Evaluation of the impact of continuous Kangaroo Mother Care (KMC) initiated immediately after birth compared to KMC initiated after stabilization in newborns with birth weight 1.0 to < 1.8 kg on neurodevelopmental outcomes: Protocol for a follow-up study.

BACKGROUND: Preterm birth or low birth weight is the single largest cause of death in newborns, however this mortality can be reduced through newborn care interventions, including Kangaroo Mother Care (KMC). Previously, a multi-country randomized controlled trial, coordinated by the World Health Organization (WHO), reported a significant survival advantage with initiation of continuous KMC immediately after birth compared with initiation of continuous KMC a few days after birth when the baby is considered clinically stable. Whether the survival advantage would lead to higher rates of neurodevelopmental morbidities, or the immediate KMC will also have a beneficial effect on cognitive development also, has not been investigated. We therefore propose to test the hypothesis that low-birth-weight infants exposed to immediate KMC will have lower rates of neurodevelopmental impairment in comparison to traditional KMC-treated infants, by prospectively following up infants already enrolled in the immediate KMC trial for the first 2 years of life, and assessing their growth and neurodevelopment. METHODS: This prospective cohort study will enroll surviving neonates from the main WHO immediate KMC trial. The main trial as well as this follow-up study are being conducted in five low- and middle-income countries in South Asia and sub-Saharan Africa. The estimated sample size for comparison of the risk of neurodevelopmental impairment is a total of 2200 children. The primary outcome will include rates of cerebral palsy, hearing impairment, vision impairment, mental and motor development, and epilepsy and will be assessed by the age of 3 years. The analysis will be by intention to treat. DISCUSSION: Immediate KMC can potentially reduce low-birth-weight-associated complications such as respiratory disease, hypothermia, hypoglycemia, and infection that can result in impaired neurocognitive development. Neuroprotection may also be mediated by improved physiological stabilization that may lead to better maturation of neural pathways, reduced risk of hypoxia, positive parental impact, improved sleep cycles, and improved stress responses. The present study will help in evaluating the overall impact of KMC by investigating the long-term effect on neurodevelopmental impairment in the survivors. TRIAL REGISTRATION: Clinical Trials Registry-India CTRI/2019/11/021899. Registered on 06 November 2019. Trials registration of parent trial: ACTRN12618001880235; Clinical Trials Registry-India: CTRI/2018/08/015369.

Scaling up Integrated Early Childhood Development programs: lessons from four countries.

BACKGROUND: There is still limited knowledge regarding the translation of early child development (ECD) knowledge into effective policies and large-scale programmes. A variety of frameworks that outline the key steps in scaling up exist, but we argue that taking a complex adaptive systems (CAS) approach assists in understanding the complex, dynamic processes that result in programmes being taken to scale. OBJECTIVES: The objective of this study is to examine the process of scaling up four major country-level ECD programmes through the application of a CAS framework. METHODS: Nine key informants with a deep knowledge of how each ECD programme was established and brought to scale were interviewed via Skype or phone by using open-ended interviews. The interviews were tape recorded and then transcribed verbatim for subsequent coding by using CAS domains. The coding and integration of the results to identify unique and common CAS scaling up features across the case studies involved an iterative process of reaching consensus. RESULTS: The scaling up of all four programmes behaved as a CAS including as follows: (i) positive feedback loops (five themes) and negative feedback loops (two themes); (ii) scale-free networks (two themes); (iii) phase transitions (four themes); (iv) path dependence (two themes); and (v) emergent behaviour (six themes). Five additional themes were identified for sustainability, which was repeatedly mentioned as an important consideration when deciding how to scale up programmes. CONCLUSIONS: CAS analysis is likely to improve our understanding of how effective ECD programmes become scaled up. Prospective CAS implementation research is needed to continue advancing the knowledge in the field.

Mapping actions to improve access to medicines for mental disorders in low and middle income countries.

AIMS: In recent years a number of intergovernmental initiatives have been activated in order to enhance the capacity of countries to improve access to essential medicines, particularly for mental disorders. In May 2013 the 66th World Health Assembly adopted the World Health Organization (WHO) Comprehensive Mental Health Action Plan 2013-2020, which builds upon the work of WHO's Mental Health Gap Action Programme. Within this programme, evidence-based guidelines for mental disorders were developed, including recommendations on appropriate use of medicines. Subsequently, the 67th World Health Assembly adopted a resolution on access to essential medicines, which urged Member States to improve national policies for the selection of essential medicines and to promote their availability, affordability and appropriate use. METHODS: Following the precedent set by these important initiatives, this article presents eleven actions for improving access and appropriate use of psychotropic medicines. RESULTS: A 4 × 4 framework mapping actions as a function of the four components of access - selection, availability, affordability and appropriate use - and across four different health care levels, three of which belong to the supply side and one to the demand side, was developed. The actions are: developing a medicine selection process; promoting information and education activities for staff and end-users; developing a medicine regulation process; implementing a reliable supply system; implementing a reliable quality-control system; developing a community-based system of mental health care and promoting help-seeking behaviours; developing international agreements on medicine affordability; developing pricing policies and a sustainable financing system; developing or adopting evidence-based guidelines; monitoring the use of psychotropic medicines; promoting training initiatives for staff and end-users on critical appraisal of scientific evidence and appropriate use of psychotropic medicines. CONCLUSIONS: Activating these actions offers an unique opportunity to address the broader issue of increasing access to treatments and care for mental disorders, as current lack of attention to mental disorders is a central barrier across all domains of the 4 × 4 access framework.

Excess mortality from mental, neurological and substance use disorders in the Global Burden of Disease Study 2010.

AIMS: Mortality-associated burden of disease estimates from the Global Burden of Disease 2010 (GBD 2010) may erroneously lead to the interpretation that premature death in people with mental, neurological and substance use disorders (MNSDs) is inconsequential when evidence shows that people with MNSDs experience a significant reduction in life expectancy. We explore differences between cause-specific and excess mortality of MNSDs estimated by GBD 2010. METHODS: GBD 2010 cause-specific death estimates were produced using the International Classification of Diseases death-coding system. Excess mortality (all-cause) was estimated using natural history models. Additional mortality attributed to MNSDs as underlying causes but not captured through GBD 2010 methodology is quantified in the comparative risk assessments. RESULTS: In GBD 2010, MNSDs were estimated to be directly responsible for 840 000 deaths compared with more than 13 million excess deaths using natural history models. CONCLUSIONS: Numbers of excess deaths and attributable deaths clearly demonstrate the high degree of mortality associated with these disorders. There is substantial evidence pointing to potential causal pathways for this premature mortality with evidence-based interventions available to address this mortality. The life expectancy gap between persons with MNSDs and the general population is high and should be a focus for health systems reform.

Headache disorders in developing countries: research over the past decade.

The majority of people with primary headache disorders live in the developing world. The contribution of low and middle income (LAMI) countries to headache research has not been previously characterized. A search was performed for clinical research publications between the years 1997 and 2006, using the search terms 'headache' OR 'headache disorders' AND 'primary' OR 'migraine' AND 'each of the LAMI countries' in 67 databases. Articles in English or with abstracts in English translation were included. These publications were scrutinized for study characteristics. Two hundred and twenty-seven publications from 32 LAMI countries were found. Half (50.2%) of these were from three middle-income countries (Brazil, Turkey and Iran), whereas 24 (10.6%) came from low-income countries. Most of the research focused on migraine. Only 29.5% of the articles involved treatment of headache. The understanding of headache disorders in LAMI countries is derived from a limited number of publications from relatively few countries. Identifying gaps in headache research in the developing world is strategic for targeting research policy.

Cardiac syncope from occult transposition masquerading as convulsive epilepsy.

A four-year-old boy on Valproate therapy for a presumed diagnosis of epilepsy presented with a recurrence of tonic spasms. A history of precipitation of these episodes with exercise prompted a search for an underlying cardiac disorder. The child was ultimately diagnosed to have corrected transposition of great arteries with 2:1 atrioventricular block. This case illustrates that cardiac syncope due to underlying congenital heart disease can masquerade as epilepsy in children.

Spectrum of floppy children in Indian scenario.

OBJECTIVE: To study the clinical profile of paralytic floppy infants undertaking available investigations and detect the frequency of exon7 of survival motor neuron (SMNT) gene deletion among the spinal muscular atrophy (SMA) cases. DESIGN: Descriptive study. SETTING: Tertiary care teaching hospital. SUBJECTS: 70 paralytic floppy infants (40 males/30 females) with age less than 13 years were included in the study. Exclusion criteria included central hypotonia of any cause. Detailed clinical evaluation was done followed by serum creatine phosphokinase levels, electrophysiological studies, muscle biopsy including immunohistochemistry and electron microscopy. Exon7 of SMNT gene deletion studies was done by PCR. RESULTS: Final diagnosis of SMA was assigned to 37 patients followed by congenital myopathy (n = 7), cogenital muscular dystrophy (n = 5), mitochondrial myopathy (n = 4), neuropathies (n = 5) and diaphragmatic SMA (n = 1). Only 15.7% of cases remained unclassified. When EMG was correlated with final diagnosis, it was 80.6% and 75% sensitive and 68.8% and 87.5% specific for neurogenic and muscle disease, respectively. Muscle biopsy revealed neurogenic atrophy in 47.8% cases followed by normal in 37.3% and myopathic pattern in 14.97% cases. Exon7 of SMNT gene was deleted in only 50% of SMA cases. CONCLUSIONS: Spinal muscular atrophy was the commonest cause of floppy children. The low rate of SMNT gene deletion detected needs confirmation with further studies.

Adhalin deficiency: an unusual cause of muscular dystrophy.

Childhood muscular dystrophies have a wide clinical spectrum, motor disability and are variably inherited. Although the phenotype may appear similar they may represent distinct genetic entities. Advances in immunohistochemistry, gene deletion and linkage studies have enabled precise characterization. We report a family with an early onset weakness and calf pseudo hypertrophy in 2 male sibs with an usually mild course. Deletion screening was negative for 24 exons of the DMD gene in both. Muscle immunohistochemistry revealed normal dystrophin I and II staining but complete absence for adhalin, a dystrophin associated glycoprotein. Classifying them as adhalinopathy. Severe childhood autosomal recessive muscular dystrophies (SCARMD) result from mutation in the sarcoglycan complex (59). Adhalinopathy is now used to describe SCARMD. The adhalinopathy described in our patients is the first report from India.

Idiopathic pulmonary hemosiderosis.

Two cases of idiopathic pulmonary hemosiderosis in children are reported. Both cases presented with a combination of acute/recurrent respiratory symptoms along with iron deficiency anemia. In one case diagnosis was delayed for 18 months after onset of symptoms. After initial stabilisation with corticosteroid therapy, both cases were put on chloroquine therapy and showed improvement. Various other forms of therapy and outcome are discussed. It is suggested that in cases with recurrent respiratory symptoms, idiopathic pulmonary hemosiderosis should also be considered after excluding infectious etiology.

Role of protozoa as risk factors for persistent diarrhea.

A case control study including 175 children aged 0-36 months suffering from diarrhea of > or = 14 days duration was undertaken to determine whether there is an association between Giardia lamblia, Entamoeba histolytica or Cryptosporidium infection and persistent diarrhea (PD). Subjects were identified by ongoing household surveillance and enrolled as cases. For each case two controls were selected by survey of neighbouring households--a child with acute diarrhea and one without diarrhea. Both the controls were matched with the case for age and nutritional status. Two fresh stool samples were collected from all cases and controls at enrollment and examined for trophozoites of Giardia lamblia, Entamoeba histolytica and Cryptosporidium. Giardia lamblia trophozoites were detected in a significantly higher proportion of PD cases (20.0%) than acute diarrheal and non diarrheal controls (4.6% each, p < 0.0001). There were no significant differences in the proportion of cases and controls who passed E. histolytica trophozoites or cryptosporidium in their stools. There was a consistent trend towards poorer weight gain in PD cases who passed Giardia trophozoites in stool; the differences were statistically significant at days 14 and 21, after enrollment. Giardia lamblia infection is more prevalent in PD cases than in acute diarrhea or non-diarrheal controls. This prevalence is not high enough to warrant routine anti-giardia therapy in patients with PD. However, as giardiasis was observed to have adverse growth impact in PD cases, stool microscopy for detection and subsequent treatment of Giardia lamblia seems to be justified.

Lessons learnt from Diarrheal Diseases Control Program and implications for the future.

The national Diarrheal Disease Control Program was launched with the aim of improving the knowledge and practice of appropriate case management among caretakers of young children as well as health care providers. The National Family Health Survey (1992-3) revealed that 42.7% of mothers knew about ORS packets and 25.9% had ever used them. ORS use rates in children who suffered from diarrhea during the previous two weeks varied from 8.3% in Rajasthan to 50.1% in West Bengal. These findings represent substantial accomplishment, and also are a reminder that we still have to reach more than half of the households. Further analysis of the NFHS data showed that exposure to electronic mass media had a significant impact on mothers' awareness about ORS packets (56% in exposed, 32% in unexposed) and ORT use rates (38% in exposed, 25% in unexposed). In this review, future strategies for increasing the impact of the program are discussed. These include involvement of licensed and unlicensed medical practitioners, greater use of the electronic mass media, ORS standardization, greater focus on poorly performing states and resolving residual issues in the case management of diarrhea in malnourished children and infants under 6 months of age.

Status of lipid peroxidation and antioxidant enzymes in hypoxic ischemic encephalopathy.

OBJECTIVE: To compare the activities of key antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase] and the level of malonyl dialdehyde (MDA) in neonates with hypoxic ischemic encephalopathy (HIE) and controls. DESIGN: Prospective cross sectional study. SETTING: Tertiary care level II neonatal unit of teaching hospital. METHODS: Fifteen term new borns with HIE were registered for the study whereas normal term appropriate for gestational age babies were enrolled as controls. Clinical features were recorded. Activities of SOD, GPx, catalase and the content of MDA were estimated at 24 hours of age. The results obtained were statistically analyzed. RESULTS: Activities of SOD and Catalase and the level of MDA were significantly higher in cases as compared to the controls. There was however no significant alternation in the activity of GPx levels in both the groups. CONCLUSION: The increased activities of antioxidant enzymes are unable to counteract the excessively generated oxidants in vivo, as is evident from the increased MDA levels. Hence, oxygen free radicals may play a significant role in the pathogenesis of HIE.

Clinical assessment of nutritional status at birth.

OBJECTIVE: Clinical assessment of nutritional status of neonate using CAN score and comparison with other methods of determining intrauterine growth. DESIGN: Cross sectional study. SETTING: Tertiary care hospital. SUBJECTS: 637 consecutive, liveborn singleton neonates with known gestational age and no major congenital malformation. METHODS: Birth weight, length, midarm circumference and head circumference recorded in newborns. Ponderal index and mid arm to head circumference ratio was calculated. Clinical assessment of nutritional status was done on the basis of CAN score and compared with other methods. RESULTS: CAN score < 25 separated 60% of the babies as well nourished and 40% as malnourished. Weight for age and Ponderal Index classified 70-75% of babies as well nourished (AGA) and 25-30% as malnourished. Also MAC/HC classified nearly half the babies as well nourished and half as malnourished. CONCLUSION: CAN score may be a simple clinical index for identifying fetal malnutrition and for prediction of neonatal morbidity associated with it, without the aid of any sophisticated equipments.