DEVELOPMENT AND VALIDATION OF STABILITY INDICATING GREEN HPLC-UV METHOD FOR DETERMINATION OF CEPHALEXIN IN PHARMACEUTICAL DOSAGE FORMS AND HUMAN URINE USING MICELLAR MOBILE PHASE

Objective: Development and validation of simple, stability indicating and green high performance liquid chromatographic (HPLC) method with ultraviolet (UV) detection for determination of cephalexin in pure form, pharmaceutical dosage forms and human urine samples.Methods: The method is based on using of a micellar mobile phase for separation of cephalexin and its degradation products. The analyte was chromatographed on a Kinetex C18 75×4.6 mm, 2.6 μm column. Micellar mobile phase composed of 0.1M sodium dodecyl sulphate (SDS) and 10 % isopropanol (IPA), pH was adjusted to 3±0.05 with phosphoric acid, the flow-rate was 1.0 mL/min, the UV detector was set at 254 nm and the injection volume was 20 µl. Stability indicating properties of the proposed method was proved through exposure of the analyte solutions to 4 different stress conditions of acidic, basic, oxidative and photo-irradiation conditions.Results: Under optimized conditions the average recovery was ranged from 100.4–101.7%. The lower limit of quantification (LOQ) and the lower limit of detection (LOD) were 0.097 and 0.029 μg/ml, respectively. A linear correlation in the range of 1–200 μg/ml with the correlation coefficient (r2) of ≥ 0.999 was obtained. Relatively high inter-and intra-day precisions were achieved, the percentage RSD values were lower than 2. The obtained results were validated according to USP validation parameters.Conclusion: The proposed method was found to be not only a greener method but also faster and more convenient than the USP compendial method. Greener here means that the method is more eco-friendly as it avoids usage of toxic solvent and reagent and switch to more benign chemicals. In addition, allow for injection of urine samples directly into an analytical column without pretreatment due to micellar solubilization of the interfering components of the biological samples.Â

COMPARISON OF FT-NIR TRANSMISSION AND HPLC FOR GREEN APPROACH TO DETERMINE PARACETAMOL AND ITS DEGRADATION PRODUCT 4-AMINOPHENOL IN PARACETAMOL TABLETS

Objective: Development and validation of Near infrared (NIR) spectroscopic method for determination of paracetamol and its major degradation product 4-aminophenol in paracetamol tablets and show the agreement between the NIR as a greener technique and the conventional high performance liquid chromatography (HPLC) method, official in British pharmacopeia (BP).Methods: Calibration model for paracetamol and its degradation product 4-aminophenol was built by utilizing chemometric processing which is the most critical step in the development of specific and robust NIR models. It is based mainly on a partial least square regression fit on the transmission mode using paracetamol, 4-aminophenol and excipient materials of the drug products. The results obtained by NIR spectroscopy were compared with the compendial HPLC method in the BP.Results: The chosen models had a root mean square error of the cross validation (RMSECV) values of 1.38, 1.42 and coefficient of correlation (r2) of 99.1, 99.05 for paracetamol and 4-aminophenol respectively, which indicates good fitness and accuracy of the model.Conclusion: The present study showed that NIR could be used with high accuracy for determination of for parent drug and its major degradation product in paracetamol tablets. This proposed technique realizes many of green analytical aspects in developing eco-friendly analytical methods and may replace safely the conventional chromatographic technique without compromising efficacy. Â

RAPID AND VALIDATED HPLC-UV METHOD FOR DETERMINATION OF GEMIFLOXACIN IN HUMAN URINE

Objective: To develop and validate a simple and rapid reversed phase high performance liquid chromatographic (RP-HPLC) method for the determination of Gemifloxacin (GFX) in human urine.Methods: GFX was isolated from urine samples after acidification using methylene chloride. Good chromatographic separation was achieved using C18 Ultrasphere (250 mm × 4.6 mm, 5 µm.) analytical column maintained at 25 °C. The mobile phase consisted of methanol and 0.1 M phosphate buffer pH 3 in the ratio of (48: 52, v/v), respectively. The analysis time was 10 min at a 1.0 ml/min flow rate. The UV detection was carried out at 272 nm.Results: GFX has been eluted at 7.5 min. Linearity was obtained over a concentration range of 20-200 ng/ml (r2>0.999). The extraction recovery of GFX from urine samples was 60%. The proposed method demonstrated excellent intra-and inter-day precision and accuracy within 1.19% and 100.65 %, respectively. The limit of detection (LOD) was found to be 6.3 ng/ml.Conclusion: Simple and accurate RP-HPLC method for determination of GFX in human urine was developed and validated. The method was successfully applied for determination of GFX in human urine samples from healthy volunteers up to 24 hours after oral administration of 320 mg gemi floxacin tablets.Â

Development of Simple Green Spectrophotometric and Conductometric Methods for Determination of Cephalosporins in Pure, Pharmaceutical Dosage forms and Human Urine

Five Simple, accurate and rapid spectrophotometric and conductometric methods were developed for the determination of four third generation cephalosporins, namely, cefotaxime sodium (I) , cefoperazone sodium (II), ceftazidime pentahydrate (III) and cefdinir (IV) in pure active ingredient, pharmaceutical dosage forms and human urine. Method A: is based on the reaction of the sulphide ions produced from the alkaline hydrolysis of the cited four drugs with P- aminophenol (PAP). This reaction results in a thionine dye (phenothiazine derivative) formation which exhibits maximum absorbance at 545 nm. Method B: is based on oxidation of drug (I and III) with a known excess of n-bromosuccinimide (NBS) in acidic medium followed by the determination of unreacted amount of n-bromosuccinimide  with metol and sulphanilic acid. The purple-red reaction product exhibits maximum absorbance at 520 nm. Method C: is based on the formation of yellow chelate between drug (IV) and palladium (II) chloride in buffered medium (pH  3.5) with an absorption maximum at 314 nm.  Method D: is based on the reaction of drug (IV) with aqueous ninhydrin to give yellow colored product in the presence of bicarbonate with an absorption maximum at 433 nm . Method E: A conductometric method is based on the reaction of the four cited drugs with phosphotungstic acid (PTA) forming an ion associate in aqueous medium. Validation of the proposed methods was carried out. All proposed methods were successfully applied for the commercial dosage forms of the cited drugs. Method C was successfully applied for the determination of cefdinir in human urine

Single puncture percutaneous nephrolithomy for management of complex renal stones

<p>Abstract</p> <p>Background</p> <p>The purpose of this report is to assess the safety and efficacy of single lower pole access for multiple and branched renal calculi. A prospective non randomized clinical study included 26 patients with complex renal stones (9 patients had branched renal stones and the other 17 had multiple renal stones) in the period from May 2003 to May 2004. Mean patient age was 42 years ± 13.2 (range 18 to 67 years). All patients underwent percutaneous nephrolithotomy (PCNL) via a single lower calyceal puncture. Small stones were intactly extracted by a range of stone graspers while large stones (smallest diameter more than 1 cm) were disintegrated using either the pneumatic EMS Swiss lithoclast or Holmium YAG laser. Flexible nephroscope was used for stones inaccessible by the rigid instruments.</p> <p>Findings</p> <p>Overall stone-free rate was 74.8%. Patients with residual stones were managed by one session of shock wave lithotripsy (SWL). Mean operative time was (80 minutes ± 27.4) for branched stones and (49.1 minutes ± 15.9) for multiple stones. No significant blood loss reported. Perforation of pelvicalyceal system occurred in 2 patients (11.5%) with no serious sequelae. Only 1 patient developed secondary hemorrhage which necessitated blood transfusion and selective angio-embolization.</p> <p>Conclusion</p> <p>In our hands, the efficacy and safety of single lower calyceal puncture PCNL in management of complex renal stones are comparable to those of the general procedure stated in literature.</p

Selenium and Nano-Selenium Biofortification for Human Health

Selenium is an essential micronutrient required for the health of humans and lower plants, but its importance for higher plants is still being investigated. The biological functions of Se related to human health revolve around its presence in 25 known selenoproteins (e.g., selenocysteine or the 21st amino acid). Humans may receive their required Se through plant uptake of soil Se, foods enriched in Se, or Se dietary supplements. Selenium nanoparticles (Se-NPs) have been applied to biofortified foods and feeds. Due to low toxicity and high e ciency, Se-NPs are used in applications such as cancer therapy and nano-medicines. Selenium and nano-selenium may be able to support and enhance the productivity of cultivated plants and animals under stressful conditions because they are antimicrobial and anti-carcinogenic agents, with antioxidant capacity and immune-modulatory efficacy. Thus, nano-selenium could be inserted in the feeds of fish and livestock to improvise stress resilience and productivity. This review offers new insights in Se and Se-NPs biofortification for edible plants and farm animals under stressful environments. Further, extensive research on Se-NPs is required to identify possible adverse effects on humans and their cytotoxicity.Peer Reviewe

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication