Research by staff affiliated to Tallaght University Hospital (formerly Adelaide Meath Hospital, Tallaght)

Recent Submissions

  • Gait speed, cognition and falls in people living with mild-to-moderate Alzheimer disease: data from NILVAD.

    Dyer, Adam H; Lawlor, Brian; Kennelly, Sean P (2020-03-30)
    Background: Previous evidence suggests that slower gait speed is longitudinally associated with cognitive impairment, dementia and falls in older adults. Despite this, the longitudinal relationship between gait speed, cognition and falls in those with a diagnosis of dementia remains poorly explored. We sought to assess this longitudinal relationship in a cohort of older adults with mild to-moderate Alzheimer Disease (AD). Methods: Analysis of data from NILVAD, an 18-month randomised-controlled trial of Nilvadipine in mild to moderate AD. We examined: (i) the cross-sectional (baseline) association between slow gait speed and cognitive function, (ii) the relationship between baseline slow gait speed and cognitive function at 18 months (Alzheimer Disease Assessment Scale, Cognitive Subsection: ADAS-Cog), (iii) the relationship between baseline cognitive function and incident slow gait speed at 18 months and finally (iv) the relationship of baseline slow gait speed and incident falls over the study period. Results: Overall, one-tenth (10.03%, N = 37/369) of participants with mild-to-moderate AD met criteria for slow gait speed at baseline and a further 14.09% (N = 52/369) developed incident slow gait speed at 18 months. At baseline, there was a significant association between poorer cognition and slow gait speed (OR 1.05, 95% CI 1.01-1.09, p = 0.025). Whilst there was no association between baseline slow gait speed and change in ADAS-Cog score at 18 months, a greater cognitive severity at baseline predicted incident slow gait speed over 18 months (OR 1.04, 1.01-1.08, p = 0.011). Further, slow gait speed at baseline was associated with a significant risk of incident falls over the study period, which persisted after covariate adjustment (IRR 3.48, 2.05-5.92, p < 0.001). Conclusions: Poorer baseline cognition was associated with both baseline and incident slow gait speed. Slow gait speed was associated with a significantly increased risk of falls over the study period. Our study adds further evidence to the complex relationship between gait and cognition in this vulnerable group and highlights increased falls risk in older adults with AD and slow gait speed.
  • Determinants of healthcare seeking for childhood illnesses among caregivers of under-five children in urban slums in Malawi: a population-based cross-sectional study.

    Lungu, Edgar Arnold; Darker, Catherine; Biesma, Regien (2020-01-17)
    Background: There is considerable evidence that health systems, in so far as they ensure access to healthcare, promote population health even independent of other determinants. Access to child health services remains integral to improving child health outcomes. Cognisant that improvements in child health have been unevenly distributed, it is imperative that health services and research focus on the disadvantaged groups. Children residing in urban slums are known to face a health disadvantage that is masked by the common view of an urban health advantage. Granted increasing urbanisation rates and proliferation of urban slums resulting from urban poverty, the health of under-five children in slums remains a public health imperative in Malawi. We explored determinants of healthcare-seeking from a biomedical health provider for childhood symptoms of fever, cough with fast breathing and diarrhoea in three urban slums of Lilongwe, Malawi. Methods: This was a population-based cross-sectional study involving 543 caregivers of under-five children. Data on childhood morbidity and healthcare seeking in three months period were collected using face-to-face interviews guided by a validated questionnaire. Data were entered in CS-Pro 5.0 and analysed in SPSS version 20 using descriptive statistics and logistic regression analyses. Results: 61% of caregivers sought healthcare albeit 53% of them sought healthcare late. Public health facilities constituted the most frequently used health providers. Healthcare was more likely to be sought: for younger than older under-five children (AOR = 0.54; 95% CI: 0.30-0.99); when illness was perceived to be severe (AOR = 2.40; 95% CI: 1.34-4.30); when the presenting symptom was fever (AOR = 1.77; 95% CI: 1.10-2.86). Home management of childhood illness was negatively associated with care-seeking (AOR = 0.54; 95% CI: 0.36-0.81) and timely care-seeking (AOR = 0.44; 95% CI: 0.2-0.74). Caregivers with good knowledge of child danger signs were less likely to seek care timely (AOR = 0.57; 95% CI: 0.33-0.99). Conclusions: Even in the context of geographical proximity to healthcare services, caregivers in urban slums may not seek healthcare or when they do so the majority may not undertake timely healthcare care seeking. Factors related to the child, the type of illness, and the caregiver are central to the healthcare decision making dynamics. Improving access to under-five child health services therefore requires considering multiple factors.
  • An Update on Health-Related Quality of Life and Patient-Reported Outcomes in Hidradenitis Suppurativa.

    Mac Mahon, J; Kirthi, S; Byrne, N; O'Grady, C; Tobin, A M (2020-02-10)
    Hidradenitis suppurativa is a common inflammatory skin condition which causes recurrent abscesses, sinuses and scarring in the axillae, groin and inframammary areas. As well as causing significant physical distress due to pain and discharge, the condition impacts psychological well-being with markedly impaired quality of life. Patients suffer pain, embarrassment and psychological distress with impairment of their work and intimate relationships marking it as one of the most distressing dermatological conditions. Numerous studies have documented markers of psychological distress encompassing the physical effects such as pain and itch, affects on mood and impaired function.
  • Lower gastrointestinal symptoms and symptoms-based triaging systems are poor predictors of clinical significant disease on colonoscopy.

    Ismail, Mohd Syafiq; Aoko, Olufemi; Sihag, Sandeep; Connolly, Eimear; Omorogbe, Joseph; Semenov, Serhiy; O'Morain, Neil; O'Connor, Anthony; Breslin, Niall; Ryan, Barbara; et al. (2020-03-31)
    Introduction: Lower gastrointestinal symptoms (LGS) are a common cause of referral to the gastroenterology service. International guidelines are available to prioritise referrals. Some studies have reported that symptoms alone are a poor marker of clinically significant disease (CSD) but symptoms remain the main way to prioritise referrals in routine clinical practice. Aims/background: To correlate LGS with colonoscopy findings in an unselected patient cohort and to investigate whether using National Institute for Health and Care Excellence (NICE) guidelines improve risk stratification. Method: Colonoscopy data over a 2-year period were obtained from our endoscopy database. Only patients with assessment of symptoms as their primary indication for colonoscopy were included. Patient records were retrospectively reviewed. Exclusion criteria: known inflammatory bowel disease (IBD), familial cancer syndromes, polyp and colorectal cancer (CRC) surveillance, and prior colonoscopy within 5 years. Demographics, symptoms and colonoscopy findings were recorded and analysed. Results: 1116 cases were reviewed; 493 (44%) males, age 54.3 years (16-91). CSD occurred in only 162 (14.5%); CRC 19 (1.7%), high-risk adenoma 40 (3.6%), inflammation 97 (8.7%) (IBD 65 (5.8%), microscopic colitis 9 (0.8%) and indeterminate-inflammation 23 (2%)), angiodysplasia 6 (0.5%). Diarrhoea gave the highest diagnostic yield for CSD of 5.3% (OR 3.15, 95% CI 2.2 to 4.7, p<0.001), followed by PR bleeding, 2.9% (OR 1.9, 95% CI 1.24 to 2.9, p=0.003). Weight loss gave the lowest diagnostic yield of 0.4%; (OR 0.79, 95% CI 0.28 to 2.24, p=0.65). 592 (53%) and 517 (46%) fitted the NICE guidelines for CRC and IBD, respectively. Using NICE positivity improved detection but overall yield remained low 3% vs 0.4% (OR 7.71, 95% CI 1.77 to 33.56, p=0.0064) for CRC, and 9% vs 2.8% (OR 3.5, 95% CI 1.99 to 6.17, p<0.0001) for IBD. Conclusions: The overall prevalence of CSD in our unselected symptomatic patients is low (14.5%). A holistic approach including combining symptoms and demographics with novel tools including stool biomarkers and minimally invasive colonoscopy alternatives should be applied to avoid unnecessary colonoscopy.
  • COVID-19 highlights the need for universal adoption of standards of medical care for physicians in nursing homes in Europe.

    O'Neill, Desmond; Briggs, Robert; Holmerová, Iva; Samuelsson, Olafur; Gordon, Adam L; Martin, Finbarr C (2020-06-17)
    The nursing home sector has seen a disproportionately high number of deaths as part of the COVID-19 pandemic. This reflects, in part, the frailty and vulnerability of older people living in care homes but has also, in part, been a consequence of the failure to include care homes in the systematic planning of a response to COVID, as well as a measure of neglect of standards and quality improvement in the sector. In response, the EUGMS published a set of medical standards of care developed in consultation with experts across its member national societies in 2015. The standards consisted of seven core principles of medical care for physicians working in nursing homes as a first step in developing a programme of clinical, academic and policy engagement in improving medical care for older people who are living and frequently also dying as residents in nursing homes. The gravity of the concerns arising for nursing home care from the COVID-19 pandemic, as well as emerging insights on care improvement in nursing homes indicate that an update of these medical standards is timely. This was performed by the writing group from the original 2015 guidelines and is intended as an interim measure pending a more formal review incorporating a systematic review of emerging literature and a Delphi process.
  • Towards European harmonisation of healthcare for patients with rare immune disorders: outcome from the ERN RITA registries survey.

    Papa, Riccardo; Cant, Andrew; Klein, Christoph; Little, Mark A; Wulffraat, Nico M; Gattorno, Marco; Ruperto, Nicolino (2020-01-30)
    The Rare Immunodeficiency, AutoInflammatory and AutoImmune Disease (RITA) network is a European Research Network (ERN) that brings together the leading centres for rare immune disorders. On April 2018 an online survey was sent to all RITA members in order to facilitate the harmonization of data collection in rare immune disorders registries. Currently, as many as 52 different registries collect data on rare immune disorders, of whom 30 (58%) are dedicated primarily to autoimmune diseases, 15 (29%) to primary immunodeficiencies and 12 (23%) to autoinflammatory disorders. Improving data on patient safety, outcome, and quality of life measures is warranted to unfold the full potential of RITA registries.
  • Self-reported and actual adherence to the Tokyo guidelines in the European snapshot audit of complicated calculous biliary disease.

    Bass, G A; Gillis, A E; Cao, Y; Mohseni, S (2020-05-17)
    Background: Complicated acute biliary calculous disease poses clinical challenges. The European Society of Trauma and Emergency Surgery (ESTES) snapshot audit of complicated biliary calculous disease aims to make novel comparisons between self-reported institutional adherence to the Tokyo guidelines (TG18) and 'real-world' contemporary practice across Europe. Methods: A preplanned analysis of a prospective observational multicentre audit that captured patients undergoing emergency admission for complicated biliary calculous disease (complicated cholecystitis, biliary pancreatitis, or choledocholithiasis with or without cholangitis) between 1 and 31 October 2018 was performed. An anonymized survey was administered to participating sites. Results: Following an open call for participation, 25 centres from nine countries enrolled 338 patients. All centres completed the anonymized survey. Fifteen centres (60 per cent) self-reported that a minority of patients were treated surgically on index admission, favouring interval cholecystectomy. This was replicated in the snapshot audit, in which 152 of 338 patients (45·0 per cent) underwent index admission cholecystectomy, 17 (5·0 per cent) had interval cholecystectomy, and the remaining 169 (50·0 per cent) had not undergone surgery by the end of the 60-day follow-up. Centres that employed a dedicated acute care surgery model of care were more likely to perform index admission cholecystectomy compared with a traditional general surgery 'on call' service (57 versus 38 per cent respectively; odds ratio 2·14 (95 per cent c.i. 1·37 to 3·35), P < 0·001). Six centres (24 per cent) self-reported routinely performing blood cultures in acute cholecystitis; patient-level audit data revealed that blood cultures were done in 47 of 154 patients (30·5 per cent). No centre self-reported omitting antibiotics in the management of acute cholecystitis, and 144 of 154 (93·5 per cent) of patients in the snapshot audit received antibiotics during their index admission.
  • The statistical importance of P-POSSUM scores for predicting mortality after emergency laparotomy in geriatric patients.

    Cao, Yang; Bass, Gary A; Ahl, Rebecka; Pourlotfi, Arvid; Geijer, Håkan; Montgomery, Scott; Mohseni, Shahin (2020-05-07)
    Background: Geriatric patients frequently undergo emergency general surgery and accrue a greater risk of postoperative complications and fatal outcomes than the general population. It is highly relevant to develop the most appropriate care measures and to guide patient-centered decision-making around end-of-life care. Portsmouth - Physiological and Operative Severity Score for the enumeration of Mortality and morbidity (P-POSSUM) has been used to predict mortality in patients undergoing different types of surgery. In the present study, we aimed to evaluate the relative importance of the P-POSSUM score for predicting 90-day mortality in the elderly subjected to emergency laparotomy from statistical aspects. Methods: One hundred and fifty-seven geriatric patients aged ≥65 years undergoing emergency laparotomy between January 1st, 2015 and December 31st, 2016 were included in the study. Mortality and 27 other patient characteristics were retrieved from the computerized records of Örebro University Hospital in Örebro, Sweden. Two supervised classification machine methods (logistic regression and random forest) were used to predict the 90-day mortality risk. Three scalers (Standard scaler, Robust scaler and Min-Max scaler) were used for variable engineering. The performance of the models was evaluated using accuracy, sensitivity, specificity and area under the receiver operating characteristic curve (AUC). Importance of the predictors were evaluated using permutation variable importance and Gini importance. Results: The mean age of the included patients was 75.4 years (standard deviation =7.3 years) and the 90-day mortality rate was 29.3%. The most common indication for surgery was bowel obstruction occurring in 92 (58.6%) patients. Types of post-operative complications ranged between 7.0-36.9% with infection being the most common type. Both the logistic regression and random forest models showed satisfactory performance for predicting 90-day mortality risk in geriatric patients after emergency laparotomy, with AUCs of 0.88 and 0.93, respectively. Both models had an accuracy > 0.8 and a specificity ≥0.9. P-POSSUM had the greatest relative importance for predicting 90-day mortality in the logistic regression model and was the fifth important predictor in the random forest model. No notable change was found in sensitivity analysis using different variable engineering methods with P-POSSUM being among the five most accurate variables for mortality prediction. Conclusion: P-POSSUM is important for predicting 90-day mortality after emergency laparotomy in geriatric patients. The logistic regression model and random forest model may have an accuracy of > 0.8 and an AUC around 0.9 for predicting 90-day mortality. Further validation of the variables' importance and the models' robustness is needed by use of larger dataset.
  • Mindfulness moments for clinicians in the midst of a pandemic.

    Hedderman, E; O'Doherty, V; O'Connor, S (2020-05-21)
    Clinicians are routinely subjected to intense and stressful working environments, and the current COVID-19 crisis increases their risk of psychological distress. Mindfulness has been shown to improve life satisfaction, resilience to stress, self-compassion, compassion and general well-being in healthcare workers. Based on their clinical experience, the authors present mindfulness moments for clinicians (MMFC), a selection of short, simple and accessible mindfulness practices to promote resilience and compassion among clinicians working in this pandemic. The practices can be used on the job and are accessible to both novice and experienced meditators. Most of these practices are extracted from evidence-based mindfulness programmes. Further research is indicated to assess the effectiveness of using MMFC to support clinicians in their work and to promote resilience.
  • Emerging treatments for inflammatory bowel disease.

    Hazel, Karl; O'connor, Anthony (2020-02-05)
    Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic inflammation, a relapsing and remitting clinical course, requirement for lifelong medication and often, significant morbidity. While multiple effective therapeutic options exist for the treatment of IBD, a proportion of patients will either fail to respond or lose response to therapy. Advances in therapeutics, such as the gut-specific anti-integrins, now offer patients an alternative option to systemic immunosuppression. Anti-interleukin 12 (anti-IL-12)/IL-23 agents offer new and effective treatment options for CD, while the oral small molecules now offer an oral alternative for the treatment of moderate-to-severe disease, previously requiring subcutaneous injection or intravenous infusion. Alternatives to pharmacological treatment such as stem-cell transplant and faecal microbiota transplant are also showing some promise in the treatment of both CD and UC.
  • Effect of Glyceryl Trinitrate on Hemodynamics in Acute Stroke.

    Appleton, Jason P; Woodhouse, Lisa J; Bereczki, Daniel; Berge, Eivind; Christensen, Hanne K; Collins, Rónán; Gommans, John; Ntaios, George; Ozturk, Serefnur; Szatmari, Szabolcs; et al.
    Background and Purpose- Increased blood pressure (BP), heart rate, and their derivatives (variability, pulse pressure, rate-pressure product) are associated with poor clinical outcome in acute stroke. We assessed the effects of glyceryl trinitrate (GTN) on hemodynamic parameters and these on outcome in participants in the ENOS trial (Efficacy of Nitric Oxide in Stroke). Methods- Four thousand and eleven patients with acute stroke and raised BP were randomized within 48 hours of onset to transdermal GTN or no GTN for 7 days. Peripheral hemodynamics were measured at baseline (3 measures) and daily (2 measures) during treatment. Between-visit BP variability over days 1 to 7 (as SD) was assessed in quintiles. Functional outcome was assessed as modified Rankin Scale and cognition as telephone mini-mental state examination at day 90. Analyses were adjusted for baseline prognostic variables. Data are mean difference or odds ratios with 95% CI. Results- Increased baseline BP (diastolic, variability), heart rate, and rate-pressure product were each associated with unfavorable functional outcome at day 90. Increased between-visit systolic BP variability was associated with an unfavourable shift in modified Rankin Scale (highest quintile adjusted odds ratio, 1.65; 95% CI, 1.37-1.99), worse cognitive scores (telephone mini-mental state examination: highest quintile adjusted mean difference, -2.03; 95% CI, -2.84 to -1.22), and increased odds of death at day 90 (highest quintile adjusted odds ratio, 1.57; 95% CI, 1.12-2.19). GTN lowered BP and rate-pressure product and increased heart rate at day 1 and reduced between-visit systolic BP variability. Conclusions- Increased between-visit BP variability was associated with poor functional and cognitive outcomes and increased death 90 days after acute stroke. In addition to lowering BP and rate-pressure product, GTN reduced between-visit systolic BP variability. Agents that lower BP variability in acute stroke require further study.
  • Proficiency-based progression training: an 'end to end' model for decreasing error applied to achievement of effective epidural analgesia during labour: a randomised control study.

    Kallidaikurichi Srinivasan, Karthikeyan; Gallagher, Anthony; O'Brien, Niall; Sudir, Vinod; Barrett, Nick; O'Connor, Raymund; Holt, Francesca; Lee, Peter; O'Donnell, Brian; Shorten, George (2018-10-15)
    Background: Training procedural skills using proficiency-based progression (PBP) methodology has consistently resulted in error reduction. We hypothesised that implementation of metric-based PBP training and a valid assessment tool would decrease the failure rate of epidural analgesia during labour when compared to standard simulation-based training. Methods: Detailed, procedure-specific metrics for labour epidural catheter placement were developed based on carefully elicited expert input. Proficiency was defined using criteria derived from clinical performance of experienced practitioners. A PBP curriculum was developed to train medical personnel on these specific metrics and to eliminate errors in a simulation environment.Seventeen novice anaesthetic trainees were randomly allocated to undergo PBP training (Group P) or simulation only training (Group S). Following training, data from the first 10 labour epidurals performed by each participant were recorded. The primary outcome measure was epidural failure rate. Results: A total of 74 metrics were developed and validated. The inter-rater reliability (IRR) of the derived assessment tool was 0.88. Of 17 trainees recruited, eight were randomly allocated to group S and six to group P (three trainees did not complete the study). Data from 140 clinical procedures were collected. The incidence of epidural failure was reduced by 54% with PBP training (28.7% in Group S vs 13.3% in Group P, absolute risk reduction 15.4% with 95% CI 2% to 28.8%, p=0.04). Conclusion: Procedure-specific metrics developed for labour epidural catheter placement discriminated the performance of experts and novices with an IRR of 0.88. Proficiency-based progression training resulted in a lower incidence of epidural failure compared to simulation only training.
  • Psychiatry in Ireland: A Lot Done, More to Do

    Kelly, B.D.; Department of Psychiatry, Trinity Centre for Health Sciences (Irish Medical Journal, 2019-10)
    Four decades ago, in April 1979, Time magazine printed a dramatic cover story titled “Psychiatry’s depression”, diagnosing psychiatry with “a bad case of mid-life blues” 1. The magazine pointed to a lack of knowledge about the biology of mental illness, recruitment problems into the profession, uncertainties about treatments, and the inadequacy of community care. Precisely forty years later, in April 2019, the Economist magazine, in a very similar tone, referred to “today’s crisis in the psychiatric profession” 2 and, the following month, the New Yorker cited many of the same problems again in an article about “psychiatry’s fraught history” 3.
  • Incidence of Asymptomatic Chiari Malformation

    O’Reilly, E.M; Torreggiani, W (Irish Medical Journal, 2019-07)
    Aim The aim of this study is to define the incidence of asymptomatic Chiari malformation in an Irish population. Methods MRIs performed over 24 months were analysed. Exclusion criteria include: space occupying lesion, hydrocephalus, Chiari symptoms and inadequate views. Data were analysed to give incidence of asymptomatic Chiari and to analyze the relationship between symptom and position of the cerebellar tonsils (Chi square and Fishers exact test). Results Sample Characteristics: 147 patients (Male = 65: Female = 82), age range 15 to 93 years (M age = 53.35, SD= 16.67). 2%had a Chiari malformation (n=2). There was no significant association between symptom and tonsil position (Fishers exact test, ² (8) = 9.98, p = .23.) Conclusion This study shows an asymptomatic Chiari Malformation rate of 2%. This study supports the idea that in asymptomatic patients, a tonsil herniation of up to 5 millimeters may be an incidental and inconsequent finding.
  • Hip Fracture and the Weekend Effect in an Irish Trauma Hospital

    Downey, C; Flannery, S; Izydorczyk, A; Quinlan, J.F. (2019-06)
    We examined the relationship between the 1-year mortality (OYM) rate and (i) those admitted at the weekend, (ii) those who underwent surgery at the weekend and (iii) those admitted during the NCHD changeover months (January & July) for the management of hip fracture in Tallaght University Hospital (TUH).
  • Where does Pelvic and Acetabular Fracture Treatment fit into the Newly Proposed Major Trauma Model in Ireland?

    Fenelon, C; Murphy, E.P; O’Daly, B.J; Leonard, M (Irish Medical Journal, 2019-04)
    Major trauma continues to be the biggest cause of death in people aged between 5 and 45 years of age. Suboptimal trauma management results in greater ongoing costs to patients, hospitals and society. Trauma networks in the United States, Australia and more recently the United Kingdom have proven successful in significantly reducing morbidity and mortality. In the UK, analysis by the Trauma Audit Research Network (TARN) has shown that a major trauma patient has a 19% increase in the odds of survival following major trauma since its introduction in 2012. No integrated trauma network yet exists in Ireland but a recent report “A Trauma System for Ireland” published in January of 2018 outlined plans of how such a trauma network would be introduced. The report called for the introduction of two regional trauma networks, a central and south network, with one major trauma centre for each. However, the report made no mention of where the treatment of pelvic and acetabular fractures fell within it.
  • Infliximab Induced Cardiac Tamponade

    O’Morain, N; Kumar, L; O’Carroll-Lolait, C; Alakkari, A; Ryan, B (Irish Medical Journal, 2019-03)
    Biologic therapies are increasingly used in the treatment of Inflammatory Bowel Disease. Reactions to infusion therapy are not uncommon but are mostly benign and self-limiting. Rarely, life-threatening complications can occur.
  • Are we Over-Imaging the Obese Patient with Suspected Pulmonary Embolus in Ireland

    Gargan, M.L; O'Sullivan, M.; Hunter, K.; Buckley, O.; Torreggiani, W.C (Irish Medical Journal, 2019-02)
    To assess if there was a significant difference in the number of positive studies for pulmonary embolism between obese and non obese patients.
  • “Semenly” Harmless Back Pain: An Unusual Presentation of a Subcutaneous Abscess

    Dunne, L; Murphy, E; Rutledge, R (Irish Medical Journal, 2019-01)
    We report, with review of the literature, the case of a patient who developed a subcutaneous abscess after intravenously injecting his own semen in an attempt to treat longstanding back pain. He had devised this “cure” independent of medical advice.
  • Individualized dosing with axitinib: rationale and practical guidance.

    Schmidinger, Manuela; Danesi, Romano; Jones, Robert; McDermott, Ray; Pyle, Lynda; Rini, Brian; Négrier, Sylvie; 1 Clinical Division of Oncology, Department of Medicine I & Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. 2 Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy. 3 Institute of Cancer Sciences, University of Glasgow, The Beatson West of Scotland Cancer Centre, Glasgow, UK. 4 Department of Medical Oncology, St Vincent's University Hospital & The Adelaide & Meath Hospital, Dublin, Ireland. 5 Renal Cancer Unit, Department of Medicine, Royal Marsden Hospital, London, UK. 6 Department of Hematology & Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA. 7 Medical Oncology Department, University of Lyon, Centre Léon Bérard, Lyon, France. (Future Science Group, 2018-04-01)
    Axitinib is a potent, selective, vascular endothelial growth factor receptor inhibitor with demonstrated efficacy as second-line treatment for metastatic renal cell carcinoma. Analyses of axitinib drug exposures have demonstrated high interpatient variability in patients receiving the 5 mg twice-daily (b.i.d.) starting dose. Clinical criteria can be used to assess whether individual patients may benefit further from dose modifications, based on their safety and tolerability data. This review provides practical guidance on the 'flexible dosing' method, to help physicians identify who would benefit from dose escalations, dose reductions or continuation with manageable toxicity at the 5 mg b.i.d. dose. This flexible approach allows patients to achieve the best possible outcomes without compromising safety.

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