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 < 0⋅001) or low (363 of 860, 42⋅2 percent; OR 0⋅08, 0⋅07 to 0⋅10, P < 0⋅001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference −9⋅4 (95 per cent c.i. −11⋅9 to −6⋅9) per cent; P < 0⋅001), but the relationship was reversed in low-HDI countries (+12⋅1 (+7⋅0 to +17⋅3) per cent; P < 0⋅001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0⋅60, 0⋅50 to 0⋅73; 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

Novel anti-inflammatory film as a delivery system for the external medication with bioactive phytochemical “Apocynin”

Hend Mohamed Anter,1 Irhan Ibrahim Abu Hashim,1 Walaa Awadin,2 Mahasen Mohamed Meshali1 1Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia, Egypt; 2Department of Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Dakahlia, Egypt Purpose: Recently, Apocynin (APO) has emerged as a bioactive phytochemical with potent antioxidant and anti-inflammatory properties. No reports have been published so far concerning its topical application as a pharmaceutical dosage form for prospective use. To the best of our knowledge, this is the first study to fabricate novel anti-inflammatory film for external medication with APO. Methods: APO film was prepared using casein (CAS) as a natural protein film former by solvent casting technique. The medicated film was extensively evaluated in terms of its various physicochemical characteristics, ex vivo skin permeation profile, stability, and finally in vivo anti-inflammatory activity on carrageenan-induced rat paw edema. Results: The film represented satisfactory mechanical properties along with good flexibility. Fourier transform-infrared spectroscopy, differential scanning calorimetry, and X-ray diffractometry revealed possible solubility of APO in the amorphous CAS and inter- and intramolecular hydrogen bonding between the film components. The ex vivo skin permeation results of the medicated film demonstrated non-Fickian diffusion mechanism of the permeated drug. Application of APO film to rat paw before carrageenan-induced paw edema or after induction disclosed eminent anti-inflammatory activity expressed by marked decrease in paw swelling (%) and increase in edema inhibition rate (%). In addition, histopathologic examination revealed a significant decrease in inflammatory scores. The immunohistochemical expression levels of both nuclear factor kappa B and cyclooxygenase-2 were significantly suppressed. Conclusion: These results indicated that CAS film could be applied as a promising external delivery system for the anti-inflammatory APO. Keywords: Apocynin, casein, topical film, in vivo studies, inflammation, pharmacodynamic

Pivotal role of Acitretin nanovesicular gel for effective treatment of psoriasis: ex vivo–in vivo evaluation study

Irhan Ibrahim Abu Hashim,1 Noha Fawzy Abo El-Magd,1 Ahmed Ramadan El-Sheakh,2 Mohammed Fawzy Hamed,3 Abd El-Gawad Helmy Abd El-Gawad1 1Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; 2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; 3Department of Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt Abstract: The goal of the current study was to explore the potential benefits of Acitretin (Act) nanovesicular gel as a prospective antipsoriatic topical delivery system counteracting the drug challenges in terms of its extremely low aqueous solubility, instability, skin irritation, and serious systemic adverse effects. Act-loaded niosomes were successfully developed, entirely characterized, and optimized. Further evaluation of the optimized formula was conducted regarding its stability and ex vivo cytotoxicity on different cell lines. The optimized niosomal vesicles were then incorporated in gel base matrix and investigated by sequential ex vivo (skin permeation and deposition) and in vivo (skin irritation and antipsoriatic activity using mouse tail model) experiments. The optimized Act-loaded niosomes (span 60:cholesterol molar ratio 1:1) were spherical in shape and exhibited the highest entrapment efficiency (90.32±3.80%) with appropriate nanosize and zeta potential of 369.73±45.45 nm and –36.33±1.80 mV, respectively. Encapsulation of the drug in the nanovesicles was further emphasized by differential scanning calorimetric and powder X-ray diffraction studies. After 3 months storage at 4±1°C, the optimized formula preserved its stability. Act nano niosomal gel produced a remarkable enhanced ex vivo permeation profile up to 30 h and significant drug deposition in the viable epidermal–dermal layers compared with those of Act gel. The pronounced antipsoriatic activity of the medicated nano niosomes was proved ex vivo in HaCaT cells (a keratinocyte cell line). Topical application of Act nano niosomal gel to mouse tail model further established its distinct in vivo antipsoriatic superiority in terms of significantly higher orthokeratosis, drug activity, and reduction in epidermal thickness compared with the control and other gel formulations. Also, negligible skin irritation and better skin tolerability of Act nanovesicular gel were revealed by primary irritation index and histopathologic examination. Keywords: Acitretin, nanovesicular gel, drug deposition, HaCaT cells, mouse tail model, antipsoriatic activit

Polymeric micelles for potentiated antiulcer and anticancer activities of naringin

Elham Abdelmonem Mohamed,1 Irhan Ibrahim Abu Hashim,1 Rehab Mohammad Yusif,1,2 Ahmed Abdel Aziz Shaaban,3 Ahmed Ramadan El-Sheakh,3 Mohammed Fawzy Hamed,4 Farid Abd Elreheem Badria5 1Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; 2Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah, Saudi Arabia; 3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt; 4Department of Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt; 5Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt Abstract: Naringin is one of the most interesting phytopharmaceuticals that has been widely investigated for various biological actions. Yet, its low water solubility, limited permeability, and suboptimal bioavailability limited its use. Therefore, in this study, polymeric micelles of naringin based on pluronic F68 (PF68) were developed, fully characterized, and optimized. The optimized formula was investigated regarding in vitro release, storage stability, and in vitro cytotoxicity vs different cell lines. Also, cytoprotection against ethanol-induced ulcer in rats and antitumor activity against Ehrlich ascites carcinoma in mice were investigated. Nanoscopic and nearly spherical 1:50 micelles with the mean diameter of 74.80±6.56 nm and narrow size distribution were obtained. These micelles showed the highest entrapment efficiency (EE%; 96.14±2.29). The micelles exhibited prolonged release up to 48 vs 10 h for free naringin. The stability of micelles was confirmed by insignificant changes in drug entrapment, particle size, and retention (%) (91.99±3.24). At lower dose than free naringin, effective cytoprotection of 1:50 micelles against ethanol-induced ulcer in rat model has been indicated by significant reduction in mucosal damage, gastric level of malondialdehyde, gastric expression of tumor necrosis factor-alpha, caspase-3, nuclear factor kappa-light-chain-enhancer of activated B cells, and interleukin-6 with the elevation of gastric reduced glutathione and superoxide dismutase when compared with the positive control group. As well, these micelles provoked pronounced antitumor activity assessed by potentiated in vitro cytotoxicity particularly against colorectal carcinoma cells and tumor growth inhibition when compared with free naringin. In conclusion, 1:50 naringin–PF68 micelles can be represented as a potential stable nanodrug delivery system with prolonged release and enhanced antiulcer as well as antitumor activities. Keywords: naringin, pluronic F68, polymeric micelles, in vitro cytotoxicity, antiulcer, antitumor activit