IMGs face a series of obstacles to practise in Australia, which regulatory agencies should address

Background:International medical graduates (IMGs) have made important contributions to Australian healthcare since colonization. Recent published data have documented source countries and characteristics of IMGs undertaking the examinations of the Australian Medical Council. However, information about those currently practicing in Australia is limited.Objective:To analyze a cross section of IMGs currently practicing in Australia to determine patterns of change in donor countries, other demographic characteristics, geographical locations, and their areas of specialization.Methods:A random sample of all practitioners on a national database was interrogated for their country of first medical qualification. Those who qualified outside Australia were then analyzed for demographic variables such as age, gender, country of origin, and years of graduation and immigration. Their practice locations were matched to the Australian Bureau of Statistics geographical framework, and their specialties compared with those of a random sample of graduates from Australian medical schools.Results:Over the approximately 60 years since those surveyed arrived in Australia, IMGs' countries/regions of origin have changed from mainly the UK and Ireland to Southern Asia, in line with demographic changes in Australia as a whole. Most arrived soon after graduation, and IMGs are twice IMGs as likely as local graduates to be working in a rural area of workforce shortage. Compared with local graduates, significantly more IMGs are working in general practice.Conclusions:IMGs currently practicing in Australia make up a substantial proportion of the workforce and are more likely than local graduates to provide health services in regional and remote areas.

LINKED CONTENT This article is linked to Nguyen et al papers. To view these articles, visit https://doi.org/10.1111/apt.17050

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Between 1861 and 1900, 1,352 overseas-trained doctors were registered to practise in Victoria, Australia. This paper discusses the causes of death in seventy-five who survived no more than three years after receiving their medical licence in the colony. The largest group died from tuberculosis, at an average age of thirty-one years. Probably all had left Europe with the infection, hoping that a cure would result from their `therapeutic migration'. Whether that was likely to be a vain hope is discussed. The next largest group died by their own hand, and this paper argues that loneliness, alcoholism, and the stresses of adapting to an unfamiliar country may all have played apart.

Summary Background Calcineurin‐inhibitor immunosuppressants (tacrolimus and ciclosporin) have been associated with an exposure‐related increase in tumour recurrence following liver transplantation for hepatocellular carcinoma (HCC). Conversely, mechanistic target of rapamycin (mTOR) inhibitors (sirolimus and everolimus) have been suggested to reduce recurrence rates and improve survival in this patient group. Aim To clarify the potential benefit of mTOR‐inhibitors in HCC transplant patients by comparing recurrence and survival outcomes with calcineurin‐inhibitor‐based immunosuppression. Methods A systematic review and meta‐analysis was performed. The inclusion criteria were observational or interventional studies reporting the effect of early‐initiated (<6 months post‐transplant) mTOR‐inhibitor‐based immunosuppression on survival or tumour recurrence in patients transplanted with HCC, compared to a control of calcineurin‐inhibitor‐based therapy. Results Meta‐analysis demonstrated that compared with calcineurin‐inhibitor controls, recurrence‐free‐survival was significantly increased with mTOR‐inhibitor‐based therapy at 1‐year (Risk‐Ratio (RR): 1.09, 95% CI: 1.01‐1.18) and 3‐years (RR: 1.1, 95% CI: 1.01‐1.21) post‐transplant, with a nonsignificant increase at 5‐years (RR: 1.15, 95% CI: 0.99‐1.35). Overall survival was improved at 1‐year (RR: 1.07, 95% CI: 1.02‐1.12), 3‐years (RR: 1.1, 95% CI: 1.02‐1.19), and 5‐years (RR: 1.18, 95% CI: 1.08‐1.29). Recurrence‐rate was lower in the mTOR‐inhibitor arm (RR: 0.67, 95% CI: 0.56‐0.82), with no significant increase in acute rejection (RR: 1.1, 95% CI: 0.94‐1.28). Conclusions mTOR‐inhibitor‐based immunosuppression may be a preferable option in patients transplanted with HCC. It improves recurrence‐free‐survival over at least three years and reduces the recurrence rate compared with standard calcineurin‐inhibitor‐based therapy, with no significant increase in the rate of acute rejection. Future research should clarify the effect in higher vs lower risk cohorts.

BACKGROUND:Infliximab is an effective salvage therapy in acute severe ulcerative colitis; however, the optimal dosing strategy is unknown. We performed a systematic review and meta-analysis to examine the impact of infliximab dosage and intensification on colectomy-free survival in acute severe ulcerative colitis.METHODS:Studies reporting outcomes of hospitalized steroid-refractory acute severe ulcerative colitis treated with infliximab salvage were identified. Infliximab use was categorized by dose, dose number, and schedule. The primary outcome was colectomy-free survival at 3 months. Pooled proportions and odds ratios with 95% confidence intervals were reported.RESULTS:Forty-one cohorts (n = 2158 cases) were included. Overall colectomy-free survival with infliximab salvage was 79.7% (95% confidence interval [CI], 75.48% to 83.6%) at 3 months and 69.8% (95% CI, 65.7% to 73.7%) at 12 months. Colectomy-free survival at 3 months was superior with 5-mg/kg multiple (≥2) doses compared with single-dose induction (odds ratio [OR], 4.24; 95% CI, 2.44 to 7.36; P < 0.001). However, dose intensification with either high-dose or accelerated strategies was not significantly different to 5-mg/kg standard induction at 3 months (OR, 0.70; 95% CI, 0.39 to 1.27; P = 0.24) despite being utilized in patients with a significantly higher mean C-reactive protein and lower albumin levels.CONCLUSIONS:In acute severe ulcerative colitis, multiple 5-mg/kg infliximab doses are superior to single-dose salvage. Dose-intensified induction outcomes were not significantly different compared to standard induction and were more often used in patients with increased disease severity, which may have confounded the results. This meta-analysis highlights the marked variability in the management of infliximab salvage therapy and the need for further studies to determine the optimal dose strategy.

Linked ContentThis article is linked to Menon et al papers. To view these articles visit https://doi.org/10.1111/apt.12185 and https://doi.org/10.1111/apt.15038.

AIM:To evaluate GI safety of celecoxib compared with 2 nonselective (ns) NSAIDs, as a secondary objective of a large trial examining multiorgan safety.METHODS:This randomised, double-blind controlled trial analysed 24 081 patients. Osteoarthritis or rheumatoid arthritis patients, needing ongoing NSAID treatment, were randomised to receive celecoxib 100-200 mg b.d., ibuprofen 600-800 mg t.d.s. or naproxen 375-500 mg b.d. plus esomeprazole, and low-dose aspirin or corticosteroids if already prescribed. Clinically significant GI events (CSGIE-bleeding, obstruction, perforation events from stomach downwards or symptomatic ulcers) and iron deficiency anaemia (IDA) were adjudicated blindly.RESULTS:Mean treatment and follow-up durations were 20.3 and 34.1 months. While on treatment or 30 days after, CSGIE occurred in 0.34%, 0.74% and 0.66% taking celecoxib, ibuprofen and naproxen. Hazard ratios (HR) were 0.43 (95% CI 0.27-0.68, P = 0.0003) celecoxib vs ibuprofen and 0.51 (0.32-0.81, P = 0.004) vs naproxen. There was also less IDA on celecoxib: HR 0.43 (0.27-0.68, P = 0.0003) vs ibuprofen; 0.40 (0.25-0.62, P < 0.0001) vs naproxen. Even taken with low-dose aspirin, fewer CSGIE occurred on celecoxib than ibuprofen (HR 0.52 [0.29-0.94], P = 0.03), and less IDA vs naproxen (0.42 [0.23-0.77, P = 0.005]). Corticosteroid use increased total GI events and CSGIE. H. pylori serological status had no influence.CONCLUSIONS:Arthritis patients taking NSAIDs plus esomeprazole have infrequent clinically significant gastrointestinal events. Co-prescribed with esomeprazole, celecoxib has better overall GI safety than ibuprofen or naproxen at these doses, despite treatment with low-dose aspirin or corticosteroids.

Thirty percent of patients with acute severe ulcerative colitis (ASUC) require emergency colectomy within 3 months of admission. Infliximab (IFX) is effective as salvage therapy and recent data on IFX pharmacokinetics suggest that dose intensification schedules (DIS) beyond standard induction schedules (SIS) may be of benefit. However, data supporting DIS therapy are conflicting and the optimal IFX dosing strategy is unknown. We performed a systematic review and meta-analysis to examine the impact of IFX dose number and intensification on colectomy free survival (CFS) in ASUC. MEDLINE, PubMed, and EMBASE were searched from January 2000 to September 2017 to identify studies reporting outcomes of hospitalised steroid refractory ASUC treated with IFX salvage. CFS was examined for: all pooled patients; 5 mg/kg single dose vs. 5 mg/kg multiple dose induction, and; SIS (5 mg/kg at 0, 2, and 6 weeks) vs. DIS (multiple 10 mg/kg or 5 mg/kg using accelerated schedules). Thirty-nine studies (n = 1827 patients) were included in this analysis. 11 contained comparative data and 28 had non-comparative data. Pooled CFS with IFX salvage was 84.0% (95%Cl 81.9–86.0%) at 1 month, 79.8% (77.7–81.8%) at 3 months and 70.5% (68.1–72.8%) at 12 months. Multiple dose induction (5 mg/kg) was superior to single dose (5 mg/kg) induction with respect to CFS at 1 and 3 months but not 12 months [odds ratio (OR) 8.86 (95% CI 1.04–75.8), I2 = 0%, p = 0.05, n = 127; OR 4.31 (2.46–7.56), I2 = 0%, p < 0.001, n = 421, and; OR 2.02 (0.81–5.01), I2 = 0%, p = 0.13, n = 127, respectively]. DIS was not found to be superior to SIS for CFS at 1, 3, or 12 months in five evaluable studies (n = 337) [OR 0.59 (0.17–2.04), I2 = 52%, p = 0.41; OR 0.64 (0.27–1.50), I2 = 43%, p = 0.31, and; OR 0.73 (0.39–1.35), I2 = 20%, p = 0.53, favouring standard induction]. DIS was utilised in patients who had a significantly higher mean CRP compared with SIS [mean difference 14.31mg/l (0.35–28.32), p = 0.04] as well as significantly lower serum albumin [mean difference 2.75g/l (1.26–4.23), p < 0.001]. There was no significant difference in age, disease duration or IV steroid duration. There are few high-quality studies available to guide the use of IFX in ASUC. Whilst multiple 5 mg/kg doses appear superior to single 5 mg/kg dose rescue therapy, dose intensification (with high dose or accelerated strategies) was not superior to standard induction in this analysis. However, dose intensification was utilised in patient groups with adverse biochemical profiles known to be associated with increased colectomy risk, thus the finding may be confounded. Controlled interventional studies are therefore required to investigate whether IFX dose intensification is able to mitigate the risk of colectomy.

Objective: To determine whether the risk of upper gastrointestinal bleeding in patients taking low dose aspirin (≤ 325 mg/day) is increased in people with Helicobacter pylori infections.

Yeomans, Neville D. MD, FACG1; Graham, David Y. MD, MACG2; Wang, Qiuqing MS3; Wolski, Kathy MPH3; Borer, Jeffrey MD4; Husni, Elaine M. MD, MPH3; Libby, Peter MD5; Lincoff, Michael A MD3; Lüscher, Thomas MD6; Wisniewski, Lisa M. RN3; Bao, Warren PhD7; Walker, Chris PhD8; Nissen, Steven E. MD3 Author Information

"Sirolimus in Liver Transplant Recipients With Hepatocellular Carcinoma." Journal of Investigative Surgery, 33(4), pp. 389–390

Owing to wide‐spread use, low‐dose aspirin (LDA) produces a substantial amount of peptic ulcer disease. Current guidelines are ambivalent about the need for Helicobacter pylori eradication to protect against LDA ulcers. This study aimed to determine, through meta‐analysis, if (and by how much) infection alters the baseline risk of peptic ulcers during LDA therapy.

BACKGROUND The safety of nonsteroidal anti-inflammatory drug (NSAID) and aspirin coadministration is uncertain. OBJECTIVES The aim of this study was to compare the safety of combining NSAIDs with low-dose aspirin. METHODS This analysis of the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen) trial included 23,953 patients with osteoarthritis or rheumatoid arthritis at increased cardiovascular risk randomized to celecoxib, ibuprofen, or naproxen. The on-treatment population was used for this study. Outcomes included composite major adverse cardiovascular events, noncardiovascular death, gastrointestinal or renal events, and components of the composite. Cox proportional hazards models compared outcomes among NSAIDs stratified by aspirin use following propensity score adjustment. Kaplan-Meier analysis was used to compare the cumulative probability of events. RESULTS When taken without aspirin, naproxen or ibuprofen had greater risk for the primary composite endpoint compared with celecoxib (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.22 to 1.90, p < 0.001; and HR: 1.81; 95% CI: 1.46 to 2.26; p < 0.001, respectively). Compared with celecoxib, ibuprofen had more major adverse cardiovascular events (p < 0.05), and both ibuprofen and naproxen had more gastrointestinal (p < 0.001) and renal (p < 0.05) events. Taken with aspirin, ibuprofen had greater risk for the primary composite endpoint compared with celecoxib (HR: 1.27; 95% CI: 1.06 to 1.51; p < 0.01); this was not significantly higher with naproxen (HR: 1.18; 95% CI: 0.98 to 1.41; p = 0.08). Among patients on aspirin, major adverse cardiovascular events were similar among NSAIDs, and compared with celecoxib, ibuprofen had more gastrointestinal and renal events (p < 0.05), while naproxen had more gastrointestinal events (p < 0.05), without a difference in renal events. Similar results were seen on adjusted Kaplan-Meier analysis. CONCLUSIONS Celecoxib has a more favorable overall safety profile than naproxen or ibuprofen when taken without aspirin. Adding aspirin attenuates the safety advantage of celecoxib, although celecoxib is still associated with fewer gastrointestinal events than ibuprofen or naproxen and fewer renal events than ibuprofen. (Prospective Randomized Evaluation of Celecoxib Integrated Safety vs Ibuprofen or Naproxen [PRECISION]; NCT00346216) (c) 2018 the American College of Cardiology Foundation. Published by Elsevier. All rights reserved.

Objective: To determine whether the risk of upper gastrointestinal bleeding in patients taking low dose aspirin (<= 325 mg/day) is increased in people with Helicobacter pylori infections. Study design: A systematic search for all publications since 1989 (when H. pylori was named) using search term equivalents for "upper gastrointestinal haemorrhage" and "aspirin". Articles were assessed individually for inclusion of data on H. pylori infection, as not all relevant papers were indexed with this term. Data that could be pooled were then subjected to meta-analysis, using a random effects model. Data sources: MEDLINE, Embase, Scopus, the Cochrane Library. Data synthesis: Of 7599 retrieved publications, reports for seven case-control studies contained data suitable for meta-analysis; four were deemed high quality on the Newcastle-Ottawa scale. Upper gastrointestinal haemorrhage was more frequent in aspirin users infected with H. pylori than in those who were not (odds ratio [OR], 2.32; 95% CI, 1.25-4.33; P = 0.008). The heterogeneity of the studies was significant (Q = 19.3, P = 0.004; I-2 = 68.9%, 95% CI, 31.5-85.9%), but the pooled odds ratio was similar after removing the two studies that contributed most to heterogeneity (OR, 2.34; 95% CI, 1.56-3.53; P < 0.001). The number needed to treat to prevent one bleeding event annually was estimated to be between 100 and more than 1000. Conclusions: The odds of upper gastrointestinal bleeding in patients taking low dose aspirin is about twice as great in those infected with H. pylori. Testing for and treating the infection should be considered in such patients, especially if their underlying risk of peptic ulcer bleeding is already high.

The PRECISION trial demonstrated the non-inferiority of celecoxib to ibuprofen or naproxen for cardiovascular (CV) safety in patients with arthritis. A comparison of the overall safety of each agent stratified by drug dose has yet to be reported. Patients were randomized to lower-dose celecoxib 100

Background: Gastroesophageal reflux (GER) is prevalent among idiopathic pulmonary fibrosis (IPF) patients.However, the directionality of this association remains debated; while micro-aspiration from GER may lead to lung injury, altered respiratory mechanics may also worsen GER.Abnormal bolus reflux has been associated with worse outcomes from IPF over 1 year.However, the value of objective GER measures in predicting long-term IPF disease progression is unclear.Understanding the longitudinal relationships between GER and IPF may help define the role of GER in IPF pathogenesis and the need for objective GER testing in management of these patients.Aim: To assess the association between objective measures of GER on multichannel intraluminal impedance and pH testing (MII-pH) and development of poor clinical outcomes over 3 years in IPF patients.Methods: This was a retrospective cohort study of adults with IPF who underwent pre-lung transplant evaluation with MII-pH off proton pump inhibitors (PPI) at a tertiary care center in 6/2008-11/2015.Patients with fundoplication prior to MII-pH were excluded.All patients were followed for up to 3 years from time of MII-pH for development of poor outcomes, defined by hospitalization for respiratory exacerbation or death.The association between baseline GER parameters on MII-pH and time to poor pulmonary outcome was evaluated by Kaplan-Meier analysis with censoring at anti-reflux surgery, lung transplant, or last clinic followup within 3 years, whichever was earliest.Multivariate time-to-event analysis using Cox proportional hazard model was performed to control for potential confounders.Results: 84 subjects (mean age=61.1 yrs, 64% male) were included in the study.On Kaplan-Meier analysis, increased bolus exposure time (BET) on MII-pH was associated with decreased time to poor pulmonary outcome within 3 years (log-ranked p=0.02) (figure 1).Subgroup analysis showed that increased BET remained predictive of decreased time to death when mortality was considered as the sole outcome (log-ranked p=0.05) (figure 2).On Cox regression analysis, after controlling for age, gender, BMI, smoking, baseline lung disease severity, PPI use, and anti-fibrotic therapy, increased BET remained an independent predictor of decreased time to poor pulmonary outcome (HR 2.52, p= 0.035).Subgroup Cox regression analysis showed a similar trend between increased BET and decreased time to death over 3 years (HR 2.83, p = 0.20).Conclusion: Abnormal BET on MII-pH is an independent predictor of respiratory hospitalization and death over 3 years in IPF patients.BET may be useful as a prognostic marker for IPF disease and clinical decline in the pre-lung transplant setting.These findings also support a role for GER in IPF pathogenesis.MII-pH should be considered routinely in the care of IPF patients to help optimize clinical outcomes.