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High prevalence of antibiotic allergies in cladribine-treated patients with hairy cell leukemia - lessons for immunopathogenesis and prescribing.
Meher-Homji Z, Tam CS, Siderov J, Seymour JF, Holmes NE, Chua KYL, Phillips EJ, Slavin MA, Trubiano JA
(2019) Leuk Lymphoma 60: 3455-3460
MeSH Terms: Adult, Aged, Anti-Bacterial Agents, Antineoplastic Combined Chemotherapy Protocols, Australia, Case-Control Studies, Cladribine, Drug Hypersensitivity, Female, Follow-Up Studies, Humans, Leukemia, Hairy Cell, Male, Middle Aged, Prevalence, Prognosis, Retrospective Studies, Survival Rate, Vidarabine
Show Abstract · Added March 30, 2020
The relationship between hematological malignancy and chemotherapy on the prevalence of antibiotic allergy label (AAL) is ill-defined. We performed a multicenter retrospective case-control study comparing AAL rates among cladribine-treated hairy cell leukemia (C-HCL) cases, non-HCL cladribine-treated controls (control-1), and fludarabine-treated controls (control-2). The prevalence of AALs in C-HCL patients was 60%, compared with control-1 (14%,  < .01) and control-2 patients (25%,  < .01). The predominant phenotype was maculopapular exanthem (92%). The drugs implicated in AAL causality in C-HCL patients included beta-lactams (81%), trimethoprim-sulfamethoxazole (58%), and allopurinol (69%). C-HCL patients demonstrate high rates of AAL, potentially due to immune dysregulation, impacting beta-lactam utilization.
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High and variable population prevalence of HLA-B*56:02 in indigenous Australians and relation to phenytoin-associated drug reaction with eosinophilia and systemic symptoms.
Somogyi AA, Barratt DT, Phillips EJ, Moore K, Ilyas F, Gabb GM
(2019) Br J Clin Pharmacol 85: 2163-2169
MeSH Terms: Adolescent, Adult, Aged, Australia, Biological Variation, Population, Cohort Studies, Cytochrome P-450 CYP2C9, Drug Hypersensitivity Syndrome, Female, Gene Frequency, Genetic Predisposition to Disease, Genotyping Techniques, HLA-B Antigens, Humans, Indigenous Peoples, Male, Middle Aged, Phenytoin, Young Adult
Show Abstract · Added March 30, 2020
Phenytoin drug reaction with eosinophilia and systemic symptoms (DRESS) in 3 Aboriginal Australians positive for HLA-B*56:02 has been previously reported. We report the allele frequency of HLA-B*56:02 in 2 South Australian populations, 1 Aboriginal (4.8%, 95% confidence interval 2.4-7.8%) and the other European (0%). We compared the frequency with publicly available information on HLA-B*56:02 status in other Indigenous Australian (n = 4) and European Australian cohorts (n = 1). In the Indigenous Australian cohorts, HLA-B*56:02 allele frequency ranged from 1.3 to 19%. We also describe an additional case of phenytoin DRESS (RegiSCAR DRESS score 7) in an Aboriginal Australian that was associated with HLA-B*56:02 and with CYP2C9*1/*3 genotype. In Aboriginal Australians, phenytoin DRESS appears distinctly linked to HLA-B*56:02 with an allele carriage rate substantially higher than in Europeans, but also with considerable regional variation. Investigations of human leucocyte antigen and other contributing genes and severe adverse drug reactions in understudied non-European populations are required to optimize safe medication use and inform risk mitigation strategies.
© 2019 The British Pharmacological Society.
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Sex-Based Differences in Incidence of Inflammatory Bowel Diseases-Pooled Analysis of Population-Based Studies From Western Countries.
Shah SC, Khalili H, Gower-Rousseau C, Olen O, Benchimol EI, Lynge E, Nielsen KR, Brassard P, Vutcovici M, Bitton A, Bernstein CN, Leddin D, Tamim H, Stefansson T, Loftus EV, Moum B, Tang W, Ng SC, Gearry R, Sincic B, Bell S, Sands BE, Lakatos PL, Végh Z, Ott C, Kaplan GG, Burisch J, Colombel JF
(2018) Gastroenterology 155: 1079-1089.e3
MeSH Terms: Adolescent, Adult, Age Distribution, Age of Onset, Aged, Australia, Child, Child, Preschool, Colitis, Ulcerative, Crohn Disease, Europe, Female, Humans, Incidence, Infant, Infant, Newborn, Male, Middle Aged, New Zealand, North America, Risk Factors, Sex Distribution, Sex Factors, Time Factors, Young Adult
Show Abstract · Added March 3, 2020
BACKGROUND & AIMS - Although the incidence of inflammatory bowel diseases (IBDs) varies with age, few studies have examined variations between the sexes. We therefore used population data from established cohorts to analyze sex differences in IBD incidence according to age at diagnosis.
METHODS - We identified population-based cohorts of patients with IBD for which incidence and age data were available (17 distinct cohorts from 16 regions of Europe, North America, Australia, and New Zealand). We collected data through December 2016 on 95,605 incident cases of Crohn's disease (CD) (42,831 male and 52,774 female) and 112,004 incident cases of ulcerative colitis (UC) (61,672 male and 50,332 female). We pooled incidence rate ratios of CD and UC for the combined cohort and compared differences according to sex using random effects meta-analysis.
RESULTS - Female patients had a lower risk of CD during childhood, until the age range of 10-14 years (incidence rate ratio, 0.70; 95% CI, 0.53-0.93), but they had a higher risk of CD thereafter, which was statistically significant for the age groups of 25-29 years and older than 35 years. The incidence of UC did not differ significantly for female vs male patients (except for the age group of 5-9 years) until age 45 years; thereafter, men had a significantly higher incidence of ulcerative colitis than women.
CONCLUSIONS - In a pooled analysis of population-based studies, we found age at IBD onset to vary with sex. Further studies are needed to investigate mechanisms of sex differences in IBD incidence.
Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.
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Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3).
Fanidi A, Muller DC, Yuan JM, Stevens VL, Weinstein SJ, Albanes D, Prentice R, Thomsen CA, Pettinger M, Cai Q, Blot WJ, Wu J, Arslan AA, Zeleniuch-Jacquotte A, McCullough ML, Le Marchand L, Wilkens LR, Haiman CA, Zhang X, Han J, Stampfer MJ, Smith-Warner SA, Giovannucci E, Giles GG, Hodge AM, Severi G, Johansson M, Grankvist K, Langhammer A, Krokstad S, Næss M, Wang R, Gao YT, Butler LM, Koh WP, Shu XO, Xiang YB, Li H, Zheng W, Lan Q, Visvanathan K, Bolton JH, Ueland PM, Midttun Ø, Ulvik A, Caporaso NE, Purdue M, Ziegler RG, Freedman ND, Buring JE, Lee IM, Sesso HD, Gaziano JM, Manjer J, Ericson U, Relton C, Brennan P, Johansson M
(2018) J Natl Cancer Inst 110:
MeSH Terms: Adult, Aged, Aged, 80 and over, Asia, Australia, Case-Control Studies, Cotinine, Europe, Female, Folic Acid, Humans, Incidence, Lung Neoplasms, Male, Methionine, Middle Aged, Prospective Studies, Protective Factors, Risk Factors, Sex Factors, Smoking, United States, Vitamin B 6
Show Abstract · Added April 3, 2018
Background - Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown.
Methods - Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models.
Results - Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1 ) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups.
Conclusions - Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who avoid low concentrations of circulating folate and vitamin B6.
© The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Impact of an Integrated Antibiotic Allergy Testing Program on Antimicrobial Stewardship: A Multicenter Evaluation.
Trubiano JA, Thursky KA, Stewardson AJ, Urbancic K, Worth LJ, Jackson C, Stevenson W, Sutherland M, Slavin MA, Grayson ML, Phillips EJ
(2017) Clin Infect Dis 65: 166-174
MeSH Terms: Aged, Anti-Bacterial Agents, Antimicrobial Stewardship, Australia, Drug Hypersensitivity, Drug-Related Side Effects and Adverse Reactions, Female, Hospitals, Humans, Inappropriate Prescribing, Male, Microbial Sensitivity Tests, Middle Aged, Penicillins, Skin Tests
Show Abstract · Added March 30, 2020
Background - Despite the high prevalence of patient-reported antibiotic allergy (so-called antibiotic allergy labels [AALs]) and their impact on antibiotic prescribing, incorporation of antibiotic allergy testing (AAT) into antimicrobial stewardship (AMS) programs (AAT-AMS) is not widespread. We aimed to evaluate the impact of an AAT-AMS program on AAL prevalence, antibiotic usage, and appropriateness of prescribing.
Methods - AAT-AMS was implemented at two large Australian hospitals during a 14-month period beginning May 2015. Baseline demographics, AAL history, age-adjusted Charlson comorbidity index, infection history, and antibiotic usage for 12 months prior to testing (pre-AAT-AMS) and 3 months following testing (post-AAT-AMS) were recorded for each participant. Study outcomes included the proportion of patients who were "de-labeled" of their AAL, spectrum of antibiotic courses pre- and post-AAT-AMS, and antibiotic appropriateness (using standard definitions).
Results - From the 118 antibiotic allergy-tested patients, 226 AALs were reported (mean, 1.91/patient), with 53.6% involving 1 or more penicillin class drug. AAT-AMS allowed AAL de-labeling in 98 (83%) patients-56% (55/98) with all AALs removed. Post-AAT, prescribing of narrow-spectrum penicillins was more likely (adjusted odds ratio [aOR], 2.81, 95% confidence interval [CI], 1.45-5.42), as was narrow-spectrum β-lactams (aOR, 3.54; 95% CI, 1.98-6.33), and appropriate antibiotics (aOR, 12.27; 95% CI, 5.00-30.09); and less likely for restricted antibiotics (aOR, 0.16; 95% CI, .09-.29), after adjusting for indication, Charlson comorbidity index, and care setting.
Conclusions - An integrated AAT-AMS program was effective in both de-labeling of AALs and promotion of improved antibiotic usage and appropriateness, supporting the routine incorporation of AAT into AMS programs.
© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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Circulating concentrations of biomarkers and metabolites related to vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations.
Midttun Ø, Theofylaktopoulou D, McCann A, Fanidi A, Muller DC, Meyer K, Ulvik A, Zheng W, Shu XO, Xiang YB, Prentice R, Thomson CA, Pettinger M, Giles GG, Hodge A, Cai Q, Blot WJ, Wu J, Johansson M, Hultdin J, Grankvist K, Stevens VL, McCullough ML, Weinstein SJ, Albanes D, Langhammer A, Hveem K, Næss M, Sesso HD, Gaziano JM, Buring JE, Lee IM, Severi G, Zhang X, Han J, Stampfer MJ, Smith-Warner SA, Zeleniuch-Jacquotte A, le Marchand L, Yuan JM, Butler LM, Koh WP, Wang R, Gao YT, Ericson U, Sonestedt E, Ziegler RG, Freedman ND, Visvanathan K, Jones MR, Relton C, Brennan P, Johansson M, Ueland PM
(2017) Am J Clin Nutr 105: 1314-1326
MeSH Terms: Aged, Asia, Australia, Biomarkers, Carbon, Cross-Sectional Studies, Dietary Supplements, Female, Humans, Kynurenine, Laboratories, Male, Middle Aged, Scandinavian and Nordic Countries, Tryptophan, United States, Vitamin A, Vitamin B Complex, Vitamin D, alpha-Tocopherol
Show Abstract · Added April 21, 2017
Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies. We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions. The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory. Circulating concentrations of riboflavin, pyridoxal 5'-phosphate, folate, vitamin B-12, all- retinol, 25-hydroxyvitamin D, and α-tocopherol as well as combined vitamin scores that were based on these nutrients showed that the general B-vitamin concentration was highest in the United States and that the B vitamins and lipid soluble vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-vitamin concentration in the United States appears to be driven mainly by multivitamin-supplement users. The observed differences likely reflect the variation in intake of vitamins and, in particular, the widespread multivitamin-supplement use in the United States. The results provide valuable information about the differences in biomarker concentrations in populations across continents.
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Return to sender: the need to re-address patient antibiotic allergy labels in Australia and New Zealand.
Trubiano JA, Worth LJ, Urbancic K, Brown TM, Paterson DL, Australasian Society for Infectious Diseases Clinical Research Network, Lucas M, Australasian Society of Clinical Immunology and Allergy, Phillips E
(2016) Intern Med J 46: 1311-1317
MeSH Terms: Anti-Bacterial Agents, Australia, Clinical Competence, Cross Reactions, Demography, Drug Hypersensitivity, Health Knowledge, Attitudes, Practice, Humans, Hypersensitivity, Delayed, Hypersensitivity, Immediate, New Zealand, Pharmacists, Physicians, Referral and Consultation, Skin Tests
Show Abstract · Added March 30, 2020
BACKGROUND/AIM - Antibiotic allergies are frequently reported and have significant impacts upon appropriate prescribing and clinical outcomes. We surveyed infectious diseases physicians, allergists, clinical immunologists and hospital pharmacists to evaluate antibiotic allergy knowledge and service delivery in Australia and New Zealand.
METHODS - An online multi-choice questionnaire was developed and endorsed by representatives of the Australasian Society of Clinical Immunology and Allergy (ASCIA) and the Australasian Society of Infectious Diseases (ASID). The 37-item survey was distributed in April 2015 to members of ASCIA, ASID, the Society of Hospital Pharmacists of Australia and the Royal Australasian College of Physicians.
RESULTS - Of 277 respondents, 94% currently use or would utilise antibiotic allergy testing (AAT) and reported seeing up to 10 patients/week labelled as antibiotic-allergic. Forty-two per cent were not aware of or did not have AAT available. Most felt that AAT would aid antibiotic selection, antibiotic appropriateness and antimicrobial stewardship (79, 69 and 61% respectively). Patients with the histories of immediate hypersensitivity were more likely to be referred than those with delayed hypersensitivities (76 vs 41%, P = 0.0001). Lack of specialist physicians (20%) and personal experience (17%) were barriers to service delivery. A multidisciplinary approach was a preferred AAT model (53%). Knowledge gaps were identified, with the majority overestimating rates of penicillin/cephalosporin (78%), penicillin/carbapenem (57%) and penicillin/monobactam (39%) cross-reactivity.
CONCLUSIONS - A high burden of antibiotic allergy labelling and demand for AAT is complicated by a relative lack availability or awareness of AAT services in Australia and New Zealand. Antibiotic allergy education and deployment of AAT, accessible to community and hospital-based clinicians, may improve clinical decisions and reduce antibiotic allergy impacts. A collaborative approach involving infectious diseases physicians, pharmacists and allergists/immunologists is required.
© 2016 Royal Australasian College of Physicians.
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Improving the Effectiveness of Penicillin Allergy De-labeling.
Bourke J, Pavlos R, James I, Phillips E
(2015) J Allergy Clin Immunol Pract 3: 365-34.e1
MeSH Terms: Administration, Oral, Adolescent, Adult, Aged, Aged, 80 and over, Anti-Bacterial Agents, Drug Hypersensitivity, Female, Guideline Adherence, Hospitals, Public, Humans, Intradermal Tests, Male, Middle Aged, Patient Selection, Penicillins, Practice Guidelines as Topic, Predictive Value of Tests, Risk Assessment, Risk Factors, Time Factors, Western Australia, Young Adult
Show Abstract · Added March 30, 2020
BACKGROUND - Approximately 10-20% of hospitalized patients are labeled as penicillin allergic, and this is associated with significant health and economic costs.
OBJECTIVES - We looked at the effectiveness of penicillin allergy de-labeling in clinical practice with the aim of deriving risk stratification models to guide testing strategies.
METHODS - Consecutive patients aged 15 years or more, referred to a Western Australian public hospital drug allergy service between 2008 and 2013 for beta-lactam allergy, were included. Follow-up surveys were conducted. Results of skin prick testing and intradermal testing (SPT/IDT) and oral challenge (OC), and follow-up of post testing antibiotic usage were the main outcomes.
RESULTS - SPT/IDT was performed in 401 consecutive patients with immediate (IMM) (≤ 1 hour) (n = 151) and nonimmediate (NIM) (>1 hour) (n = 250) reactions. Of 341 patients, 42 (12.3%) were SPT/IDT+ to ≥ 1 penicillin reagents, including 35/114 (30.4%) in the IMM group and 7/227 (3.1%) in the NIM group (P < .0001). Of 355 SPT/IDT patients, 3 (0.8%), all in the IMM group, had nonserious positive OC reactions to single dose penicillin VK (SPT/IDT negative predictive value [NPV] 99.2%). Selective or unrestricted beta-lactam was recommended in almost 90% overall, including 238/250 (95.2%) in the NIM group and 126/151 (83.4%) in the IMM group (P = .0001). Of 182 patients, 137 (75.3%) were following the allergy label modifications (ALM) at the time of follow-up.
CONCLUSIONS - Penicillin SPT/IDT/OC safely de-labels penicillin-allergic patients and identifies selective beta-lactam allergies; however, incomplete adherence to ALM recommendations impairs effectiveness. Infrequent SPT/IDT+ and absent OC reactions in patients with NIM reactions suggest OC alone to be a safe and cost-effective de-labeling strategy that could improve the coverage of penicillin allergy de-labeling in lower risk populations.
Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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Nutrition competencies in health professionals' education and training: a new paradigm.
Kris-Etherton PM, Akabas SR, Douglas P, Kohlmeier M, Laur C, Lenders CM, Levy MD, Nowson C, Ray S, Pratt CA, Seidner DL, Saltzman E
(2015) Adv Nutr 6: 83-7
MeSH Terms: Australia, Clinical Competence, Disease Management, Education, Medical, Health Personnel, Humans, Nutrition Therapy, Nutritional Sciences, United Kingdom, United States
Show Abstract · Added September 30, 2015
Most health care professionals are not adequately trained to address diet and nutrition-related issues with their patients, thus missing important opportunities to ameliorate chronic diseases and improve outcomes in acute illness. In this symposium, the speakers reviewed the status of nutrition education for health care professionals in the United States, United Kingdom, and Australia. Nutrition education is not required for educating and training physicians in many countries. Nutrition education for the spectrum of health care professionals is uncoordinated, which runs contrary to the current theme of interprofessional education. The central role of competencies in guiding medical education was emphasized and the urgent need to establish competencies in nutrition-related patient care was presented. The importance of additional strategies to improve nutrition education of health care professionals was highlighted. Public health legislation such as the Patient Protection and Affordable Care Act recognizes the role of nutrition, however, to capitalize on this increasing momentum, health care professionals must be trained to deliver needed services. Thus, there is a pressing need to garner support from stakeholders to achieve this goal. Promoting a research agenda that provides outcome-based evidence on individual and public health levels is needed to improve and sustain effective interprofessional nutrition education.
© 2015 American Society for Nutrition.
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10 MeSH Terms
Hemodialysis patient preference for type of vascular access: variation and predictors across countries in the DOPPS.
Fissell RB, Fuller DS, Morgenstern H, Gillespie BW, Mendelssohn DC, Rayner HC, Robinson BM, Schatell D, Kawanishi H, Pisoni RL
(2013) J Vasc Access 14: 264-72
MeSH Terms: Age Factors, Aged, Aged, 80 and over, Australia, Canada, Catheterization, Central Venous, Central Venous Catheters, Cross-Sectional Studies, Cultural Characteristics, Europe, Female, Health Care Surveys, Health Knowledge, Attitudes, Practice, Healthcare Disparities, Humans, Japan, Logistic Models, Male, Middle Aged, Multivariate Analysis, New Zealand, Odds Ratio, Patient Preference, Practice Patterns, Physicians', Renal Dialysis, Sex Factors, United States
Show Abstract · Added August 21, 2013
PURPOSE - Catheters are associated with worse clinical outcomes than fistulas and grafts in hemodialysis (HD) patients. One potential modifier of patient vascular access (VA) use is patient preference for a particular VA type. The purpose of this study is to identify predictors of patient VA preference that could be used to improve patient care.
METHODS - This study uses a cross-sectional sample of data from the Dialysis Outcomes and Practice Patterns Study (DOPPS 3, 2005-09), that includes 3815 HD patients from 224 facilities in 12 countries. Using multivariable models we measured associations between patient demographic and clinical characteristics, previous catheter use and patient preference for a catheter.
RESULTS - Patient preference for a catheter varied across countries, ranging from 1% of HD patients in Japan and 18% in the United States, to 42% to 44% in Belgium and Canada. Preference for a catheter was positively associated with age (adjusted odds ratio per 10 years=1.14; 95% CI=1.02-1.26), female sex (OR 1.49; 95% CI=1.15-1.93), and former (OR=2.61; 95% CI=1.66-4.12) or current catheter use (OR=60.3; 95% CI=36.5-99.8); catheter preference was inversely associated with time on dialysis (OR per three years=0.90; 95% CI=0.82-0.97).
CONCLUSIONS - Considerable variation in patient VA preference was observed across countries, suggesting that patient VA preference may be influenced by sociocultural factors and thus could be modifiable. Catheter preference was greatest among current and former catheter users, suggesting that one way to influence patient VA preference may be to avoid catheter use whenever possible.
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