A pseudo-randomised clinical trial of in situ gels of fluconazole for the treatment of oropharngeal candidiasis

<p>Abstract</p> <p>Background</p> <p>Oropharyngeal candidasis is a common opportunistic infection seen in immunocompromised patients. Fluconazole has a broad spectrum antifungal activity including a wide variety of <it>candida </it>species. Aim of the present investigation was to formulate and find out the relative efficacy of <it>in situ </it>gels of fluconazole.</p> <p>Method</p> <p>The <it>in situ </it>gels were prepared using polymers which exhibited sol-to-gel phase transition due to change in specific physico-chemical parameters, such as ion triggered system using gellan gum (0.5% w/v) along with sodium carboxylmethylcellulose (0.35%w/v). The study design was bicenter, 'pseudo-randomised, single blind trial conducted in Mangalore., India, which includes 15 HIV positive patients, 15 patients with partial or completes dentures, and 15 patients who were treated with (active control) fluconazole tablets 100 mg/day for 14 days. Severity of disease was scored clinically before treatment and at clinical evaluations on day 3, 7, 14, 18, 21, 35, and 42. Semiquantitative microbiological cultures of oral swabs were also obtained on same days.</p> <p>Results</p> <p>All patients had mycological documented oropharyngeal candidiasis and were treated with fluconazole (0.5%w/v) <it>in situ </it>gels for 14 days Severity of disease was scored clinically before treatment and at different predetermined time intervals along with semi quantitative culture of oral swabs. The clinical response rate showed 97% cure after 14 days in the treated with <it>in situ </it>gel. In comparison, the control group treated with fluconazole tablets showed 85% improvement in symptoms of oral candidiasis. The patients suffering from HIV infection showed relapse in oral candidiasis at the end of 21 days. The patients having oral candidiasis due to partial or complete dentures showed complete recovery and were free from signs and symptoms of oral candidiasis.</p> <p>Conclusions</p> <p>The <it>in situ </it>gel formulation of fluconazole was well tolerated with no severe adverse reaction and offers a better alternative to tablet formulation in the treatment of oropharyngeal candidasis.</p> <p>Trial registration</p> <p>Current Controlled Trails <a href="http://www.controlled-trials.com/ISRCTN90634047">ISRCTN90634047</a></p

Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970–2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. METHODS: We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. FINDINGS: Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7-87·2), and for men in Singapore, at 81·3 years (78·8-83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, an

Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015

Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61.7 years (95% uncertainty interval 61.4-61.9) in 1980 to 71.8 years (71.5-72.2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11.3 years (3.7-17.4), to 62.6 years (56.5-70.2). Total deaths increased by 4.1% (2.6-5.6) from 2005 to 2015, rising to 55.8 million (54.9 million to 56.6 million) in 2015, but age-standardised death rates fell by 17.0% (15.8-18.1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14.1% (12.6-16.0) to 39.8 million (39.2 million to 40.5 million) in 2015, whereas age-standardised rates decreased by 13.1% (11.9-14.3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42.1%, 39.1-44.6), malaria (43.1%, 34.7-51.8), neonatal preterm birth complications (29.8%, 24.8-34.9), and maternal disorders (29.1%, 19.3-37.1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Copyright (C) The Author(s). Published by Elsevier Ltd.Peer reviewe

Antibiotic prescribing knowledge, attitudes, and practice among physicians in teaching hospitals in South India

Background: Antibiotic overuse is a major public health challenge worldwide. Data from India related to physician antibiotic prescribing patterns are limited. Aims: We assessed antibiotic prescribing knowledge, attitudes, and practices among physicians in Mangalore, South India. Materials and Methods: Using a cross-sectional descriptive study design, physicians at academic tertiary hospitals completed an anonymous on-site survey. The survey items incorporated Likert scales, and data were analyzed using SPSS version 15.0. Results: Of the 350 physicians approached using a convenient sampling method, 230 (66%) consented and interviewed. The physician's knowledge of resistance patterns of common bacteria was related to receiving periodic updates on resistance patterns of bacteria (P = 0.019) and participation in courses on antibiotics (P = 0.026). Individuals with more number of years of experience (mean of 11 years) were less likely to justify antibiotic use for uncomplicated bronchitis (P = 0.015) and acute gastroenteritis (P = 0.001). Most respondents (n = 204, 89%) believed that physicians overprescribed antibiotics in routine clinical practice. Forty-five percent (n = 104) stated that their hospitals did not have an infection control policy in place. Conclusions: This study provides some understanding of physician's antibiotic prescribing patterns from teaching hospitals in India. Judicious antimicrobial use through educational and antimicrobial stewardship programs remains critical to control the spread of antibiotic resistance

Prevalence and Characterization of Diarrheagenic Escherichia coli Isolated from Adults and Children in Mangalore, India

Background: Diarrheal diseases are a major cause of morbidity and mortality in resource-limited countries. Among the bacterial pathogens, diarrheagenic E. coli (DEC) are most frequently implicated in cases of epidemic and endemic diarrhea worldwide. The objective of this study was to determine the prevalence of DEC in stool specimens from patients with acute diarrhea using polymerase chain reaction (PCR). Materials and Methods: Escherichia coli stool samples were collected from 115 hospitalized children and adults with acute diarrhea in Mangalore, a coastal city, in southern India. PCR amplification of eae, bfp, stx, ehx genes were used for detection of enteropathogenic (EPEC) and shigatoxigenic E. coli (STEC), lt and st genes were used for enterotoxigenic E. coli (ETEC) and astA gene for enteroaggregative E. coli (EAEC). Results: During the 24 month study period, of the 115 stool samples, DEC type was detected in 20 (17.4%) using the PCR method. The most prevalent DEC was atypical EPEC accounting for 12 (10.4%) cases followed by 4 cases of EAEC (3.4%) and 4 of STEC (3.4%). No ETEC strains were isolated from any of the examined stool samples. Conclusion: This study suggests that the atypical EPEC are the newly emerging group among DEC stains in Southern India. Further studies are needed to evaluate the epidemiology and virulence properties of atypical EPEC strains

In vitro antimicrobial and cytotoxic effects of Anacardium occidentale and Mangifera indica in oral care

Background: Oral health is an integral and important component of general health. Infectious diseases such as caries, periodontal, and gingivitis indicate the onset of imbalance in homeostasis between oral micro biota and host. The present day medicaments used in oral health care have numerous side effects. The uses of herbal plants as an alternative have gained popularity due to side effects of antibiotics and emergence of multidrug resistant strains. Anacardium occidentale (cashew) and Mangifera indica (mango) have been used as traditional oral health care measures in India since time immemorial. Materials and Methods: The ethanol extracts of cashew and mango leaves were obtained by maceration method. The antimicrobial activity was evaluated by clear zone produced by these plant extracts against Enterococcus faecalis, Staphylococcus aureus, Streptococcus mutans, Escherichia coli, and Candida albicans in agar plate method, determination of minimum inhibitory concentration (MIC), minimum bactericidal/fungicidal concentration (MBC/MFC), and suppression of biofilm. The cytotoxic effects of plants extract was determined by microculture tetrazolium assay on human gingival fibroblast and Chinese hamster lung fibroblast (V79) cell lines. Results: Cashew and mango leaf extract significantly (P < 0.05) produced larger zone of inhibition against test pathogens when compared to povidone---iodine-based mouth rinses. Although the MIC and MBC/MFC values of mouth rinses were effective in lower concentrations; plant extracts significantly (P < 0.001) suppressed the biofilms of oral pathogens. The leaf extracts were less cytotoxic (P < 0.001) compared to mouth rinses. Conclusions: Plant extracts are superior to the mouth rinses and have a promising role in future oral health care

Antimicrobial assay of combination surfactant irrigant regimen on vancomycin-resistant Enterococcus faecalis. An in vitro direct contact test

Background: Vancomycin-resistant enterococci (VRE) are on the rise globally in primary intraradicular infections and resistant to most intracanal irrigants and medicaments. The aim of this study was to evaluate the efficacy of irrigants and identify a cost-effective regimen to eradicate VRE. Materials and Methods: In this in vitro study irrigants were categorized as primary and surfactant groups with individual concentrations consisting of 10 samples each. Primary irrigants; sodium hypochlorite (NaOCl), chlorhexidine (CHX), and iodine potassium iodide (IKI) were prepared in concentrations of 5%, 2.5%, 2%, and 1%. Surfactants cetrimide (CTR) and sodium dodecyl sulfate (SDS) were prepared in concentrations of 0.25%, 0.5%, 1%, and 2%. Biopure MTAD was chosen as the control group. ATCC 51299 (VRE) was evaluated for antimicrobial susceptibility to the above irrigants by direct contact test for 5 min. The effect of each test irrigant was determined by calculating the percentage kill of viable bacteria by spectrophotometer. Statistical analysis was done by means of a one-way ANOVA and Mann–Whitney U-test (P < 0.05 consider significant). Results: About 2.5% and 5% CHX were significant over mixture of tetracycline, acid and detergent (MTAD) (P < 0.05). 5% CHX could achieve 100% elimination while 2.5% CHX and 5% IKI had 99.90%. 2% CHX and 2.5% IKI had 99% effective kill percentage. All concentrations of NaOCl were ineffective (90%) as compared to MTAD (95%). CTR (0.5%, 1% and 2%) and SDS (2%) were significant (P < 0.05) over MTAD. Combination surfactant regimens of 2% CHX +0.5% CTR and 2% CHX +1% SDS achieved 99.90% eradication potential and were significant (P < 0.05) over MTAD. Conclusion: Surfactant regimens were highly effective and superior to MTAD. CTR and SDS by their organic solvent property enhanced the antibacterial action of CHX

Antimicrobial susceptibility, risk factors and prevalence of bla cefotaximase, temoneira, and sulfhydryl variable genes among Escherichia coli in community-acquired pediatric urinary tract infection

INTRODUCTION: The emergence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has become an important challenge among pediatric patients with community-acquired urinary tract infection (UTI). OBJECTIVES: The aim of this study was to assess the antimicrobial susceptibility patterns, associated risk factors and to survey the frequency of bla cefotaximase (CTX-M), bla temoneira (TEM), and bla sulfhydryl variable (SHV) genotypes in ESBL-producing E. coli isolated from children with community-acquired UTI. METHODS: This was a prospective study conducted from November 2012 to March 2016 in a tertiary care center. E. coli isolated in urine cultures from children aged ≤18 years was identified and confirmed for ESBL production. ESBL-positive strains were screened for ESBL encoding genes. Chi-square test and Fisher’s exact test were used to compare the difference in antibiotic susceptibility with respect to ESBL positive and negative, and binary logistic regression was used to identify the risk factors associated with ESBL production. RESULTS: Among 523 E. coli isolates, 196 (37.5%) were ESBL positive, >90% were resistant to cephalosporins, and 56% were resistant to fluoroquinolones. Least resistance was observed for imipenem, netilmicin, and nitrofurantoin (2%, 8.6%, 15.3%). Association between ESBL production and drug resistance was significant for ceftazidime (P < 0.001), cefixime (P < 0.001), cefotaxime (P = 0.010), ceftazidime-clavulanic acid (P < 0.001), levofloxacin (P = 0.037), and gentamicin (P = 0.047) compared to non-ESBL E. coli. CTX-M gene was the most prevalent (87.5%), followed by TEM (68.4%) and SHV (3.1%). Previous history of UTI and intake of antibiotics were the common risk factors. CONCLUSION: ESBL-producing E. coli from community-acquired pediatric UTI carries more than one type of beta-lactamase coding genes correlating their increased antibiotic resistance. Aggressive infection control policy, routine screening for detecting ESBL isolates in clinical samples, and antimicrobial stewardship are the keys to prevent their dissemination in community settings

Mutagenicity potential (affect) of new atraumatic restorative treatment (ART) material incorporated with Azadirachta indica (Neem) against Salmonella typhimurium

Background The mutagenicity potential of a new atraumatic restorative treatment (ART) material against Salmonella typhimurium without metabolic activity using the Ames test (genotoxicity) was carried out. Methods and materials The potential mutagenicity of new atraumatic restorative treatment materials (ART-I and ART-II) was analyzed using the Ames test. The materials were eluted in dimethyl sulphoxide, 0.9% NaCl solution and sterilized de-ionized water and the aliquots were used after an incubation period of 24 h at 37 °C. Mutagenic effects of the materials were tested on Salmonella typhimurium strains TA 98 and TA 100 using the standard assay, and in absence of S9 fraction from rat liver. Result No mutagenic effects were detected for these new ART materials on S. typhimurium TA100. The incubated DMSO extract and 0.9% NaCl extract (50 μl/plate) of the ART-I exhibited a weak mutagenic potential on S. typhimurium TA 98. In particular, Aqua extract (50 μl/plate) of ART-II, was associated with a weak mutagenic potential on S. typhimurium TA98. Conclusion Both ART materials (ART–I and II) exhibited weak mutagenic effects on S. typhimurium TA98 whereas no mutagenic effect was detected on S. typhimurium TA100. ART-II is safer than ART-I

Age estimation of an individual by using Olze′s method in South Indian population

Background: The present study was conducted to assess age of adults by using Olze′s method and also to estimate the efficacy of Olze′s method in south Indian population. Materials and Methods: The present study comprised of 25 subjects ranging from 12 to 26 years from Mangalore. Dental age was assessed by using the Olze′s method based on upper and lower third molar. Panoramic radiographs were taken for the same. The obtained data were analyzed by using paired t-test, intraclass correlation coefficient, and regression analysis using Statistical Package for Social Sciences (SPSS) 13 software for statistical analysis. Results: Average chronological age was 16.11. Average age estimated by Olze′s method was 16.05. The intraclass correlation coefficient between the two methods showed excellent agreement between the two. Statistical analysis indicated that there is no significant difference between chronological age and age obtained by Olze′s method. Conclusion: Olze′s method has been experimented by many authors. An attempt was made to apply original method in our population and check its reliability. The present study indicated that, Olze′s method was reliable for age estimation in our sample. This method of age estimation was accurate in both males and females