Diagnosis, Treatment and Prevention of Nutritional Anemia in Children: Recommendations of the Joint Committee of Pediatric Hematology-Oncology Chapter and Pediatric and Adolescent Nutrition Society of the Indian Academy of Pediatrics.

JUSTIFICATION: Anemia in children is a significant public health problem in our country. Comprehensive National Nutrition Survey 2016-18 provides evidence that more than 50% of childhood anemia is due to an underlying nutritional deficiency. The National Family Health Survey-5 has reported an increase in the prevalence of anemia in the under-five age group from 59% to 67.1% over the last 5 years. Clearly, the existing public health programs to decrease the prevalence of anemia have not shown the desired results. Hence, there is a need to develop nationally acceptable guidelines for the diagnosis, treatment and prevention of nutritional anemia. OBJECTIVE: To review the available literature and collate evidence-based observations to formulate guidelines for diagnosis, treatment and prevention of nutritional anemia in children. PROCESS: These guidelines have been developed by the experts from the Pediatric Hematology-Oncology Chapter and the Pediatric and Adolescent Nutrition (PAN) Society of the Indian Academy of Pediatrics (IAP). Key areas were identified as: epidemiology, nomenclature and definitions, etiology and diagnosis of iron deficiency anemia (IDA), treatment of IDA, etiology and diagnosis of vitamin B12 and/or folic acid deficiency, treatment of vitamin B12 and/or folic acid deficiency anemia and prevention of nutritional anemia. Each of these key areas were reviewed by at least 2 to 3 experts. Four virtual meetings were held in November, 2021 and all the key issues were deliberated upon. Based on review and inputs received during meetings, draft recommendations were prepared. After this, a writing group was constituted which prepared the draft guidelines. The draft was circulated and approved by all the expert group members. RECOMMENDATIONS: We recommend use of World Health Organization (WHO) cut-off hemoglobin levels to define anemia in children and adolescents. Most cases suspected to have IDA can be started on treatment based on a compatible history, physical examination and hemogram report. Serum ferritin assay is recommended for the confirmation of the diagnosis of IDA. Most cases of IDA can be managed with oral iron therapy using 2-3 mg/kg elemental iron daily. The presence of macro-ovalocytes and hypersegmented neutrophils, along with an elevated mean corpuscular volume (MCV), should raise the suspicion of underlying vitamin B12 (cobalamin) or folic acid deficiency. Estimation of serum vitamin B12 and folate level are advisable in children with macrocytic anemia prior to starting treatment. When serum vitamin B12 and folate levels are unavailable, patients should be treated using both drugs. Vitamin B12 should preferably be started 10-14 days ahead of oral folic acid to avoid precipitating neurological symptoms. Children with macrocytic anemia in whom a quick response to treatment is required, such as those with pancytopenia, severe anemia, developmental delay and infantile tremor syndrome, should be managed using parenteral vitamin B12. Children with vitamin B12 deficiency having mild or moderate anemia may be managed using oral vitamin B12 preparations. After completing therapy for nutritional anemia, all infants and children should be advised to continue prophylactic iron-folic acid (IFA) supplementation as prescribed under Anemia Mukt Bharat guidelines. For prevention of anemia, in addition to age-appropriate IFA prophylaxis, routine screening of infants for anemia at 9 months during immunization visit is recommended.

Placebo-Related Adverse Events in Rheumatoid Arthritis.

Prospective, double-blind, randomized, placebo-controlled studies are considered to provide the highest quality of interventional evidence. This meta-analysis summarizes the frequencies of adverse events according to the Medical Dictionary for Regulatory Activities (MedDRA) in the placebo arms of 101 such studies in rheumatoid arthritis, including a total of 17,150 patients in the placebo arms and 37,819 patients in the verum arms. Placebo-treated patients reported more than one adverse event in a median of 55.0%, 65.5%, and 72.5% (compared to 72.3% in the verum arms), and a serious adverse event in 2.5%, 5.8%, and 8.6% (compared to 5.9% in the verum arms), with stable doses of corticosteroids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), and biological DMARDs as background therapies, respectively. Odds ratios were comparable between placebo and verum arms for nausea (1.00 with 95% confidence interval (CI) 0.86-1.17), for hepatobiliary disorders (1.08 with CI 0.85-1.36), for abnormal hepatic functions (1.09 with CI 0.83-1.44), and general disorders and administration site conditions (1.39 with CI 0.95-2.03). A publication bias has to be assumed for nausea (p = 0.018; Egger's test), diarrhoea (p = 0.022), and serious infections and infestations (p = 0.009). In conclusion, patients should be aware that "adverse events" may occur even with placebo medication, independent from an additional verum medication added to the background therapy. Further studies are warranted to respect and overcome the psychological and other issues related to these placebo-related "adverse events".

Vitamin C Deficiency and Oxidant Levels in Children With Transfusion-Dependent b-Thalassemia.

OBJECTIVES: To study vitamin C levels in children with transfusion-dependent b-thalassemia and correlate with age, transfusions received and iron overload; and to study the effect of administering vitamin C on its levels and Malondialdehyde (MDA) in deficient patients. METHODS: This case-control study enrolled 100 children with transfusion-dependent b-thalassemia and 30 healthy controls. MDA levels before and after administration of vitamin C were performed randomly in 36 children with low vitamin C levels. RESULTS: 81/95 (85.3%) study subjects vs none in control group, had low plasma vitamin C levels (P<0.001). Vitamin C levels were low in 64 of 71 (74.7%) subjects with dietary deficiency, while none of the 19 (63.3%) controls with dietary deficiency had low levels (P=0.04). Increasing serum ferritin values correlated with vitamin C deficiency (P=0.02). The mean level of MDA reduced (P<0.001) with vitamin C supplementation. CONCLUSIONS: Low levels of vitamin C are common in children with thalassemia. Dietary counseling along with supplementation with vitamin C, in those with low levels may prevent oxidative stress.

Holy basil (Ocimum sanctum Linn.) leaf extract enhances specific cognitive parameters in healthy adult volunteers: A placebo controlled study.

INTRODUCTION: Ocimum sanctum (OS), known as Holy basil, has been documented to possess neuroprotective, cognition-enhancing and stress relieving effects in animal models. However there is paucity of clinical studies to document these effects. MATERIALS AND METHODS: Effect of OS on parameters related to cognition and stress in humans was evaluated with administration of 300 milligram capsules of ethanolic leaf extracts of Ocimum sanctum (EtOS) or placebo per day, over 30 days. RESULTS: Intra-group comparison of Sternberg and Stroop test showed improvement in both the placebo and EtOS groups, however, the improvement stabilized after day 15 in the placebo group. Intergroup comparison revealed a significant improvement of the following cognitive parameters in the EtOS as compared to the placebo: reaction time (RT) and error rate (ER) of Sternberg test, RT of neutral task of Stroop, RT and ER of interference task of Stroop. The intra-group comparison of P300 latency, salivary cortisol, and State-Trait Anxiety Inventory showed improvement over time in the EtOS group alone, though the inter-group difference was significant in the P300 latency alone. There were no changes in heart rate (HR), AHR, or galvanic skin response (GSR) or AGSR. CONCLUSION: Ocimum sanctum leaf extract seems to have potential cognition-enhancing properties in humans.

Immediate and long-term effects of meditation on acute stress reactivity, cognitive functions, and intelligence.

CONTEXT: With the current globalization of the world's economy and demands for enhanced performance, stress is present universally. Life's stressful events and daily stresses cause both deleterious and cumulative effects on the human body. The practice of meditation might offer a way to relieve that stress. OBJECTIVE: The research team intended to study the effects of meditation on stress-induced changes in physiological parameters, cognitive functions, intelligence, and emotional quotients. METHODS: The research team conducted the study in two phases, with a month between them. Each participant served as his own control, and the first phase served as the control for the second phase. In phase 1, the research team studied the effects of a stressor (10 minutes playing a computer game) on participants' stress levels. In phase 2, the research team examined the effects of meditation on stress levels. SETTING: The research team conducted the study in a lab setting at the All India Institute of Medical Sciences (AIIMS), New Delhi, India. PARTICIPANTS: The participants were 34 healthy, male volunteers who were students. INTERVENTION: To study the effects of long-term meditation on stress levels, intelligence, emotional quotients, and cognitive functions participants meditated daily for 1 month, between phases 1 and 2. To study the immediate effects of meditation on stress levels, participants meditated for 15 minutes after playing a computer game to induce stress. OUTCOME MEASURES: The research team measured galvanic skin response (GSR), heart rate (HR), and salivary cortisol and administered tests for the intelligence and emotional quotients (IQ and EQ), acute and perceived stress (AS and PS), and cognitive functions (ie, the Sternberg memory test [short-term memory] and the Stroop test [cognitive flexibility]). Using a pre-post study design, the team performed this testing (1) prior to the start of the study (baseline); (2) in phase 1, after induced stress; (3) in part 1 of phase 2, after 1 month of daily meditation, and (4) in part 2 of phase 2, after induced stress, both before and after 15 minutes of meditation. RESULTS: Induced stress from the computer game resulted in a significant increase in physiological markers of stress such as GSR and HR. In the short term, meditation was associated with a physiological relaxation response (significant decrease in GSR) and an improvement in scores on the Stroop test of reaction times. In the long-term, meditation brought significant improvements in IQ and scores for cognitive functions, whereas participants' stress levels (GSR and AS) decreased. EQ, salivary cortisol, and HR showed no significant changes. CONCLUSIONS: The practice of meditation reduced psychological stress responses and improved cognitive functions, and the effects were pronounced with practice of meditation for a longer duration (1 month).

Efficacy of a short-term yoga-based lifestyle intervention in reducing stress and inflammation: preliminary results.

OBJECTIVES: Previously it was shown that a brief yoga-based lifestyle intervention was efficacious in reducing oxidative stress and risk of chronic diseases even in a short duration. The objective of this study was to assess the efficacy of this intervention in reducing stress and inflammation in patients with chronic inflammatory diseases. DESIGN: This study reports preliminary results from a nonrandomized prospective ongoing study with pre-post design. SETTING/LOCATION: The study was conducted at the Integral Health Clinic, an outpatient facility conducting these yoga-based lifestyle intervention programs for prevention and management of chronic diseases. SUBJECTS: Patients with chronic inflammatory diseases and overweight/obese subjects were included while physically challenged, and those on other interventions were excluded from the study. INTERVENTION: A pretested intervention program included asanas (postures), pranayama (breathing exercises), stress management, group discussions, lectures, and individualized advice. OUTCOME MEASURES: There was a reduction in stress (plasma cortisol and ß-endorphin) and inflammation (interleukin [IL]-6 and tumor necrosis factor [TNF]-α) at day 0 versus day 10. RESULTS: Eighty-six (86) patients (44 female, 42 male, 40.07 ± 13.91 years) attended this program. Overall, the mean level of cortisol decreased from baseline to day 10 (149.95 ± 46.07, 129.07 ± 33.30 ng/mL; p=0.001) while ß-endorphins increased from baseline to day 10 (3.53 ± 0.88, 4.06 ± 0.79 ng/mL; p=0.024). Also, there was reduction from baseline to day 10 in mean levels of IL-6 (2.16 ± 0.42, 1.94 ± 0.10 pg/mL, p=0.036) and TNF-α (2.85 ± 0.59, 1.95 ± 0.32 pg/mL, p=0.002). CONCLUSIONS: This brief yoga-based lifestyle intervention reduced the markers of stress and inflammation as early as 10 days in patients with chronic diseases; however, complete results of this study will confirm whether this program has utility as complementary and alternative therapy.

Effect of meditation on stress-induced changes in cognitive functions.

OBJECTIVES: The objective of this study was to study the effects of meditation on stress-induced changes in cognitive functions. METHODS: The study was conducted on 32 healthy adult male student volunteers who had never practiced meditation before the study. The study consisted of practicing 20 minutes of guided meditation and administration of psychologic stress to the subjects. The psychologic stress was administered to the subjects by asking them to play a (preselected) stressful computer game. The subjects were asked to meditate either before or after the administration of psychologic stress. For the control group measurements, the subjects were asked to wait quietly for an equivalent period of meditation time. OUTCOME MEASURES: The outcome measures were galvanic skin response (GSR), heart rate (HR), electromyography (EMG), sympathetic reactivity (QTc/QS2 ratio), cortisol, and acute psychologic stress scores. The central nervous system functions were assessed using Wechsler memory scale and visual-choice reaction time (VCRT). These parameters were measured both at the beginning and at the end of the intervention, using a pre-post experimental test design. RESULTS: Computer game stress was associated with a significant increase in physiologic (GSR, EMG, HR, QTc/QS2) and psychologic (acute stress questionnaire scores) markers of stress. Meditation was associated with relaxation (significant decrease in GSR, EMG, QTc/QS2, and acute stress questionnaire scores). Meditation, if practiced before the stressful event, reduced the adverse effects of stress. Memory quotient significantly increased, whereas cortisol level decreased after both stress and meditation. VCRT showed no significant change. CONCLUSIONS: Practice of meditation produced a relaxation response even in the young adult subjects who had never practiced meditation before. The practice of meditation reduced the physiologic stress responses without taking away the beneficial effect of stress, namely, improved memory scores.

Effect of yoga based lifestyle intervention on subjective well-being.

Yoga is assuming importance in improving mental health and quality of life in the treatment of a number of psychiatric and psychosomatic disorders. The present study was a prospective controlled study to explore the short-term impact of a comprehensive but brief lifestyle intervention, based on yoga, on subjective well being levels in normal and diseased subjects. Normal healthy individuals and subjects having hypertension, coronary artery disease, diabetes mellitus or a variety of other illnesses were included in the study. The outcome measures were 'subjective well being inventory' (SUBI) scores, taken on the first and last day of the course. The inventory consists of questions related to one's feelings and attitude about various areas of life, such as happiness, achievement and interpersonal relationship. There was significant improvement in the subjective well being scores of the 77 subjects within a period of 10 days as compared to controls. These observations suggest that a short lifestyle modification and stress management educational program leads to remarkable improvement in the subjective well being scores of the subjects and can therefore make an appreciable contribution to primary prevention as well as management of lifestyle diseases.

Effect of yoga based lifestyle intervention on state and trait anxiety.

Considerable evidence exists for the place of mind body medicine in the treatment of anxiety disorders. Excessive anxiety is maladaptive. It is often considered to be the major component of unhealthy lifestyle that contributes significantly to the pathogenesis of not only psychiatric but also many other systemic disorders. Among the approaches to reduce the level of anxiety has been the search for healthy lifestyles. The aim of the study was to study the short-term impact of a comprehensive but brief lifestyle intervention, based on yoga, on anxiety levels in normal and diseased subjects. The study was the result of operational research carried out in the Integral Health Clinic (IHC) at the Department of Physiology of All India Institute of Medical Sciences. The subjects had history of hypertension, coronary artery disease, diabetes mellitus, obesity, psychiatric disorders (depression, anxiety, 'stress'), gastrointestinal problems (non ulcer dyspepsia, duodenal ulcers, irritable bowel disease, Crohn's disease, chronic constipation) and thyroid disorders (hyperthyroidism and hypothyroidism). The intervention consisted of asanas, pranayama, relaxation techniques, group support, individualized advice, and lectures and films on philosophy of yoga, the place of yoga in daily life, meditation, stress management, nutrition, and knowledge about the illness. The outcome measures were anxiety scores, taken on the first and last day of the course. Anxiety scores, both state and trait anxiety were significantly reduced. Among the diseased subjects significant improvement was seen in the anxiety levels of patients of hypertension, coronary artery disease, obesity, cervical spondylitis and those with psychiatric disorders. The observations suggest that a short educational programme for lifestyle modification and stress management leads to remarkable reduction in the anxiety scores within a period of 10 days.

A brief but comprehensive lifestyle education program based on yoga reduces risk factors for cardiovascular disease and diabetes mellitus.

OBJECTIVES: The objective of the study was to study the short-term impact of a brief lifestyle intervention based on yoga on some of the biochemical indicators of risk for cardiovascular disease and diabetes mellitus. DESIGN: The variables of interest were measured at the beginning (day 1) and end (day 10) of the intervention using a pre-post design. SETTING: The study is the result of operational research carried out in our Integral Health Clinic (IHC). The IHC is an outpatient facility which conducts 8-day lifestyle modification programs based on yoga for prevention and management of chronic disease. A new course begins every alternate week of the year. SUBJECTS: The study is based on data collected on 98 subjects (67 male, 31 female), ages 20-74 years, who attended one of our programs. The subjects were a heterogeneous group of patients with hypertension, coronary artery disease, diabetes mellitus, and a variety of other illnesses. INTERVENTION: The intervention consisted of asanas (postures), pranayama (breathing exercises), relaxation techniques, group support, individualized advice, lectures and films on the philosophy of yoga and the place of yoga in daily life, meditation, stress management, nutrition, and knowledge about the illness. OUTCOME MEASURES: The outcome measures were fasting plasma glucose and serum lipoprotein profile. These variables were determined in fasting blood samples, taken on the first and last day of the course. RESULTS: Fasting plasma glucose, serum total cholesterol, low-density lipoprotein (LDL) cholesterol, very- LDL cholesterol, the ratio of total cholesterol to high density lipoprotein (HDL) cholesterol, and total triglycerides were significantly lower, and HDL cholesterol significantly higher, on the last day of the course compared to the first day of the course. The changes were more marked in subjects with hyperglycemia or hypercholesterolemia. CONCLUSIONS: The observations suggest that a short lifestyle modification and stress management education program leads to favorable metabolic effects within a period of 9 days.

Effect of deferiprone on urinary zinc excretion in multiply transfused children with thalassemia major.

A prospective multi-centric study was conducted to determine if iron-chelating agent deferiprone also chelates zinc. Twenty four-hour urinary zinc levels were compared in multiply transfused children with thalassemia major not receiving any chelation therapy (Group A, n = 28), those receiving deferiprone (Group B, n = 30) and age and sex-matched controls of subjects in Group B (Group C, n = 29) by a colorimetric method. The 24-hour mean urinary excretion of zinc was significantly higher in Group B than in the other two groups indicating that deferiprone chelates zinc.

Effect of prenatal species-specific and music stimulation on the postnatal auditory preference of domestic chick.

Perinatal sensory experience plays an important role in the development of perceptual preferences. In the present study prenatal enrichment with sound stimulus was given to see its effect on the development of postnatal auditory preference. Auditory stimulation with either species-specific (chicken maternal and hatching calls) or music (slow and fast sitar music) sounds was provided to two separate sets of fertilized eggs from the day 10 of incubation. The postnatal auditory preference of the chicks to either species-specific or music sounds was then tested at different time periods after hatching. All the chicks, irrespective of the type of prenatal exposure, showed preference for species-specific maternal calls. Notably, the music stimulated chicks did not show preference for either slow or fast music. In both the experimental groups, the number of chicks responding to the species-specific maternal calls was significantly (P<0.001) more at 24 h and 48 h post hatch, when compared with the unstimulated control group. Comparison of the species-specific stimulated group with the music stimulated group, for auditory preference to the maternal calls, did not show any significant difference. Further, in the species-specific sound stimulated groups, there was a significant (P<0.001) increase in the number of chicks responding to maternal calls at 60 h of age with repeated testing. However, there was no effect of peer imprinting on the auditory preference of the chicks, in both the experimental groups. The results indicate that prenatal auditory experience with either species-specific or non-specific music enhances the postnatal auditory preference of chicks for the species-specific sounds.