Assessment of the phenotypic severity of hemophilia A: using rotational thromboelastometry (ROTEM) and APTT-clot waveform analysis.

BACKGROUND: Hemophilia A (HA) is an X-linked inherited bleeding disorder caused by reduced factor VIII (FVIII) levels. Approximately 10-15% of patients with severe HA (SHA) do not present with the anticipated bleeding pattern. Here, we assessed the phenotypic severity of hemophilia A using rotational thromboelastometry (ROTEM) and activated partial thromboplastin time-clot waveform analysis (APTT-CWA). METHODS: Patients diagnosed with hemophilia A were enrolled. Clinical phenotype assignment was performed according to the published literature, and patients were classified into four phenotypic subgroups. The whole blood sample was first run on ROTEM in INTEM mode using platelet-poor plasma, APTT was run, and the APTT-CWA graph was simultaneously recorded. RESULTS: A total of 66 patients were recruited for this study. Statistically significant differences were observed between the four phenotypically categorized groups using ROTEM and APTT-CWA. On comparing patients with mild/moderate-to-severe phenotypes (Group II) with SHA without inhibitors (Group IV), no significant difference was found for all parameters of ROTEM or APTT-CWA. The MCF, MA30, MAXV, and Alpha angle values using ROTEM were found to be the lowest in patients with SHA with inhibitors, which helped differentiate them from those with SHA without inhibitors. However, these two groups could not be differentiated using the APTT-CWA parameters. CONCLUSION: ROTEM can be used to distinguish patients with SHA with inhibitors from those with SHA without inhibitors using a combination of parameters with high sensitivity and specificity. However, APTT-CWA cannot be used to differentiate these patient groups.

Acute panmylelosis with myelofibrosis - A rare case report with review of literature.

ABSTRACT: Acute panmyelosis with myelofibrosis (APMF) corresponds to <1% cases of acute myeloid leukemia, which could be an underestimation due to missed diagnosis. Due to its rapidly fatal course, it warrants a timely and correct diagnosis. We present a case of a 44-year male who came with a short history of fever, generalised weakness, revealed pancytopenia with occasional circulating blast in the peripheral blood smear. Bone marrow aspirate was dry tap,biopsy revealed panmyelosis with myelofibrosis with increased (22%) blasts. Flowcytometric immunophenotyping, cytogenetics and molecular tests were undertaken. Together with clinical details, immunophenotypic profile, cytogenetics and molecular studies, the diagnosis of Acute panmyelosis with myelofibrosis was made and managed accordingly. 32 The WHO 2017 describes APMF as an acute panmyeloid proliferation with increased blasts (≥20% in the bone marrow or peripheral blood) and accompanying marrow fibrosis. APMF is rare with poor prognosis thus, must be differentiated especially from Acute megakaryoblastic leukemia to arrive at the correct diagnosis which will help reduce/prevent the early mortality by providing timely chemotherapy followed by upfront hemopoietic stem cell transplantation.

The effect of psychological factors on financial behaviour among older Australians: Evidence from the early stages of COVID-19 pandemic.

The current study investigated the association between psychological factors and financial behaviour during the COVID-19 pandemic in older people. Older people were chosen compared to other age groups because of the relatively greater impact in this age group of suboptimal financial decisions on future financial wellbeing. We hypothesised that the psychological factors facilitating general wellbeing during the COVID-I9 pandemic, i.e., positive mental wellbeing, hope, and positive coping, will have positive effects on financial behaviour. Based on telephone interviews, 1501 older Australians (Men = 750 and Women = 751; 55-64y = 630; > 65y = 871) completed an omnibus questionnaire examining coping, hope, mental wellbeing, and financial behaviour. Data was analysed using logistic regression and an ordinary and two-stage least square frameworks. Analyses revealed that the psychological factors identified as facilitating general wellbeing during the COVID-I9 pandemic also facilitated positive financial behaviour with hope and mental wellbeing emerging as significant determinants. Based on weightings from principal component analysis, one item each from the hope and mental wellbeing scale with eigenvalues > 1 were found to be robust predictors of positive financial behaviours. In conclusion, the findings support the assumption that the psychological factors associated with general wellbeing during the COVID-19 pandemic are also associated with positive financial behaviour. They further raise the possibility that single hope and positive mental well-being items can also be used to monitor psychological health and predict financial behaviour in older people and, in particular, at times of crisis. The latter may be useful measures for government to monitor psychological and financial wellbeing and inform policy for supporting older people at times of crisis.

Online Interactive Flipped Classroom Teaching in Pediatrics for Medical Undergraduates.

OBJECTIVES: To introduce online flipped classroom teaching for medical undergraduates in Pediatrics and to assess students' engagement and satisfaction with the students and faculty with the flipped classroom teaching method. METHODS: An interventional education study was conducted on online flipped classrooms for final-year medical undergraduates. The core team of faculty members was identified, students and faculty were sensitized, and pre-reading material and feedback forms were validated. Students were engaged using the Socrative app, and feedback from students and faculty was collected using Google Forms. RESULTS: One hundred sixty students and six faculty members participated in the study. During the scheduled class, 91.9% of students were engaged. The majority of the students strongly agreed that the flipped classroom was interesting (87.2%) and interactive (87%) and developed an interest in the subject of Pediatrics (86%). Faculty were also motivated to adopt this method. CONCLUSION: The present study revealed that introducing flipped classroom strategy in an online model improved students' engagement and increased their interest in the subject.

Depression, Anxiety, and Parenting Stress among Mothers of Children with West Syndrome.

The present cross-sectional study was designed to determine the prevalence of depression, anxiety, and parenting stress in mothers of children aged 6 mo to 5 y with West syndrome compared to mothers of healthy children. The enrolled mothers were subjected to interview-based administration of the Hamilton Anxiety Scale (HAS), Beck Depression Inventory (BDI-II), and Parenting Stress Scale (PSS). Maternal anxiety [HAM score: 9 (5, 14) vs. 1 (0, 2.2); p < 0.01], depression [BDI score: 11 (7, 19) vs. 1 (0, 3); p < 0.01], and parental stress [PSS score: 40 (32, 45) vs. 22 (20, 24); p < 0.01] were significantly higher among mothers of children with West syndrome when compared to controls. Logistic regression revealed maternal education to be a significant predictor of depression among mothers of children with West syndrome. Anxiety, depression, and parental stress were higher among mothers of children with West syndrome and they should be additionally screened.

Clinical profile of children with West syndrome: A retrospective chart review.

BACKGROUND: This study was intended to document the clinical profile and treatment outcome of West syndrome in children attending a tertiary care centre in Northern India. METHODS: Data were collected by a retrospective chart review of children diagnosed with West syndrome between January 2017 to January 2018. Information was recorded pertaining to the age at onset and presentation, etiology, and associated co-morbidities; results of electroencephalography (EEG) and neuroimaging; treatment given; and final outcome. The following drugs were used for treatment: ACTH (n = 7), prednisolone (n = 17), vigabatrin (n = 25), sodium valproate (n = 28), clonazepam (n = 30), and levetiracetam (n = 13) and modified Atkins diet (n = 7). The response was categorized as spasm cessation, partial improvement (>50% improvement), or no improvement. RESULTS: Records of 30 children (21 boys) were analyzed. The median (IQR) age at onset was 4 (3, 6.5) months. The median (IQR) lag time to treatment was 5 (2,14) months. Eight (26%) were premature, 2 (7%) were small for gestational age, birth asphyxia in 56%, neonatal encephalopathy in 62%. EEG findings were hypsarrhythmia in 13 (43.3%) children and modified hypsarrhythmia in 9 (30%) children. MRI finding was periventricular leukomalacia (54.1%), cystic encephalomalacia (13.8%), normal MRI (20.7%) and one had arrested hydrocephalus. There was no improvement with valproate (93%), clonazepam (89%), levetiracetam (78%). Cessation of spasm was achieved with vigabatrin (28%), prednisolone (38.2%), ACTH (42.8%). Hypsarrhythmia resolved with improvement in of background and other epileptiform abnormalities in 17 children. CONCLUSION: The present research highlights favourable response of West syndrome to oral steroids, vigabatrin and ACTH with limited role of conventional antiepileptic drugs like sodium valporate, levetiracetam and clonazepam. Primary care physician plays a vital role in early recognition and treatment of epileptic spasm.

Flipped classroom versus traditional lecture in training undergraduates in pediatric epilepsy.

INTRODUCTION: Pedagogical constructs such as flipped classroom are used to engage students in the learning process by their active participation. The aim of the present study was to compare the two models of flipped classroom and traditional lecture in training undergraduates in pediatric epilepsy. METHODS: The study was conducted among the 3rd-year undergraduate medical students. They were divided to either of Group I or II. Pediatric epilepsy was taught in two parts (clinical diagnosis and management). Group I received Part A as traditional lecture and Part B as the flipped classroom and the reverse for Group II. The difference in posttest and pretest scores was compared between two groups for each part. RESULTS: There was a significant increase in posttest scores when compared to pretest scores in both the groups. Mean (standard deviation [SD]) difference in scores for epilepsy diagnosis was comparable in Group I (3.33 [2.3]) and Group II (2.46 [2.17]) (P = 0.16). Mean (SD) difference in scores for epilepsy management was significantly higher in Group I (3.41 [2.09]) when compared to Group II (1.30 [1.84]) (P < 0.01). CONCLUSION: Flipped classroom model resulted in better scores than the traditional teaching method for training undergraduates in the management of epilepsy in children. This teaching-learning method could be adopted in training of primary care physicians.

Evaluation of multiparametric flow cytometry in diagnosis & prognosis of myelodysplastic syndrome in India.

Background & objectives: Diagnosis of myelodysplastic syndromes (MDS) is subjective in low-grade cases with <5 per cent blasts or <15 per cent ring sideroblasts. Flow cytometry (FCM) has been used to diagnose MDS; but, it still has only an adjunctive role. This study was conducted to evaluate the role of FCM to diagnose MDS and correlate the number of aberrancies with revised international prognostic scoring system (R-IPSS). Methods: This study included 44 consecutive clinically suspected cases of MDS with refractory cytopenia(s) and 10 controls. Patients were divided into two groups: (i) proven MDS cases (n=26), and (ii) suspected MDS (n=18). Ogata quantitative approach, pattern analysis and aberrant antigen expression were studied. Results: Ogata score ≥2 correctly diagnosed 80.7 per cent (21/26) while aberrant antigen and pattern analysis with flow score of ≥3 could diagnose 92.3 per cent (24/26) patients with proven MDS. Combination of both with flow score ≥3 could diagnose 100 per cent patients. Eight patients in suspected MDS group with persistent cytopenia on follow up were labelled as probable MDS. Ogata score ≥2 was present in 5 of 8 and pattern analysis score ≥3 was present in six probable MDS patients. Combination of both with flow score ≥3 was present in seven of eight patients. Spearman's correlation between Ogata score and R-IPSS, pattern analysis and R-IPSS and combination of both scores and R-IPSS showed significant positive correlation in proven MDS as well as when proven and probable MDS patients were combined. Interpretation & conclusions: Our results showed that combined Ogata approach and pattern analysis, demonstration of ≥3 aberrancies in >1 cell compartment could diagnose most MDS patients. Patients with high flow scores had high R-IPSS scores. Patient with flow score ≥3 and borderline cytomorphology should be observed closely for the development of MDS.

Do managed exchange rates and monetary sterilization encourage capital inflows?

Economies with exchange rate pegs generally attract higher capital inflows either through lower transaction costs of trade and finance, or by encouraging investors to exploit any interest differentials, or where foreign exchange (FX) interventions are sterilized, any previous interest differentials are preserved. This paper examines these relationships using FDI, portfolio and bank inflows for 28 emerging market economies. We find that greater fixity of the exchange rate and sterilized intervention can potentially encourage capital inflows, and that the effect is magnified when combined. Further, we find that the effect differs by region, and it is larger for higher inflows.

A Prospective, Cross Sectional Study of PNH Clone in MDS Patients Using High Sensitivity Flowcytometry: A Single Center Experience.

Subclinical PNH can be present in patients with bone marrow failure like aplastic anemia and myelodysplastic syndrome (MDS). Such clone may have prognostic and therapeutic implications. In literature around 1-10% MDS cases have shown a PNH clone, however, data from India is relatively scarce. A high sensitivity PNH assay was employed using a single tube combination of FLAER, CD157, CD64, CD15 and CD45 antibodies in adult patients of MDS at presentation. A clone size of  > 0.01% was taken as significant. A total of 30 patients were included. PNH clone was present in 30% cases. Correlation done between PNH clone size and LDH values showed moderately positive correlation (r = 0.735, p = 0.001, r2 = 0.541). As per this study a LDH cut off of 247 IU is likely to predict a PNH clone (> 1%) with moderate sensitivity and specificity. High sensitivity PNH assay is able to detect small PNH clone. Calculating the cut-off of LDH to predict PNH positivity can help us judiciously prescribe this test in MDS patients in resource constrained settings.

Acute Cerebellitis as a Rare Treatable Cause of Obstructive Hydrocephalus.

Acute cerebellitis commonly presents as acute ataxia in children. Rarely, it can result in obstructive hydrocephalus. We report a 10-year-old boy with Mycoplasma infection-associated acute cerebellitis and obstructive hydrocephalus that responded well to conservative management with no residual neurological deficit. Wide recognition of this treatable clinical entity among neurologist would avert unnecessary investigations and ensure rationale management.

Evaluation of high-fluorescence body fluid (HF-BF) parameter as a screening tool of malignancy in body fluids.

INTRODUCTION: Automated body fluid (BF) analysis is gradually replacing the traditional methods of cell counting in all BFs. This study was done to analyze the high-fluorescence (HF)-BF parameter generated on Sysmex XN-1000 and study its correlation with the presence of malignant cells in the body fluids. A correlation between manual and automated differential counts was also done. MATERIALS AND METHODS: A total of 1985 samples including 797 ascitic fluids (AF), 532 pleural fluids (PF), and 656 cerebrospinal fluids (CSF) were run on Sysmex XN-1000 in BF mode and cytopathology was available for 924 BFs including 389 AF, 379 PF, and 156 CSF. Both manual and automated methods were used for cell differential and cell morphology. RESULTS: Of the 924 samples with corresponding cytopathology, malignancy was found in 59 samples. The HF-BF%/100 WBCs (24.8 ± 72.5) and HF-BF#/µL (329.86 ± 932.35) for malignant BF samples were found to be significantly higher than the nonmalignant samples (4.41 ± 8.1) and (19.57 ± 61.91), respectively. Receiver-operator-characteristic curve cutoffs for all BF for percentage and absolute HF-BF were 2.85%/100 WBCs and >12/µL. A good correlation was found between the manual and automated WBC differential counts in all fluids except CSF with total count < 5/µL. CONCLUSIONS: BFs can be reliably analyzed on automated analyzers. HF-BF parameter is helpful in identifying malignant samples but cannot be totally relied upon. If HF-BF%/# are above the lab-generated cutoffs, microscopy should be done. A complete validation study on HF-BF parameter in BF mode is desired to set the standards for the analysis of serious effusions.

Aspirin and Clopidogrel Resistance in Indian Patients with Ischemic Stroke and its Associations with Gene Polymorphisms: A Pilot Study.

INTRODUCTION: Antiplatelet resistance is one of the urgent issues in current stroke care. One-third to one-half of the patients who experience a recurrent stroke is already on antiplatelet medications. We studied resistance to aspirin and clopidogrel in Indian stroke patients and its association with gene polymorphisms. METHODS: Platelet function testing by light transmission aggregometry was performed on 65 patients with ischemic stroke who were stable on dual antiplatelet therapy (clopidogrel 75 mg OD and aspirin 75 mg OD) along with 65 age-matched controls. Aspirin resistance was considered as mean platelet aggregation ≥70% with 10 µM adenosine diphosphate (ADP) and ≥20% with 0.75 mM arachidonic acid. Clopidogrel resistance was defined as <10% decrease from the baseline in platelet aggregation in response to ADP 10 µM and semi-response as <30% decrease from the baseline. Polymorphisms CYP2C19 * 2 and GPIIb/IIIa (PLA1/A2) were genotyped by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: We found 64.6% (42/65) patients with inadequate response to clopidogrel (15.4% [10/65] resistant and 49.2% [32/65] semi-responders) and 4.6% (3/65) patients with inadequate response to aspirin (3.1% [2/65] resistant and 1.5% [1/65] semi-responder). The frequency of CYP2C19*2 mutant genotype was significantly higher in clopidogrel nonresponders compared to responders (P = 0.014). Clopidogrel nonresponsiveness was much higher in small vessel stroke. CONCLUSION: Unlike aspirin, a high proportion of nonresponders to clopidogrel was identified. In an interim analysis on 65 Indian patients, a significant association was found between CYP2C19*2 and clopidogrel nonresponsiveness.

Utility of mean sphered cell volume and mean reticulocyte volume for the diagnosis of hereditary spherocytosis.

INTRODUCTION: Hereditary spherocytosis (HS) is the most common congenital hemolytic anemia, characterized by anemia, jaundice, and splenomegaly. The diagnosis of HS relies on symptoms of hemolysis, a family history of HS, and a positive laboratory test which is usually the osmotic fragility test (OFT). We conducted a study to assess the utility of mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), mean sphered cell volume (MSCV), and mean reticulocyte volume (MRV) in the diagnosis of HS and if these are helpful in distinguishing cases of HS from immune hemolytic anemia. METHODS: A total of 102 patients suspected to have HS were enrolled. In addition 10 cases of immune hemolytic anemia (IHA) were included in the study and performance of the above screening tests was evaluated. The diagnosis of HS was based on incubated OFT, eosin 5'-maleimide (EMA) dye binding test, and flowcytometric OFT. RESULTS: A total of 29 patients were diagnosed as having HS. The sensitivity and specificity for diagnosis HS by MCHC > 35 g/dL was 44.82%, and ΔMCV-MSCV > 10 fL has a sensitivity and specificity of 82.75% and 95.9% for diagnosis of HS. Using an algorithm of ΔMCV-MSCV > 10 fL and ΔMRV-MSCV < 25, for the differentiation of HS from IHA had sensitivity of 68.9% and specificity of 98.8%.

Predictors for critical care admission among children presenting to emergency department with recurrent wheezing.

CONTEXT: Children with recurrent wheezing contribute to a significant burden of inpatient hospital admission in developing countries. However, many patients could be managed at home following a short observation period in emergency unit. AIM: This study aimed to determine the predictors of critical care admission in a population of children aged 6 months to 2 years attending pediatric emergency department (ED) for recurrent wheezing. SETTING AND DESIGN: This is a case-control study conducted in pediatric ED of a tertiary care center in North India. PATIENTS AND METHODS: Demographic and clinical details were recorded for children aged 6 months to 2 years who presented to ED for "recurrent wheezing" within 48 h of onset of symptoms. Those who were admitted to critical care unit were considered cases and those who were discharged within 6 h of stay at short observation units of ED were considered controls. STATISTICAL ANALYSIS: Logistic regression model was used to determine which of the various demographic and clinical factors best predicted the need for critical care admission. RESULTS: The cases (n = 58) had significantly higher number of emergency visits in the preceding 1 month (P = 0. 018), had more episodes of wheezing in the last 3 months (P = 0.025), had higher respiratory rate (P < 0.001), and had higher clinical severity score (P < 0.001) when compared to control (n = 58) group. Logistic regression model revealed incomplete immunization status of children (P = 0.005) to be a significant risk factor that determine the need for critical care admission. CONCLUSION: The present cross-sectional study with limited sample size revealed incomplete immunization status of children to be a significant risk factor that determined the need for critical care admission among children below 2 years of age presenting to ED with recurrent wheezing.

A Case of Deep Vein Thrombosis and Intracranial Sinus Thrombosis: Possible rare complications of childhood abdominal tuberculosis.

Severe pulmonary tuberculosis (TB) complicated by deep vein thrombosis (DVT) in adults has been reported previously in the medical literature; however, childhood extrapulmonary TB complicated by DVT is rare. We report a 13-year-old girl who presented to the Department of Pediatrics at the Postgraduate Institute of Medical Sciences in Rohtak, India, in 2012 with abdominal TB complicated by DVT and intracranial sinus thrombosis. She was treated with a course of four antitubercular drugs and short-term anticoagulation therapy with a positive outcome over the next six months. To the best of the authors' knowledge, no previous reports have yet suggested a possible association between childhood TB and intracranial sinus thrombosis.

Clinicopathological correlation of Bcl-2 oncoprotein expression in oral precancer and cancer.

UNLABELLED: Oral squamous cell carcinoma is the most common malignant tumor of the oral cavity. Normally the death of cell and the growth are active processes and depend not only on external factors but also on the expression of genes such as Bcl-2, which activate and inhibit apoptosis. The term Bcl-2 is an acronym for B-cell lymphoma/leukemia-2 genes. It has been reported that there is deregulation of Bcl-2 expression during progression from oral epithelial dysplasia to squamous cell carcinoma. Expression of this oncoprotein can be detected by immunohistochemistry. AIMS AND OBJECTIVES: An attempt was made to evaluate Bcl-2 oncoprotein expression in patients with oral precancer and cancer. MATERIALS AND METHODS: A selective prospective clinical and immunohistochemical study. Clinicopathological examination was correlated with immunohistochemical findings. The immunolocalization of Bcl-2 protein was performed using the labeled streptavidin biotin method. To visualize the reaction, 3,3-diaminobenzidine was used. RESULTS: Bcl-2 expression was positive in 11 [36.66%, low Bcl-2 expression 3 (10.00%), moderate Bcl-2 expression 7 (23.33%), and high Bcl-2 expression 1 (3.33%)] oral cancer cases and 14 [87.50%, low expression 8 (50%), moderate expression 6 (37.50%)] precancer cases. CONCLUSION: On the basis of the results of our study, we conclude that positive Bcl-2 expression may be an indicator of poor prognosis in oral cancer and precancer.