LOS), hospital costs, and discharge disposition, were compared using chi-square tests for categorical variables and t-tests for continuous variables. A Bonferroni correction was applied, with significance set at P < 0.002.ResultsA total of 36,000 matched cases were analyzed (12,000 OSA and 24,000 controls). OSA patients had significantly higher rates of acute respiratory failure (4.7% vs 1.9%; P < 0.001) and mechanical ventilation (1.5% vs 0.6%; P < 0.001). The OSA cohort also had a longer LOS (2.3 vs 1.9 days; P < 0.001), higher hospital costs ($23,300 vs $21,100; P < 0.001), and greater non-routine discharge rates (20.4% vs 16.8%; P < 0.001).ConclusionsOSA is associated with increased respiratory complications, prolonged LOS, and higher costs in single-level ACDF. These findings underscore the importance of preoperative screening and tailored perioperative management to improve outcomes in this high-risk population.
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Neurocognitive and genetic influences on post-traumatic stress and risky alcohol use in traumaexposed adolescents and young adult offspring from families enriched with Alcohol UsePost-traumatic stress disorder (PTSD) is a psychiatric disorder that is triggered by a stressor involving threat of death or serious injury, and is associated with symptoms of re-experiencing, avoidance, and hyper-arousal. While over half of the United States population is exposed to a traumatic event at some point in their lifetime, only 6-8% of the population will develop PTSD. Further, PTSD is associated with increased risk for adverse conditions, such as suicidal ideations, chronic pain, major depression, alcohol and other substance use disorders. Alcohol use disorders (AUDs) occur in approximately 12-30% of the population and have been associated with impaired cognitive function, physical health problems, job loss, and relationship problems. PTSD and AUD commonly co-occur, with approximately one-third of individuals with PTSD reporting a lifetime diagnosis of AUD. Individuals with PTSD and co-occurring AUD have greater cognitive impairment, worse treatment outcomes, increased risk for legal problems, higher rates of unemployment, interpersonal problems, and poor quality of life. Therefore, there is great need to better understand the etiology of co-occurring PTSD-AUD. While previous research has pointed to the multifactorial risk for these disorders, including socio-demographic characteristics, adverse life experiences, genomic and neurodevelopmental risk factors, little research has integrated data across these domains to study pathways of risk for PTSD and co-occurring AUD. This dissertation study aims to investigate the influence of trauma exposure, family history of AUD, and other important risk factors (i.e., sex, neurocognitive function, response inhibition, genetic vulnerability) during adolescence and young adulthood, on risk for PTSD and co-occurring AUD. This research will be carried out using data from the Collaborative Studies on Genetics of Alcoholism (COGA), a deeply characterized sample of families densely affected with AUD. Overall, the findings from this dissertation demonstrate the importance of considering genetic, social environmental, and neurocognitive factors together when investigating influences of risk for the development of PTSD and co-occurring AUDs, especially during the vulnerable and critical developmental period of adolescence. These findings suggest that trauma exposure during adolescence, specifically assaultive trauma (nonsexual and sexual), influences critical aspects of executive function (e.g., response inhibition) in adulthood. Further, polygenic risk for cognitive function may interact with these traumatic exposures, further impairing executive function by influencing neural processes, specifically seen through frontal theta event-related oscillations during response inhibition. Therefore, trauma-exposed adolescents with a family history of AUDs may benefit from early intervention and treatment strategies aimed at reducing the severity and endurance of PTSD and co-occurring AUD and related impaired cognitive function in adulthood.
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Plasma Uric Acid Helps Predict Cognitive Impairment in Patients With Amyotrophic Lateral SclerosisObjective: Uric acid as an antioxidant plays an important role in neurodegenerative disease. Our objective is to investigate the relationship between plasma uric acid and cognitive impairment in patients with amyotrophic lateral sclerosis (ALS). Methods: In this cross-sectional study, 124 ALS patients were screened by the Edinburgh Cognitive and Behavioral Screen (ECAS) and classified according to the revised Strong's criteria. Additionally, based on total ECAS cut-off score patients were categorized into those with cognitive impairment (ALS-cie) and those without cognitive impairment (ALS-ncie), and clinical data and uric acid level were compared between the two groups. Parameters with significant differences were further included in a multivariate linear regression analysis with ECAS score as a dependent variable. Hold-out validation was performed to evaluate the fitness of regression model. Results: Up to 60% of ALS patients showed cognitive or/and behavioral impairment. The ALS-cie group had lower education level (p < 0.001), older age at symptom onset (p = 0.001), older age at testing (p = 0.001), and lower plasma uric acid (p = 0.01). Multivariate analysis showed increased uric acid (β = 0.214, p = 0.01), lower age at testing (β = -0.378, p < 0.001), and higher education level (β = 0.424, p < 0.001) could predict higher ECAS score (F = 19.104, R 2 = 0.381, p < 0.0001). Validation analysis showed that predicted ECAS score was significantly correlated with raw ECAS score in both the training set (rs = 0.621, p < 0.001) and the testing set (rs = 0.666, p < 0.001). Conclusions: Cognitive impairment was a common feature in our Chinese ALS patients. Plasma uric acid might help evaluate the risk of cognitive impairment in ALS patients when combined with education level and age at testing.
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COVID‐19 disease in hospitalized young adults in India and China: Evaluation of risk factors predicting progression across two major ethnic groupsData pertaining to risk factor analysis in coronavirus disease 2019 (COVID-19) is confounded by the lack of data from an ethnically diverse population. In addition, there is a lack of data for young adults. This study was conducted to assess risk factors predicting COVID-19 severity and mortality in hospitalized young adults. A retrospective observational study was conducted at two centers from China and India on COVID-19 patients aged 20-50 years. Regression analysis to predict adverse outcomes was performed using parameters including age, sex, country of origin, hospitalization duration, comorbidities, lymphocyte count, and National Early Warning Score 2 (NEWS2) score at admission. A total of 420 patients (172 East Asians and 248 South Asians) were included. The predictive model for intensive care unit (ICU) admission with variables NEWS2 Category II and higher, diabetes mellitus, liver dysfunction, and low lymphocyte counts had an area under the curve (AUC) value of 0.930 with a sensitivity of 0.931 and a specificity of 0.784. The predictive model for mortality with NEWS2 Category III, cancer, and decreasing lymphocyte count had an AUC value of 0.883 with a sensitivity of 0.903 and a specificity of 0.701. A combined predictive model with bronchial asthma and low lymphocyte count, in contrast, had an AUC value of 0.768 with a sensitivity of 0.828 and a specificity of 0.719 for NEWS2 score (5 or above) at presentation. NEWS2 supplemented with comorbidity profile and lymphocyte count could help identify hospitalized young adults at risk of adverse COVID-19 outcomes.
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Gut microbiota links with cognitive impairment in amyotrophic lateral sclerosis: A multi-omics studyRecently, cognitive impairments (CI) and behavioral abnormalities in patients with amyotrophic lateral sclerosis (ALS) have been reported. However, the underlying mechanisms have been poorly understood. In the current study, we explored the role of gut microbiota in CI of ALS patients. We collected fecal samples from 35 ALS patients and 35 healthy controls. The cognitive function of the ALS patients was evaluated using the Edinburgh Cognitive and Behavioral ALS Screen. We analyzed these samples by using 16S rRNA gene sequencing as well as both untargeted and targeted (bile acids) metabolite mapping between patients with CI and patients with normal cognition (CN). We found altered gut microbial communities and a lower ratio of Firmicutes/ Bacteroidetes in the CI group, compared with the CN group. In addition, the untargeted metabolite mapping revealed that 26 and 17 metabolites significantly increased and decreased, respectively, in the CI group, compared with the CN group. These metabolites were mapped to the metabolic pathways associated with bile acids. We further found that cholic acid and chenodeoxycholic acid were significantly lower in the CI group than in the CN group. In conclusion, we found that the gut microbiota and its metabolome profile differed between ALS patients with and without CI and that the altered bile acid profile in fecal samples was significantly associated with CI in ALS patients. These results need to be replicated in larger studies in the future.
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The role of self-esteem and emotion regulation in the associations between childhood trauma and mental health in adulthood: a moderated mediation modelBackground: High levels of childhood trauma (CT) have been observed in adults with mental health problems. Herein, we investigated whether self-esteem (SE) and emotion regulation strategies (cognitive reappraisal (CR) and expressive suppression (ES)) affect the association between CT and mental health in adulthood, including depression and anxiety symptoms. Methods: We performed a cross-sectional study of 6057 individuals (39.99% women, median age = 34 y), recruited across China via the internet, who completed the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Childhood Trauma Questionnaire (CTQ), Self-esteem Scale (SES), and Emotion Regulation Questionnaire (ERQ). Multivariate linear regression analysis and bias-corrected percentile bootstrap methodologies were used to assess the mediating effect of SE, and hierarchical regression analysis and subgroup approach were performed to examine the moderating effects of emotion regulation strategies. Results: After controlling for age and sex, we found that (1) SE mediated the associations between CT and depression symptoms in adulthood (indirect effect = 0.05, 95% confidence interval [CI]: 0.04-0.05, 36.2% mediated), and CT and anxiety symptoms in adulthood (indirect effect = 0.03, 95% CI: 0.03-0.04, 32.0% mediated); (2) CR moderated the association between CT and SE; and (3) ES moderated the association between of CT and mental health in adulthood via SE, and such that both the CT-SE and SE-mental health pathways were stronger when ES is high rather than low, resulting the indirect effect was stronger for high ES than for low ES. Conclusions: These findings suggested that SE plays a partially mediating role in the association between CT and mental health in adulthood. Furthermore, ES aggravated the negative effect of CT on mental health in adulthood via SE. Interventions such as emotional expression training may help reduce the detrimental effects of CT on mental health. Trial registration: The study was registered on http://www.chictr.org.cn/index.aspx and the registration number was ChiCTR2200059155.
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The role of ALDH2 rs671 polymorphism and C-reactive protein in the phenotypes of male ALS patientsBackground: The aldehyde dehydrogenase 2 (ALDH2) rs671 (A) allele has been implicated in neurodegeneration, potentially through oxidative and inflammatory pathways. The study aims to investigate the effects of the ALDH2 rs671 (A) allele and high sensitivity C-reactive protein (hs-CRP) on the clinical phenotypes of amyotrophic lateral sclerosis (ALS) in male and female patients. Methods: Clinical data and ALDH2 rs671 genotype of 143 ALS patients, including 85 males and 58 females, were collected from January 2018 to December 2022. All patients underwent assessment using the Chinese version of the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). Complete blood count and metabolic profiles were measured. Clinical and laboratory parameters were compared between carriers and non-carriers of the rs671 (A) allele in males and females, respectively. The significant parameters and rs671 (A) Allele were included in multivariate linear regression models to identify potential contributors to motor and cognitive impairment. Mediation analysis was employed to evaluate any mediation effects. Results: Male patients carrying rs671 (A) allele exhibited higher levels of hs-CRP than non-carriers (1.70 mg/L vs. 0.50 mg/L, p = 0.006). The rs671 (A) allele was identified as an independent risk factor for faster disease progression only in male patients (β = 0.274, 95% CI = 0.048-0.499, p = 0.018). The effect of the rs671 (A) allele on the executive function in male patients was fully mediated by hs-CRP (Indirect effect = -1.790, 95% CI = -4.555--0.225). No effects of the rs671 (A) allele or hs-CRP were observed in female ALS patients. The effects of the ALDH2 rs671 (A) allele and the mediating role of hs-CRP in male patients remained significant in the sensitivity analyses. Conclusion: The ALDH2 rs671 (A) allele contributed to faster disease progression and hs-CRP mediated cognitive impairment in male ALS patients.
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Association between cardiac autonomic dysfunction, cognitive impairment, and survival in patients with amyotrophic lateral sclerosisPurpose: The aim of this study was to investigate the relationship between cardiac autonomic dysfunction, cognitive impairment, and survival in patients with amyotrophic lateral sclerosis (ALS). Methods: The heart activity of 65 patients with ALS (28 with normal cognition [ALS-CN]; 37 with impaired cognition [ALS-CI]) and 38 healthy controls (HCs) was measured by 24-h Holter monitoring. Heart rate (HR) measures and heart rate variability (HRV) parameters were compared between the three study groups and, additionally, correlated with five Edinburgh Cognitive and Behavioral ALS Screen (ECAS) domains in the ALS subgroups. Age, gender, and educational level were adjusted. Factors associated with cognitive status were assessed using logistic regression. Survival predictors in patients with ALS were analyzed using the Kaplan-Meier estimator and Cox regression. Results: Compared to the HCs, patients with ALS-CI exhibited lower RRI (R-R-interval; P = 0.017), SDNN (standard deviation of all normal RR intervals; P = 0.013), SDNN Index (P = 0.044), and VLF power (very low-frequency power; P = 0.012). Total power was reduced in the ALS-CI group compared to the HCs (P = 0.036) and ALS-CN group (P = 0.048). In patients with ALS-CN, language negatively correlated with mean HR (P = 0.001) and positively with the RRI (P = 0.003), SDNN (P = 0.001), SDANN (standard deviation of the average NN intervals; P = 0.005), total power (P = 0.006), VLF power (P = 0.011), and low-frequency power (P = 0.026). Visuospatial function correlated positively with the SDNN Index (P = 0.041). In patients with ALS-CI, executive function (P = 0.015) and ECAS total score (P = 0.009) negatively correlated with the RMSSD (square root of mean sum-of-squares of differences between adjacent NN intervals), while visuospatial function correlated positively with normalized LF value (LFnu; P = 0.049). No associations were observed between the other cognitive domains and any of the 14 HRV/HR measures in patients with either ALS-CI or ALS-CN. SDNN ≤ 100 ms was linked to cognitive impairment (P = 0.039) and also showed a borderline association (P = 0.066) with poorer survival, while cognitive impairment (P = 0.010) was significantly linked to worse outcomes. Conclusions: Patients with ALS with cognitive impairment demonstrated reduced cardiac autonomic modulations and altered cognitive autonomic associations. Cognitive impairment was linked to reduced survival, with baseline SDNN ≤ 100 ms identified as a potential marker.
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A REVIEW OF RECENT STUDIES ON DIFFERENTIAL REINFORCEMENT DURING SKILL ACQUISITION IN EARLY INTERVENTIONAlthough the use of differential reinforcement has been recommended in previous investigations and in early intervention curriculum manuals, few studies have evaluated the best method for providing differential reinforcement to maximize independent responding. This paper reviews previous research on the effectiveness of differential reinforcement as treatment and describes important areas of future research.
