Leishmanicidal Activity of Films Containing Paromomycin and Gentamicin Sulfate both In Vitro and In Vivo

Background: Based on the efficacy of paromomycin ointment and recent ongoing clinical trials of combination of paromomycin and gentamicin, a new physical form of films of the paromomy­cin and gentamicin was prepared and anti-Leishmania activities of the prepared films were as­sessed in vitro and in vivo.Methods: Paromomycin 15% and gentamicin 0.5% was incorporated in a film using ethyl cellu­lose and HPMC (Hydroxyl Propyl Methyl Cellulose). In order to assess the drug release and anti-Leishmania activities of the preparation, a clone L. major parasite was established using a set of modified NNN medium without overlay liquid layer. Therapeutic effects of the films were evalu­ated using Balb/c mice model. The mice were inoculated with 2×106 L. major promastigotes (MRHO/IR/75/ER) and then when the lesions developed the mice were randomly divided in 3 groups, 10 mice per group, and treated with either perpetrated films or placebo for 28 days or left untreated.Results: Growth inhibition of cloned promastigotes showed that the films have enough releasing capacity and in vivo system, the films containing paromomycin and gentamicin was able to re­duce the lesion size and induced complete cure in 80% of the mice but relapse was seen in 60% of the cured mice and overall 50% cure rate was seen during 20 weeks period of the study.Conclusion: It seems that the prepared films might be further used in human clinical trials

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Mortality of emergency abdominal surgery in high-, middle- and low-income countries

Background: Surgical mortality data are collected routinely in high-income countries, yet virtually no low- or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI). Methods: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression. Results: Data were obtained for 10 745 patients from 357 centres in 58 countries; 6538 were from high-, 2889 from middle- and 1318 from low-HDI settings. The overall mortality rate was 1⋅6 per cent at 24 h (high 1⋅1 per cent, middle 1⋅9 per cent, low 3⋅4 per cent; P < 0⋅001), increasing to 5⋅4 per cent by 30 days (high 4⋅5 per cent, middle 6⋅0 per cent, low 8⋅6 per cent; P < 0⋅001). Of the 578 patients who died, 404 (69⋅9 per cent) did so between 24 h and 30 days following surgery (high 74⋅2 per cent, middle 68⋅8 per cent, low 60⋅5 per cent). After adjustment, 30-day mortality remained higher in middle-income (odds ratio (OR) 2⋅78, 95 per cent c.i. 1⋅84 to 4⋅20) and low-income (OR 2⋅97, 1⋅84 to 4⋅81) countries. Surgical safety checklist use was less frequent in low- and middle-income countries, but when used was associated with reduced mortality at 30 days. Conclusion: Mortality is three times higher in low- compared with high-HDI countries even when adjusted for prognostic factors. Patient safety factors may have an important role. Registration number: NCT02179112 (http://www.clinicaltrials.gov)

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

The Effect of Using Patency File on Apical Transportation in Canals Prepared with Passive Step Back Technique

Background: The purpose of this study was to assess the effect of patency file on apical transportation in curved canals prepared with passive step back (P.S.B) technique. Methods: This is an interceptive experimental, Invitro, study. Human extracted first permanent molars with 19-23mm length and curvature of 15-35 degrees (Schneider method) were considered for use in this study. Simple sampling was done and 35 teeth for each group was selected. In experimental group A canal preparation was done with P.S.B technique and usage of a # 10 file (as Patency file) between successive files. In experimental group B preparation was done in the same way except for usage of patency file. Pre and post operative radiographs were taken with similar condition. Radiographs were scanned and changes in canal curvature was determined using four different methods [Schneider, Weine, Long – Axis techniques (L. A.T), and Digital image overlay technique (overlay. T)] , using Idrisi for windows and AutoCAD softwares. Results: The mean of canal transportation angle in experimental group A with Schneider, Weine , LAT, and Over Lay techniques was: 7.006 ± 3.478, 12. 285 ± 6.032, 4.376 ± 3.516, 3.147 ± 2.744 respectively. Mean of canal transportation angle in experimental group B with the same methods was also determined: 8.009 ± 4.178, 13.55 ± 7.602, 9.464 ± 5.384, and 9.641 ± 5.382 respectively. T- test statistical analysis shows that there are no significant differences between the mean of canal transportation angles in two groups as measured by Schneider and Weine method (P&gt;0.05). Mann- Whitney test shows that there are statistically significant differences between two groups as measured by LAT and Over Lay techniques (P&lt;0.001). Conclusions: Results of this study shows that patency file in conjunction with P.S.B techniques causes significant reduction in apical transportation angle. Shortcomings of Schneider method in determination of canal curvature and specially assessment of apical transportation after instrumentation is mentioned in several studies. Our study shows that both Schneider and Weine techniques are not reliable methods for transportation assessment when compared with Image Over Lay technique. The result of LAT Shows close proximity with Over Lay technique and can be used for evaluation of apical transportation as a simple and reliable technique. Keywords: Apical transportation, Passive step back, Apical patency, Schneider technique, Weine technique, Long axis technique, OverLay technique

Using Discrete Wavelet Transform for Trend Analysis and Oscillatory Patterns Identification of Temperature (Case Study: Mashhad Synoptic Station)

Introduction: Studying long-term trend changes of meteorological parameters is one of the routine methods in atmospheric studies, especially in the climate change subject. Among the meteorological parameters, temperature is always considered as one of the most atmospheric elements and studying it in order to gain a better understanding of the climate change phenomenon, has been effective. In addition to identifying trends, extraction of oscillatory patterns in the atmospheric phenomena and parameters occurrence can be an applicable and reliable method to explore the complex relations between atmospheric-oceanic cycles and short term or long term consequences of meteorological parameters. Materials and Methods: In this paper, monthly average temperature time series in Mashhad synoptic station in 55 years period (from 1956 to 2010) in monthly, seasonal, annual and seasons separately (winter, spring, summer and autumn) have been analyzed. Discrete wavelet transform and Mann-Kendall trend test were the main methods for performing this research. Wavelet transform is a powerful method in signal processing and it is an advanced version of short time Fourier transforms. Moreover, it has many improvements and more capabilities compared with Fourier transform. In the first step, temperature time series in various time scales (which was mentioned above) have been decomposed via discrete wavelet transforms into approximation (A) and detail (D) components. For the second step, Mann-Kendall trend test was applied to the various combinations of these decomposed components. For detecting the most dominant periodic component for each of the time scales datasets, results of Mann-Kendall test for the original time series and the decomposed components were compared to each other. The nearest value indicated the most dominant periodicity based on the D component’s level. To detect the similarity between results of the Mann-Kendall test, relative error method was employed. Additionally, it must be noted that before applying Mann-Kendall test, time series has to be assessed for its autocorrelation status. If there are seasonality patterns in the studied time series or lag-1 autocorrelation coefficient of data is significant, then some modified versions of the Mann-Kendall test have to be employed. Results and Discussion: Results of this study showed that the temperature trend at every time scaled dataset (monthly, seasonal, annual and seasons separately) is positive and significant. Autocorrelation coefficients indicated that only seasonal time series and winter datasets did not have significant ACFs. On the other hand, monthly and seasonal datasets had seasonality pattern. Based on these results, Hirsch and Slack’s modified version of Mann-Kendall test was employed for monthly and seasonal time series and for the winter temperature data, the original version of the Mann-Kendall test was applied. For the remaining time series, the Hamed and Rao’s modified version of the Mann-Kendall trend test was employed. Dominant periodicities in monthly, seasonal and annual, confirmed the oscillatory behavior of each other. However, in the seasons, it seems that periodic patterns with the same temperature ranges are more similar. On the other hand, due to the greater similarity between the results of the Mann-Kendall test in the warmer seasons and the data with monthly, seasonal and annual time scale, it seems that yearly warm period has more noticeable impacts on the positive and significant trend of temperature in the study area. It must be noted that in any of the studied time series, results of the Mann-Kendall test for detail (D) component was not significant and after adding approximation (A) component, Mann-Kendall statistics turned to a significant value. This happens because the long term variations or trends appear in approximation components in most of the time series. Conclusion: In this study, a powerful signal processing method called wavelet transform was employed to detect the most dominant periodic components in temperature time series in various time scales, in Mashhad synoptic station. Results showed that using frequency-time analysis methods has more benefits compared with the use of only classic statistical methods, since one can explore any time series with more accuracy. Because most of the meteorological variables have periodic structures, it seems that using advanced signal processing methods like wavelet for analysis of these variables can have many advantages compared with linear-based methods. It can be suggested for future studies to use and employ signal processing methods for exploring the large scaled phenomena (e.g. ENSO, NAO, etc.) and discovering the relationship between these phenomena and climate change in recent decades. Keywords: Discrete wavelet transforms, Mann-Kendall test, Oscillatory pattern, Tren

Calibration and Validation Parameter of Hydrologic Model HEC-HMS using Particle Swarm Optimization Algorithms – Single Objective

Introduction: Planning and management of water resource and river basins needs use of conceptual hydrologic models which play a significant role in predicting basins response to different climatic and meteorological processes. Evaluating watershed response through mathematical hydrologic models requires finding a set of parameter values of the model which provides thebest fit between observed and estimated hydrographs in a procedure called calibration. Asmanual calibration is tedious, time consuming and requires personal experience, automaticcalibration methods make application of more significant CRR models which are based onusing a systematic search procedure to find good parameter sets in terms of at least oneobjective function. Materials and Methods: Conceptual hydrologic models play a significant role inpredicting a basin’s response to different climatic and meteorological processes within natural systems. However, these models require a number of estimated parameters. Model calibration is the procedure of adjusting the parametervalues until the model predictions match the observed data. Manual calibration of high-fidelity hydrologic (simulation) models is tedious, time consuming and sometimesimpractical, especially when the number of parameters islarge. Moreover, the high degrees of nonlinearity involved in different hydrologic processes and non-uniqueness ofinverse-type calibration problems make it difficult to find asingle set of parameter values. In this research, the conceptual HEC-HMS model is integrated with the Particle Swarm Optimization (PSO) algorithm.The HEC-HMS model was developed as areplacement for HEC-1, which has long been considered as astandard model for hydrologic simulation. Most of thehydrologic models employed in HEC-HMS are event-basedmodels simulating a single storm requiring the specificationof all conditions at the beginning of the simulation. The soil moistureaccounting model in the HEC-HMS is the onlycontinuous model that simulates both wet and dry weatherbehavior.Programming of HEC –HMS has been done by MATLAB and techniques such as elite mutation and creating confusion have been used in order to strengthen the algorithm and improve the results. The event-based HEC-HMS model simulatesthe precipitation-runoff process for each set of parameter values generated by PSO. Turbulentand elitism with mutation are also employed to deal with PSO premature convergence. The integrated PSO-HMS model is tested on the Kardeh dam basin located in the Khorasan Razavi province. Results and Discussion: Input parameters of hydrologic models are seldomknown with certainty. Therefore, they are not capable ofdescribing the exact hydrologic processes. Input data andstructural uncertainties related to scale and approximationsin system processes are different sources of uncertainty thatmake it difficult to model exact hydrologic phenomena.In automatic calibration, the parameter values dependon the objective function of the search or optimization algorithm.In characterizing a runoff hydrograph, threecharacteristics of time-to-peak, peak of discharge and totalrunoff volume are of the most importance. It is thereforeimportant that we simulate and observe hydrographs matchas much as possible in terms of those characteristics. Calibration was carried out in single objective cases. Model calibration in single-objective approach with regard to the objective function in the event of NASH and RMSE were conducted separately.The results indicated that the capability of the model was calibrated to an acceptable level of events. Continuing calibration results were evaluated by four different criteria.Finally, to validate the model parameters with those obtained from the calibration, tests perfomed indicated poor results. Although, based on the calibration and verification of individual events one event remains, suggesting set is a possible parameter. Conclusion: All events were evaluated by validations and the results show that the performance model is not desirable. The results emphasized the impossibility of obtaining unique parameters for a basin. This method of solution, because of non-single solutions of calibration, could be helpful as an inverse problem that could limit the number of candidates. The above analysis revealed the existence of differentparameter sets that can altogether simulate verificationevents quite well, which shows the non-uniqueness featureof the calibration problem under study. However, the methodologyhas benefited from that feature by finding newparameter intervals that should be fine-tuned further inorder to decrease input and model prediction uncertainties.The proposed methodology performed well in the automatedcalibration of an event-based hydrologic model;however, the authors are aware of a drawback of the presentedanalysis – this undertakingwas not a completely fair validationprocedure. It is because validation events represent possiblefuture scenarios and thus are not available at the time ofmodel calibration. Hence, an event being selected as a validationevent should not be used to receive any morefeedback for adjusting parameter values and ranges.However,this remark was not fully taken into consideration, mostlybecause of being seriously short of enough observed eventsin this calibration study. Therefore, the proposed methodology,although sound and useful, should be validated inother case studies with more observed flood events