FORMULATION AND CHARACTERIZATION OF NANO LIPID CARRIER DRY POWDER INHALER CONTAINING CIPROFLOXACIN HYDROCHLORIDE AND N-ACETYL CYSTEINE

ABSTRACT Nanolipid carriers (NLC) are developed as an alternative to solid lipid nanocarriers in order to increase the payload and to prevent drug expulsion. In this study, NLCs loaded with ciprofloxacin hydrochloride (CIP) and N-Acetyl cysteine (NAC) were prepared and evaluated for its delivery to the lung for treatment of the symptoms of cystic fibrosis and chronic obstructive pulmonary disorder. NLCs prepared by emulsification and sonication technique using cetyl palmitate (the solid lipid, 2%) and oleic acid (as the liquid lipid, 2%) and Tween80 (surfactant, 0.25%) showed smaller particle sizes (of199.1 ±1.859 nm) and relatively high encapsulation efficiencies (72.143±1.8 %.) and optimum zeta potential (-38.27 ± 0.384 mV).A novel DPI formulations loaded with the NLC containing CIP(CIP-DPI), NAC (NAC-DPI) and CIP/NAC combination (CIP-NAC-DPI) were prepared by freeze drying method using Lactose (8%w/v) as a cryoprotectant. The DPI prepared showed good flow properties, prolonged drug release and improved stability. In-vitro drug release profile of CIP HCl in case of CIP-NLC showed 55 % release in 15 hours while it was 60% in case of CIP-NLC-DPI formulation. Similar is the case with NAC formulations. Following intratracheal administration in rat model, the percentage of CIP extracted from lungs was 70.2% in case on CIP-NAC-DPI against 49.8% for CIP-DPI and 42.1% for plain CIP. This amount is about 1.6 times increase in CIP in lungs by co-administration with NAC. However, no appreciable change in the residence time of CIP in lungs after intratracheal administration of CIP-DPI and combined DPI (CIP-NAC-DPI) was noted. Keywords: Ciprofloxacin Hydrochloride, N-Acetyl Cysteine, Nano lipid Carriers, Dry powder inhaler, cystic fibrosis.

FORMULATION AND CHARACTERIZATION OF NANO LIPID CARRIER DRY POWDER INHALER CONTAINING CIPROFLOXACIN HYDROCHLORIDE AND N-ACETYL CYSTEINE

ABSTRACT Nanolipid carriers (NLC) are developed as an alternative to solid lipid nanocarriers in order to increase the payload and to prevent drug expulsion. In this study, NLCs loaded with ciprofloxacin hydrochloride (CIP) and N-Acetyl cysteine (NAC) were prepared and evaluated for its delivery to the lung for treatment of the symptoms of cystic fibrosis and chronic obstructive pulmonary disorder. NLCs prepared by emulsification and sonication technique using cetyl palmitate (the solid lipid, 2%) and oleic acid (as the liquid lipid, 2%) and Tween80 (surfactant, 0.25%) showed smaller particle sizes (of199.1 ±1.859 nm) and relatively high encapsulation efficiencies (72.143±1.8 %.) and optimum zeta potential (-38.27 ± 0.384 mV).A novel DPI formulations loaded with the NLC containing CIP(CIP-DPI), NAC (NAC-DPI) and CIP/NAC combination (CIP-NAC-DPI) were prepared by freeze drying method using Lactose (8%w/v) as a cryoprotectant. The DPI prepared showed good flow properties, prolonged drug release and improved stability. In-vitro drug release profile of CIP HCl in case of CIP-NLC showed 55 % release in 15 hours while it was 60% in case of CIP-NLC-DPI formulation. Similar is the case with NAC formulations. Following intratracheal administration in rat model, the percentage of CIP extracted from lungs was 70.2% in case on CIP-NAC-DPI against 49.8% for CIP-DPI and 42.1% for plain CIP. This amount is about 1.6 times increase in CIP in lungs by co-administration with NAC. However, no appreciable change in the residence time of CIP in lungs after intratracheal administration of CIP-DPI and combined DPI (CIP-NAC-DPI) was noted. Keywords: Ciprofloxacin Hydrochloride, N-Acetyl Cysteine, Nano lipid Carriers, Dry powder inhaler, cystic fibrosis.

Discussion on a possible neutrino detector located in India

We have identified some important and worthwhile physics opportunitites with a possible neutrino detector located in India. Particular emphasis is placed on the geographical advantage with a stress on the complimentary aspects with respect to other neutrino detectors already in operation.Comment: 9 pages; arXiv copy of published proceedings contributio

Prevalence of childhood and early adolescence mental disorders among children attending primary health care centers in Mosul, Iraq: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Children and adolescents are more vulnerable to the affects of war and violence than adults. At the time of initiation of this study, nothing was known about the prevalence of childhood and early adolescence mental disorders. The aim of the present study is to measure the point prevalence of mental disorders among children of 1–15 years age in the city of Mosul, Iraq.</p> <p>Methods</p> <p>A cross-sectional study design was adopted. Four primary health care centers were chosen consecutively as a study setting. The subjects of the present study were mothers who came to the primary health care center for vaccination of their children. The chosen mothers were included by systematic sampling randomization. All children (aged 1–15) that each mother had were considered in the interview and examination.</p> <p>Results</p> <p>Out of 3079 children assessed, 1152 have childhood mental disorders, giving a point prevalence of 37.4%, with a male to female ratio of to 1.22:1. The top 10 disorders among the examined children are post-traumatic stress disorder (10.5%), enuresis (6%), separation anxiety disorder (4.3%), specific phobia (3.3%) stuttering and refusal to attend school (3.2% each), learning and conduct disorders (2.5% each), stereotypic movement (2.3%) and feeding disorder in infancy or early childhood (2.0%). Overall, the highest prevalence of mental disorders was among children 10–15 years old (49.2%) while the lowest was among 1–5 year olds (29.1%). Boys are more affected than girls (40.2% and 33.2%, respectively).</p> <p>Conclusion</p> <p>Childhood mental disorders are a common condition highly prevalent amongst the children and early adolescents in Mosul. Data from the present study mirrors the size of the problem in local community. Several points deserve attention, the most important of which include giving care at the community level, educating the public on mental health, involving communities and families, monitoring community mental health indicators, and providing treatment at primary health care level.</p

Comparative Effectiveness Research: An Empirical Study of Trials Registered in ClinicalTrials.gov

Background The $1.1 billion investment in comparative effectiveness research will reshape the evidence-base supporting decisions about treatment effectiveness, safety, and cost. Defining the current prevalence and characteristics of comparative effectiveness (CE) research will enable future assessments of the impact of this program. Methods We conducted an observational study of clinical trials addressing priority research topics defined by the Institute of Medicine and conducted in the US between 2007 and 2010. Trials were identified in ClinicalTrials.gov. Main outcome measures were the prevalence of comparative effectiveness research, nature of comparators selected, funding sources, and impact of these factors on results. Results 231 (22.3%; 95% CI 19.8%–24.9%) studies were CE studies and 804 (77.7%; 95% CI, 75.1%–80.2%) were non-CE studies, with 379 (36.6%; 95% CI, 33.7%–39.6%) employing a placebo control and 425 (41.1%; 95% CI, 38.1%–44.1%) no control. The most common treatments examined in CE studies were drug interventions (37.2%), behavioral interventions (28.6%), and procedures (15.6%). Study findings were favorable for the experimental treatment in 34.8% of CE studies and greater than twice as many (78.6%) non-CE studies (P<0.001). CE studies were more likely to receive government funding (P = 0.003) and less likely to receive industry funding (P = 0.01), with 71.8% of CE studies primarily funded by a noncommercial source. The types of interventions studied differed based on funding source, with 95.4% of industry trials studying a drug or device. In addition, industry-funded CE studies were associated with the fewest pediatric subjects (P<0.001), the largest anticipated sample size (P<0.001), and the shortest study duration (P<0.001). Conclusions In this sample of studies examining high priority areas for CE research, less than a quarter are CE studies and the majority is supported by government and nonprofits. The low prevalence of CE research exists across CE studies with a broad array of interventions and characteristics.National Library of Medicine (U.S.) (5G08LM009778)National Institutes of Health (U.S.

Use of the Pediatric Symptom Checklist for the detection of psychosocial problems in preventive child healthcare

BACKGROUND: Early detection and treatment of psychosocial problems by preventive child healthcare may lead to considerable health benefits, and a short questionnaire could support this aim. The aim of this study was to assess whether the Dutch version of the US Pediatric Symptom checklist (PSC) is valid and suitable for the early detection of psychosocial problems among children. METHODS: We included 687 children (response 84.3%) aged 7–12 undergoing routine health assessments in nine Preventive Child Health Services across the Netherlands. Child health professionals interviewed and examined children and parents. Before the interview, parents completed an authorised Dutch translation of the PSC and the Child Behavior Checklist (CBCL). The CBCL and data on the child's current treatment status were used as criteria for the validity of the PSC. RESULTS: The consistency of the Dutch PSC was good (Cronbach alpha 0.89). The area under the ROC curve using the CBCL as a criterion was 0.94 (95% confidence interval 0.92 to 0.96). At the US cut-off (28 and above), the prevalence rate of an increased score and sensitivity were lower than in the USA. At a lower cut-off (22 and above), sensitivity and specificity were similar to that of the US version (71.7% and 93.0% respectively). Information on the PSC also helped in the identification of children with elevated CBCL Total Problems Scores, above solely clinical judgment. CONCLUSION: The PSC is also useful for the early detection of psychosocial problems in preventive child healthcare outside the USA, especially with an adjusted cut-off

Evaluation of acceptability and use of lockable storage devices for pesticides in Sri Lanka that might assist in prevention of self-poisoning

<p>Abstract</p> <p>Background</p> <p>Self-poisoning with pesticides is a major reason for high suicide rates in rural areas of many developing countries. Safer storage of pesticides may be one means of prevention. We have conducted a study to assess the acceptability and use of lockable boxes for storing pesticides in rural Sri Lanka.</p> <p>Methods</p> <p>Four hundred lockable metal storage boxes were given to farming households, 100 in each of four villages. Assessment interviews were conducted by Sumithrayo (NGO) field workers immediately after boxes were supplied (T1), 11 – 14 weeks later (T2), 30 weeks later (T3), and 18 months later (T4). Data on suicide and self-harm were collected from local police and hospitals.</p> <p>Results</p> <p>At T1 only 1.8% (7/396) of households reported locking up pesticides, 72.5% (279/385) easy access to pesticides for adults and 50.4% (195/387) easy access for children. At T3 most informants in households using pesticides reported using the box all (82.3%, 298/362) or most of the time (7.2%, 26/362). Informants usually reported always locking the box (92.8%, 336/362) and most boxes were locked on inspection (93.6%, 339/362). By T4 there was some reduction in reporting that the box was kept locked all of the time (75.2%, 267/355) and the box being locked on inspection (73.8%, 262/355). Easy child access to the key was reported in relatively few households (10.7% at T4), although interviewers judged that this was possible in rather more (20.6%). Most informants regarded the box as useful (100% at T3 and 99.4% at T4), with convenience for storage, security, avoiding wastage, and protection of children being major factors. A message on the box about how to deal with bad feelings and the importance of safer storage was well received. The locks had been broken or the key lost in a few households.</p> <p>Conclusion</p> <p>Introduction of lockable boxes for storing pesticides to farming households in Sri Lanka appeared to be acceptable. Most households used the boxes responsibly, although there was some decline in the proper usage over time. A large-scale trial of lockable storage devices in farming households in rural areas as a means of prevention of suicide and accidental poisoning is now indicated.</p

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation