Cisplatin augments the anti-schistosomal effect of praziquantel in a schistosoma-infected cancer model

Schistosomiasis is the third most devastating tropical disease worldwide caused by blood flukes of the genus Schistosoma. Praziquantel (PZQ) is the drug of choice for treating all species of schistosomes. However, PZQ kills only adult Schistosoma worms, not immature stages. The inability of PZQ to abort early infection or prevent re-infection, and the lack of prophylactic effect prompt the need for novel drugs and strategies for the prevention of schistosomiasis. Tumor burden can be developed in Schistosoma-infected patients. The present study aimed to determine the host responses to mutual interaction between cancer, represented by Ehrlich ascites, and infection, represented by Schistosomiasis. Mice infected with Schistosoma and challenged with tumor 4-5 weeks later showed the same anti-schistosomal (worm and egg burden) and antitumor (total tumor cell count and mouse survival) parameters when compared to mice infected with Schistosoma alone or challenged with tumor cells alone. As expected, combinatorial treatment with PZQ and cisplatin of Schistosoma-infected mice that were challenged with tumor cell line decreased the tumor burden as well as the worm and egg burden after treatment as compared to the non-treated controls; while the worm burden and egg counts were significantly decreased (P <0.001) in treated group (VI) treated with cisplatin (0.5 mg/kg), group (VII) treated with cisplatin (2 mg/kg), group (VIII) treated with PZQ/ cisplatin (0.5 mg/kg) and group (IX) treated with PZQ / cisplatin (2 mg/kg) by 44.55% , 74%, 100% and 97.8% in worm burden, and by 47%, 78.7%, 96% and 97% in liver egg count , respectively than that of group (II) non treated S. mansoni infected alone and (IV) non treated S. mansoni/EAC alone. Also, Group IX caused a significant reduction (P <0.05) in worm burden than that of group VI. Also, total ascetic volume and the tumor cell counts in Ehrlich's ascites carcinoma (EAC)-cells were significantly decreased (P <0.001) in groups VIII and IX than that of the group (III) non-treated (EAC) inoculated alone. There was no mutual interaction between schistosomiasis infection and tumor burden. Also, whereas, PZQ did not affect on the antitumor parameters, cisplatin even at low doses had anti-schistosomal effects

Evaluation of knowledge, experiences, and fear toward prescribing and dispensing corticosteroids among Egyptian healthcare professionals: A cross-sectional study

Background: Corticosteroids (CS) are essential drugs in the treatment of several medical conditions. Assuming different roles, physicians and pharmacists play a primary role in prescribing and dispensing these medications to optimize patients' clinical management. The data on assessing knowledge and experience of healthcare professionals toward CS is scarce. Therefore, this study aimed to assess and compare knowledge, experience, and fears towards CS among Egyptian physicians and pharmacists. Methods: A cross-sectional, self-administrated, validated online questionnaire was used to collect the data from Egyptian healthcare professionals. The questionnaire consisted of four sections with multiple choice questions: sociodemographic (7 questions), knowledge about CS (13 questions), experience with CS prescription/dispensing (5 questions), and fears and preferences toward CS prescription/dispensing (13 questions). Descriptive and inferential statistics were used to analyze the data. Results: A total of 600 responses were analyzed in this study. The study sample was almost two-half of healthcare providers: 303 (50.5%) pharmacists and 297 (49.5%) physicians. Pharmacists had marginally higher knowledge scores as compared to those recorded for physicians (11.29 versus 10.16, respectively; P = 0.047). Physicians had more experience choosing corticosteroids in treatment plans based on their experience (51.8% vs 38.5%) and guideline recommendations (72.8% vs 50.9%) than pharmacists. However, pharmacists had more experience dealing with corticosteroid use based on patients' preferences (19.5% vs 4.9%) and showed a broader scope of experiencing side effects of corticosteroids with their patients. The two professions demonstrated high levels of fear, with pharmacists acknowledging significantly lower concerns about CS than physicians (3.72 versus 4.0, respectively; P = 0.003). Conclusion: Discrepancies exist among healthcare professionals in knowledge and experience, favoring better scientific knowledge of pharmacists related to corticosteroids. Based on these findings, the interprofessional collaborative efforts would provide comprehensive, patient-centered care that maximizes the benefits of CS while minimizing their risks

Incidence and clinical outcomes of nosocomial infections in patients presenting with STEMI complicated by cardiogenic shock in the United States

OBJECTIVES: This study addresses the incidence, trends, and impact of nosocomial infections (NI) on the outcomes of patients admitted with ST-segment elevation myocardial infarction (STEMI) and cardiogenic shock (STEMI-CS) using the United States National Inpatient Sample (NIS) database. METHODS: We analyzed data from 105,184 STEMI-CS patients using the NIS database from the years 2005-2014. NI was defined as infections of more than or equal to three days, comprising of central line-associated bloodstream infection (CLABSI), urinary tract infection (UTI), hospital-acquired pneumonia (HAP), Clostridium difficile infection (CDI), bacteremia, and skin related infections. Outcomes of the impact of NI on STEMI-CS included in-hospital mortality, length of hospital stay (LOS) and costs. Significant associations of NI in patients admitted with STEMI-CS were also identified. RESULTS: Overall, 19.1% (20,137) of patients admitted with STEMI-CS developed NI. Trends of NI have decreased from 2005-2014. The most common NI were UTI (9.2%), followed by HAP (6.8%), CLABSI (1.5%), bacteremia (1.5%), skin related infections (1.5%), and CDI (1.3%). The strongest association of developing a NI was increasing LOS (7-9 days; OR: 1.99; 95% CI: 1.75-2.26; \u3e9 days; OR: 4.51; 95% CI: 4.04-5.04 compared to 4-6 days as reference). Increased mortality risk among patients with NI was significant, especially those with sepsis-associated NI compared to those without sepsis (OR: 2.95; 95% CI: 2.72-3.20). Patients with NI were found to be associated with significantly longer LOS and higher costs, irrespective of percutaneous mechanical circulatory support placement. CONCLUSIONS: NI were common among patients with STEMI-CS. Those who developed NI were at a greater risk of in-hospital mortality, increased LOS and costs

Clinical Pathways for Non-ST Elevation Acute Coronary Syndrome in Oman: An Oman Heart Association Protocol for Hospital Quality Improvement Initiative

In 2012, Oman Heart Association (OHA) published its own guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction, the aim was not to be comprehensive but rather simplified and practical in order to reduce the gap between the long comprehensive guidelines and our actual practice. However, we still feel that the busy registrars and residents need simpler and direct clinical pathways or protocol to be used in the emergency departments, coronary care units and in the wards. Clinical pathways are now one of the main tools used to manage the quality in healthcare concerning the standardization of care processes. It has been shown that their implementation reduces the variability in clinical practice and improves outcomes in acute care

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

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 years; 78.2% included were male with a median age of 37 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

Regional research priorities in brain and nervous system disorders

The characteristics of neurological, psychiatric, developmental and substance-use disorders in low-and middle-income countries are unique and the burden that they have will be different from country to country. Many of the differences are explained by the wide variation in population demographics and size, poverty, conflict, culture, land area and quality, and genetics. Neurological, psychiatric, developmental and substance-use disorders that result from, or are worsened by, a lack of adequate nutrition and infectious disease still afflict much of sub-Saharan Africa, although disorders related to increasing longevity, such as stroke, are on the rise. In the Middle East and North Africa, major depressive disorders and post-traumatic stress disorder are a primary concern because of the conflict-ridden environment. Consanguinity is a serious concern that leads to the high prevalence of recessive disorders in the Middle East and North Africa and possibly other regions. The burden of these disorders in Latin American and Asian countries largely surrounds stroke and vascular disease, dementia and lifestyle factors that are influenced by genetics. Although much knowledge has been gained over the past 10 years, the epidemiology of the conditions in low-and middle-income countries still needs more research. Prevention and treatments could be better informed with more longitudinal studies of risk factors. Challenges and opportunities for ameliorating nervous-system disorders can benefit from both local and regional research collaborations. The lack of resources and infrastructure for health-care and related research, both in terms of personnel and equipment, along with the stigma associated with the physical or behavioural manifestations of some disorders have hampered progress in understanding the disease burden and improving brain health. Individual countries, and regions within countries, have specific needs in terms of research priorities.Fil: Ravindranath, Vijayalakshmi. Indian Institute of Science; IndiaFil: Dang, Hoang Minh. Vietnam National University; VietnamFil: Goya, Rodolfo Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata ; ArgentinaFil: Mansour, Hader. University of Pittsburgh; Estados Unidos. Mansoura University; EgiptoFil: Nimgaonkar, Vishwajit L.. University of Pittsburgh; Estados UnidosFil: Russell, Vivienne Ann. University of Cape Town; SudáfricaFil: Xin, Yu. Peking University; Chin

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