Madhuri Kanitkar

Treatment with tacrolimus and prednisolone is preferable to intravenous cyclophosphamide as the initial therapy for children with steroid-resistant nephrotic syndrome

There are limited data on the relative efficacy and safety of calcineurin inhibitors and alkylating agents for idiopathic steroid-resistant nephrotic syndrome in children. To clarify this, we compared tacrolimus and intravenous cyclophosphamide therapy in a multicenter, randomized, controlled trial of 131 consecutive pediatric patients with minimal change disease, focal segmental glomerulosclerosis, or mesangioproliferative glomerulonephritis, stratified for initial or late steroid resistance. Patients were randomized to receive tacrolimus for 12 months or 6-monthly infusions of intravenous cyclophosphamide with both arms receiving equal amounts of alternate-day prednisolone. The primary outcome of complete or partial remission at 6 months, based on spot urine protein to creatinine ratios, was significantly higher in children receiving tacrolimus compared to cyclophosphamide (hazard ratio 2.64). Complete remission was significantly higher with tacrolimus (52.4%) than with cyclophosphamide (14.8%). The secondary outcome of sustained remission or steroid-sensitive relapse of nephrotic syndrome at 12 months was significantly higher with tacrolimus than cyclophosphamide. Treatment withdrawal was higher with cyclophosphamide, chiefly due to systemic infections. Compared to cyclophosphamide, 3 patients required treatment with tacrolimus to achieve 1 additional remission. Thus, tacrolimus and prednisolone are effective, safe, and preferable to cyclophosphamide as the initial therapy for patients with steroid-resistant nephrotic syndrome.

Management of Respiratory Distress in the Newborn.

Respiratory distress is a common emergency responsible for 30-40% of admissions in the neonatal period. A working diagnosis should be made in the first few minutes of seeing the baby and immediate lifesaving measures should be undertaken till further management plans are drawn up. Respiratory distress in the neonate is diagnosed when one or more of the following is present; tachypnoea or respiratory rate of more than 60/minute retractions or increased chest in drawings on respirations (subcostal intercostal sternal suprasternal) and noisy respiration in the form of a grunt stridor or wheeze. The distress may or may not be associated with cyanosis and desaturation on pulse oximetry. (excerpt)

Incidence of thrombocytopenia in the neonatal intensive care unit

BACKGROUND Thrombocytopenia is the commonest haematological abnormality encountered in the neonatal intensive care unit (NICU). The incidence in neonates varies greatly, depending upon the population studied. The aim of the present study was to study the incidence of thrombocytopenia in the neonates admitted to the NICU. METHOD The study was carried out in 258 consecutive eligible neonates from August 2007 to August 2009. Neonates were placed in two risk groups for thrombocytopenia, viz. high risk and low risk, depending upon the presentation, maternal history and any antenatal/perinatal events. Platelet counts were done on the first, third and fifth day of admission and thereafter every 72 hours till counts were normal. Low counts were collaborated with a peripheral blood smear. RESULTS AND CONCLUSION The overall incidence of thrombocytopenia in the study group was 70% (182/258). The incidence in the high-risk group was 93.7% cases (134/143) and in the low-risk group was 41.7% (48/115). This difference was statistically significant. Factors associated with thrombocytopenia were sepsis, extreme low birth weight, intra-uterine growth restriction, birth asphyxia and pre-eclampsia in mothers. The most common severe bleeding manifestation was pulmonary haemorrhage. The overall mortality in babies with thrombocytopenia was 33% despite > 90% of these cases having received platelet transfusion. Of these pulmonary haemorrhage was the main cause of death in five cases. It is concluded that thrombocytopenia is very common in the NICU and should be actively looked for so that it can be managed appropriately.

Chronic Kidney Disease in Children: An Indian Perspective.

Chronic renal failure (CRF) is an insidious and irreversible condition that eventually progresses to end stage renal failure. It is an important cause of morbidity and mortality in children worldwide. The disease process is better termed as chronic kidney disease (CKD), in order to encompass the entire spectrum and severity of renal disease. In the past various terminologies have been used to describe its severity from chronic renal insufficiency to end stage renal disease (ESRD). This classification did not include the ‘at risk’ population where intervention could modify the outcome. In order to reduce ambiguity and use more objective terms of reference the new name of CKD was introduced. Chronic kidney disease is defined primarily as an abnormality of kidney function or structure as determined by laboratory tests, urinalysis or imaging tests, which have been present for three or more months. Importantly, the classification system describes the stages according to level of estimated glomerular filtration rate (GFR), not serum creatinine levels. This staging uses various clinical, laboratory and imaging parameters [1] and is depicted in Table 1. These stages correspond to the severity of kidney function loss and the prevalence of co-morbidities associated with kidney disease. The identification of low GFR states may allow the implementation of simple measures to prevent worsening. For these reasons, it may be prudent to adopt the system of defining kidney disease according to kidney function, not serum creatinine values. However certain grey areas exist with this classification. The staging takes into consideration normal GFR for a western population. It has been noted that healthy Indians especially on a vegetarian diet have a lower GFR [2]. Secondly, correct interpretation of GFR values in children and adolescents, requires a clear understanding that it varies according to age, gender, and body size. The normal GFR in young adults is 120 to 130 mL/min/1.73 m2, whereas in infancy it is much lower. Even when corrected for body surface area it increases in relationship to body size up to two years. Kidney disease is characteristically asymptomatic and is often not diagnosed until it is relatively advanced. Table 1 Stages of chronic kidney disease

Spectrum of Childhood Tuberculosis in BCG Vaccinated and Unvaccinated Children

BACKGROUND Childhood tuberculosis remains a major public health problem in India. We evaluated the impact of BCG vaccination on childhood tuberculosis and the underlying risk factors. METHODS 100 consecutive children below 12 years diagnosed to have tuberculosis based on the WHO and IAP consensus statement were included in the study. RESULT Majority(42%) of children with tuberculosis were below four years of age. History of contact with a case of tuberculosis was present in 41 cases. BCG scar was present in 77 cases indicating a poor coverage/uptake of BCG vaccination. Pulmonary form of tuberculosis was seen in 52 and extra pulmonary form in 41 cases. Tubercular lymphadenitis was seen in seven cases, of which more than 70 % were in BCG vaccinated group. There was no statistically significant difference in the type of tuberculosis (pulmonary or extra pulmonary) and BCG vaccination. In the extra pulmonary form, 13 children had neuro-tuberculosis, of which 66% were in BCG unvaccinated group, which was statistically significant (p=0.011). The underlying risk factors were poor socioeconomic status (62%), malnutrition (61%) and poor immunization coverage. CONCLUSION Higher incidence of pulmonary tuberculosis in BCG vaccinated group was not statistically significant. However, high incidence of neuro-tuberculosis in BCG unvaccinated group was statistically significant. The underlying risk factors were poor socio-economic status, malnutrition and poor immunization coverage and should be taken into consideration in order to prevent morbidity and mortality due to tuberculosis in children.

Bed Wetting — Silent Suffering: An Approach to Enuresis and Voiding Disorders in Children

Bed wetting or nocturnal enuresis is a common problem among children. It is either monosymptomatic or may be associated with a voiding disorder. Many factors may contribute towards enuresis such as developmental delay, heredity, inappropriate nocturnal anti diuretic hormone secretion and reduced bladder capacity. Any child presenting with bed-wetting should be evaluated for any underlying bladder dysfunction before labeling as monosymptomatic enuresis. The evaluation consists of structured bowel and bladder history, detailed clinical examination, frequency volume record and appropriate investigations. The frequency volume diary is an indispensible component of evaluation and helps in establishing diagnosis and tailoring therapy. The treatment of monosymptomatic enuresis consists of positive psychological support, alarms and medication (desmopressin/ anticholinergics/ imiprammine). Children with features of underlying bladder dysfunction, anatomical anomalies and neurological disorders should be referred to a pediatrician without delay. The outcome of therapy is usually rewarding but varies, depending on the underlying etiology, motivation, compliance and family support. The cure rates with alarms are better than with desmopressin in monosymptomatic enuresis. Timely and appropriate therapy yields better outcomes. Thus, a thorough, scientific and evidence based approach is essential in children presenting with bed-wetting.

Varied presentations of hypothyroidism in children.

Hypothyroidism is among the most common endocrine disorders in children. Congenital hypothyroidism is reported to occur with an incidence of 1:2640 live births in India,1 and the most common cause is thyroid dysgenesis. Acquired hypothyroidism in children is less common, and in a hospital based study of 100 hypothyroid children in a developing country, only 9% were acquired.2 Hypothyroidism is an endocrine disorder of varied clinical presentation. Manifestations range from subclinical hypothyroidism, which requires high index of suspicion for diagnosis to myxoedema coma. There may be situations where in a given patient an alternative diagnosis may explain the clinical features, and hypothyroidism may be missed. We report four such cases of cryptic hypothyroidism, which we encountered in different clinical situations.

Bartter's Syndrome Masquerading as a Neurometabolic Disorder.

Fredrick Bartter first described Bartters syndrome in 1962 [1]. It is a rare autosomal recessive disorder of the renal tubules resulting in hypokalemic metabolic alkalosis, hyperreninism and hyperaldosteronism with normal blood pressure. This disorder has a varied spectrum of presentation [2]. We report a case of Bartters syndrome presenting as a neurometabolic disorder.

Status Epilepticus in Children

Status epilepticus (SE) is a life-threatening emergency that requires prompt treatment, including basic neuroresuscitation principles (the ABCs), antiepileptic drugs to stop the seizure and identification of etiology. It results from an inability to normally abort an isolated seizure either due to ineffective inhibition, or due to abnormally persistent excessive excitation. Symptomatic SE is more common in younger children and the likely etiology depends on the age of the child. Treating the precipitating cause may prevent ongoing neurologic injury and facilitates seizure control. Benzodiapenes, phenytoin and phenobarbital form the mainstay of treatment. A systematic treatment regimen, planned in advance, is needed, including one for refractory status epilepticus (RSE). Patient education and home management of seizures is important to reduce the morbidity and mortality associated with SE.

Rejected but not dejected: Dealing with an unfavourable decision on a scientific manuscript

Unfavourable decisions and rejections on submitted manuscripts are not uncommon in scholarly publications. Rejection in a particular journal need not be viewed as end of all hopes for aspiring authors. Substantial number of rejected manuscripts find their final place in one or the other journal after suitable revision. As an author, it is extremely important to be familiar with common reasons for unfavourable decision/rejection in order to prevent them or to find solutions.