Evaluation of symptoms & spirometry in children treated for asthma.

BACKGROUND & OBJECTIVES: Spirometry plays an important role in the assessment and long term monitoring of patients with asthma. Difficulty in performing spirometry in children has resulted in a paucity of Indian studies using spirometry regularly for research in the paediatric population. This study was undertaken to assess the clinical improvement and changes in spirometric measurements with treatment in children with newly diagnosed asthma and to compare the changes in the symptom score and spirometric measurements. METHODS: This prospective study included 32 children between 6 to 12 yr of age (enrolled over a period of one year with follow up of six months) who were newly diagnosed as cases of asthma on the basis of symptoms and medical history. Baseline symptom score and spirometric measurements were determined at the first visit. The children were treated and followed up at six weeks, three and six months of initiating treatment. Symptom score and spirometric measurements were repeated at every visit. RESULTS: Significant improvement in symptom score was evident at six weeks of therapy ( P<0.05) while the lung function parameters FEV 1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) showed significant improvement at three months of therapy. Peak expiratory flow rate (PEFR) was found to improve at six months. There was a positive linear correlation between the changes in symptom score and FEV 1, FVC and PEFR with treatment. INTERPRETATION & CONCLUSIONS: Symptomatic improvement became apparent before the improvement in spirometric parameters in children with asthma (after treatment initiation).

Efficacy and safety of Bacillus clausii (O/C, N/R, SIN, T) probiotic combined with oral rehydration therapy (ORT) and zinc in acute diarrhea in children: a randomized, double-blind, placebo-controlled study in India.

BACKGROUND: Childhood diarrhea remains a major disease burden, particularly in developing countries, and is a leading cause of death in children aged < 5 years, worldwide. Treatment of acute diarrhea now includes probiotics to potentially reduce the duration and severity of the illness. This phase 3, randomized, placebo-controlled, double-blind study assessed the efficacy and safety of four strains (O/C, N/R, SIN, T) of Bacillus clausii probiotic (Enterogermina®) plus oral rehydration therapy (ORT) and zinc, versus placebo plus ORT and zinc, in infants and children in India with acute moderate diarrhea. METHODS: Patients aged 6 months to 5 years with acute moderate diarrhea (WHO 2005 definition) of < 48 h' duration were randomly assigned to receive one mini bottle of either polyantibiotic-resistant B. clausii (oral suspension of 2 billion spores per 5 mL bottle) or matching placebo twice daily (morning and evening) for 5 days. Exclusion criteria included known hypersensitivity to B. clausii or excipients in the study treatment, or to other probiotics. Patients were admitted to hospital from Day 1 and discharged ≥6 h after diarrhea resolution, or a maximum of 5 days. The primary endpoint was duration of acute diarrhea from randomization to recovery. Secondary endpoints included frequency of stools, diapers with stools, or dehydration status. RESULTS: In total, 457 patients were randomized; 454 were treated. Similar proportions of patients showed recovery from diarrhea over the 120 h after randomization (97.0% in the B. clausii group [n = 227]; 98.0% on placebo [n = 227]). Median time to recovery was also similar: 42.83 (95% CI: 40.90-44.90) hours for B. clausii and 42.13 (95% CI: 39.80-43.87) hours for placebo. However, no statistically significant difference was observed between groups (hazard ratio = 0.93 [95% CI: 0.77-1.13]; p = 0.6968); nor were there statistically significant differences between groups for the secondary endpoints. Treatment with B. clausii was well tolerated with incidence of adverse events (9.7%) similar to that for placebo (12.3%). CONCLUSIONS: No significant difference in efficacy between B. clausii and placebo was demonstrated. Sample size may have been inadequate to allow detection of a between-group difference in efficacy, given the mild/moderate severity (only ~ 20% of patients had nausea/vomiting or abdominal pains) and short duration of disease among subjects, the relatively late start of treatment (most were already on Day 2 of their disease episode when study treatment started) and the effectiveness of the standard of care with ORT and zinc in both treatment groups. TRIAL REGISTRATION: CTRI number CTRI/2018/10/016053 . Registered on 17 October 2018. EudraCT number 2016-005165-31 . Registered 14 May 2020 (retrospectively registered).

Device-handling study of a novel breath-actuated inhaler, Synchrobreathe®, versus a pMDI.

INTRODUCTION: Synchrobreathe®, a new-generation, novel breath-actuated inhaler (BAI) can address the key issues arising during the use of both pressurised metered dose inhalers ([pMDIs]; hand-breath coordination) and dry powder inhalers ([DPIs]; high inspiratory flow required) with respect to optimal drug deposition. MATERIALS AND METHODS: This was an open-label, prospective, 2-week, multicentre study that assessed device handling, ease of use, errors and participant perception regarding the use of Synchrobreathe® versus a pMDI in patients with chronic obstructive pulmonary disease (COPD) (n = 162) or asthma (n = 239) and inhaler-naïve healthy volunteers (n = 59). Ability to use the device without errors at the first attempt, total number of errors before and after training, time taken to use the device correctly and total number of training sessions, and number of attempts to perform the correct technique on Day 1 and Day 14 were evaluated. Device handling and preference questionnaires were also administered on Day 14. RESULTS: Of 460 participants, 421 completed the study. The number of participants using Synchrobreathe without any error after reading the patient information leaflet (PIL) was significantly low (p < 0.05) on Day 1. On Day 14, significantly more number of participants used Synchrobreathe without any error (p < 0.001). The total number of errors before and after training with Synchrobreathe was significantly less (p < 0.001). The average time required to perform the inhalation technique correctly (p < 0.01) and the total number of attempts (P < 0.001) with Synchrobreathe were significantly lower. The average number of attempts to inhale correctly was significantly (p < 0.001) less with Synchrobreathe on Day1 and Day 14. Most participants rated Synchrobreathe as their choice of inhaler. CONCLUSION: Synchrobreathe is an easy-to-use and easy-to-handle device with significantly less number of errors, which may have positive implications for disease control in asthma and COPD.

Recommendations for the adjuvant use of the poly-antibiotic-resistant probiotic Bacillus clausii (O/C, SIN, N/R, T) in acute, chronic, and antibiotic-associated diarrhea in children: consensus from Asian experts.

This paper proposes recommendations for probiotics in pediatric gastrointestinal diseases in the Asia-Pacific region. Evidence-based recommendations and randomized controlled trials in the region are included. Cultural aspects, health management issues and economic factors were also considered. Final recommendations were approved by utilizing a modified Delphi process and applying the Likert scale in an electronic voting process. Bacillus clausii was recommended as an adjunct treatment with oral rehydration solution for acute viral diarrhea. B. clausii may also be considered for prevention of antibiotic-associated diarrhea, Clostridium difficile-induced diarrhea, and as adjunct treatment of Helicobacter pylori. There is insufficient evidence for recommendations in other conditions. Despite a diversity of epidemiological, socioeconomical and health system conditions, similar recommendations currently apply to most Asia-Pacific countries. Ideally, these need to be validated with local randomized-controlled trials.

Moyamoya syndrome in a child with Down syndrome.

Moyamoya syndrome has rarely been reported in association with Down syndrome. We report a case of an 11-year-old female child with Down syndrome who presented with hemiparesis and facial palsy. Imaging investigations (magnetic resonance angiography and digital subtraction angiography) revealed the classical Moyamoya pattern. Work-up for prothrombotic and autoimmune disorders was negative. The neurological deficits recovered well. The association of Moyamoya syndrome in patients with Down syndrome has been highlighted. The possible causes for the association and management have been reviewed briefly.

Minimal access therapy in pediatric pulmonary hydatid cysts.

Hydatid cysts occur commonly in lungs in the pediatric age group. Though medical management has been tried, definitive management of the condition is essentially surgical. Use of video-assisted thoracic surgery (VATS) has been rarely employed for the management of pulmonary hydatid cysts. We present a 10-year-old boy with pulmonary hydatid cysts treated with VATS-assisted minithoracotomy with hydatid cyst enucleation and capitonnage. The patient developed a lung abscess postoperatively and had to undergo lobectomy. The surgical management of pulmonary hydatid cysts is discussed here. The role of minimal access therapy for pulmonary hydatid cysts is highlighted.

The face of lysosomal storage disorders in India: a need for early diagnosis.

OBJECTIVES: To study the temporal pattern of lysosomal storage disorders (LSD) from onset of symptoms to the final diagnosis and to study the type and the frequency of the disease. METHODS: Retrospective analysis of the case record forms of the patients attending the Genetic Clinic over a period of 12 y (January 2002- December 2013) was undertaken. Only the data of the patients who had confirmatory enzyme analysis or mutation study for LSD was further analysed. The age at onset, suspicion of the illness, first clinical presentation to a tertiary Genetic centre, and the age at the final diagnosis of these confirmed cases was noted. RESULTS: A total of 5,858 patients were referred to the Genetic clinic in this period. The diagnosis of LSD was suspected in 532 patients (9.08 % of all referrals) and it could be confirmed in 119 cases (2.03 % of all referrals). Maximum patients were diagnosed with Gaucher disease (31.93 %) followed by Mucopolysaccharidoses (20.16 %). Mutation analysis was available in 21 patients (17.64 % of the diagnosed cases). The median time interval between onset and suspicion was 6 mo. The median interval between onset and presentation to the authors' Genetic clinic was 12 mo. The median interval between the onset of the disease and its confirmation was 14 mo. The median interval between presentation to the Genetic centre and diagnosis was barely 1 mo. CONCLUSIONS: The incidence of LSD at authors' centre was 2.03 %, though it was suspected in 9.08 % of patients. The delay in diagnosis was hugely due to the late suspicion and thereby the late referral to a tertiary centre.

Incomplete monosymptomatic leptomeningeal angiomatosis.

Phakomatoses or neurocutaneous syndromes are an important cause of seizures in the pediatric age group. The Sturge-Weber syndrome may affect the eye, skin and brain at different times. The skin lesions need not always manifest. We report a case of isolated affection of the central nervous system in a case of Sturge-Weber syndrome in the absence of ocular or cutaneous manifestations. Our case qualifies to be called incomplete monosymptomatic leptomeningeal angiomatosis.

Approach to chronic cough.

Chronic cough does affect quality of life in children. Most of the times it is treated with over-the-counter cough syrups and antibiotics. The etiology of chronic cough is so diverse, that treatment needs to be directed to the specific etiology, rather than treating symptomatically. Grossly, chronic cough is classified as specific and non-specific cough. Allergic conditions, followed by tuberculosis are more commonly encountered etiologies in India. Baseline investigations to be performed are chest radiograph and peak flow metry. If specific cause of cough is not obvious, then therapeutic trial with ß2 agonist, followed by peak flowmetry to evaluate reversibility of airway hypersensitivity, is useful to label the child asthmatic or non-asthmatic. Rampant uses of antibiotics need to be avoided for conditions like asthma. If tuberculosis is diagnosed or suspected, it is better to treat the child, rather than giving therapeutic trial. Over-the-counter cough syrups are as good as placebo, and should be avoided. Trial of anti asthma, anti allergic rhinitis and anti reflux therapies are avoided, unless the diagnosis is one of these conditions. If the child is distressed or the case seems to be complicated, it is best to refer the child to a tertiary care centre and keep a close follow up.

Left ventricular failure due to a rare variant of congenital adrenal hyperplasia.

"Hypertensive" variant of congenital adrenal hyperplasia is rare. The authors describe an interesting case of a 6-y-old boy who presented with an acute respiratory illness and progressive breathlessness since 1 y. Genital hyperpigmentation was noticed since 2 y of age; the onset of pubarche and increasing penile size at 4 y. He was admitted in congestive cardiac failure with a blood pressure of 150/100 mm Hg. Facial acne; slight facial, pubic hair and penile enlargement were additionally noted. Chest radiograph revealed cardiomegaly. Basal ACTH and 17-OHP levels were high. A diagnosis of congenital adrenal hyperplasia (11ß-hydroxylase deficiency) was made due to hypertension with virilized genitalia. Cardiac failure was controlled with fluid restriction and diuretics; he was started on prednisolone, spironolactone and nifedipine. This case is presented for its rarity where hypertension can cause complication of cardiac failure, if diagnosis is delayed despite early features of pseudoprecocious puberty.

Novel biochemical abnormalities and genotype in Farber disease.

Farber disease caused by acid ceramidase deficiency is characterised by a triad of painful and swollen joints, subcutaneous nodules, and laryngeal involvement. A one year old female with overlapping features of the classical and type 5 variants is reported. Sialuria and elevated plasma chitotriosidase were unusual findings. A novel mutation of the ASAH 1 gene was detected from DNA extracted from the umbilical stump.

Human immunodeficiency virus (HIV) infection in a child presenting as acute disseminated encephalomyelitis.

Acute disseminated encephalomyelitis is an extremely rare occurrence in human immunodeficiency virus (HIV) infection. We describe an 8-year-old male child who presented with weakness of both lower limbs for 10 days and focal convulsions for 2 days. The child had left, upper motor neuron facial palsy, lower limb hypotonia, and exaggerated deep tendon reflexes. Enzyme-linked immunosorbent assay antibodies for HIV tested positive and the CD4 count was 109 cells/µL. The magnetic resonance imaging (MRI, brain) revealed extensive confluent hyperintensities (on T2-weighted images) in left parietal, right temporal, and right occipital regions of the white matter, and similar signals were seen in right lentiform nucleus and right posterior thalami, suggesting acute disseminated encephalomyelitis. There was transient improvement with intravenous methyl prednisolone. The patient succumbed to the illness. Perinatally transmitted pediatric HIV infection presenting with acute disseminated encephalomyelitis has not yet been reported in the medical literature.

Performance of PRISM (Pediatric Risk of Mortality) score and PIM (Pediatric Index of Mortality) score in a tertiary care pediatric ICU.

OBJECTIVE: To validate Pediatric Risk of Mortality (PRISM) and Pediatric Index of Mortality (PIM) score. METHODS: All consecutive patients over a six month period were included in the study except patients with a PICU stay of less than 2 hours, those transferred to other PICUs, pediatric surgical cases, trauma patients and those dying within 24 hours of admission. The PRISM and PIM scores of all patients included in the study were computed and the outcome was noted in terms of survival or non-survival. Mortality discrimination was quantified by calculating the area under the receiver operating characteristic (ROC) curve. Hosmer and Lemeshow goodness-of-fit test was used to calibrate the scores. RESULTS: Two hundred and thirty patients were enrolled with mean age of 40.6 months and male to female ratio of 1.2:1. There were 56 deaths (mortality rate 24.3%). The mortality in infants was higher (37.8 %) as compared to non-infants (16.2 %) (p = 0.011). The predicted deaths with PRISM score was 24.3%. The area under the ROC curve was 0.851 (95% CI 0.790-0.912). The Hosmer and Lemeshow goodness-of-fit test showed good calibration (p = 0.627, chi square = 1.75, degree of freedom = 3). The predicted deaths with the PIM score was 7.38%. The area under the ROC curve for PIM score was 0.838 (95 % CI 0.776-0.899). The Hosmer and Lemeshow goodness-of-fit showed a poor calibration for PIM score (p = 0.0281, chi-square = 10.866, degree of freedom = 4). CONCLUSION: Both PRISM and PIM scores have a good discriminatory performance. The calibration with PRISM score is good but the PIM score displays poor calibration.

Anterior sacral pyocele with meningitis: a rare presentation of occult spinal dysraphism with congenital dermal sinus.

The authors describe an interesting case of a hitherto asymptomatic occult spinal defect with a congenital sacral dermal sinus which proved to be the entry point for bacterial meningitis in an otherwise healthy 9-year-old female child. The patient presented with fever and neck stiffness, and a dermal sinus in the lumbosacral region was identified on examination. Cerebrospinal fluid analysis confirmed bacterial meningitis and a spinal magnetic resonance imaging scan revealed a dermal sinus tract with an anterior spinal meningocele, caudal regression syndrome, and a tethered spinal cord. In addition to administration of intravenous antimicrobial agents, surgical exploration of the sacral dermal sinus tract was performed and an anterior sacral pyocele was drained. The pyocele cavity was disconnected from the thecal sac, and the thickened and fatty filum terminale was sectioned. Although congenital sacral dermal sinus manifesting as bacterial meningitis is known, the occurrence of an anterior sacral pyocele has not yet been described in children.

Candida tropicalis endocarditis: Treatment in a resource-poor setting.

Fungal endocarditis (FE) is rare in children and does not usually occur in structurally normal hearts. The commonest causative agent is Candida albicans. We report a 5-year-old female child presenting with high-grade fever and cardiac failure. Anemia, leukocytosis and high CRP were found, but bacterial blood culture was sterile. There was no response to antimicrobial agents. Two-dimensional echocardiography revealed a large heterogeneous mass attached to the right ventricle and tricuspid valve. Provisional diagnosis of FE was made, which was confirmed by growth of Candida tropicalis in blood culture. Liposomal amphotericin B was started, followed by radical curative surgery including excision of the entire vegetation with total tricuspid valve excision. Histopathology and culture of the resected vegetation confirmed the diagnosis. The patient was given antifungal therapy for a total of 7 weeks, including 2 weeks of post-operative treatment, following which she was afebrile.

Extrapontine myelinolysis in a child with nephrotic syndrome.

Extrapontine myelinolysis is rare in children. We describe a 6-year-old girl with nephrotic syndrome who presented with symptomatic hyponatremia, and who developed acute quadriparesis with pseudobulbar palsy during rapid correction of the hyponatremia. Cranial magnetic resonance imaging demonstrated bilateral, symmetric basal ganglia lesions (extrapontine myelinolysis). The extrapontine myelinolysis was caused by rapid correction of severe and prolonged hyponatremia with intravenous 3% sodium chloride. The child demonstrated complete neurologic recovery. Prevention of this rare condition involves recognizing patients at risk for the disorder, and avoiding rapid correction of severe and prolonged hyponatremia. To the best of our knowledge, this is the first case report of extrapontine myelinolysis in a child with nephrotic syndrome.