Effect of Sacubitril/Valsartan on Cognitive Function in Patients With Heart Failure With Preserved Ejection Fraction: A Prespecified Analysis of PARAGON-HF.

BACKGROUND: A hypothetical concern has been raised that sacubitril/valsartan might cause cognitive impairment because neprilysin is one of several enzymes degrading amyloid-ß peptides in the brain, some of which are neurotoxic and linked to Alzheimer-type dementia. To address this, we examined the effect of sacubitril/valsartan compared with valsartan on cognitive function in patients with heart failure with preserved ejection fraction in a prespecified substudy of PARAGON-HF (Prospective Comparison of Angiotensin Receptor Neprilysin Inhibitor With Angiotensin Receptor Blocker Global Outcomes in Heart Failure With Preserved Ejection Fraction). METHODS: In PARAGON-HF, serial assessment of cognitive function was conducted in a subset of patients with the Mini-Mental State Examination (MMSE; score range, 0-30, with lower scores reflecting worse cognitive function). The prespecified primary analysis of this substudy was the change from baseline in MMSE score at 96 weeks. Other post hoc analyses included cognitive decline (fall in MMSEs score of ≥3 points), cognitive impairment (MMSE score <24), or the occurrence of dementia-related adverse events. RESULTS: Among 2895 patients included in the MMSE substudy with baseline MMSE score measured, 1453 patients were assigned to sacubitril/valsartan and 1442 to valsartan. Their mean age was 73 years, and the median follow-up was 32 months. The mean±SD MMSE score at randomization was 27.4±3.0 in the sacubitril/valsartan group, with 10% having an MMSE score <24; the corresponding numbers were nearly identical in the valsartan group. The mean change from baseline to 96 weeks in the sacubitril/valsartan group was -0.05 (SE, 0.07); the corresponding change in the valsartan group was -0.04 (0.07). The mean between-treatment difference at week 96 was -0.01 (95% CI, -0.20 to 0.19; P=0.95). Analyses of a ≥3-point decline in MMSE, decrease to a score <24, dementia-related adverse events, and combinations of these showed no difference between sacubitril/valsartan and valsartan. No difference was found in the subgroup of patients tested for apolipoprotein E ε4 allele genotype. CONCLUSIONS: Patients with heart failure with preserved ejection fraction in PARAGON-HF had relatively low baseline MMSE scores. Cognitive change, measured by MMSE, did not differ between treatment with sacubitril/valsartan and treatment with valsartan in patients with heart failure with preserved ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.

Achieved dose and treatment discontinuation of candesartan in men and women with chronic heart failure: data from CHARM.

AIMS: Angiotensin receptor blockers have been shown to reduce heart failure hospitalization and cardiovascular mortality in men and women with heart failure with reduced ejection fraction (HFrEF). It is unknown whether there are differences between men and women in achieved dose and treatment discontinuation due to adverse events of candesartan. METHODS AND RESULTS: We conducted a post hoc analysis of the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. A total of 3172 men and 1106 women with HFrEF [left ventricular ejection fraction (LVEF) ≤ 40%] in New York Heart Association class II-IV were randomized to candesartan or placebo. Every 2 weeks, patients were up-titrated from 4 or 8, to16, to 32 mg once daily, unless a higher dose was contraindicated or not tolerated. Women were older (66 vs. 64 years), had a higher LVEF (29.9% vs. 28.6%), and had more hypertension (54% vs. 47%) than men. The mean achieved dose of candesartan was 21.5 ± 12.6 mg in men and 20.7 ± 12.9 mg in women (P = 0.19). In both the candesartan and placebo groups, cardiovascular death and heart failure hospitalizations were higher in men and women who achieved lower dose levels. Event rates for achieved dose levels of 0, 4 or 8, 16, and 32 mg candesartan were 20.8, 17.2, 14.0, and 10.1 per 100 person-years in men, respectively, and 23.6, 13.7, 14.0, and 9.1 per 100 person-years in women, respectively. In each of the achieved dose levels, there was no sex difference in the proportion of patients with an event, neither in the candesartan group nor in the placebo group (P-value for all > 0.05). There was no significant interaction between sex and treatment-related discontinuation for hypotension (P = 0.520), an increase in creatinine (P = 0.102), and hyperkalaemia (P = 0.905). CONCLUSIONS: In a randomized clinical trial in patients with HFrEF, men and women achieved similar doses of candesartan. Primary event rates and treatment-related discontinuation due to adverse events were also similar between men and women.

Hematological Indices for Identifying Adverse Outcomes in Children Admitted to Pediatric ICUs.

BACKGROUND: The pediatric ICU (PICU) is a specialized area where critically sick children are managed. The mortality rates in PICUs are higher in developing countries as compared to developed nations. Many of these deaths could be prevented if very sick children were identified soon after they arrived at the health facility. Hematological indices like platelet lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) have been frequently used in adults as indicators of mortality. However, their use in the pediatric population is limited due to a lack of validated reference intervals. OBJECTIVE: The objective of the study is to assess the role of hematological indices in identifying adverse outcomes in terms of mortality in children admitted to the PICU. MATERIALS AND METHODS: It is a prospective, observational study done at a tertiary care hospital. All children aged one year to 12 years admitted to the PICU were enrolled in the study. A sample for complete blood count was taken within one hour of admission to the PICU. Children who had received blood products in the last two months, those on chronic medications (>two weeks) that can affect bone marrow cellularity, and known cases of hematological disorders such as megaloblastic anemia, hematological malignancies, immune thrombocytopenia, and aplastic anemia were excluded from the study. PLR, NLR, and platelets to mean platelet volume ratio (PLT/MPV) were determined and compared among the survivors and non-survivors. RESULTS:  Out of 275 enrolled patients, 119 (43.3%) patients expired during the study period. While PLR had high sensitivity and NLR had high specificity (85.71% and 92.31%, respectively) for predicting mortality, none of these parameters had a good area under the curve (AUC) in our study. PLT/MPV of ≥32 had a sensitivity of 39.5% and a specificity of 56.41% for predicting mortality. CONCLUSIONS: Hematological parameters have been used across the world to predict ICU mortality. PLR and NLR are simple hematological biomarkers, easy to calculate, and cost-effective, and ratios are better than individual parameters. More studies and stratified samples are required to evaluate the role of hematological markers in identifying the risk of mortality in children admitted to PICUs.

Peer Support for Type 2 Diabetes Management in Low- and Middle-Income Countries (LMICs): A Scoping Review.

Background: Although there is evidence of peer support in high-income countries, the use of peer support as an intervention for cardiometabolic disease management, including type 2 diabetes (T2DM), in low- and middle-income countries (LMICs), is unclear. Methods: A scoping review methodology was used to search the databases MEDLINE, Embase, Emcare, PsycINFO, LILACS, CDSR, and CENTRAL. Results: Twenty-eight studies were included in this scoping review. Of these, 67% were developed in Asia, 22% in Africa, and 11% in the Americas. The definition of peer support varied; however, peer support offered a social and emotional dimension to help individuals cope with negative emotions and barriers while promoting disease management. Conclusions: Findings from this scopingreview highlight a lack of consistency in defining peer support as a component of CMD management in LMICs. A clear definition of peer support and ongoing program evaluation is recommended for future research.

Raised circulatory T regulatory cells in paediatric tuberculosis - An environment for bacterial persistence?

OBJECTIVES: T-regulatory cells (Tregs) restrain the Th1-mediated immune response and thus may help in persistence and dissemination of childhood Tuberculosis. This study compared the percentage of Tregs in peripheral blood of paediatric TB patients (severe and non severe) with healthy individuals by flow cytometry. METHODS: Study enrolled 40 subjects, less than 12 years along with 20 age matched healthy controls. Cases were further classified as severe TB and non severe TB. Haematological work-up and flow-cytometry for Tregs was done. Tregs were quantified as CD4CD25 high and CD4FoxP3 cells and compared in different groups using the Mann-Whitney U test. RESULTS: In cases, CD4CD25 high Tregs (%) ranged from 0.55 to 12.8 with a Mean ± SD of 3.61 ± 2.98 and CD4FoxP3 Tregs (%) ranged from 0.02 to 13.44 with a Mean ± SD of 3.56 ± 2.76. In controls, CD4CD25 high Tregs (%) ranged from 0.3 to 6.5 with a Mean ± SD of 1.29 ± 1.4 and CD4FoxP3 Tregs (%) ranged from 0.33 to 2.59 with a Mean ± SD of 1.57 ± 0.58. Thus the percentage of both CD4CD25 high and CD4FoxP3 Tregs were significantly higher in cases as compared to controls (p value, 0.001 and 0.001 respectively), however the difference was not significant between severe versus non-severe TB (p value, 0.827 and 0.880 respectively). CONCLUSION: Children with TB (both pulmonary and extra-pulmonary) demonstrate increased number of T regulatory cells as compared to healthy controls. However, the number of Tregs are not significantly different between cases with severe versus non severe TB.

Seroprotection With Three Dose vs Four Dose Schedule for Hepatitis B Vaccination in Children Living With Human Immunodeficiency Virus: Follow-up Data at 36-42 Months From a Randomized Controlled Trial.

OBJECTIVE: To compare the long-term seroprotection (anti-HBs ≥10 IU/L) in children living with HIV (CLHIV) receiving a 3- or 4-dose double-strength (20 µg) recombinant Hepatitis B virus (rHBV) vaccination. METHODS: We present anti-retroviral therapy (ART) clinic based follow-up data collected from January, 2021 to August, 2022, from CLHIV who had received either 3-dose or 4-dose double-strength (20 µg) rHBV vaccination, after 36-42 months and assessed for anti-HBs titres, naïve and memory T-helper lymphocytes, CD4 counts and HIV viral load. Children found unprotected after primary immunization, were administered a single double-strength rHBV vaccine booster dose (20 µg) and seroprotection was reassessed after 4 and 12 weeks. RESULTS: Out of 50 children initially vaccinated, 45 were followed up 36-42 months after primary immunization; median (IQR) anti-HBs titres (IU/L) were 230 (80.5 - 305.7) in the 3-dose group (n=23) and 263.5 (47.1-332.9) in the 4-dose group (n=22) (P=0.33). 19 and 20 children in the 3-dose and 4-dose group, respectively, were seroprotected (P=0.24). Anti-HBs titres at 36-42 months correlated with CD4 counts at baseline, anti-HBs titres at 1 and 6 months after completion of primary immunization and percentage of memory T-helper lymphocytes. All the five children (3-dose group: 4; 4-dose group: 1) who received rHBV vaccine booster dose attained seroprotection one-month later. CONCLUSION: Three-dose double strength rHBV vaccination schedule offers comparable seroprotection to a 4-dose double strength rHBV vaccination schedule in CLHIV receiving ART.

COVID-19 Antibody Response in Patients with Thalassemia.

Background The coronavirus disease 2019 (COVID-19) can severely affect people with comorbidities such as those with diabetes, hypertension, chronic lung disease, cancer, and hemoglobinopathies. Studies assessing the clinical characteristics and immune response to COVID-19 infection in patients with thalassemia are limited. Objectives The primary objective of the study was to study the clinical pattern and the immunoglobulin G (IgG) antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with transfusion-dependent thalassemia (TDT) compared to patients without thalassemia. The secondary objective wasto study the relationship of COVID-19 severity with IgG antibody titers. Setting, Design, and Participants This case-control study was conducted at a tertiary care hospital between January 2021 and August 2022. A total of 30 patients with TDT (mean age: 12.7 years, SD: 4.7) and 30 patients without thalassemia (mean age: 13.9 years, SD: 7) who tested positive for COVID-19 in the preceding six weeks were recruited. Methods Serum samples from the cases and controls were collected after 6, 12, and 24 weeks of COVID-19 infection for IgG antibody estimation using chemiluminescent immunoassay. Outcome variables The primary variable was comparative analysis of antibody levels and clinical profile of COVID-19 in cases and controls. The secondaryvariable was association of the severity of COVID-19 with the antibody titers produced. Results Symptomatic individuals among cases (n=12) were significantly lesser than controls (n=22) (p=0.009). The median IgG titers of cases and controls were comparable at six weeks (p=0.40), but the titers were significantly lower for cases at 12 weeks (p=0.011) and 24 weeks (p=0.006). There was significant fall in titers from 6 to 12 and 24 weeks in both the groups. The titers were not affected by COVID-19 severity and pre-existing comorbidities. Conclusion Patients with TDT manifest with mild or asymptomatic COVID-19 and mount a comparable IgG antibody response to COVID-19 akin to controls. However, this serological response could not sustain over three to six months advocating the need for protection through vaccination.

Therapeutic Response to Sublingual Methylcobalamin in Children With Vitamin B12 Deficiency Anemia.

OBJECTIVE: To evaluate the efficacy and safety of sublingual methylcobalamin for the treatment of vitamin B12 deficiency anemia in children. METHODS: A single arm intervention study was conducted between November, 2020 and April, 2022 in children aged 1-12 years with vitamin B12 deficiency anemia. Children aged 1-6 years received a tablet of methylcobalamin (1500 mcg) by sublingual route every alternate day (three doses) while those aged 7-12 years received five such doses. Thereafter, one such sublingual tablet was given weekly and all participants were followed-up for 6 weeks. RESULTS: 37 children with a mean (SD) age of 8.2 (4.1) years were treated and followed up prospectively. On day 10, no child needed rescue therapy with parenteral methylcobalamin. After 6 weeks, the mean (SD) serum cobalamin (mL) increased from 123.3 (35.5) pg/mL to 507.3 (274.2) pg/mL (P<0.001), plasma homocysteine (L) decreased from 48.9 (17.8) pg/mL to 16.3 (8.5) µmol/L (P<0.001), the mean (SD) hemoglobin increased by 2.3 (1.1) g/dL (P<0.001), and MCV decreased by 12.9 (6.8) fL (P<0.001). 67.6% children persisted to have anemia, albeit majority of them had mild or moderate anemia. There were no unsolicited side-effect reported. CONCLUSION: Sublingual methylcobalamin is effective for the treatment of vitamin B12 deficiency anemia in children; although, the duration of treatment needs to be longer than six weeks.

Clinical Characteristics and Outcomes in Patients With Heart Failure: Are There Thresholds and Inflection Points in Left Ventricular Ejection Fraction and Thresholds Justifying a Clinical Classification?

BACKGROUND: Recent guidelines proposed a classification for heart failure (HF) on the basis of left ventricular ejection fraction (LVEF), although it remains unclear whether the divisions chosen were biologically rational. Using patients spanning the full range of LVEF, we examined whether there was evidence of LVEF thresholds in patient characteristics or inflection points in clinical outcomes. METHODS: Using patient-level information, we created a merged dataset of 33 699 participants who had been enrolled in 6 randomized controlled HF trials including patients with reduced and preserved ejection fraction. The relationship between the incidence of all-cause death (and specific causes of death) and HF hospitalization, and LVEF, was evaluated using Poisson regression models. RESULTS: As LVEF increased, age, the proportion of women, body mass index, systolic blood pressure, and prevalence of atrial fibrillation and diabetes increased, whereas ischemic pathogenesis, estimated glomerular filtration rate, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) decreased. As LVEF increased >50%, age and the proportion of women continued to increase, and ischemic pathogenesis and NT-proBNP decreased, but other characteristics did not change meaningfully. The incidence of most clinical outcomes (except noncardiovascular death) decreased as LVEF increased, with a LVEF inflection point of around 50% for all-cause death and cardiovascular death, around 40% for pump failure death, and around 35% for HF hospitalization. Higher than those thresholds, there was little further decline in the incidence rate. There was no evidence of a J-shaped relationship between LVEF and death; no evidence of worse outcomes in patients with high-normal ("supranormal") LVEF. Similarly, in a subset of patients with echocardiographic data, there were no structural differences in patients with a high-normal LVEF suggestive of amyloidosis, and NT-proBNP levels were consistent with this conclusion. CONCLUSIONS: In patients with HF, there was a LVEF threshold of around 40% to 50% where the pattern of patient characteristics changed, and event rates began to increase compared with higher LVEF values. Our findings provide evidence to support current upper LVEF thresholds defining HF with mildly reduced ejection fraction on the basis of prognosis. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifiers: NCT00634309, NCT00634400, NCT00634712, NCT00095238, NCT01035255, NCT00094302, NCT00853658, and NCT01920711.

Impact of multimorbidity on mortality in heart failure with reduced ejection fraction: which comorbidities matter most? An analysis of PARADIGM-HF and ATMOSPHERE.

AIMS: Multimorbidity, the coexistence of two or more chronic conditions, is synonymous with heart failure (HF). How risk related to comorbidities compares at individual and population levels is unknown. The aim of this study is to examine the risk related to comorbidities, alone and in combination, both at individual and population levels. METHODS AND RESULTS: Using two clinical trials in HF - the Prospective comparison of ARNI (Angiotensin Receptor-Neprilysin Inhibitor) with ACEI (Angiotensin-Converting Enzyme Inhibitor) to Determine Impact on Global Mortality and morbidity in HF trial (PARADIGM-HF) and the Aliskiren Trial to Minimize Outcomes in Patients with Heart Failure trials (ATMOSPHERE) - we identified the 10 most common comorbidities and examined 45 possible pairs. We calculated population attributable fractions (PAF) for all-cause death and relative excess risk due to interaction with Cox proportional hazard models. Of 15 066 patients in the study, 14 133 (93.7%) had at least one and 11 867 (78.8%) had at least two of the 10 most prevalent comorbidities. The greatest individual risk among pairs was associated with peripheral artery disease (PAD) in combination with stroke (hazard ratio [HR] 1.73; 95% confidence interval [CI] 1.28-2.33) and anaemia (HR 1.71; 95% CI 1.39-2.11). The combination of chronic kidney disease (CKD) and hypertension had the highest PAF (5.65%; 95% CI 3.66-7.61). Two pairs demonstrated significant synergistic interaction (atrial fibrillation with CKD and coronary artery disease, respectively) and one an antagonistic interaction (anaemia and obesity). CONCLUSIONS: In HF, the impact of multimorbidity differed at the individual patient and population level, depending on the prevalence of and the risk related to each comorbidity, and the interaction between individual comorbidities. Patients with coexistent PAD and stroke were at greatest individual risk whereas, from a population perspective, coexistent CKD and hypertension mattered most.

Chemotherapy-Induced Oxidative Stress in Pediatric Acute Lymphoblastic Leukemia.

Introduction Plasma antioxidant capacity in children receiving chemotherapy decreases due to the effect of the disease and chemotherapy. Increased oxidative stress (OS) predisposes to an increased risk for chemotherapy-related toxicity and febrile neutropenic episodes. Materials and methods We conducted this case-control study in the hematology-oncology unit of the department of pediatrics of a tertiary hospital in Delhi, India, from November 2017 to March 2019 to compare OS between children with acute lymphoblastic leukemia (ALL) and healthy controls. We estimated the trends in OS as measured by the plasma total antioxidant capacity (TAC) and thiobarbituric acid reactive substance (TBARS) levels at baseline and at the completion of induction I (four weeks), induction II (eight weeks), and induction IIA-consolidation (16 weeks) phases of chemotherapy in children with ALL. We also assessed the change in OS during different phases of initial treatment and studied the association between OS and the hematological toxicity of chemotherapy (determined by the need for blood component therapy and the number of febrile neutropenic episodes) and serum cobalamin and folate levels. Results OS was significantly higher in children with ALL at diagnosis (n=23) compared to controls (n=19). The median (interquartile range (IQR)) TAC levels (mM) were significantly lower (1.21 (1.05-1.26) versus 1.28 (1.26-1.32), P=0.006), and TBARS levels (nmol/mL) were significantly higher (312.0 (216.6-398.0) versus 58.5 (46.2-67.2), P<0.001) in children with ALL at diagnosis compared to controls. OS was highest at the end of the induction I phase (four weeks) despite the patients being in clinical and hematological remission. OS at the completion of intensive chemotherapy (16 weeks) was higher than at diagnosis. A significant correlation was found between serum folate levels and TAC levels at baseline (P=0.03). Serum cobalamin levels, the need for blood component therapy, and the number of febrile neutropenic episodes did not have any association with OS. Conclusion Children with ALL had significantly higher OS compared to controls, indicating that underlying disease affects the oxidative balance unfavorably. Chemotherapy itself increases oxidative stress.

Correlation of T-regulatory Cells and Iron Status in ß-Thalassemia Major Patients.

Background The increased risk of infections in transfusion-dependent ß-thalassemia major (TDT) patients is mainly due to underlying immune dysfunction; however, its cause is largely unidentified. There is sufficient evidence to suggest immune changes due to iron deficiency; however, similar studies demonstrating the effects of iron excess on immune cells in these cases are limited. Aim and objectives To analyze the correlation between T-regulatory cells and iron stores in ß-thalassemia major patients. Methods In this study, 20 ß-thalassemia major cases and 20 healthy controls were studied for complete hemogram, iron profile, and flow cytometric immunophenotyping for CD3+, CD4+, CD8+, and T-regulatory cells markers (CD4+CD25+ and CD4+CD25+FOXP3+). Result Significantly higher levels of serum iron, ferritin, transferrin saturation, and CD4+ cell percentage were observed in cases than in controls. In 70% of cases with serum ferritin cut-off levels of less than 1000 µg/L, the T-regulatory cell marker CD4+CD25+ and serum ferritin revealed a significant moderate positive correlation (p=0.031, r=0.627). These same 70% cases also demonstrated a moderately significant positive correlation between serum iron and absolute lymphocyte count (r=0.529, p=0.042). Conclusion The results suggest that serum ferritin in excess amounts can increase T-regulatory cells, which may further alter the immune status of TDT patients; however, the absence of such a correlation in cases with serum ferritin of more than 1000 µg/L remains unanswered. It is important to understand immune system alterations as this will help provide new modalities for managing thalassemia patients in the form of immunoregulatory therapies.

Urinary cGMP (Cyclic Guanosine Monophosphate)/BNP (B-Type Natriuretic Peptide) Ratio, Sacubitril/Valsartan, and Outcomes in Heart Failure With Reduced Ejection Fraction: An Analysis of the PARADIGM-HF Trial.

BACKGROUND: The ratio of ucGMP (urinary cyclic guanosine monophosphate) to BNP (B-type natriuretic peptide) is thought to reflect the responsiveness of tissues to natriuretic peptides. METHODS: We examined the relationship between ucGMP/BNP ratio and clinical outcomes, the effect of sacubitril/valsartan, compared with enalapril, on the ucGMP/BNP ratio, and the efficacy of sacubitril/valsartan on clinical outcomes according to baseline ucGMP/BNP ratio in PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). ucGMP/BNP ratio was available at baseline (N=2031), 1 month (N=1959), and 8 months after randomization (N=1746). The primary outcome was a composite of heart failure hospitalization or cardiovascular death. RESULTS: Compared with the lowest tertile of baseline ucGMP/BNP ratio, patients in the higher tertiles had a lower risk of the primary outcome (tertile 1, reference; tertile 2, hazard ratio 0.57 [95% CI, 0.45-0.71]; tertile 3, hazard ratio, 0.54 [0.43-0.67]). Compared with baseline, the ucGMP/BNP ratio at 1 month and 8 months after randomization was higher with sacubitril/valsartan than with enalapril: ratio of geometric mean ratios at 1 month, 1.38 (95% CI, 1.27-1.51) and 8 months, 1.32 (95% CI, 1.20-1.45), and this difference was consistent across tertiles of ucGMP/BNP ratio at baseline (Pinteraction=0.19 and 0.91, respectively). The effect of sacubitril/valsartan, compared with enalapril, was consistent across tertiles of ucGMP/BNP ratio at baseline for all outcomes (Pinteraction ≥0.31). CONCLUSIONS: In patients with heart failure and reduced ejection fraction, higher ucGMP/BNP ratio was associated with better outcomes. Sacubitril/valsartan increased the ucGMP/BNP ratio, compared with enalapril, and the effect of sacubitril/valsartan on clinical outcomes was not modified by baseline ucGMP/BNP ratio. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique Identifier: NCT01035255.

A Composite Score Summarizing Use and Dosing of Evidence-Based Medical Therapies in Heart Failure: A Nationwide Cohort Study.

BACKGROUND: As heart failure therapeutic care becomes increasingly complex, a composite medical therapy score could be useful to conveniently summarize background medical therapy. We applied the composite medical therapy score developed by the Heart Failure Collaboratory (HFC) to the Danish heart failure with reduced ejection fraction population to evaluate its external validation including assessing the distribution of the score and its association with survival. METHODS: In a retrospective nationwide cohort study, we identified all Danish heart failure with reduced ejection fraction patients alive on July 1, 2018, and assessed their treatment doses. Patients were excluded if they did not have at least 365 days for up-titration of medical therapy prior to identification. The HFC score (range 0-8) accounts for use and dosing of multiple therapies prescribed to each patient. Risk-adjusted association between the composite score and all-cause mortality was examined. RESULTS: In total, 26 779 patients (mean age 71.9 years; 32% women) were identified. At baseline, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker was used in 77%, ß-blocker in 81%, mineralocorticoid receptor antagonist in 30%, angiotensin receptor-neprilysin inhibitor in 2%, and ivabradine in 2%. The median HFC score was 4. After multivariable adjustment, higher HFC scores were independently associated with lower mortality (≥median versus

Iron Profile in Term Small for Gestational Age Infants at 10 Weeks of Age and Correlation With Maternal Iron Profile : A Prospective Cohort Study.

BACKGROUND: Term small for gestational age (SGA) babies are at risk for developing iron deficiency anemia. The association between maternal and infant iron stores is not clear. OBJECTIVE: To assess proportion of term SGA neonates developing iron deficiency anemia by 10 weeks of age, and measure correlation between iron profile and hepcidin of babies at birth and at 10 weeks of age with maternal iron profile. DESIGN: Prospective cohort study conducted from November, 2018 to April, 2020. PARTICIPANTS: 120 term SGA babies and their mothers. INTERVENTION: Hemogram, iron profile and serum hepcidin (every fourth case) estimated in mother, cord blood and baby at 10 weeks. Babies developing anemia at 6 weeks detected by hemogram and ferritin were started on iron supplementation and excluded from the study. OUTCOME: Proportion of babies developing iron deficiency anemia at 10 weeks of age. RESULTS: 35 (29.2%) of 120 term SGA babies developed anemia (hemoglobin <9 g/dL) at 6 weeks. Proportion of infants who developed iron deficiency anemia (hemoglobin <9 g/dL and serum ferritin <40 µ/dL) at 6 and 10 weeks of age was 14.2% and 23.3%, respectively. No significant correlation was found bet-ween hemoglobin, iron and hepcidin of the baby in cord blood and at 10 weeks of age with that of mothers. Serum hepcidin in babies at birth (137.5 ng/mL) were higher than maternal values (128 ng/mL). CONCLUSION: A significant proportion of term SGA infants deve-loped anemia during early infancy, irrespective of maternal iron status.

Antibiotic Susceptibility, Carrier State and Predictors of Outcome of Staphylococcus aureus Infections in Hospitalized Children.

OBJECTIVES: To evaluate the antibiotic resistance pattern, clinical profile and predictors for adverse outcomes in children hospitalized due to staphylococcal infection; and the frequency of nasal and axillary carrier states in these children. METHODS: This descriptive study enrolled 100 symptomatic children (aged 1 month - 12 years) in whom S. aureus was isolated from cultures of blood, pus or cerebrospinal fluid. All samples were processed as per the Clinical and Laboratory Standards Institute (CLSI) standards. Antimicrobial susceptibility was tested using disc diffusion method; minimum inhibitory concentration (MIC) for vancomycin was measured using E strips. Predictors for poor recovery were determined by univariate and multivariable logistic regression analysis. RESULTS: Skin and soft tissue infections were the most common (47%) followed by respiratory infections (37%). Methicillin-resistant Staphylococcus aureus (MRSA) was detected in 62%, out of which 63% (39/62) were multi-drug resistant. Carrier state was present in 49% (93% MRSA); 80% were axillary carriers. High MIC (>1 µg/mL) for vancomycin was seen in 65% of patients, and was the only factor associated with poor recovery [aOR (95%CI) 5.3 (1.6,18.5); P=0.008] on multivariable logistic regression analysis. CONCLUSION: MRSA is the predominant strain in severe staphylococcal infections requiring hospitalization, and majority of them are multidrug resistant. High MIC to vancomycin among S. aureus is an emerging concern.

Effect of Antiretroviral Therapy on Neutrophil Oxidative Burst in Children.

OBJECTIVE: To ascertain the effect of human immunodeficiency virus (HIV) infection, as well as, antiretroviral therapy (ART) on neutrophil oxidative burst in children. METHODS: Fifty-five children living with HIV infection (30 receiving ART for ≥ 2 y, 25 treatment-naïve) and 30 healthy controls, aged 18 mo-18 y, were assessed for hemogram and neutrophil oxidative burst. The treatment-naïve children were followed up and the above tests were repeated after 6 mo of ART. RESULTS: Mean (SD) serum MPO activity at 6 mo after ART [32.1 (± 19.9) U/L] was comparable to that at disease onset [17.2 (± 23.0) U/L], although it was significantly higher compared to that in children on ART ≥ 2 y [13.3 (± 15.8) U/L] and controls [12.1 (± 11.9) U/L]. Median fluorescence intensity (MFI) of unstimulated DHR was highest at 6 mo after ART and in the treatment-naïve group, which was significantly higher than in the controls, as well as, children receiving ART ≥ 2 y. Stimulation index was highest in the control group [442.4 (341.9-562.9)], which was comparable to that in children on ART ≥ 2 y [304.2 (153.2-664.8)], but was significantly higher than the treatment-naïve cohort [266.1 (148.2-339.4)] and children on ART for 6 mo [318.8 (154.9-395.6)]. CONCLUSION: A hyperinflammatory state caused by an increased serum myeloperoxidase enzyme activity and increased basal neutrophil oxidative burst was seen in untreated HIV infection and during initial 6 mo of ART. ART given for ≥ 2 y normalized the impaired neutrophilic phagocytic functions.