Paternal Alcohol Consumption and Childhood Malnutrition: A Community-based Participatory Case-control Study among Adivasis in Rural South India.

BACKGROUND: Childhood malnutrition in India remains among the highest in the world. Adult alcohol consumption and severe malnutrition have increased among indigenous people in South India. However, the association between them is poorly understood. OBJECTIVES: We aimed to evaluate this association, which could help design better intervention strategies. METHODS: This case-control observational study was conducted in the Nilgiri district in South India. Cases included children aged 1-5 years with moderate malnutrition. Controls were defined as children in the same age group with normal weight-for-age. A questionnaire was used to collect data on demographics, socioeconomic status (SES), and parental education. The WHO Alcohol Use Disorders Identification Test (AUDIT) questionnaire was used to estimate parental alcohol use. Health-care workers collected data from within the community. RESULTS: The baseline demographics of the children in the control (n = 250) and case groups (n = 177) were similar. Paternal age and AUDIT scores were not different in the two groups. SES was lower in the malnourished group, while maternal education among cases was significantly lower. Maternal and paternal education were associated with childhood malnutrition (odds ratio [OR]: 0.728 [95% confidence interval (CI): 0.583-0.903] and OR: 0.753 [95% CI: 0.589-0.957], respectively). After adjustment for covariates, paternal alcohol use was associated with a higher risk of malnutrition (OR: 1.56 [95% CI: 1.00-2.47]), which SES partly mediated. CONCLUSION: Paternal alcohol consumption is associated with childhood malnutrition, partially mediated by lower SES. Furthermore, lower SES appeared to be strongly associated with paternal alcohol consumption.

Severe Hyponatremia Triggered by Immune Checkpoint Inhibitor Therapy in a Patient With Mulvihill-Smith Syndrome.

Background/Objective: Immune checkpoint inhibitors (ICI), including Programmed Cell Death 1, Programmed Cell Death Ligand 1, and Cytotoxic T-lymphocyte Associated Antigen 4 inhibitors, upregulate T-cell responses against tumor cells and are becoming a cornerstone in the treatment of various advanced solid and hematological cancers. Mulvihill-Smith Syndrome (MSS) is a rare genetic syndrome that has been associated with metabolic abnormalities and early-onset tumors, including malignancies. We report the first known case of ICI-induced hyponatremia attributable to syndrome of inappropriate antidiuretic hormone ADH release (SIADH) in a patient with MSS. Case Report: A 23-year-old female patient with MSS and hepatocellular carcinoma presented with recurrent hyponatremia. Assessment of fluid status and electrolytes revealed a euvolemic, hypotonic process consistent with SIADH shortly after initiating adjuvant therapy with atezolizumab, a Programmed Cell Death Ligand 1 inhibitor. Discussion: Endocrine etiologies for euvolemic hypotonic hyponatremia, including adrenal insufficiency and hypothyroidism, were excluded. The diagnosis of SIADH was confirmed based on electrolyte and osmolality studies. Sodium levels normalized with fluid restriction. Given the onset of hyponatremia 30 days after atezolizumab initiation, we posit that atezolizumab triggered severe hyponatremia due to SIADH. Conclusion: With the expanding utilization of ICIs, including in patients predisposed to malignancies such as MSS, vigilant monitoring for ICI-mediated electrolyte imbalances is crucial. Monitoring for hyponatremia and SIADH in the setting of ICI therapy is recommended.

Understanding Providers' Readiness and Attitudes Toward Autoantibody Screening: A Mixed-Methods Study.

Screening for autoantibodies associated with type 1 diabetes can identify people most at risk for progressing to clinical type 1 diabetes and provide an opportunity for early intervention. Drawbacks and barriers to screening exist, and concerns arise, as methods for disease prevention are limited and no cure exists today. The availability of novel treatment options such as teplizumab to delay progression to clinical type 1 diabetes in high-risk individuals has led to the reassessment of screening programs. This study explored awareness, readiness, and attitudes of endocrinology providers toward type 1 diabetes autoantibody screening.

Young Adults with Type 1 Diabetes.

Young adults experience multiple developmental transitions across social, educational, vocational, residential, and financial life domains. These transitions are potential competing priorities to managing a chronic condition such as type 1 diabetes and can contribute to poor psychosocial and medical outcomes. In this narrative review, we describe population outcomes of young adult populations and the unique considerations associated with managing type 1 diabetes in young adulthood. We provide an overview of the current evidence-based strategies to improve care for young adults with type 1 diabetes and recommendations for future directions in the field.

The clinical utility of plasma and urine metanephrines in hypertensive emergency.

INTRODUCTION: Metanephrines (MTNs) are metabolites of catecholamines and are constantly produced in high amounts by pheochromocytomas and paragangliomas (PPGLs). Marked MTN elevations (> 3 times the upper limit of normal [ULN]) are highly suggestive of PPGL. The frequency of marked MTN elevations in non-PPGL hypertensive emergencies (HTNEs) is unknown. METHODS: We retrospectively analyzed plasma free metanephrine (PMTN) and 24-h urinary fractionated metanephrine (UMTN) levels in 48 consecutive patients (59.7 ± 15.6 years; 48% female; BMI: 31 ± 9.7 kg/m2) hospitalized for HTNE, defined as systolic blood pressure (SBP) > 180 mmHg or diastolic blood pressure (DBP) > 120 mmHg with end-organ damage. PMTNs were measured in 47 patients, UMTNs were measured in 16 patients, and both PMTNs and UMTNs were measured in 15 patients. RESULTS: PMTN/UMTN levels were not associated with SBP/DBP, comorbidities, end-organ damage, or interfering medications, the exception being that plasma normetanephrines (PNMNs) were significantly associated with comorbidities (Adj. R2 = 0.16; p = 0.04) and interfering medications (Adj. R2 = 0.15; p = 0.03), although with weak correlation. Marked MTN (specifically PNMN) elevations (647, 521, and 453 pg/mL; normal ≤ 148 pg/mL) were noted in only three patients (6%). DISCUSSION: Marked MTN elevations in HTNE are uncommon. Therefore, we recommend against measuring MTN in the setting of an apparent precipitating cause of HTNE to avoid unnecessary testing and imaging. Testing for MTN in HTNE should be pursued only when there is no clear precipitating cause and in cases where there is strong underlying clinical suspicion for PPGL. However, should testing be performed, marked MTN elevations should not be disregarded as being a commonly occurring result of HTNE.

Impact of diabetes status and related factors on COVID-19-associated hospitalization: A nationwide retrospective cohort study of 116,370 adults with SARS-CoV-2 infection.

AIMS: We examined diabetes status (no diabetes; type 1 diabetes [T1D]; type 2 diabetes [T2D]) and other demographic and clinical factors as correlates of coronavirus disease 2019 (COVID-19)-related hospitalization. Further, we evaluated predictors of COVID-19-related hospitalization in T1D and T2D. METHODS: We analyzed electronic health record data from the de-identified COVID-19 database (December 2019 through mid-September 2020; 87 US health systems). Logistic mixed models were used to examine predictors of hospitalization at index encounters associated with confirmed SARS-CoV-2 infection. RESULTS: In 116,370 adults (>=18 years old) with COVID-19 (93,098 no diabetes; 802 T1D; 22,470 T2D), factors that independently increased risk for hospitalization included diabetes, male sex, public health insurance, decreased body mass index (BMI; <25.0-29.9 kg/m2), increased BMI (>25.0-29.9 kg/m2), vitamin D deficiency/insufficiency, and Elixhauser comorbidity score. After further adjustment for concurrent hyperglycemia and acidosis in those with diabetes, hospitalization risk was substantially higher in T1D than T2D and in those with low vitamin D and elevated hemoglobin A1c (HbA1c). CONCLUSIONS: The higher hospitalization risk in T1D versus T2D warrants further investigation. Modifiable risk factors such as vitamin D deficiency/insufficiency, BMI, and elevated HbA1c may serve as prognostic indicators for COVID-19-related hospitalization in adults with diabetes.

Achieving Equity in Diabetes Research: Borrowing From the Field of Quality Improvement Using a Practical Framework and Improvement Tools.

There are limited tools to address equity in diabetes research and clinical trials. The T1D Exchange has established a 10-step equity framework to advance equity in diabetes research. Herein, the authors outline this approach and expand on its practical application.

Targeting Technology in Underserved Adults With Type 1 Diabetes: Effect of Diabetes Practice Transformations on Improving Equity in CGM Prescribing Behaviors.

OBJECTIVE: Continuous glucose monitoring (CGM) is associated with improved outcomes in type 1 diabetes, but racial-ethnic disparities exist in use. We were interested in examining whether addressing structural health care barriers would change provider prescribing behaviors to make CGM access more equitable. RESEARCH DESIGN AND METHODS: From January 2019 to December 2021, we used multilevel stakeholder input to develop and implement several non-grant-funded practice transformations targeted toward equity, which included 1) developing a type 1 diabetes clinic, 2) conducting social needs assessments and management, 3) training support staff to place trial CGMs at the point of care, 4) optimizing prescription workflows, and 5) educating providers on CGM. Transformations were prioritized based on feasibility, acceptability, and sustainability. To examine effect on prescribing behaviors, we collected monthly aggregate data from the electronic medical record and performed multiple linear regression to examine and compare change in CGM prescriptions over the 3 years of transformation. RESULTS: In total, we included 1,357 adults with type 1 diabetes in the analysis (mean ± SD age 38 ± 18 years; 30% Black [n = 406], 45% Hispanic [n = 612], 12% White [n = 164]; and 74% publicly insured [n = 1,004]). During the period of transformation, CGM prescription rates increased overall from 15% to 69% (P < 0.001). Improvements were seen equally among Black (12% to 72%), Hispanic (15% to 74%), and White adults (20% to 48%) (between-group P = 0.053). CONCLUSIONS: Diabetes practice transformations that target equity, offload provider burdens, and focus on feasible sustainable stakeholder-driven solutions can have powerful effects on provider prescribing behaviors to reduce root causes of inequity in CGM among underserved adults with type 1 diabetes. Continued focus is needed on upstream determinants of downstream CGM use.

An Atypical Form of Diabetes Among Individuals With Low BMI.

OBJECTIVE: Diabetes among individuals with low BMI (<19 kg/m2) has been recognized for >60 years as a prevalent entity in low- and middle-income countries (LMICs) and was formally classified as "malnutrition-related diabetes mellitus" by the World Health Organization (WHO) in 1985. Since the WHO withdrew this category in 1999, our objective was to define the metabolic characteristics of these individuals to establish that this is a distinct form of diabetes. RESEARCH DESIGN AND METHODS: State-of-the-art metabolic studies were used to characterize Indian individuals with "low BMI diabetes" (LD) in whom all known forms of diabetes were excluded by immunogenetic analysis. They were compared with demographically matched groups: a group with type 1 diabetes (T1D), a group with type 2 diabetes (T2D), and a group without diabetes. Insulin secretion was assessed by C-peptide deconvolution. Hepatic and peripheral insulin sensitivity were analyzed with stepped hyperinsulinemic-euglycemic pancreatic clamp studies. Hepatic and myocellular lipid contents were assessed with 1H-nuclear magnetic resonance spectroscopy. RESULTS: The total insulin secretory response was lower in the LD group in comparison with the lean group without diabetes and the T2D group. Endogenous glucose production was significantly lower in the LD group than the T2D group (mean ± SEM 0.50 ± 0.1 vs. 0.84 ± 0.1 mg/kg · min, respectively; P < 0.05). Glucose uptake was significantly higher in the LD group in comparison with the T2D group (10.1 ± 0.7 vs. 4.2 ± 0.5 mg/kg · min; P < 0.001). Visceral adipose tissue and hepatocellular lipids were significantly lower in LD than in T2D. CONCLUSIONS: These studies are the first to demonstrate that LD individuals in LMICs have a unique metabolic profile, suggesting that this is a distinct entity that warrants further investigation.

Diabetes is associated with increased risk for in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis comprising 18,506 patients.

PURPOSE: Infectious diseases are more frequent and can be associated with worse outcomes in patients with diabetes. The aim of this study was to systematically review and conduct a meta-analysis of the available observational studies reporting the effect of diabetes on mortality among hospitalized patients with COVID-19. METHODS: The Medline, Embase, Google Scholar, and medRxiv databases were reviewed for identification of eligible studies. A random effects model meta-analysis was used, and I2 was utilized to assess the heterogeneity. In-hospital mortality was defined as the endpoint. Sensitivity, subgroup, and meta-regression analyses were performed. RESULTS: A total of 18,506 patients were included in this meta-analysis (3713 diabetics and 14,793 non-diabetics). Patients with diabetes were associated with a higher risk of death compared with patients without diabetes (OR 1.65; 95% CI 1.35-1.96; I2 77.4%). The heterogeneity was high. A study-level meta-regression analysis was performed for all the important covariates, and no significant interactions were found between the covariates and the outcome of mortality. CONCLUSION: This meta-analysis shows that that the likelihood of death seems to be higher in diabetic patients hospitalized with COVID-19 compared with non-diabetic patients. Further studies are needed to assess whether this association is independent or not, as well as to investigate the role of adequate glycemic control prior to infection with COVID-19.

COVID-19 Hospitalization in Adults with Type 1 Diabetes: Results from the T1D Exchange Multicenter Surveillance Study.

CONTEXT: Diabetes mellitus is associated with increased COVID-19 morbidity and mortality, but there are few data focusing on outcomes in people with type 1 diabetes. OBJECTIVE: The objective of this study was to analyze characteristics of adults with type 1 diabetes for associations with COVID-19 hospitalization. DESIGN: An observational multisite cross-sectional study was performed. Diabetes care providers answered a 33-item questionnaire regarding demographics, symptoms, and diabetes- and COVID-19-related care and outcomes. Descriptive statistics were used to describe the study population, and multivariate logistic regression models were used to analyze the relationship between glycated hemoglobin (HbA1c), age, and comorbidities and hospitalization. SETTING: Cases were submitted from 52 US sites between March and August 2020. PATIENTS OR OTHER PARTICIPANTS: Adults over the age of 19 with type 1 diabetes and confirmed COVID-19 infection were included. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Hospitalization for COVID-19 infection. RESULTS: A total of 113 cases were analyzed. Fifty-eight patients were hospitalized, and 5 patients died. Patients who were hospitalized were more likely to be older, to identify as non-Hispanic Black, to use public insurance, or to have hypertension, and less likely to use continuous glucose monitoring or insulin pumps. Median HbA1c was 8.6% (70 mmol/mol) and was positively associated with hospitalization (odds ratio 1.42, 95% confidence interval 1.18-1.76), which persisted after adjustment for age, sex, race, and obesity. CONCLUSIONS: Baseline glycemic control and access to care are important modifiable risk factors which need to be addressed to optimize care of people with type 1 diabetes during the worldwide COVID-19 pandemic.

IATROGENIC CUSHING SYNDROME IN AN HIV-INFECTED PATIENT SECONDARY TO CONCOMITANT THERAPY WITH GENVOYA AND EPIDURAL TRIAMCINOLONE.

OBJECTIVE: We report the first known case of Cushing syndrome and secondary adrenal insufficiency in a patient with concomitant use of epidural triamcinolone and Genvoya® (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg) for the human immunodeficiency viruses (HIV). The prompt recognition of this drug-drug interaction is critical to avoid adverse outcomes when glucocorticoids are used with anti-retroviral treatment containing cobicistat, a potent cytochrome P450 3A (CYP3A4) inhibitor. METHODS: The patient was evaluated by determining morning serum cortisol concentrations, the serum cortisol response to cosyntropin, and a urine synthetic glucocorticoid panel that is capable of measuring triamcinolone. We also employed the Naranjo Nomogram for Causality as well as a Drug Interaction Probability scale to assess medication-related adverse effects. Long term outcome was assessed by measuring morning serum cortisol and adrenocorticotropic hormone levels. RESULTS: A 76-year-old female with HIV on Genvoya® presented with fatigue, weight loss, and hyperglycemia. She had received multiple epidural triamcinolone injections for chronic back pain before her presentation. We hypothesized that the patient's presentation of Cushing syndrome and adrenal insufficiency was caused by the inhibition of triamcinolone metabolism by cobicistat. The patient's antiretroviral therapy was changed to a regimen without cobicistat. She was started on maintenance hydrocortisone to prevent an adrenal crisis. A repeat urine glucocorticoid panel, within 3 days of the patient's HIV regimen being changed, showed a significant decrease in triamcinolone levels. CONCLUSION: It is essential to avoid drugs that include cobicistat when administering glucocorticoids that are metabolized via the CYP3A4 pathway due to the risk of developing Cushing syndrome and secondary adrenal insufficiency.

Health Care Utilization and Burden of Diabetic Ketoacidosis in the U.S. Over the Past Decade: A Nationwide Analysis.

OBJECTIVE: Diabetes is one of the most common chronic diseases and a leading cause of morbidity and mortality in the U.S. Although our ability to treat diabetes and its associated complications has significantly improved, presentation with uncontrolled diabetes leading to ketoacidosis remains a significant problem. RESEARCH DESIGN AND METHODS: We aimed to determine the incidence and costs of hospital admissions associated with diabetic ketoacidosis (DKA). We reviewed the National Inpatient Sample database for all hospitalizations in which DKA (ICD-9 codes 250.10, 250.11, 250.12, and 250.13) was the principal discharge diagnosis during 2003-2014 and calculated the population incidence by using U.S. census data. Patients with ICD-9 codes for diabetic coma were excluded because the codes do not distinguish between hypoglycemic and DKA-related coma. We then analyzed changes in temporal trends of incidence, length of stay, costs, and in-hospital mortality by using the Cochrane-Armitage test. RESULTS: There were 1,760,101 primary admissions for DKA during the study period. In-hospital mortality for the cohort was 0.4% (n = 7,031). The total number of hospital discharges with the principal diagnosis of DKA increased from 118,808 in 2003 to 188,965 in 2014 (P < 0.0001). The length of stay significantly decreased from an average of 3.64 days in 2003 to 3.24 days in 2014 (P < 0.01). During this period, the mean hospital charges increased significantly from $18,987 (after adjusting for inflation) per admission in 2003 to $26,566 per admission in 2014. The resulting aggregate charges (i.e., national bill) for diabetes with ketoacidosis increased dramatically from $2.2 billion (after adjusting for inflation) in 2003 to $ 5.1 billion in 2014 (P < 0.001). However, there was a significant reduction in mortality from 611 (0.51%) in 2003 to 620 (0.3%) in 2014 (P < 0.01). CONCLUSIONS: Our analysis shows that the population incidence for DKA hospitalizations in the U.S. continues to increase, but the mortality from this condition has significantly decreased, indicating advances in early diagnosis and better inpatient care. Despite decreases in the length of stay, the costs of hospitalizations have increased significantly, indicating opportunities for value-based care intervention in this vulnerable population.

Efficacy of modified Tochen's formula for optimum endotracheal tube placement in low birth weight neonates: an RCT.

OBJECTIVE: To assess the efficacy of modified Tochen's formula (birth weight + 5 cm) when compared to Tochen's formula for optimum placement of endotracheal tubes (ET) in low birth weight (LBW) neonates. STUDY DESIGN: In the NICU of a tertiary care hospital, LBW babies requiring intubation were randomized to Tochen's formula or modified Tochen's formula. The incidence of inadequate placement and optimum length of ET insertion were estimated. Analysis was done by the Chi square and 't'-tests. RESULTS: Sixty-seven babies were included: 34 in Tochen's group and 33 in modified Tochen's group. Baseline characteristics were similar. Modified Tochen's formula was significantly (p = 0.006) closer to the optimum position when compared to Tochen's formula. The percentages of optimum and adequate placements of the ET tube was higher in the modified Tochen's group, though not statistically significant. CONCLUSION: Modified Tochen's formula in LBW babies may enable more optimum placement of ETs.

Dual Antiplatelet Therapy Duration: A Review of Current Available Evidence.

PURPOSE: Multiple regimens of antiplatelet and anticoagulation therapy have been used in the past in patients undergoing percutaneous coronary intervention (PCI). Later trials of PCI stenting demonstrated the efficacy of dual-antiplatelet therapy (DAPT) in reducing stent- and non-stent-related thrombotic events in this specific population. Nonetheless, the required duration of DAPT has not yet been elucidated. In this article we sought to identify various randomized clinical trials (RCTs), pooled analyses, meta-analyses, and data pertaining to the optimal duration of DAPT and attempt some recommendations based on patients' clinical and procedural profiles. METHODS: We performed an extensive search using MEDLINE, Scopus, Cochrane Library, and Internet sources for abstracts, manuscripts, and conference reports without any language or date restrictions. In our review we included all available evidence from RCTs, meta-analyses, observational studies, and abstracts pertaining to our topic. Search results that were deemed irrelevant or that would not serve the goal or topic of our review were excluded. RESULTS: Our search yielded 10 RCTs directly comparing different durations of DAPT, 3 meta-analyses amassing the evidence resulting from randomized data, and numerous observational studies that served the aim of our review. The observational studies included in the manuscript are directly related to instances in which RCTs could not be performed or introduce important concepts related to the duration of DAPT. IMPLICATIONS: There is no conclusive evidence that determines the mandatory DAPT duration after PCI. In addition, there are distinct patient populations that need specific treatment regimens, such as diabetic patients or those on long-term oral anticoagulation. Therefore, clinical judgement and meticulous examination of all pertaining risk factors are required for each individual. These factors include those related to a patient's characteristics, treatment procedures, lesion complexity, and stent type. Currently ongoing studies are anticipated to further elucidate and integrate our understanding with regard to DAPT.

An IL-13 promoter polymorphism associated with liver fibrosis in patients with Schistosoma japonicum.

The aim of this study was to determine whether two polymorphisms in the gene encoding IL13 previously associated with Schistosoma hematobium (S. hematobium) and S. mansoni infection are associated with S. japonicum infection. Single nucleotide polymorphisms (SNPs) rs1800925 (IL13/-1112C>T) and rs20541 (IL13R130Q) were genotyped in 947 unrelated individuals (307 chronically infected, 339 late-stage with liver fibrosis, 301 uninfected controls) from a schistosomiasis-endemic area of Hubei province in China. Regression models were used to evaluate allelic and haplotypic associations with chronic and late-stage schistosomiasis adjusted for non-genetic covariates. Expression of IL-13 was measured in S. japonicun-infected liver fibrosis tissue and normal liver tissue from uninfected controls by immunohistochemistry (IHC). The role of rs1800925 in IL-13 transcription was further determined by Luciferase report assay using the recombinant PGL4.17-rs180092 plasmid. We found SNP rs1800925T was associated with late-stage schistosomiasis caused by S. japonicum but not chronic schistosomiasis (OR = 1.39, 95%CI = 1.02-1.91, p = 0.03) and uninfected controls (OR = 1.49, 95%CI = 1.03-2.13, p = 0.03). Moreover, the haplotype rs1800925T-rs20541C increased the risk of disease progression to late-stage schistosomiasis (OR = 1.46, p = 0.035), whereas haplotype rs1800925C-rs20541A showed a protective role against development of late-stage schistosomiasis (F = 0.188, OR = 0.61, p = 0.002). Furthermore, S. japonicum-induced fibrotic liver tissue had higher IL13 expression than normal liver tissue. Plasmid PGL4.17-rs1800925T showed a stronger relative luciferase activity than Plasmid PGL4.17-rs1800925C in 293FT, QSG-7701 and HL-7702 cell lines. In conclusion, the functional IL13 polymorphism, rs1800925T, previously associated with risk of schistosomiasis, also contributes to risk of late-stage schistosomiasis caused by S. japonicum.