India's RMNCH+A Strategy: approach, learnings and limitations.

Building on the gains of the National Health Mission, India's Reproductive, Maternal, Newborn, Child and Adolescent Health (RMNCH+A) Strategy, launched in 2013, was a milestone in the country's health planning. The strategy recognised the interdependence of RMNCH+A Interventions across the life stages and adopted a comprehensive approach to address inequitable distribution of healthcare services for the vulnerable population groups and in poor-performing geographies of the country. Based on innovative approaches and management reforms, like selection of poor-performing districts, prioritisation of high-impact RMNCH+A healthcare interventions, engagement of development partners and institutionalising a concurrent monitoring system the strategy strived to improve efficiency and effectiveness within the public healthcare delivery system of the country. 184 High Priority Districts were identified across the country on a defined set of indicators for implementation of critical RMNCH+A Interventions and a dedicated institutional framework comprising National and State RMNCH+A Units and District Level Monitors supported by the development partners was established to provide technical support to the state and district health departments. Health facilities based on case load and available services across the High Priority Districts were prioritised for strengthening and were monitored by an RMNCH+A Supportive Supervision mechanism to track progress and generate evidence to facilitate actions for strengthening ongoing interventions. The strategy helped develop an integrated systems-based approach to address public health challenges through a comprehensive framework, defined priorities and robust partnerships with the partner agencies. However, lack of a robust monitoring and evaluation framework and sub-optimal focus on social determinants of health possibly limited its overall impact and ability to sustain improvements. Guided by the learnings and limitations, the Government of India has now designed the 'Aspirational Districts Program' to holistically address health challenges in poor-performing districts within the overall sociocultural domain to ensure inclusive and sustained improvements.

A 2018 Approach to Combating Methotrexate Toxicity Folic Acid and Beyond.

Methotrexate (MTX) is the cornerstone to management across a variety of rheumatic diseases. Effective use and adherence to MTX treatment is dependent on toxicity prevention and management. The major deterrents to patient tolerability and adherence can include GI upset, hepatic transaminase elevation, stomatitis, hair loss, and CNS toxicity. Many rheumatologists are familiar with employing supplementation of folic acid and folinic acid, as well as a change from oral to subcutaneous (SC) MTX, to help combat MTX toxicity. There are, however, more potential strategies in a rheumatologist's armamentarium to ameliorate side effects and improve adherence, including vitamin A supplementation and dextromethorphan. Herein, we will provide a review of the literature (both rheumatologic and oncologic) and expert opinion in terms of managing methotrexate toxicity and improving adherence in rheumatic diseases.

Improving Adolescent Health Services across High Priority Districts in 6 States of India: Learnings from an Integrated Reproductive Maternal Newborn Child and Adolescent Health Project.

BACKGROUND: India has been at the forefront of designing adolescent health (AH) policies. The National Adolescent Reproductive and Sexual Health policy (2006), the Reproductive, Maternal, Newborn Child, and AH strategy (2013), and the "Rashtriya Kishor Swasthya Karyakram (RKSK)" (2014) have been the critical milestones in this direction. However, despite policies being available, the AH outcomes need improvement through operationalization of focused and need-based AH interventions. OBJECTIVES: The objectives of this study were to improve services for RKSK interventions across select geographies of India. MATERIALS AND METHODS: USAID's VRIDDHI Project has been providing technical support at the national level and in six focus states to improve uptake of evidence-based high-impact reproductive, maternal, newborn, child, and AH interventions. To improve AH services and outcomes, two approaches were implemented, namely (a) strengthen the functioning of adolescent-friendly health clinics in 95 high caseload health facilities in 26 high priority districts across six states and (b) demonstrate other operational strategies outlined in RKSK program including strengthening of district committees on AH, undertaking formative research for developing adolescent-focused communication strategy, and operationalizing weekly iron and folic acid supplementation program. RESULTS: As a result of ongoing technical support over 2-year period (January 2016-December 2017), improvements were noted across multiple AH indicators. In addition, evidence-based learnings were also generated from the demonstration models for potential scale up to other geographies. CONCLUSION: The project was successful in improving AH services in the intervention facilities through an integrated approach which is replicable, sustainable, and scalable for driving the AH program in India.

Helping Babies Breathe (HBB) training: What happens to knowledge and skills over time?

BACKGROUND: The first minutes after birth are critical to reducing neonatal mortality. Helping Babies Breathe (HBB) is a simulation-based neonatal resuscitation program for low resource settings. We studied the impact of initial HBB training followed by refresher training on the knowledge and skills of the birth attendants in facilities. METHODS: We conducted HBB trainings in 71 facilities in the NICHD Global Network research sites (Nagpur and Belgaum, India and Eldoret, Kenya), with a 6:1 ratio of facility trainees to Master Trainers (MT). Because of staff turnover, some birth attendants (BA) were trained as they joined the delivery room staff, after the initial training was completed (catch-up initial training). We compared pass rates for skills and knowledge pre- and post- initial HBB training and following refresher training among active BAs. An Objective Structured Clinical Examination (OSCE) B tested resuscitation skill retention by comparing post-initial training performance with pre-refresher training performance. We identified factors associated with loss of skills in pre-refresher training performance using multivariable logistic regression analysis. Daily bag and mask ventilation practice, equipment checks and supportive supervision were stressed as part of training. RESULTS: One hundred five MT (1.6 MT per facility) conducted initial and refresher HBB trainings for 835 BAs; 76% had no prior resuscitation training. Initial training improved knowledge and skills: the pass percentage for knowledge tests improved from 74 to 99% (p < 0.001). Only 5% could ventilate a newborn mannequin correctly before initial training but 97% passed the post-initial ventilation training test (p < 0.0001) and 99% passed the OSCE B resuscitation evaluation. During pre-refresher training evaluation, a mean of 6.7 (SD 2.49) months after the initial training, 99% passed the knowledge test, but the successful completion rate fell to 81% for the OSCE B resuscitation skills test. Characteristics associated with deterioration of resuscitation skills were BAs from tertiary care facilities, no prior resuscitation training, and the timing of training (initial vs. catch-up training). CONCLUSIONS: HBB training significantly improved neonatal resuscitation knowledge and skills. However, skills declined more than knowledge over time. Ongoing skills practice and monitoring, more frequent retesting, and refresher trainings are needed to maintain neonatal resuscitation skills. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01681017 ; 04 September 2012, retrospectively registered.

Curcuma oil ameliorates insulin resistance & associated thrombotic complications in hamster & rat.

BACKGROUND & OBJECTIVES: Curcuma oil (C. oil) isolated from turmeric (Curcuma longa L.) has been shown to have neuro-protective, anti-cancer, antioxidant and anti-hyperlipidaemic effects in experimental animal models. However, its effect in insulin resistant animals remains unclear. The present study was carried out to investigate the disease modifying potential and underlying mechanisms of the C. oil in animal models of diet induced insulin resistance and associated thrombotic complications. METHODS: Male Golden Syrian hamsters on high fructose diet (HFr) for 12 wk were treated orally with vehicle, fenofibrate (30 mg/kg) or C. oil (300 mg/kg) in the last four weeks. Wistar rats fed HFr for 12 wk were treated orally with C. oil (300 mg/kg) in the last two weeks. To examine the protective effect of C. oil, blood glucose, serum insulin, platelet aggregation, thrombosis and inflammatory markers were assessed in these animals. RESULTS: Animals fed with HFr diet for 12 wk demonstrated hyperlipidaemia, hyperglycaemia, hyperinsulinaemia, alteration in insulin sensitivity indices, increased lipid peroxidation, inflammation, endothelial dysfunction, platelet free radical generation, tyrosine phosphorylation, aggregation, adhesion and intravascular thrombosis. Curcuma oil treatment for the last four weeks in hamsters ameliorated HFr-induced hyperlipidaemia, hyperglycaemia, insulin resistance, oxidative stress, inflammation, endothelial dysfunction, platelet activation, and thrombosis. In HFr fed hamsters, the effect of C. oil at 300 mg/kg [ ] was comparable with the standard drug fenofibrate. Curcuma oil treatment in the last two weeks in rats ameliorated HFr-induced hyperglycaemia and hyperinsulinaemia by modulating hepatic expression of sterol regulatory element binding protein 1c (SREBP-1c), peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1)α and PGC-1ß genes known to be involved in lipid and glucose metabolism. INTERPRETATION & CONCLUSIONS: High fructose feeding to rats and hamsters led to the development of insulin resistance, hyperglycaemia, endothelial dysfunction and oxidative stress. C. oil prevented development of thrombotic complications associated with insulin resistance perhaps by modulating genes involved in lipid and glucose metabolism. Further studies are required to confirm these findings.

Curcuma oil attenuates accelerated atherosclerosis and macrophage foam-cell formation by modulating genes involved in plaque stability, lipid homeostasis and inflammation.

In the present study, the anti-atherosclerotic effect and the underlying mechanism of curcuma oil (C. oil), a lipophilic fraction from turmeric (Curcuma longa L.), was evaluated in a hamster model of accelerated atherosclerosis and in THP-1 macrophages. Male golden Syrian hamsters were subjected to partial carotid ligation (PCL) or FeCl3-induced arterial oxidative injury (Ox-injury) after 1 week of treatment with a high-cholesterol (HC) diet or HC diet plus C. oil (100 and 300 mg/kg, orally). Hamsters fed with the HC diet were analysed at 1, 3 and 5 weeks following carotid injury. The HC diet plus C. oil-fed group was analysed at 5 weeks. In hyperlipidaemic hamsters with PCL or Ox-injury, C. oil (300 mg/kg) reduced elevated plasma and aortic lipid levels, arterial macrophage accumulation, and stenosis when compared with those subjected to arterial injury alone. Similarly, elevated mRNA transcripts of matrix metalloproteinase-2 (MMP-2), MMP-9, cluster of differentiation 45 (CD45), TNF-α, interferon-γ (IFN-γ), IL-1ß and IL-6 were reduced in atherosclerotic arteries, while those of transforming growth factor-ß (TGF-ß) and IL-10 were increased after the C. oil treatment (300 mg/kg). The treatment with C. oil prevented HC diet- and oxidised LDL (OxLDL)-induced lipid accumulation, decreased the mRNA expression of CD68 and CD36, and increased the mRNA expression of PPARα, LXRα, ABCA1 and ABCG1 in both hyperlipidaemic hamster-derived peritoneal and THP-1 macrophages. The administration of C. oil suppressed the mRNA expression of TNF-α, IL-1ß, IL-6 and IFN-γ and increased the expression of TGF-ß in peritoneal macrophages. In THP-1 macrophages, C. oil supplementation prevented OxLDL-induced production of TNF-α and IL-1ß and increased the levels of TGF-ß. The present study shows that C. oil attenuates arterial injury-induced accelerated atherosclerosis, inflammation and macrophage foam-cell formation.

Curcuma oil ameliorates hyperlipidaemia and associated deleterious effects in golden Syrian hamsters.

Essential oil components from turmeric (Curcuma longa L.) are documented for neuroprotective, anti-cancer, anti-thrombotic and antioxidant effects. The present study aimed to investigate the disease-modifying potential of curcuma oil (C. oil), a lipophilic component from C. longa L., in hyperlipidaemic hamsters. Male golden Syrian hamsters were fed a chow or high-cholesterol (HC) and fat-rich diet with or without C. oil (30, 100 and 300 mg/kg) for 28 d. In HC diet-fed hamsters, C. oil significantly reduced plasma total cholesterol, LDL-cholesterol and TAG, and increased HDL-cholesterol when compared with the HC group. Similar group comparisons showed that C. oil treatment reduced hepatic cholesterol and oxidative stress, and improved liver function. Hyperlipidaemia-induced platelet activation, vascular dysfunction and repressed eNOS mRNA expression were restored by the C. oil treatment. Furthermore, aortic cholesterol accumulation and CD68 expression were also reduced in the C. oil-treated group. The effect of C. oil at 300 mg/kg was comparable with the standard drug ezetimibe. Delving into the probable anti-hyperlipidaemic mechanism at the transcript level, the C. oil-treated groups fed the chow and HC diets were compared with the chow diet-fed group. The C. oil treatment significantly increased the hepatic expression of PPARa, LXRa, CYP7A1, ABCA1, ABCG5, ABCG8 and LPL accompanied by reduced SREBP-2 and HMGCR expression. C. oil also enhanced ABCA1, ABCG5 and ABCG8 expression and suppressed NPC1L1 expression in the jejunum. In the present study, C. oil demonstrated an anti-hyperlipidaemic effect and reduced lipid-induced oxidative stress, platelet activation and vascular dysfunction. The anti-hyperlipidaemic effect exhibited by C. oil seems to be mediated by the modulation of PPARa, LXRa and associated genes involved in lipid metabolism and transport.

EGb 761 promotes osteoblastogenesis, lowers bone marrow adipogenesis and atherosclerotic plaque formation.

AIM OF THE STUDY: Our earlier study has demonstrated that EGb 761 (standardized extract of Ginkgo) has the bone sparing effect on the estrogen deficiency induced bone loss model. In the present study, we have addressed the question whether treatment of osteoporosis benefits arterial calcification or vice versa, because both adipocyte and osteoblast originate from the same mesenchymal cell of the bone marrow cell (BMC) population. MATERIALS AND METHODS: Bone marrow cells were isolated to study the effect of EGb 761 on osteoblast and adipocytes. For in vivo effect hamsters were fed high fat diet and the effect of EGb 761 studied on atherosclerotic plaque formation and endothelial function. RESULTS: BMC's undergoing induced osteogenic or adipogenic differentiations in the presence of EGb 761 show increase and decrease in mineralization and adipogenesis respectively. Osteogenic and adipogenic mRNAs, reveal lineage dependent expression patterns. Runx-2 (osteoblast transcription factor) showed a progressive increase, whereas PPAR-γ (adipogenic regulator) was attenuated, with same pattern of expression being for late osteogenic and adipogenic genes. EGb 761 led to increase in apoptotic cells and ROS, an important upstream signal. In vivo experiments in hamsters after induction with high cholesterol diet (HCD) show improvement in endothelial function by EGb 761 with lowering in total plasma cholesterol levels. EGb 761 led to vascular preservation of the aortic lumen with impairment of the endothelium dependent relaxation which was corroborated by micro-CT and histological sections of the thoracic region of the aorta. CONCLUSION: From this data, it can be implied that EGb 761 controls bone loss, adiposity and lowers atherogenic risk factor after HCD induction.

Anti-platelet effects of Curcuma oil in experimental models of myocardial ischemia-reperfusion and thrombosis.

Extensive research on the mechanism of action and medicinal importance of curcumin obtained from turmeric (Curcuma longa) has unfolded its potential therapeutic value against many chronic ailments. Curcuma oil (C.oil), the highly lipophilic component from Curcuma longa has been documented for its neuroprotective efficacy against rat cerebral ischemia-reperfusion injury; however its effect on myocardial reperfusion injury remains unexplored. In the present study, effect of C.oil (500 mg/kg, po) was evaluated against myocardial ischemia-reperfusion induced injury in the rat model. C.oil failed to confer protection against cardiac injury, however significant reversal of ADP induced platelet aggregation (p<0.05) was evident in the same animals. Moreover, collagen and thrombin induced platelet aggregation (p<0.001) as well as tyrosine phosphorylation of various proteins in activated platelets was also suppressed. C.oil also offered significant protection against collagen-epinephrine induced thromboembolism in mice as well as augmented total time to occlusion against FeCl(3) induced arterial thrombosis in rats. C.oil however had no effect on coagulation parameters (TT, PT and aPTT) and exerted a mild effect on the bleeding time. Bioavailability of C.oil, as assessed by monitoring ar-turmerone, α,ß-turmerone and curlone, was 13%, 11% and 7% respectively, indicating high systemic exposure. Moreover, longer mean residence time (MRT) of ar-turmerone (13.2h), α,ß-turmerone (11.6h) and Curlone (14.0 h) and plasma elimination half lives in the range of 5.5 to 7.2h correlated with single 500 mg/kg dose regimen of C.oil. In the present study, C.oil thus seems to be an efficacious and safe anti-platelet agent which was protective against intravascular thrombosis.

Amaranthus paniculatus (Linn.) improves learning after radiation stress.

Brain is highly susceptible to oxidative damage due to its high utilization of oxygen and rather poorly developed antioxidative defense mechanism. Free radicals formation is greatly augmented during ionizing radiation exposure, which causes damage in cerebellum responsible for locomotor activity. Amaranthus paniculatus (Linn.) having high content of beta-carotene (about 15 mg/100g), ascorbic acid, Vitamin C and folate, may prove efficient antioxidants. To evaluate its antioxidative efficacy, healthy Swiss albino mice from an inbred colony were selected and divided into three groups having equal number of male and female in each group. All of these animals were initially trained in Hebb William's Maze, model D(1). After initial training of 10 days, two groups were supplemented with methanolic extract of A. paniculatus (Linn.) at a dose of 600 and 800 mg/kg bw per day, respectively for 15 days. One group without any treatment served as normal. It has been observed that mice, supplemented with extract took lesser time to reach goal than normal (without any treatment). Furthermore after supplementation of Amaranthus, followed by exposure to 9 Gy of gamma radiation by 60Co beam therapy unit, the survived mice took lesser time to reach to their goals than those without plant extract. Control mice (not supplemented with AE extract) showed continuous decline in their learning performance. Mice of Control group died within 12 days after exposure. Irradiated males try to recover from 10th day onwards but they died up to day 12. But in Experimental mice (AE treated), after initial decline in learning ability after exposure, recovery was noticed and not only this 70% of them survived beyond the observation period. Besides male mice showed faster learning ability as compared to females in all groups. After irradiation too, males took lesser time to reach to goals. Learning in all the groups before exposure has been much faster in between 9 and 15 days. After radiation, however it was followed by a sudden spurt and delayed learning response up to 12 days. Recovery was greater in males than females in treated groups. Recovery was greater in males of 600 mg/kg bw per day than other groups. Learning has been almost at the same level from 14th day onward, which indicates that both the dose levels have been found equally effective.