Drivers and barriers of international migration of doctors to and from the United Kingdom: a scoping review.

BACKGROUND: Many high-income countries are heavily dependent on internationally trained doctors to staff their healthcare workforce. Over one-third of doctors practising in the UK received their primary medical qualification abroad. Simultaneously, an average of around 2.1% of doctors leave the UK medical workforce annually to go overseas. The aim of this study was to identify the drivers and barriers of international migration of doctors to and from the UK. METHODS: A scoping review was conducted. We searched EMBASE, MEDLINE, CINAHL, ERIC and BEI in January 2020 (updated October 2021). Grey literature and citation searching were also carried out. Empirical studies reporting on the drivers and barriers to the international migration of doctors to and from the UK published in the English language from 2009 to present were included. The drivers and barriers were coded in NVivo 12 building on an existing framework. RESULTS: 40 studies were included. 62% were quantitative, 18% were qualitative, 15% were mixed-methods and 5% were literature reviews. Migration into and out of the UK is determined by a variety of macro- (global and national factors), meso- (profession led factors) and micro-level (personal factors). Interestingly, many of the key drivers of migration to the UK were also factors driving migration from the UK, including: poor working conditions, employment opportunities, better training and development opportunities, better quality of life, desire for a life change and financial reasons. The barriers included stricter immigration policies, the registration process and short-term job contracts. CONCLUSIONS: Our research contributes to the literature by providing a comprehensive up-to-date review of the drivers and barriers of migration to and from the UK. The decision for a doctor to migrate is multi-layered and is a complex balance between push/pull at macro-/meso-/micro-levels. To sustain the UK's supply of overseas doctors, it is vital that migration policies take account of the drivers of migration particularly working conditions and active recruitment while addressing any potential barriers. Immigration policies to address the impact of Brexit and the COVID-19 pandemic on the migration of doctors to and from the UK will be particularly important in the immediate future. Trial registration PROSPERO CRD42020165748.

PTI-125 Reduces Biomarkers of Alzheimer's Disease in Patients.

BACKGROUND: The most common dementia worldwide, Alzheimer's disease is often diagnosed via biomarkers in cerebrospinal fluid, including reduced levels of Aß1-42, and increases in total tau and phosphorylated tau-181. Here we describe results of a Phase 2a study of a promising new drug candidate that significantly reversed all measured biomarkers of Alzheimer's disease, neurodegeneration and neuroinflammation. PTI-125 is an oral small molecule drug candidate that binds and reverses an altered conformation of the scaffolding protein filamin A found in Alzheimer's disease brain. Altered filamin A links to the α7-nicotinic acetylcholine receptor to allow Aß42's toxic signaling through this receptor to hyperphosphorylate tau. Altered filamin A also links to toll-like receptor 4 to enable Aß-induced persistent activation of this receptor and inflammatory cytokine release. Restoring the native shape of filamin A prevents or reverses filamin A's linkages to the α7-nicotinic acetylcholine receptor and toll-like receptor 4, thereby blocking Aß42's activation of these receptors. The result is reduced tau hyperphosphorylation and neuroinflammation, with multiple functional improvements demonstrated in transgenic mice and postmortem Alzheimer's disease brain. OBJECTIVES: Safety, pharmacokinetics, and cerebrospinal fluid and plasma biomarkers were assessed following treatment with PTI-125 for 28 days. Target engagement and mechanism of action were assessed in patient lymphocytes by measuring 1) the reversal of filamin A's altered conformation, 2) linkages of filamin A with α7-nicotinic acetylcholine receptor or toll-like receptor 4, and 3) levels of Aß42 bound to α7-nicotinic acetylcholine receptor or CD14, the co-receptor for toll-like receptor 4. DESIGN: This was a first-in-patient, open-label Phase 2a safety, pharmacokinetics and biomarker study. SETTING: Five clinical trial sites in the U.S. under an Investigational New Drug application. PARTICIPANTS: This study included 13 mild-to-moderate Alzheimer's disease patients, age 50-85, Mini Mental State Exam ≥16 and ≤24 with a cerebrospinal fluid total tau/Aß42 ratio ≥0.30. INTERVENTION: PTI-125 oral tablets (100 mg) were administered twice daily for 28 consecutive days. MEASUREMENTS: Safety was assessed by electrocardiograms, clinical laboratory analyses and adverse event monitoring. Plasma levels of PTI-125 were measured in blood samples taken over 12 h after the first and last doses; cerebrospinal fluid levels were measured after the last dose. Commercial enzyme linked immunosorbent assays assessed levels of biomarkers of Alzheimer's disease in cerebrospinal fluid and plasma before and after treatment with PTI-125. The study measured biomarkers of pathology (pT181 tau, total tau and Aß42), neurodegeneration (neurofilament light chain and neurogranin) and neuroinflammation (YKL-40, interleukin-6, interleukin-1ß and tumor necrosis factor α). Plasma levels of phosphorylated and nitrated tau were assessed by immunoprecipitation of tau followed by immunoblotting of three different phospho-epitopes elevated in AD (pT181-tau, pS202-tau and pT231-tau) and nY29-tau. Changes in conformation of filamin A in lymphocytes were measured by isoelectric focusing point. Filamin A linkages to α7-nicotinic acetylcholine receptor and toll-like receptor 4 were assessed by immunoblot detection of α7-nicotinic acetylcholine receptor and toll-like receptor 4 in anti-filamin A immunoprecipitates from lymphocytes. Aß42 complexed with α7-nicotinic acetylcholine receptor or CD14 in lymphocytes was also measured by co-immunoprecipitation. The trial did not measure cognition. RESULTS: Consistent with the drug's mechanism of action and preclinical data, PTI-125 reduced cerebrospinal fluid biomarkers of Alzheimer's disease pathology, neurodegeneration and neuroinflammation from baseline to Day 28. All patients showed a biomarker response to PTI-125. Total tau, neurogranin, and neurofilament light chain decreased by 20%, 32% and 22%, respectively. Phospho-tau (pT181) decreased 34%, evidence that PTI-125 suppresses tau hyperphosphorylation induced by Aß42's signaling through α7-nicotinic acetylcholine receptor. Cerebrospinal fluid biomarkers of neuroinflammation (YKL-40 and inflammatory cytokines) decreased by 5-14%. Biomarker effects were similar in plasma. Aß42 increased slightly - a desirable result because low Aß42 indicates Alzheimer's disease. This increase is consistent with PTI-125's 1,000-fold reduction of Aß42's femtomolar binding affinity to α7-nicotinic acetylcholine receptor. Biomarker reductions were at least p ≤ 0.001 by paired t test. Target engagement was shown in lymphocytes by a shift in filamin A's conformation from aberrant to native: 93% was aberrant on Day 1 vs. 40% on Day 28. As a result, filamin A linkages with α7-nicotinic acetylcholine receptor and toll-like receptor 4, and Aß42 complexes with α7-nicotinic acetylcholine receptor and CD14, were all significantly reduced by PTI-125. PTI-125 was safe and well-tolerated in all patients. Plasma half-life was 4.5 h and approximately 30% drug accumulation was observed on Day 28 vs. Day 1. CONCLUSIONS: PTI-125 significantly reduced biomarkers of Alzheimer's disease pathology, neurodegeneration, and neuroinflammation in both cerebrospinal fluid and plasma. All patients responded to treatment. The magnitude and consistency of reductions in established, objective biomarkers imply that PTI-125 treatment counteracted disease processes and reduced the rate of neurodegeneration. Based on encouraging biomarker data and safety profile, approximately 60 patients with mild-to-moderate AD are currently being enrolled in a Phase 2b randomized, placebo-controlled confirmatory study to assess the safety, tolerability and efficacy of PTI-125.

Effect of treating carious teeth on children's and adolescents' anthropometric outcomes: A systematic review of randomised controlled trials.

OBJECTIVE: To examine the impact of treating carious teeth on children's and adolescents' anthropometric outcomes. BASIC RESEARCH DESIGN: Four electronic databases and four electronic clinical trials registries were searched. Two reviewers independently conducted the screening, data extraction and critical appraisal. The Cochrane Risk of Bias Tool for Randomised Controlled Trials was used to assess the risk of bias in the included studies. RESULTS: The searches yielded 399 potential studies. Following deduplication and screening of the papers, four were considered eligible for inclusion of which two referred to the same study. None of the included studies was found to have a high risk of bias in any of the domains. However, performance bias was deemed of unclear risk in all studies. One of the studies found that following extraction of pulpally involved teeth, underweight children exhibited a statistically significant improvement in their weight-for-age (change in mean=0.26; p⟨0.001) and BMI-for-age z scores (change in mean=0.52, p⟨0.001) and had a significant weight gain (change in mean=1.2; p⟨0.001). Two studies showed that dental intervention did not have a significant effect on anthropometric outcomes. Treatment of caries significantly improved children's oral health-related quality of life in two studies. CONCLUSIONS: The evidence into the impact of treating carious teeth on children's growth is mixed and inconclusive. However, there is consistent evidence that treatment of severely carious teeth can significantly improve children's oral health-related quality of life. Oral health promotion and strategies to screen for oral health problems and widen dental access should be considered as part of integrated public health programs targeting children.

Health care engagement behaviors of men who use performance- and image-enhancing drugs in Australia.

Background: Although people who inject performance- and image-enhancing drugs (PIEDs) report fewer unsafe injecting practices, stigma and discrimination may negatively impact their access to help and information. Engagement with health care services, compared with social networks (friends, relatives, and gym associates) and the Internet and media (steroid user forums, information sites, and magazines), may be important for harm minimization. Methods: A cross-sectional Internet or in-person survey of men who use PIEDs in Australia in 2014-2015 examined differences in sources for PIEDs, injecting equipment, and anabolic-androgenic steroids (AAS) information and factors associated with having periodical medical checks related to PIEDs issues using multivariate logistic regression. Results: In total, 267 men (mean age: 25 years, SD: 8.7 years; 246 of 267 [92%] reported recent AAS injection) were recruited. Most participants sourced injecting equipment from health professionals, PIEDs from their social networks, and AAS information from the Internet and media. Self-reported AAS knowledge was high and frequent. Higher income (adjusted odds ratio [AOR]: 2.04, 95% confidence interval [CI]: 1.03, 4.00), ≥2 different PIEDs used in addition to AAS (AOR: 1.94, 95% CI: 1.08, 3.49), and sourcing AAS information from health care professionals (AOR: 3.14, 95% CI: 1.81, 5.46) were independently associated with periodical medical checks. Participants nominated preference for improved health services through needle-syringe programs, primary care services, and peer educator support groups. Conclusion: Men who use PIEDs in Australia consider themselves well informed but tend to use Internet and media sources, providing potentially misleading or inaccurate information. Increasing trust between men who use PIEDs and health care providers may enable delivery of PIEDs-specific information to those at greatest need.

Evaluation of muscle tissue and liver glycogen of cattle submitted to transport over long distances and subjected to emergency slaughter / Avaliação do tecido muscular e glicogênio hepático de bovinos transportados por longas distâncias e submetidos ao abate de emergência

The study evaluated the effect of transportation over long distances on cattle muscle tissue of submitted to emergency slaughter in slaughterhouses in northern Tocantins, Brazil. The evaluations consisted in pH, muscle and liver glycogen, muscle histopathology and creatine kinase (CK), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity. Animals were placed into two groups: Experimental Group (EG), consisting of 19 bovines intended for immediate emergency slaughter, and Control Group (CG), composed of 24 bovines slaughtered in accordance with the normal flow. CK and ALT levels were high in EG. AST did not differ between groups. EG showed higher muscle pH and mean of degenerate fibers, mainly on the intercostal. However, muscle and liver glycogen did not differ between groups. In conclusion, cattle transported over long distances and subjected to immediate emergency slaughter showed markedly stress condition, with changes in biochemical parameters in the muscle tissue, determined by cellular degeneration.(AU)

O presente trabalho objetivou avaliar o efeito do transporte em longas distâncias sobre o tecido muscular de bovinos encaminhados ao abate de emergência. Foram avaliados pH, glicogênio muscular e hepático, análise histopatológica muscular, creatina quinase (CK), alanina aminotransferase (ALT) e aspartato aminotransferase (AST). Os animais foram alocados em dois grupos: grupo experimental (GE), constituído por 19 bovinos destinados ao abate de emergência, e grupo controle (GC), composto por 24 bovinos abatidos de acordo com o fluxo normal do frigorífico. A CK e a ALT estavam aumentadas no GE. O AST não diferiu entre os grupos. O GE apresentou maior percentual de fibras degeneradas, e o músculo intercostal teve maior quantidade de degenerações. O pH muscular foi superior no GE. O glicogênio muscular e o hepático não diferiram entre os grupos. Concluiu-se que bovinos encaminhados ao abate de emergência sofrem estresse severo pelo transporte por longas distâncias, com alterações bioquímicas no tecido muscular determinada pela degeneração celular.(AU)

Diagnostic accuracy of faecal biomarkers in detecting colorectal cancer and adenoma in symptomatic patients.

BACKGROUND: The diagnosis of colorectal cancer (CRC) can be difficult as symptoms are variable with poor specificity. Thus, there is a quest for simple, non-invasive testing that can help streamline those with significant colonic pathology. AIM: To assess using faecal immunochemical test for haemoglobin (FIT) or faecal calprotectin (FCP) to detect CRC and adenoma in symptomatic patients referred from primary care. METHODS: A total of 799 referred for urgent lower gastrointestinal investigations were prospectively recruited. Of these, 430 completed colonic investigations and returned stool samples, and were included in the final statistical analysis. Faecal immunochemical test for haemoglobin was performed on HM-JACKarc analyser (Kyowa Medex, Tokyo, Japan), and FCP by the EliA Calprotectin immunoassay (Thermo Fisher Scientific, Waltham, United States). RESULTS: The negative predictive value (NPV) using FIT alone or both markers (FIT and FCP) in combination was similar at 99% for CRC, with a sensitivity and specificity of 84% and 93%, respectively. FIT measurements were significantly higher in left-sided colonic lesions compared with the right side; 713 vs. 94; P = 0.0203). For adenoma, the NPV using FIT alone, or both markers (FIT and FCP) in combination, was similar at 94% with a sensitivity and specificity of 69% and 56%, respectively. CONCLUSIONS: Undetectable faecal immunochemical test for haemoglobin is sufficiently sensitive to exclude colorectal cancer, with higher values in left-sided lesions. FCP in combination does not appear to provide additional diagnostic information. Further studies to determine the health economic benefits of implementing faecal immunochemical test for haemoglobin in primary care are required.

Metabolic syndrome and cardiovascular disease following hematopoietic cell transplantation: screening and preventive practice recommendations from CIBMTR and EBMT.

Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors that increases the risk of cardiovascular disease, diabetes mellitus and all cause mortality. Long-term survivors of hematopoietic cell transplantation (HCT) have a substantial risk of developing MetS and cardiovascular disease, with the estimated prevalence of MetS being 31-49% among HCT recipients. Although MetS has not yet been proven to impact cardiovascular risk after HCT, an understanding of the incidence and risk factors for MetS in HCT recipients can provide the foundation to evaluate screening guidelines and develop interventions that may mitigate cardiovascular-related mortality. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal of reviewing literature and recommend practices appropriate to HCT recipients. Here we deliver consensus recommendations to help clinicians provide screening and preventive care for MetS and cardiovascular disease among HCT recipients. All HCT survivors should be advised of the risks of MetS and encouraged to undergo recommended screening based on their predisposition and ongoing risk factors.

Alternative donors extend transplantation for patients with lymphoma who lack an HLA matched donor.

Alternative donor transplantation is increasingly used for high-risk lymphoma patients. We analyzed 1593 transplant recipients (2000-2010) and compared transplant outcomes in recipients of 8/8 allele HLA-A, -B, -C and DRB1 matched unrelated donors (MUDs; n=1176), 7/8 allele HLA mismatched unrelated donors (MMUDs; n=275) and umbilical cord blood donors (1 or 2 units UCB; n=142). Adjusted 3-year non-relapse mortality of MMUD (44%) was higher as compared with MUD (35%; P=0.004), but similar to UCB recipients (37%; P=0.19), although UCB had lower rates of neutrophil and platelet recovery compared with unrelated donor groups. With a median follow-up of 55 months, 3-year adjusted cumulative incidence of relapse was lower after MMUD compared with MUD (25% vs 33%, P=0.003) but similar between UCB and MUD (30% vs 33%; P=0.48). In multivariate analysis, UCB recipients had lower risks of acute and chronic GVHD compared with adult donor groups (UCB vs MUD: hazard ratio (HR)=0.68, P=0.05; HR=0.35; P<0.001). Adjusted 3-year OS was comparable (43% MUD, 37% MMUD and 41% UCB). These data highlight the observation that patients with lymphoma have acceptable survival after alternative donor transplantation. MMUD and UCB can extend the curative potential of allotransplant to patients who lack suitable HLA matched sibling or MUD.

Screening, Brief Intervention, and Referral to Treatment for Older Adults With Substance Misuse.

Objectives. We compared substance use and SBIRT (Screening, Brief Intervention, and Referral to Treatment) services received for older adults screened by the Florida BRITE (BRief Intervention and Treatment of Elders) Project, across 4 categories of service providers. Methods. Staff from 29 agencies screened for substance use risk in 75 sites across 18 Florida counties. Clients at no or low risk received feedback about screening; moderate risk led to brief intervention, moderate or high risk led to brief treatment, and highest severity led to referral to treatment. Six-month follow-ups were conducted with a random sample of clients. Results. Over 5 years (September 15, 2006-September 14, 2011), 85 001 client screenings were recorded. Of these, 8165 clients were at moderate or high risk. Most received brief intervention for alcohol or medication misuse. Differences were observed across 4 categories of agencies. Health educators screening solely within medical sites recorded fewer positive screens than those from mental health, substance abuse, or aging services that screened in a variety of community-based and health care sites. Six-month follow-ups revealed a significant decrease in substance use. Conclusions. The Florida BRITE Project demonstrated that SBIRT can be extended to nonmedical services that serve older adults.

Exposure to life events as a risk factor for psychological problems in adults with intellectual disabilities: a longitudinal design.

BACKGROUND: Several cross-sectional studies have shown an association between exposure to life events and psychological problems in adults with intellectual disability (ID). To establish life events as a risk factor, prospective designs are needed. METHODS: Support staff informants provided data on the psychological problems of 68 adults with ID and their recent exposure to life events. Using data collected on the same sample 3.5 to 4 years earlier, prospective analysis of the relationships between life events exposure and psychological problems over time was explored. RESULTS: Hierarchical linear regression analyses demonstrated a contribution of life events to the prediction of later psychological problems after controlling for earlier psychological problems. Exploratory analyses showed that the relationship between life events and psychological problems might be unidirectional, and non-spurious; remaining present once the impact of other correlates of psychological problems was controlled. CONCLUSIONS: These data offer support for the status of life events (with a negative valence) as a risk factor for psychological problems in adults with ID. To establish life events as a causal risk factor, research is needed to examine the mechanisms via which life events have their impact on psychological well-being.

The relationship between age and risky injecting behaviours among a sample of Australian people who inject drugs.

BACKGROUND: Limited evidence suggests that younger people who inject drugs (PWID) engage in high-risk injecting behaviours. This study aims to better understand the relationships between age and risky injecting behaviours. METHODS: Data were taken from 11 years of a repeat cross-sectional study of sentinel samples of regular PWID (The Australian Illicit Drug Reporting System, 2001-2011). Multivariable Poisson regression was used to explore the relationship between age and four outcomes of interest: last drug injection occurred in public, receptive needle sharing (past month), experiencing injecting-related problems (e.g. abscess, dirty hit; past month), and non-fatal heroin overdose (past six months). RESULTS: Data from 6795 first-time study participants were analysed (median age: 33 years, interquartile range [IQR]: 27-40; median duration of injecting: 13 years [IQR: 7-20]). After adjusting for factors including duration of injecting, each five year increase in age was associated with significant reductions in public injecting (adjusted incidence rate ratio [AIRR]: 0.90, 95% confidence interval [CI]: 0.88-0.92), needle sharing (AIRR: 0.84, 95% CI: 0.79-0.89) and injecting-related problems (AIRR: 0.96, 95% CI: 0.95-0.97). Among those who had injected heroin in the six months preceding interview, each five year increase in age was associated with an average 10% reduction in the risk of heroin overdose (AIRR: 0.90, 95% CI: 0.85-0.96). CONCLUSIONS: Older PWID report significantly lower levels of high-risk injecting practices than younger PWID. Although they make up a small proportion of the current PWID population, younger PWID remain an important group for prevention and harm reduction.