Enhancing early detection of neurological and developmental disorders and provision of intervention in low-resource settings in Uttar Pradesh, India: study protocol of the G.A.N.E.S.H. programme.

INTRODUCTION: Around 9% of India's children under six are diagnosed with neurodevelopmental disorders. Low-resource, rural communities often lack programmes for early identification and intervention. The Prechtl General Movement Assessment (GMA) is regarded as the best clinical tool to predict cerebral palsy in infants <5 months. In addition, children with developmental delay, intellectual disabilities, late detected genetic disorders or autism spectrum disorder show abnormal general movements (GMs) during infancy. General Movement Assessment in Neonates for Early Identification and Intervention, Social Support and Health Awareness (G.A.N.E.S.H.) aims to (1) provide evidence as to whether community health workers can support the identification of infants at high-risk for neurological and developmental disorders and disabilities, (2) monitor further development in those infants and (3) initiate early and targeted intervention procedures. METHODS: This 3-year observational cohort study will comprise at least 2000 infants born across four districts of Uttar Pradesh, India. Community health workers, certified for GMA, video record and assess the infants' GMs twice, that is, within 2 months after birth and at 3-5 months. In case of abnormal GMs and/or reduced MOSs, infants are further examined by a paediatrician and a neurologist. If necessary, early intervention strategies (treatment as usual) are introduced. After paediatric and neurodevelopmental assessments at 12-24 months, outcomes are categorised as normal or neurological/developmental disorders. Research objective (1): to relate the GMA to the outcome at 12-24 months. Research objective (2): to investigate the impact of predefined exposures. Research objective (3): to evaluate the interscorer agreement of GMA. ETHICS AND DISSEMINATION: G.A.N.E.S.H. received ethics approval from the Indian Government Chief Medical Officers of Varanasi and Mirzapur and from the Ramakrishna Mission Home of Service in Varanasi. GMA is a worldwide used diagnostic tool, approved by the Ethics Committee of the Medical University of Graz, Austria (27-388 ex 14/15). Apart from peer-reviewed publications, we are planning to deploy G.A.N.E.S.H. in other vulnerable settings.

Persistence of antihypertensive efficacy after missed doses: comparison of amlodipine and nifedipine gastrointestinal therapeutic system.

OBJECTIVE: In this randomized, double-blind, crossover study, the antihypertensive efficacy of amlodipine and nifedipine gastrointestinal therapeutic system (GITS) was compared following missed doses. Design and methods In a randomized crossover design, 42 patients were randomized to receive amlodipine (5-10 mg) or the GITS formulation of nifedipine (nifedipine GITS) (30-60 mg) once daily for 12 weeks, then vice versa. During weeks 8, 10 and 12 of each treatment period, compliance failures were simulated by patients missing 0, 1 or 2 doses of their medication, and ambulatory systolic (SBP) and diastolic (DBP) blood pressure measurements were obtained. RESULTS: Following steady-state treatment (i.e. 'perfect compliance'), there was no difference between amlodipine and nifedipine GITS in SBP (140.1 versus 134.2 mmHg) or DBP (84.0 versus 85.8 mmHg) at 0-24 h post-dose. When compliance was not perfect, i.e. when one or two doses were missed, DBP was maintained at a significantly lower level with amlodipine compared with nifedipine GITS at 24-48 h post-dose (83.1 versus 86.4 mmHg, P = 0.005) and at 48-72 h post-dose (84.2 versus 89.7 mmHg, P < 0.001). Plasma concentrations of amlodipine were better maintained than those of nifedipine GITS. At 72 h post-dose, the plasma concentration of amlodipine was 61% (17.0 +/- 11.2 ng/ml) compared with < 25% (28.3 +/- 49.9 ng/ml) for nifedipine GITS. CONCLUSION: During short periods of non-compliance, antihypertensive efficacy remains more predictable with amlodipine than with nifedipine GITS.