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

Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn’s disease: long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource

Objective: Thiopurines are widely used as maintenance therapy in inflammatory bowel disease (IBD) but the evidence base for their use is sparse and their role increasingly questioned. Using the largest series reported to date, we assessed the long-term effectiveness of thiopurines in ulcerative colitis (UC) and Crohn’s disease (CD), including their impact on need for surgery. Design: Outcomes were assessed in 11 928 patients (4968 UC, 6960 CD) in the UK IBD BioResource initiated on thiopurine monotherapy with the intention of maintaining medically induced remission. Effectiveness was assessed retrospectively using patient-level data and a definition that required avoidance of escalation to biological therapy or surgery while on thiopurines. Analyses included overall effectiveness, time-to-event analysis for treatment escalation and comparison of surgery rates in patients tolerant or intolerant of thiopurines. Results: Using 68 132 patient-years of exposure, thiopurine monotherapy appeared effective for the duration of treatment in 2617/4968 (52.7%) patients with UC compared with 2378/6960 (34.2%) patients with CD (p<0.0001). This difference was corroborated in a multivariable analysis: after adjusting for variables including treatment era, thiopurine monotherapy was less effective in CD than UC (OR 0.47, 95% CI 0.43 to 0.51, p<0.0001). Thiopurine intolerance was associated with increased risk of surgery in UC (HR 2.44, p<0.0001); with a more modest impact on need for surgery in CD (HR=1.23, p=0.0015). Conclusion: Thiopurine monotherapy is an effective long-term treatment for UC but significantly less effective in CD

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

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome

From policy to practice : exploring the burden of hepatitis B & C in the UK Nepali community, and the barriers to community migrant testing.

Study Abstract: Context: The UK Nepali community is a unique migrant population, with recent expansion and presence in the UK following the approval of settlement rights to Gurkha veterans and their dependents granted from 2004 to 2008. The community is heterogeneous in relation to caste and religion, with Ghurkha military ties the principal denominator to bind this newly arrived population. Many in the community have settled close to military institutions, with a new migrant population that has emerged as a result around the Aldershot area in Hampshire and Surrey. The health awareness and needs of the UK Nepali community is poorly understood, including in chronic viral hepatitis (CVH), with increased hepatitis B and C (HBV and HCV) risks that are well described in migrant groups from the neighbouring countries of India and China, but with no previous studies in the UK Nepali population. HBV and HCV is a global disease, and carries a higher death toll than that seen in comparison to HIV or tuberculosis. CVH disproportionately affects some migrant groups, with case-finding to test at-risk groups part of national guidance by the National Institute of Health and Care Excellence (NICE), as well as the World Health Organisation (WHO), with WHO goals that look to eradicate HBV and HCV by 2030. At the same time, migrant groups such as the recently arrived Nepali community face growing political and social pressures, with rising nationalism and anti-migrant sentiment seen across Europe, and with blood borne virus rates that have been specifically targeted by right-wing political groups in the UK. CVH is typically asymptomatic until advanced and severe complications develop; but with highly effective and well-tolerated treatments available if disease is identified at the right time. Effective case-finding to identify CVH in at-risk groups is therefore a priority, and a key aim of national (NICE) CVH testing guidance. The awareness and implementation of this policy is however largely unknown, with particular deficits in our understanding of testing activity in primary care, which remains crucial to delivering CVH testing in migrant communities nationally. The following study therefore presents a comprehensive exploration of the potential barriers and facilitators that exist towards CVH testing in migrant groups, taking the Nepali community as the focus of this thesis. It explores the factors that exist at the policy level towards effective testing delivery in migrant groups, and at the local (community) level towards CVH testing in primary care, and compares the understanding and perception of the newly arrived Nepali community towards liver disease, and the development of a community based study to identify the CVH risks in the local Nepali population. Intervention: At the macro-level a policy prioritisation framework was utilised to look at the factors that influence how CVH testing policy can achieve political attention and resources for its implementation. At the community (micro) level, focus group studies were undertaken with members of the Nepali population to explore the awareness, knowledge and perception of liver disease, as well as the potential risks and barriers that may exist towards health engagement strategies. Qualitative focus studies were also conducted with General Practitioners (GPs) from 3 local GP practices who serve the recently arrived Nepali community, to understand the awareness, knowledge and perception of CVH testing in migrant groups. A dedicated community-based testing intervention was then developed to directly assess HBV and HCV prevalence in the local Nepali community, building on the findings from local focus group studies. Outcome: At the policy level, the National Institute for Health and Care Excellence has produced CVH testing recommendations that are far-reaching, and would have a positive impact on CVH testing in migrant communities, including the UK Nepali population. However, policy has been developed in a top-down approach, without clear leadership to coordinate testing activity, and without community level cohesion that is evident at the Local Authority, local health service (currently Clinical Commissioning Groups (CCG)) or primary care level. At the micro-level, focus group studies in the Nepali community identified high-levels of awareness of liver disease, and although understood principally as “jaundice”, liver disease is viewed as a disease to be feared. Whilst perceptions of stigma are evident, with associations to extrinsic agents such as Spirits and Witch Doctors in disease and cure, there is an overwhelming desire to engage with modern healthcare approaches in the UK, with primary care a trusted and well sought counsel to learn about liver disease. Focus group studies in primary care though suggest significant barriers to CVH testing in migrant groups, with low levels of awareness and knowledge towards existing policy, and with active perceptions of prejudice and harm if they were to engage in CVH testing activity in migrant communities. As part of a dedicated testing study, HBV and HCV testing was undertaken in 1005 participants (984 unique individuals) from the local Nepali population, with the close and integral involvement of a specially developed Nepali research committee. DBS (Dry-blood spot) testing was used to deliver testing at centrally located community sites. Significant anti-migrant sentiment was expressed during the study, limiting the ability for formal study advertising through written or visual media. Despite this, we were able to recruit close to 1000 members of the local community, with word-of-mouth a powerful route to disseminate testing information in the Nepali community. Absolute rates of active CVH were low, with HBsAg detected in just 3 (0.3%) of individuals and HCV Ab detected in 4 individuals(0.4%), although none of these participants had detectable RNA levels on subsequent testing. Evidence of previous HBV exposure was however raised, with 9.25% (91) of participants demonstrating HBcAb positivity. Associated risk factors for HBcAb positivity were lower educational status and male gender. Conclusion: Overall, the absolute rates of active CVH appear low in Nepali community, but with higher rates of previous hepatitis B exposure that warrant the need to understand disease risks in the wider Nepali community. At the policy level, there are gaps in the effectiveness of policy across the policy prioritisation framework, with a lack of leadership and direction to facilitate testing at the community level. Members of the Nepali community view CVH as a disease to be feared, and whilst stigma arises as a perception towards liver disease, the overwhelming emphasis is a wish to engage with health care professionals, with good levels of engagement demonstrated in our subsequent community-based testing studies. The perceptions raised in primary care though demonstrate a reluctance to engage in CVH testing activity in migrant groups, with the need for further interventions to modify testing behaviour if we are to reach global and national CVH eradication goals

An overview of the neurological correlates of Cotard syndrome

ABSTRACT -Background and objectives: Considerable etiologic ambiguity surrounds Cotard syndrome and a range of psychodynamic, existential and biological theories have been proposed to explain its etiopathogenesis. Despite the often-noted neurological abnormalities on examination and assessment in Cotard syndrome, an in-depth evaluation is lacking. In this paper, we provide an overview of the neurological (neurostructural, neurophysiological and neuropsychological) correlates of Cotard syndrome and discuss the implications of our findings from an etiological and clinical perspective. Methods: We searched electronic databases and key journals using the appropriate search terms. All reported cases of Cotard syndrome with neurological investigations published in English were included in the review. The two authors independently reviewed the full text of over 100 papers and selected the papers for inclusion in the final review. Results: Various organic conditions such as typhoid fever, temporal lobe epilepsy, brain tumours and brain injuries have been reported in association with Cotard syndrome. The most commonly reported neurological abnormalities in these patients include structural brain changes (bilateral cerebral atrophy, dilated lateral ventricles), functional brain changes (hypoperfusion in the frontal and parietal cortices) and neuropsychological abnormalities (impaired face recognition). Conclusions: In summary, although not all, some cases of Cotard syndrome are associated with structural and functional brain dysfunction. From a clinical perspective, it is crucial to maintain a low threshold for suspicion of organicity in cases of this uncommon psychiatric syndrome, and thereafter to consider appropriate neurological investigations

Assessment of total antioxidant capacity and antimicrobial activity of Glycyrrhiza glabra in saliva of HIV-infected patients

Objectives: The objectives of this study were to evaluate the antimicrobial activity and total antioxidant capacity (TAC) of licorice in Saliva of HIV/AIDS patients. Materials and Methods: Saliva specimens were collected from 20 people living with HIV infection, with CD4 count <500 cells/mm3 from people infected with HIV/AIDS in Mangalore city, India. A combination of amoxicillin-clavulanic acid and nystatin was taken as the positive control and normal saline as negative control. Results were compared using one-way analysis of variance followed by Tukey's post hoc analysis in SPSS 19. Results: The TAC was evaluated spectrophotometrically at 695nm using the phosphomolybdenum method. Glycyrrhiza glabra showed a statistically significant reduction (P < 0.05) in total Candida count. The TAC of G. glabra was found to be 4.467 mM/L. Conclusions: G. glabra extracts showed good anticandidal activity and also high antioxidant property which reduces the oxidative stress of HIV-infected people