Association of GH gene polymorphism with growth and semen traits in rabbits

[EN] Although growth hormone (GH) gene mutations are described in several species, the studies concerning their variabilities and associations with economic traits in rabbits are scarce, particularly associations with semen traits. A total of 149 rabbit bucks from five populations (V-line=36, Moshtohor line=28, APRI line=42, cross ½A½M=23, and Gabali=20) were used in the present study to identify polymorphism of c.-78 C>T single nucleotide polymorphism (SNP) of GH gene among these populations and to investigate the association of GH gene polymorphism with body weight (BW), daily weight gain (DG) and semen traits. DNA was extracted from blood samples for genotyping of c.-78 C>T SNP of GH gene based on polymerase chain reaction with the restriction fragment length polymorphism (PCR-RFLP) technique. The genetic diversity of SNP C>T of GH gene was assessed in terms of genotypic and allelic frequencies, effective number of alleles (Ne), observed (Ho) and expected (He) heterozygosity, Hardy-Weinberg equilibrium (HWE), reduction in heterozygosity due to inbreeding (FIS) and polymorphism information content (PIC). Three genotypes of TT, CC and TC of PCR product of 231 bp of GH gene were detected and all the populations were in HWE in terms of GH gene. The highest Ne was obtained for the Moshtohor line (1.978), while the lowest allelic numbers were obtained for V-line (1.715) and Gabali breed (1.800). The highest genotype frequency of GH gene was 0.48 in TT genotype of V-line, 0.21 in CC genotype of Moshtohor line, 0.67 and 0.56 in TC genotype of ½A½M and Gabali rabbits (P<0.05). The highest frequency for C allele was recorded by Moshtohor line (0.45) and the lowest frequency by Gabali (0.32). The genetic diversity scores for GH gene were intermediate (Ho=0.551, He=0.471, PIC=0.358). The values of Ho ranged from 0.444 in V-line to 0.667 in ½A½M cross, while the values of He were 0.425 in V-line and 0.508 in Moshtohor line. The values of PIC were moderate and ranged from 0.332 in V-line to 0.375 in M-line. The highest FIS was observed in Moshtohor line (0.042) and the lowest value was observed in ½A½M cross (–0.413). The CT genotype of GH gene showed the highest and significant values for body weights at 4, 8, 10 and 12 wk (542, 1131, 1465 and 1861 g) and daily gains at intervals of 4-6 and 8-10 wk (23.1 and 26.5 g). Additionally, the CT genotype recorded the highest and significant values for volume of ejaculate (1.1 mL), sperm motility (57.6%), live sperm (85.6%), normal sperm (93.1%) and sperm concentration in semen (611×106/mL), along with the lowest and significant values for dead sperms (14.4%) and abnormal sperms (6.9%).The authors are very grateful to the Central Laboratory of the Faculty of Veterinary Medicine, Benha University, Egypt for the help and support in molecular genetic analyses. This work was financially supported by the research project entitled “Genetic improvement of local rabbit breeds by using molecular genetic techniques” from the Scientific Research Fund (SRF), Benha University, Egypt.Khalil, MHE.; Zaghloul, AR.; Iraqi, MM.; El Nagar, AG.; Ramadan, SI. (2021). Association of GH gene polymorphism with growth and semen traits in rabbits. World Rabbit Science. 29(1):31-40. https://doi.org/10.4995/wrs.2021.13001OJS3140291Abdel-Kafy E., Hussein B., Abdel-Ghany S., El-Din A., Badawi Y. 2015. Single nucleotide polymorphisms in growth hormone gene are associated with some performance traits in rabbit. Int. J. Biol. Pharm. Allied Sci., 4: 490-504.Afshari K.P., Javanmard A., Asadzadeh N., Sadeghipanah H., Masomi H., Sabrivand A. 2011. Association between GH encoding gene polymorphism and semen characteristics in Iranian Holstein bulls. Afr. J. Biotechnol., 10: 882-886.Alvariño J. 2000. Reproductive performance of male rabbits. In Proc.: 7th World Rabbit Congress, 4-7 July, Valencia, Spain.Amalianingsih T., Brahmantiyo B. 2014. The variability of growth hormone gene associated with ultrasound imaging of longissimus dorsi muscle and perirenal fat in rabbits. Media Peternakan, 37: 1-7. https://doi.org/10.5398/medpet.2014.37.1.1Amiri S., Jemmali B., Ferchichi M. A., Jeljeli H., Boulbaba R., Ben Gara A. 2018. Assessment of growth hormone gene polymorphism effects on reproductive traits in Holstein dairy cattle in Tunisia. Arch. Anim. Breed., 61: 481-489. https://doi.org/10.5194/aab-61-481-2018Bindu, K., Raveendran, A., Antony, S., Raghunandanan, K. 2011. Association of myostatin gene (MSTN ) polymorphism with economic traits in rabbits. In: Fibre production in South American Camelids and other fibre animals. Springer. https://doi.org/10.3920/978-90-8686-727-1_16Darwish S.F., Tarek S.H., Badr M.R. 2016. Association between genotypes of growth hormone gene and semen quality traits in cow bulls and buffalo bulls. Alex. J. Vet. Sci., 49: 147-152. https://doi.org/10.5455/ajvs.221998El-Aksher, S.H., Sherif, H.S., Khalil, M.H., El-Garhy, H.A.S., Ramadan, S. 2017. Molecular analysis of a new synthetic rabbit line and their parental populations using microsatellite and SNP markers. Gene Rep., 8: 17-23.https://doi.org/10.1016/j.genrep.2017.05.001El-Sabrout K., Aggag S. 2017a. Associations between single nucleotide polymorphisms in multiple candidate genes and body weight in rabbits, Vet. World, 10: 136-139. https://doi.org/10.14202/vetworld.2017.136-139El-Sabrout K., Aggag S. 2017b. The gene expression of weaning age and its effect on productive performance of rabbits. World Rabbit Sci., 25: 1-7. https://doi.org/10.4995/wrs.2017.4777El-Tarabany M.S., El-Bayomi K., Abdelhamid T. 2015. Semen characteristics of purebred and crossbred male rabbits. PloS one, 10: e0128435. https://doi.org/10.1371/journal.pone.0128435Estany J., Baselga M., Blasco A., Camacho J. 1989. Mixed model methodology for the estimation of genetic response to selection in litter size of rabbits. Lives. Prod. Sci., 21: 67-75. https://doi.org/10.1016/0301-6226(89)90021-3Fontanesi L., Tazzoli M., Scotti E., Russo V. 2008. Analysis of candidate genes for meat production traits in domestic rabbit breeds. In Proc.: 9th World Rabbit Congress, 10-13 June 2008,.Verona, Italy.Fontanesi L., Dall'Olio S., Spaccapaniccia E., Scotti E., Fornasini D., Frabetti A.. 2012. A single nucleotide polymorphism in the rabbit growth hormone (GH1) gene is associated with market weight in a commercial rabbit population. Livest. Sci., 147: 84-88. https://doi.org/10.1016/j.livsci.2012.04.006Gencheva D., Georgieva S., Velikov K., Koynarski T., Tanchev S. 2017. Single nucleotide polymorphism of the Growth Hormone Receptor (GHR) encoding gene in Oryctolagus cuniculus. J. BioSci. Biotechnol. 6: 197-201.Gidenne T., Garreau H., Drouilhet L., Aubert C., Maertens L. 2017. Improving feed efficiency in rabbit production, A review on nutritional, technico-economical, genetic and environmental aspects. Anim. Feed Sci. Technol., 225: 109-122. https://doi.org/10.1016/j.anifeedsci.2017.01.016Groeneveld E. 2006. PEST user's manual. Institute of Animal Husbandry and Animal Behaviour, Mariensee, Germany, FAL, Germany.Hristova D., Tanchev S., Velikov K., Gonchev P., Georgieva S. 2017. Rabbit growth hormone and myostatin gene polymorphisms. J. Agric. Res., 2: 000133 (Open Access). https://doi.org/10.23880/OAJAR-16000133Hristova D.G., Tanchev S., Velikov K., Gonchev P., Georgieva S. 2018. Single nucleotide polymorphism of the growth hormone (GH) encoding gene in inbred and outbred domestic rabbits. World Rabbit Sci., 26: 49-55. https://doi.org/10.4995/wrs.2018.7211Iraqi M., Afifi E., Baselga M., Khalil M., García M. 2008. Additive and heterotic components for post-weaning growth traits in a crossing project of V-line with Gabali rabbits in Egypt. In Proc.: 9th World Rabbit Congress, 10-13 June 2008, Verona, Italy.Kalinowski, S.T., Taper, M.L., Marshall, T.C. 2007. Revising how the computer program CERVUS accommodates genotyping error increases success in paternity assignment. Molecular Ecology, 16: 1099-1106. https://doi.org/10.1111/j.1365-294X.2007.03089.xKhalil M., Baselga M. 2002. Rabbit genetic resources in Mediterranean countries. In M. H. Khalil & M. Baselga (Eds.), Options Méditerranéennes (Vol. Série B, pp. 262). Zaragoza, Spain: CIHEAM-IAMZ.Khalil M.H., Al-Sobayil K., Al-Saef A., García M., Baselga M. 2007. Genetic evaluation for semen characteristics in a crossbreeding project involving Saudi and Spanish V-line rabbits. Animal, 1: 923-928. https://doi.org/10.1017/S1751731107000341Kmieć M., Terman A., Wierzbicki H., Zych S. 2007. Association of GH gene polymorphism with semen parameters of boars. Acta Vet. Brno., 76: 41-46. https://doi.org/10.2754/avb200776010041Lavara R., García M., Torres C., Vicente J., Baselga M. 2008. Genetic parameters for semen traits of rabbit males: II. Motility. In Proc.: 9th World Rabbit Congress., 10-13 June 2008, Verona, Italy.Lavara, R., Vicente, J., Baselga, M. 2011. Genetic parameter estimates for semen production traits and growth rate of a paternal rabbit line. J. Anim. Breed. Genet., 128: 44-51. https://doi.org/10.1111/j.1439-0388.2010.00889.xLavara, R., David, I., Moce, E., Baselga, M., Vicente, J. 2013. Environmental and male variation factors of freezability in rabbit semen. Theriogenology, 79: 582-589. https://doi.org/10.1016/j.theriogenology.2012.11.007Maertens L., Gidenne T. 2016. Feed efficiency in rabbit production: nutritional, technico-economical and environmental aspects. In Proc.: 11th World Rabbit Congress, 15-18 June, Qingdao, China.Migdal L., Palka S., Kmiecik M., Derewicka O. 2019. Association of polymorphisms in the GH and GHR genes with growth and carcass traits in rabbits (Oryctolagus cuniculus). Czech J. Anim. Sci., 64: 255-264. https://doi.org/10.17221/27/2019-CJASNikbin S., Panandam J.M., Yaakub H., Murugaiyah M. 2018. Association of novel SNPs in gonadotropin genes with sperm quality traits of Boer goats and Boer crosses. J. Applied Anim. Res., 46: 459-466. https://doi.org/10.1080/09712119.2017.1336441Pal A., Chakravarty A.K., Chatterjee P.N. 2014. Polymorphism of growth hormone gene and its association with seminal and sexual behavioral traits in crossbred cattle. Theriogenology, 81: 474-480. https://doi.org/10.1016/j.theriogenology.2013.11.002Peakall P., Smouse R. 2012. GenAlEx 6.5: Genetic analysis in Excel. Population genetic software for teaching and research. An update. Bioinformatics, 28: 2537-2539. https://doi.org/10.1093/bioinformatics/bts460Raymond M. 1995. GENEPOP (version 1.2): Population Genetics Software for exact tests and ecumenicism. J. Hered., 86: 248-249. https://doi.org/10.1093/oxfordjournals.jhered.a111573Sahwan F.M., El-Sheik A.I., Sharaf M.M., El-Nahas A.F. 2014. Genetic polymorphism in growth hormone receptor gene (GHR) and its relationship with growth trait in pure and hybrid rabbit breeds. Alex. J. Vet. Sci., 43: 45-51. https://doi.org/10.5455/ajvs.165197Tanchev S. 2015. Conservation of genetic resources of autochthonous domestic livestock breeds in Bulgaria. A review. Bulgarian J. Agric. Sci., 21: 1262-1271.Tusell L., Legarra A., García-Tomás M., Rafel O., Ramon J., Piles M. 2012. Genetic basis of semen traits and their relationship with growth rate in rabbits. J. Anim. Sci. 90: 1385-1397. https://doi.org/10.2527/jas.2011-4165Yardibi H., Hosturk G.T., Paya I., Kaygisiz F., Ciftioglu G., Mengi A., Oztabak K. 2009. Associations of growth hormone gene polymorphisms with milk production traits in South Anatolian and East Anatolian red cattle. J. Anim. Vet. Adv. 8: 1040-1044. https://doi.org/10.3923/javaa.2009.1040.1044Youssef Y., Iraqi M., El-Raffa A., Afifi E., Khalil M., García M., et al. 2008. A joint project to synthesize new lines of rabbits in Egypt and Saudi Arabia: emphasis for results and prospects. In Proc.: 9th World Rabbit Congress, 10-13 June, Verona-Italy.Zachmann M. 1992. Interrelations between growth hormone and sex hormones: physiology and therapeutic consequences. Horm. Res. Paediat., 38: 1-8. https://doi.org/10.1159/000182562Zhang W.X., Zhang G.W., Peng J., Lai S.J. 2012. The polymorphism of GHR gene associated with the growth and carcass traits in three rabbit breeds. In Proc.: 10th World Rabbit Congress, Sharm El-Sheikh, Egypt, 75-7

A multifaceted risk model of brucellosis at the human-animal interface in Egypt

Brucellosis is a highly contagious zoonosis affecting humans and a wide range of domesticated and wild animal species. An important element for effective disease containment is to improve knowledge, attitudes and practices (KAP) of afflicted communities. This study aimed to assess the KAP related to brucellosis at the human‐animal interface in an endemic area of Egypt and to identify the risk factors for human infection. A matched case‐control study was conducted at the central fever hospitals located in six governorates in northen Egypt. Face‐to‐face interviews with cases and controls were conducted using a structured questionnaire. In total, 40.7% of the participants owned farm animals in their households. The overall mean practice score regarding animal husbandry, processing and consumption of milk and dairy products was significantly lower among cases compared to controls [‐12.7±18.1 vs 0.68±14.2 respectively; p< 0.001]. Perceived barriers for notification of animal infection/abortion were predominate among cases and positively correlated with participants’ education. The predictors of having brucellosis infection were consumption of unpasteurized milk or raw dairy products and practicing animal husbandry. Applying protective measures against infection significantly reduced its risk. A model predicting risk factors for brucellosis among those who own animal showed that frequent abortions per animal increased the chance for brucellosis infection among human cases by 50‐fold (95% CI: 8.8 – 276.9), whereas the use of protective measures in animal care reduced the odds [OR= 0.11 (95% CI: 0.03 – 0.45)]. In conclusion, consumption of unprocessed dairy products was equally important as contact with infected/aborted animals as major risk factors for Brucella spp. infection among humans in Egypt. There is poor knowledge, negative attitudes and risky behaviors among villagers which can perpetuate the risk of brucellosis transmission at the human‐animal interface. This supports the need for integrating health education into the national brucellosis control program

Biopiracy <i>versus </i>one-world medicine – from colonial relicts to global collaborative concepts

Background: Practices of biopiracy to use genetic resources and indigenous knowledge by Western companies without benefit-sharing of those, who generated the traditional knowledge, can be understood as form of neocolonialism.Hypothesis: : The One-World Medicine concept attempts to merge the best of traditional medicine from developing countries and conventional Western medicine for the sake of patients around the globe.Study design: Based on literature searches in several databases, a concept paper has been written. Legislative initiatives of the United Nations culminated in the Nagoya protocol aim to protect traditional knowledge and regulate benefit-sharing with indigenous communities. The European community adopted the Nagoya protocol, and the corresponding regulations will be implemented into national legislation among the member states. Despite pleasing progress, infrastructural problems of the health care systems in developing countries still remain. Current approaches to secure primary health care offer only fragmentary solutions at best. Conventional medicine from industrialized countries cannot be afforded by the impoverished population in the Third World. Confronted with exploding costs, even health systems in Western countries are endangered to burst. Complementary and alternative medicine (CAM) is popular among the general public in industrialized countries, although the efficacy is not sufficiently proven according to the standards of evidence-based medicine. CAM is often available without prescription as over-the-counter products with non-calculated risks concerning erroneous self-medication and safety/toxicity issues. The concept of integrative medicine attempts to combine holistic CAM approaches with evidence-based principles of conventional medicine.Conclusion: To realize the concept of One-World Medicine, a number of standards have to be set to assure safety, efficacy and applicability of traditional medicine, e.g. sustainable production and quality control of herbal products, performance of placebo-controlled, double-blind, randomized clinical trials, phytovigilance, as well as education of health professionals and patients

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

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

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

BACKGROUND: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide. METHODS: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters. RESULTS: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 per cent of patients (2901 of 4223). Major complication rates (Clavien–Dindo grade at least IIIa) were 24, 18, and 27 per cent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 per cent; however, it was 41 per cent in low-to-middle- compared with 19 per cent in very high-HDI countries. CONCLUSION: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761

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

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

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

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701