Prevalence and associated factors of impaired kidney functions among children and adolescents in India: insights from the Comprehensive National Nutrition Survey (CNNS) 2016-18.

BACKGROUND: Chronic kidney disease (CKD) is a significant public health problem. The burden of CKD in children and adolescents in India is not well described. We used data from the recent Comprehensive National Nutrition Survey (CNNS) to estimate the prevalence of impaired kidney function (IKF) and its determinants in children and adolescents between the ages of 5 and 19. METHODS: CNNS 2016-18 adopted a multi-stage sampling design using probability proportional to size sampling procedure after geographical stratification of urban and rural areas. Serum creatinine was tested once in 24,690 children and adolescents aged 5-19 years. The estimated glomerular filtration rate (eGFR) was derived using the revised Schwartz equation. The eGFR value below 60 ml/min/1.73 m2 is defined as IKF. Bivariate analysis was done to depict the weighted prevalence, and multivariable logistic regression examined the predictors of IKF. RESULTS: The mean eGFR in the study population was 113.3 + 41.4 mL/min/1.73 m2. The overall prevalence of IKF was 4.9%. The prevalence in the 5-9, 10-14, and 15-19 year age groups was 5.6%, 3.4% and 5.2%, respectively. Regression analysis showed age, rural residence, non-reserved social caste, less educated mothers, Islam religion, children with severe stunting or being overweight/obese, and residence in Southern India to be predictors of IKF. CONCLUSIONS: The prevalence of IKF among children and adolescents in India is high compared to available global estimates. In the absence of repeated eGFR-based estimates, these nationally representative estimates are intriguing and call for further assessment of socio-demographic disparities, genetics, and risk behaviours to have better clinical insights and public health preparedness.

Phenotypic similarities within the morphologic spectrum of DICER1-associated sarcomas and pleuropulmonary blastoma: Histopathologic features guide diagnosis in the LMIC setting.

Extrapulmonary DICER1-associated sarcomas (DS) can harbor morphological features overlapping with pleuropulmonary blastoma. We report three children with intracranial and genital tract sarcomas, suspected to have DS based on a heterogeneous yet defining combination of spindle-cell sarcomatous and blastemal morphology, with rhabdomyomatous differentiation. Foci of immature cartilage at diagnosis (n = 2/3) and increased neuroepithelial differentiation at recurrence (n = 1) were noted. Morphological suspicion prompted somatic testing at reference centers, confirming likely biallelic, loss-of-function, and "hotspot" missense DICER1 variants in all three tumors. This can serve as a model for this diagnosis in resource-limited settings and has implications for germline testing, surveillance, and tumor management.

Understanding fish cognition: a review and appraisal of current practices.

With over 30,000 recognized species, fishes exhibit an extraordinary variety of morphological, behavioural, and life-history traits. The field of fish cognition has grown markedly with numerous studies on fish spatial navigation, numeracy, learning, decision-making, and even theory of mind. However, most cognitive research on fishes takes place in a highly controlled laboratory environment and it can therefore be difficult to determine whether findings generalize to the ecology of wild fishes. Here, we summarize four prominent research areas in fish cognition, highlighting some of the recent advances and key findings. Next, we survey the literature, targeting these four areas, and quantify the nearly ubiquitous use of captive-bred individuals and a heavy reliance on lab-based research. We then discuss common practices that occur prior to experimentation and within experiments that could hinder our ability to make more general conclusions about fish cognition, and suggest possible solutions. By complementing ecologically relevant laboratory-based studies with in situ cognitive tests, we will gain further inroads toward unraveling how fishes learn and make decisions about food, mates, and territories.

Immunohistochemical screening for mismatch repair protein deficiency in paediatric high-grade gliomas - institutional experience and review of literature.

PURPOSE: Immunohistochemical (IHC) testing for mismatch repair (MMR) deficiency (MMRD) is used as a screening tool to identify microsatellite instability in various cancers (especially colon). This not only identifies hereditary cancer syndromes like Lynch and constitutional mismatch repair deficiency (CMMRD) but also aids in prognostication and prediction of sensitivity to checkpoint inhibitor drugs. There are very few reported studies on MMRD status of pediatric high-grade gliomas (pHGG) and none from the Indian subcontinent. The aim of this study is to evaluate the frequency of MMRD in pHGG and to assess if there is a need for universal screening with immunohistochemistry. METHODS: Paraffin blocks of consecutive cases of pHGG (< 18 years) were retrieved from 2 centres, and IHC with four MMR antibodies - MLH1, PMS2, MSH2 and MSH6 - was performed using tissue microarray-based technique. RESULTS: Three out of nine cases (33%) studied showed loss of staining. One case had loss of MSH2 and MSH6 confirmed by gene sequencing. Eight of the cases were glioblastoma. One case of IDH1-mutated anaplastic astrocytoma showed loss of MLH1 and PMS2 staining. Isolated PMS2 loss was noted in 1 case, where the non-tumour cells also showed loss of staining, indicative CMMRD syndrome. This patient had prior colon cancer with isolated PMS2 loss and responded to check-point inhibitor therapy with nivolumab. CONCLUSION: Our study shows that the frequency of MMRD to be about one-third of pHGG. Universal IHC screening for MMRD in all pHGGs may benefit early diagnosis and play a role in therapeutic decisions. A larger multi-institutional study will help better assess the prevalence and treatment implications in MMRD tumours.

A Nonchordomatous-looking Chordoma: When INI-1 and Radiology Came to the Rescue!!!

SMARCB1/integrase interactor (INI)-1 is one of the core subunit proteins of the ATP-dependent SWI/SNF chromatin remodeling complex and acts as a tumor suppressor. INI-1 loss can be easily assessed using immunohistochemistry and is an important diagnostic clue for a histopathologist. Chordoma is a malignant tumor commonly occurring in the sacrococcygeal spine of adults and is characterized by nuclear expression of brachyury. Poorly differentiated chordoma, a morphologically and molecularly distinct entity, also shows nuclear brachyury positivity along with INI-1 loss. It usually occurs in children and has a predilection to involve the base of the skull. We describe a case of a poorly differentiated chordoma in a 5-year-old girl and discuss its unusual histomorphologic and immunohistochemical features.

Lymphoma in Rheumatoid Arthritis - Catastrophic Sequela of a Common Disease.

Rheumatoid arthritis (RA) is a common rheumatological condition affecting the joints and has a wide range of extra-articular manifestations. A 69 year old male, known case of rheumatoid arthritis presented to our OPD with right lower limb redness and swelling, and left axillary lymph node swelling. Lymph node biopsy revealed a high grade diffuse large B-cell lymphoma with co-expression of c-myc and bcl-2 (double expressor). RA increases the risk of both Hodgkin's lymphoma (HL) and non-Hodgkin's Lymphoma (NHL). The association with diffuse large B-cell lymphoma (DLBCL) has been found to be particularly strong, however double expressor DLBCL is an extremely uncommon occurrence. High disease activity of rheumatoid arthritis is a major determinant in development of lymphomas.

Diffuse glioma - Rare homozygous IDH point mutation, is it an oncogenetic mechanism?

Isocitrate dehydrogenase (IDH1/IDH2) mutations in gliomas of WHO grade II/III and secondary glioblastoma are almost always heterozygous missense mutations. Here, we report an extremely rare case of homozygous IDH1R132H mutation in a recurrent WHO grade III anaplastic astrocytoma. The authors here also review the relevant literature for the possible metabolic impact of homozygous IDH1/2 mutations in the gliomagenesis.

National Survey of Medical Spanish Curriculum in U.S. Medical Schools.

BACKGROUND: Patients with limited English proficiency (LEP) may be at risk for medical errors and worse health outcomes. Language concordance between patient and provider has been shown to improve health outcomes for Spanish-speaking patients. Nearly 40 % of Hispanics, a growing population in the United States, are categorized as having limited English proficiency. Many medical schools have incorporated a medical Spanish curriculum to prepare students for clinical encounters with LEP patients. OBJECTIVE: To describe the current state of medical Spanish curricula at United States medical schools. METHODS: The Latino Medical Student Association distributed an e-mail survey comprising 39 items to deans from each U.S. medical school from July 2012 through July 2014. This study was IRB-exempt. RESULTS: Eighty-three percent (110/132) of the U.S. medical schools completed the survey. Sixty-six percent (73/110) of these schools reported offering a medical Spanish curriculum. In addition, of schools with no curriculum, 32 % (12/37) planned to incorporate the curriculum within the next two years. Most existing curricula were elective, not eligible for course credit, and taught by faculty or students. Teaching modalities included didactic instruction, role play, and immersion activities. Schools with the curriculum reported that the diverse patient populations in their respective service areas and/or student interest drove course development. Barriers to implementing the curriculum included lack of time in students' schedules, overly heterogeneous student language skill levels, and a lack of financial resources. Few schools reported the use of validated instruments to measure language proficiency after completion of the curriculum. CONCLUSIONS: Growing LEP patient populations and medical student interest have driven the implementation of medical Spanish curricula at U.S. medical schools, and more schools have plans to incorporate this curriculum in the near future. Studies are needed to reveal best practices for developing and evaluating the curriculum.

Evaluating Cognitive Impairment in a Large Health Care System: The Cognition in Primary Care Program.

Background: The prevalence of Alzheimer's disease and related disorders (ADRD) is rising. Primary care providers (PCPs) will increasingly be required to play a role in its detection but lack the training to do so. Objective: To develop a model for cognitive evaluation which is feasible in primary care and evaluate its implementation in a large health system. Methods: The Cognition in Primary Care Program consists of web-based training together with integrated tools built into the electronic record. We implemented the program among PCPs at 14 clinics in a large health system. We (1) surveyed PCPs to assess the impact of training on their confidence to evaluate cognition, (2) measured the number of cognitive assessments they performed, and (3) tracked the number of patients diagnosed with mild cognitive impairment (MCI). Results: Thirty-nine PCPs completed the training which covered how to evaluate cognition. Survey response rate from those PCPs was 74%. Six months after the end of the training, they reported confidence in assessing cognition (mean 4.6 on 5-point scale). Cognitive assessments documented in the health record increased from 0.8 per month before the training to 2.5 in the six months after the training. Patients who were newly diagnosed with MCI increased from 4.2 per month before the training to 6.0 per month in the six months after the training. Conclusions: This model for cognitive evaluation in a large health system was shown to increase cognitive testing and increase diagnoses of MCI. Such improvements are essential for the timely detection of ADRD.

Multistable Protocells Can Aid the Evolution of Prebiotic Autocatalytic Sets.

We present a simple mathematical model that captures the evolutionary capabilities of a prebiotic compartment or protocell. In the model, the protocell contains an autocatalytic set whose chemical dynamics is coupled to the growth-division dynamics of the compartment. Bistability in the dynamics of the autocatalytic set results in a protocell that can exist with two distinct growth rates. Stochasticity in chemical reactions plays the role of mutations and causes transitions from one growth regime to another. We show that the system exhibits 'natural selection', where a 'mutant' protocell in which the autocatalytic set is active arises by chance in a population of inactive protocells, and then takes over the population because of its higher growth rate or 'fitness'. The work integrates three levels of dynamics: intracellular chemical, single protocell, and population (or ecosystem) of protocells.

Hypertension Control Cascade and Regional Performance in India: A Repeated Cross-Sectional Analysis (2015-2021).

Background The weak control cascade of hypertension from the time of screening till the attainment of optimal blood pressure (BP) control is a public health challenge, particularly in resource-limited settings. The study objectives were to (1) estimate the change in the rate of prevalence of hypertension, the yield of newly diagnosed cases, initiation of treatment, and attainment of BP control in the age group 15 to 49 years; (2) ascertain the magnitude and predictors of undiagnosed hypertension, lack of initiation of treatment, and poor control of those on antihypertensive therapy; and (3) estimate the regional variation and state-level performance of the hypertension control cascade in India. Methodology We analyzed demographic and health surveillance (DHS) data from India's National Family Health Survey Fifth Series (NFHS-5), 2019-2021, and NFHS-4 (2015-2016). The NFHS-5 sample comprised 695,707 women and 93,267 men in the age group of 15 to 49 years. Multiple logistic regressions were performed to find the associated predictors, and respective adjusted odds ratios (aORs) were reported. Results The prevalence of hypertension (cumulative previously diagnosed and new cases) among individuals aged 15 to 49 years was 22.8% (22.6%, 23.1%; n = 172,532), out of which 52.06% were newly diagnosed cases. In contrast, in NFHS-4, the prevalence of hypertension among individuals aged 15 to 49 years was 20.4% (20.2%, 20.6%; n = 153,384), of which 41.65% were newly diagnosed cases. In NFHS-5, 40.7% (39.8% and 41.6%) of the previously diagnosed cases were on BP-lowering medications compared to 32.6% (31.8%, 33.6%) in NFHS-4. Furthermore, in NFHS-5, controlled BP was observed in 73.7% (72.7% and 74.7%) of the patients on BP-lowering medication compared to 80.8% (80.0%, 81.6%) in NFHS-4. Females compared to males (aOR = 0·72 and 0·007), residents of rural areas (aOR = 0·82 and 0·004), and those belonging to the socially disadvantaged groups were not initiated on treatment despite awareness of their hypertension status indicative of poor treatment-seeking behavior. Furthermore, increasing age (aOR = 0·49, P < 0·001), higher body mass index (aOR = 0·51, P < 0·001), and greater waist-to-hip ratio (aOR = 0·78, P = 0·047) were associated with uncontrolled hypertension in patients on antihypertensive drug therapy. Conclusions Hypertension control cascade in India is largely ineffectual although screening yield and initiation of antihypertensive treatment have improved in NFHS-5 compared to NFHS-4. Identification of high-risk groups for opportunistic screening, implementing community-based screening, strengthening primary care, and sensitizing associated practitioners are urgently warranted.

Quality of sleep and disability associated with headache: migraine versus tension-type headache: A comparative study.

Background: One of the commonest and most frequently said, quoted and understood by even the least educated elements of our society is the neurological symptom of headache. The commonly diagnosed and studied headaches are Migraine and Tension type headache [TTH]. Headache has the power to reduce the very essence of a peaceful life and produce a disability in a person. Aims and Objectives: The aim of our study is to approach the subject with view of correlation of quality of sleep with the disability associated with migraine and compare it to TTH. Materials and Methods: For the same a cross-sectional study design was adopted and a consecutive sampling procedure was adopted. The sample was subjected to basic socio-demography, VAS, PSQI and HDI. Statistical analysis was done on the collected data. Results: Based on scales the results were evaluated using appropriate statistical methods. It was observed that there was a higher female preponderance in both migraine and TTH, there was severe disability associated and both headaches cause poor sleep quality. Conclusion: The current study concludes that headache is a debilitating illness which causes significant disability to a person.

Pulmonary haemorrhage and extensive arterial thrombosis with anabolic steroid abuse.

Anabolic-androgenic steroids (AASs) are commonly implicated in thromboembolic events but rarely cause diffuse alveolar haemorrhage. We report the case of a Caucasian man in his late 40s who was consuming supratherapeutic doses of AAS and presented with shortness of breath and haemoptysis. Chest imaging showed bilateral patchy infiltrates in the lungs with diffuse blood throughout the airways on bronchoscopy. Extensive infectious and autoimmune workup were unremarkable. The patient then developed right foot ischaemia and was found to have extensive aortic and bilateral lower extremity arterial thrombosis. Anticoagulation was attempted despite haemoptysis. Thrombectomy procedures were unsuccessful and the patient eventually developed worsening rhabdomyolysis requiring intubation and bilateral amputation. His clinical condition continued to worsen and he passed away 10 days after admission. This case highlights the rare synchronous occurrence of two life-threatening complications secondary to anabolic steroid abuse which can pose a significant diagnostic and therapeutic challenge for clinicians.

To evaluate serum cortisol levels in patients with alcohol withdrawal delirium v/s patients with delirium due to any other disorder.

Background: Delirium is an acute confusional state characterized by changes in the mental status, level of consciousness, impaired cognition, and inattention. It can develop within hours or days. Cortisol release from the hypothalamic-pituitary-adrenal axis (HPA) is vital for the host survival in stress. Biomarkers are used as an indicator of pathogenic processes or to assess the responses to a therapeutic intervention. To improve delirium recognition and care, investigators have identified possible biomarkers that may help in diagnosing individuals with delirium, assessing the severity of delirium. Cortisol has been suggested as biomarker for the diagnosis of delirium. Aims and Objectives: To evaluate and compare levels of serum cortisol in patients with alcohol withdrawal delirium with delirium due to other disorders. Materials and Methods: It was a cross-sectional prospective observational study. A total of 30 patients in Group A and 32 in Group B were included. The participants were evaluated based on delirium rating scale (DRS). Results: It was seen that in alcohol withdrawal delirium group, there was significant positive correlation between DRS score and serum cortisol level, i.e., with increase in DRS score, there was increase in serum cortisol levels and vice versa. Conclusion: Serum cortisol levels are associated and directly correlate with the occurrence and severity of delirium. Further studies are needed to elucidate the implications of this association for diagnosis and treatment.

Cannabis Use: An Uncommon Cause of Hypokalemia-Induced Acute Paralysis.

Severe hypokalemia can have life-threatening complications such as significant muscle weakness, ileus, rhabdomyolysis, and respiratory failure. Here, we report a case of a 33-year-old male who presented with worsening lower extremity weakness and falls after smoking marijuana for six months. Initial labs showed severe hypokalemia. EKG was remarkable for a first-degree AV block, widened QRS complex, and ST segment depression. Intravenous potassium replacement resulted in complete resolution of lower extremity motor weakness. Our case highlights the underdiagnosed association of marijuana use with clinically significant hypokalemia and the rare presentation of severe hypokalemia with acute paralysis.

SAEM GRACE: Dopamine antagonists and topical capsaicin for cannabis hyperemesis syndrome in the emergency department: A systematic review of direct evidence.

BACKGROUND: Adults with cannabis hyperemesis syndrome (CHS) are increasingly presenting to the emergency department (ED), and this systematic review will evaluate the direct evidence on the effectiveness of capsaicin and dopamine antagonists in its clinical management. METHODS: A bibliographic search was conducted to address the following population-intervention-control-outcome (PICO) question: (P) adults >18 years old with a diagnosis of acute CHS presenting to the ED; (I) dopamine antagonists (e.g., haloperidol, droperidol) and topical capsaicin; (C) usual care or no active comparator; and (O) symptoms improvement/resolution in ED, ED length of stay, admission rate, ED recidivism, need for rescue medication, and adverse events. This systematic review was conducted in accordance with PRISMA reporting recommendations. RESULTS: From 53 potentially relevant articles, seven articles were included: five observational studies and two randomized controlled trials, including a total of 492 patients. Five of these studies evaluated the efficacy of capsaicin cream (n = 386), and two examined dopamine antagonists (haloperidol, droperidol; n = 106). There was mixed evidence for the efficacy of capsaicin for reducing nausea and emesis. Both studies evaluating dopamine antagonists detected clinical benefit to usual care or no active comparator. CONCLUSIONS: There is limited direct evidence on the efficacy of dopamine antagonists or capsaicin for treating CHS in the ED. Current evidence is mixed for capsaicin and potentially beneficial for dopamine antagonists. Because of the small number of studies, small number of participants, lack of standardization of treatment administration, and risk of bias of the included studies, methodologically rigorous trials on both types of intervention are needed to directly inform ED management of CHS.

Leveraging natural language processing to augment structured social determinants of health data in the electronic health record.

OBJECTIVE: Social determinants of health (SDOH) impact health outcomes and are documented in the electronic health record (EHR) through structured data and unstructured clinical notes. However, clinical notes often contain more comprehensive SDOH information, detailing aspects such as status, severity, and temporality. This work has two primary objectives: (1) develop a natural language processing information extraction model to capture detailed SDOH information and (2) evaluate the information gain achieved by applying the SDOH extractor to clinical narratives and combining the extracted representations with existing structured data. MATERIALS AND METHODS: We developed a novel SDOH extractor using a deep learning entity and relation extraction architecture to characterize SDOH across various dimensions. In an EHR case study, we applied the SDOH extractor to a large clinical data set with 225 089 patients and 430 406 notes with social history sections and compared the extracted SDOH information with existing structured data. RESULTS: The SDOH extractor achieved 0.86 F1 on a withheld test set. In the EHR case study, we found extracted SDOH information complements existing structured data with 32% of homeless patients, 19% of current tobacco users, and 10% of drug users only having these health risk factors documented in the clinical narrative. CONCLUSIONS: Utilizing EHR data to identify SDOH health risk factors and social needs may improve patient care and outcomes. Semantic representations of text-encoded SDOH information can augment existing structured data, and this more comprehensive SDOH representation can assist health systems in identifying and addressing these social needs.

Integrating patient voices into the extraction of social determinants of health from clinical notes: ethical considerations and recommendations.

Identifying patients' social needs is a first critical step to address social determinants of health (SDoH)-the conditions in which people live, learn, work, and play that affect health. Addressing SDoH can improve health outcomes, population health, and health equity. Emerging SDoH reporting requirements call for health systems to implement efficient ways to identify and act on patients' social needs. Automatic extraction of SDoH from clinical notes within the electronic health record through natural language processing offers a promising approach. However, such automated SDoH systems could have unintended consequences for patients, related to stigma, privacy, confidentiality, and mistrust. Using Floridi et al's "AI4People" framework, we describe ethical considerations for system design and implementation that call attention to patient autonomy, beneficence, nonmaleficence, justice, and explicability. Based on our engagement of clinical and community champions in health equity work at University of Washington Medicine, we offer recommendations for integrating patient voices and needs into automated SDoH systems.