2018

Prospective, multinational, observational study of real-world treatment outcomes with pazopanib in patients with advanced or metastatic renal cell carcinoma (PRINCIPAL study) (2018)

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Type of publication:
Conference abstract

Author(s):
Schmidinger M.; Procopio G.; Hawkins R.E.; Sanchez A.R.; Vazquez S.; *Srihari N.; Kalofonos H.; Bamias A.; Bono P.; Pisal C.B.; Hirschberg Y.; Dezzani L.; Ahmad Q.I.; Jonasch E.

Citation:
Journal of Clinical Oncology; May 2018; vol. 36 (no. 15)

Abstract:
Background: PRINCIPAL (NCT01649778) was the largest prospective real-world effectiveness and safety study of pazopanib (PAZ) in patients (pts) with renal cell carcinoma (RCC). Method(s): Pts with advanced and/or metastatic clear cell RCC were enrolled within 30 days of initiating firstline PAZ. Follow-up data on progression, survival, and safety was collected approximately every 3 months until death, consent withdrawal, or loss to follow-up, for up to 30 months. Primary efficacy end points were median overall survival (mOS), median progression-free survival (mPFS), and overall response rate (ORR). Safety measures included frequency of adverse events (AEs), serious AEs, and AEs of special interest. Result(s): Among 657 pts who received >=1 dose of PAZ, 76.3% completed the study (33.0% completed 30 months of follow-up and 43.2% died). Median enrollment age was 66 years, with 57.2% aged >=65 years. 4.1%, 62.6%, and 33.3% of pts were grouped as favorable, intermediate, or poor risk by Heng criteria, respectively. Most pts (84%) initiated treatment at 800 mg, and the median treatment time with or without dose interruption was 6.9 and 7.6 months, respectively. mPFS and mOS are shown in the Table. Among the measurable disease population (n = 168), ORR was 30.3%, median duration of response was 11.0 months (95% confidence interval [CI] 8.6-14.6), and time to response, evaluated every 3 months, was 3.0 months (95% CI 2.9-3.1). Most pts had an AE (74.0%) that led to dose  adjustment/interruption in 49.3% and treatment discontinuation in 14.6%. The most frequent ( > 10%) drug-related AEs were hypertension (20.9%), diarrhea (11.3%), and increased alanine aminotransferase (11.0%). Conclusion(s): Realworld effectiveness and safety outcomes in the PRINCIPAL study were consistent with clinical trials and support the first-line use of PAZ across all risk groups of pts with advanced or metastatic RCC.

Comparison of clinical outcomes with firstline pazopanib in clinical trial eligible and non-clinical trial eligible patients with renal cell carcinoma (2018)

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Type of publication:
Conference abstract

Author(s):
Jonasch E.; Procopio G.; Hawkins R.E.; Sanchez A.R.; Vazquez S.; *Srihari N.; Kalofonos H.; Bamias A.; Bono P.; Pisal C.B.; Hirschberg Y.; Dezzani L.; Ahmad Q.I.; Schmidinger M.

Citation:
Journal of Clinical Oncology; May 2018; vol. 36 (no. 15)

Abstract:
Background: Although pazopanib (PAZ) has been evaluated in clinical trials of patients (pts) with renal cell carcinoma (RCC), limited real-world data on the effectiveness and safety of PAZ exist. The PRINCIPAL study (NCT01649778) assessed the effectiveness and safety of first-line PAZ in a real-world setting. Method(s): In this nonrandomized, prospective study, pts with advanced and/or metastatic clear cell RCC were enrolled in PRINCIPAL within 30 days of initiating first-line PAZ. Data on progression, survival, and safety were collected approximately every 3 months (mos) until death, consent withdrawal, or loss to follow-up, for up to 30 mos. Pts in PRINCIPAL were separated into two groups based on key eligibility criteria from the Phase III COMPARZ trial (Motzer et al. NEJM. 2013;369:722). Key clinical trial eligible (CTE) criteria included no prior systemic therapy, presence of measurable disease per RECIST 1.1, Karnofsky performance status >=70, adequate organ system function, no history or clinical evidence of central nervous system metastases, and no coronary or cerebral artery disease at baseline. CTE pts were compared to non-CTE (NCTE) pts. Clinical effectiveness (ie, median overall survival [mOS], median progression-free survival [mPFS], and overall response rate [ORR]), adverse event (AE) measures, and relative dose intensity (RDI) were assessed in both pt populations. Result(s): Of the 657 enrolled pts who received >=1 dose of PAZ, 97 (14.8%) were CTE and 560 (85.2%) were NCTE. RDI >=85% was achieved in 70.1% and 56.6% in the CTE and NCTE populations, respectively. Effectiveness was similar in the CTE and the NCTE populations (mPFS, 9.6 vs 10.7 mos; ORR, 33.0% vs 29.8%; mOS, 26.3 vs 32.9 mos). Serious AEs were reported by 23.7% of CTE and 28.2% of NCTE pts. AEs led to dose adjustment/interruption in 83.5% and 95.2%, respectively, and AEs led to treatment discontinuation in 8.2% of the CTE and 15.5% NCTE pts. Conclusion(s): The results of the PRINCIPAL study suggest that first-line PAZ for pts with advanced or metastatic RCC remains effective and safe in a real-world setting, showing similar outcomes to those reported in large randomized clinical trials.

Lymphangioma circumscriptum of the vulva clinical picture and surgical management (2018)

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Type of publication:
Journal article

Author(s):
*Papoutsis D.; Haefner H.K

Citation:
Archives of Hellenic Medicine 35(6):809-810 · November 2018

Abstract:
Vulvar lymphangioma circumscriptum is a rare entity that may mimic many other diseases of the vulva. It presents with the non-specific symptoms of persistent vulvar itching and soreness, and the diagnosis is confirmed through vulvar biopsy. Surgical treatment has the lowest recurrence rates compared with other treatment modalities. The case is presented here of a woman diagnosed with lymphangioma circumscriptum of the vulva and its surgical management.

Audit of 2-week wait referrals to the Gynecology Department in District General Hospital and investigating patient awareness of the reasons and importance behind the referral (2018)

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Type of publication:
Conference abstract

Author(s):
Wilkinson M.; *Sahu B

Citation:
BJOG: An International Journal of Obstetrics and Gynaecology; Dec 2018; vol. 125 ; p. 48

Abstract:
Introduction Two-week wait referrals to gynecology services are at a premium with pressure on numbers. Referrals can be inappropriate. Patients are often unaware the appointment is for suspected cancer. Methods Two-week wait referrals were examined during a six month period. The gynecologist in clinic collected data. Patients were asked about their 2-week wait referral, gauging awareness around their referral. Clinical symptoms and signs were compared to those in referral. Appropriateness of the referral was assessed by symptoms fitting the 2-week wait criteria or clinical findings on referral not consistent with the presenting symptoms and findings in clinic. Results A total of 172 patients were referred under the 2-week wait criteria; mean age was 58 years, range (17-95). Referrals were from 50 separate primary care practices. Suspected cancer referrals were composed of 111 endometrial, 15 ovarian, 22 cervical, 15 vulva/vaginal and 9 of mixed pathology. There was awareness of referral for cancer in 90 cases (52%), awareness of "2-week wait" in 124 cases (72%) and aware that the appointment could be at either hospital within the trust in 96 cases (56%). The referral was considered appropriate for 2-week wait referral in 123 (72%) of cases. Conclusion The majority of patients were referred correctly. A wide range of pathologies was seen. A significant number could have been referred as routine referrals or advice requested. Patient awareness of it being a referral due to suspected cancer was poor with better appreciation of the urgency of referral.

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Cancelled operations: a 7-day cohort study of planned adult inpatient surgery in 245 UK National Health Service hospitals (2018)

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Type of publication:
Journal article

Author(s):
Wong, D.J.N.; Harris, S.K.; Moonesinghe, S.R

Collaborators at Shrewsbury and Telford Hospital NHS Trust:
*Jane Wright, *Paul Jones, *Riquella Abbott, *Lisa Bacon, *Christopher Godden, *David Howe, *Angela Loughlin, *Helen Moore, *Samuel Passey, *Rebekah Rodgers

Citation:
BJA: The British Journal of Anaesthesia; Oct 2018; vol. 121 (no. 4); p. 730-738

Abstract:
Background: Cancellation of planned surgery impacts substantially on patients and health systems. This study describes the incidence and reasons for cancellation of inpatient surgery in the UK NHS. Methods: We conducted a prospective observational cohort study over 7 consecutive days in March 2017 in 245 NHS hospitals. Occurrences and reasons for previous surgical cancellations were recorded. Using multilevel logistic regression, we identified patient- and hospital-level factors associated with cancellation due to inadequate bed capacity.Results: We analysed data from 14 936 patients undergoing planned surgery. A total of 1499 patients (10.0%) reported previous cancellation for the same procedure; contemporaneous hospital census data indicated that 13.9% patients attending inpatient operations were cancelled on the day of surgery. Non-clinical reasons, predominantly inadequate bed capacity, accounted for a large proportion of previous cancellations. Independent risk factors for cancellation due to inadequate bed capacity included requirement for postoperative critical care [odds ratio (OR)=2.92; 95% confidence interval (CI), 2.12-4.02; P<0.001] and the presence of an emergency department in the treating hospital (OR=4.18; 95% CI, 2.22-7.89; P<0.001). Patients undergoing cancer surgery (OR=0.32; 95% CI, 0.22-0.46; P<0.001), obstetric procedures (OR=0.17; 95% CI, 0.08-0.32; P<0.001), and expedited surgery (OR=0.39; 95% CI, 0.27-0.56; P<0.001) were less likely to be cancelled.Conclusions: A significant proportion of patients presenting for surgery have experienced a previous cancellation for the same procedure. Cancer surgery is relatively protected, but bed capacity, including postoperative critical care requirements, are significant risk factors for previous cancellations.

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The current standard of care and the unmet needs for axial spondyloarthritis (2018)

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Type of publication:
Journal article

Author(s):
*Noureldin, Basil; Barkham, Nick

Citation:
Rheumatology; Volume 57, Issue suppl_6, November 2018, Pages vi10–vi17

Abstract:
The aim of this article is to explore the benefits and limitations of the established treatments for axial SpA (axSpA), including physiotherapy, NSAIDs, conventional synthetic DMARDs and biologic DMARDs such as TNF inhibitors (TNFis). It also briefly discusses the emerging role of anti-IL-17 therapy, which could be used as a valuable alternative to first-line biologic DMARD treatment or as a second-line treatment for patients who are inadequate responders to TNFi therapy, as evidenced by various studies. Exercise programmes improve health related quality of life and hydrotherapy improves disease activity and functional parameters in AS. NSAIDs have been proven to substantially relieve symptoms in 70–80% of patients and enhance physiotherapy by reducing pain and stiffness. The role of NSAIDs in preventing radiographic progression remains unclear. The use of conventional synthetic DMARDs (csDMARDs) is limited to peripheral arthritis; there is insufficient evidence to support the use of csDMARDs for axial disease. TNFi therapy reduces the disease activity of axSpA, however, as not all patients respond to treatment in the same way, it is good to have other therapeutic options available. Finally, this article explores the potential for IL-17 inhibition in AS and introduces clinical data for secukinumab, a fully human monoclonal antibody targeting IL-17A.

Charcot Marie Tooth disease type 2S with late onset diaphragmatic weakness: An atypical case (2018)

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Type of publication:
Journal article

Author(s):
Kulshrestha, Richa; Forrester, Natalie; Antoniadi, Thalia; Willis, Tracey; *Sethuraman, Sethil Kumar; Samuels, Martin

Citation:
Neuromuscular disorders : NMD; Dec 2018; vol. 28 (no. 12); p. 1016-1021

Abstract:
Immunoglobulin-helicase-μ-binding protein 2 (IGHMBP2) mutations are associated with partial continuum between two extremes of rapidly lethal disorder of spinal muscular atrophy with respiratory distress type 1 (SMARD1), with infantile axonal neuropathy, diaphragmatic weakness and commonly death before 1 year of age, and Charcot-Marie-Tooth disease (CMT) type 2S with slowly progressive weakness and sensory loss but no significant respiratory compromise. We present an atypical case of CMT2S. A 9 month old boy presented with bilateral feet deformities and axonal neuropathy. Genetic testing revealed two heterozygous variants in the IGHMBP2 gene: c.1156 T>C p.(Trp386Arg) in exon 8 and c.2747G>A p.(Cys916Tyr) in exon 14, that were inherited from his father and mother respectively. At 9 years, he developed diaphragmatic weakness, following which he was established on non-invasive ventilation. Our case emphasizes the importance of life long respiratory surveillance for patients with CMT2S and expands the phenotype of this condition.

A patient-centred model to quality assure outputs from an echocardiography department: consensus guidance from the British Society of Echocardiography (2018)

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Type of publication:
Journal article

Author(s):
*Ingram, Thomas E; Baker, Steph; Allen, Jane; Ritzmann, Sarah; Bual, Nina; Duffy, Laura; Ellis, Chris; Bunting, Karina; Black, Noel; Peck, Marcus; Hothi, Sandeep S; Sharma, Vishal; Pearce, Keith; Steeds, Richard P; Masani, Navroz

Citation:
Echo research and practice; Dec 2018; vol. 5 (no. 4); p. G25

Abstract:
Background Quality assurance (QA) of echocardiographic studies is vital to ensure that clinicians can act on findings of high quality to deliver excellent patient care. To date, there is a paucity of published guidance on how to perform this QA. The British Society of Echocardiography (BSE) has previously produced an Echocardiography Quality Framework (EQF) to assist departments with their QA processes. This article expands on the EQF with a structured yet versatile approach on how to analyse echocardiographic departments to ensure high-quality standards are met. In addition, a process is detailed for departments that are seeking to demonstrate to external bodies adherence to a robust QA process. Methods The EQF consists of four domains. These include assessment of Echo Quality (including study acquisition and report generation); Reproducibility & Consistency (including analysis of individual variability when compared to the group and focused clinical audit), Education & Training (for all providers and service users) and Customer & Staff Satisfaction (of both service users and patients/their carers). Examples of what could be done in each of these areas are presented. Furthermore, evidence of participation in each domain is categorised against a red, amber or green rating: with an amber or green rating signifying that a quantifiable level of engagement in that aspect of QA has been achieved. Conclusion The proposed EQF is a powerful tool that focuses the limited time available for departmental QA on areas of practice where a change in patient experience or outcome is most likely to occur.

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Screening for colorectal cancer in defunctioned colons (2018)

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Type of publication:
Journal article

Author(s):
*Akbar, Fayyaz; Quyn, Aaron; Steele, Robert

Citation:
Journal of medical screening; Dec 2018; vol. 25 (no. 4); p. 178-182

Abstract:
OBJECTIVES Population-based colorectal (bowel) cancer screening using faecal occult blood tests leads to a reduction in cause-specific mortality. However, in people where the colon is defunctioned, the use of standard faecal occult blood test is not appropriate. The aim of this study was to examine the current trends of clinical practice for colorectal cancer screening in people with defunctioned colons.METHODS An online survey was performed using SurveyMonkey. All members of the Association of Coloproctology of Great Britain and Ireland were invited by email to participate. Reminders were sent to non-responders and partial responders till six weeks. All responses were included in our analysis. RESULTS Of the 206 (34.59%) questionnaires completed, all questions were answered in 110 (55.8%). Among responders, 94 (85.4%) were colorectal consultant surgeons, 72% had worked in their current capacity for more than five years, and 105 (50.9%) had encountered colorectal cancer in defunctioned colons during their career. Some 72.2% of responders stated that a screening test for colorectal cancer in patients with defunctioned colons was currently not offered, or that they did not know whether or not it was offered in their area.CONCLUSIONS Bowel screening in the United Kingdom is currently not offered to 72.2% of the age appropriate population with defunctioned colons. Among responding colorectal surgeons, 50% had encountered colorectal cancer in such patients. There is considerable variability in clinical practice regarding the optimal age for onset of screening, time interval, and the optimal modality to offer for screening in such cases.

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Longer duration of operative time enhances healing metabolites and improves patient outcome after Achilles tendon rupture surgery (2018)

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Type of publication:
Journal article

Author(s):
Svedman S.; Aufwerber S.; Ackermann P.W.; Westin O.; Nilsson-Helander K.; *Carmont M.R.; Karlsson J.; Edman G.

Citation:
Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA; Jul 2018; vol. 26 (no. 7); p. 2011-2020

Abstract:
PURPOSE: The relationship between the duration of operative time (DOT), healing response and patient outcome has not been previously investigated. An enhanced healing response related to DOT may potentiate repair processes, especially in hypovascular and sparsely metabolized musculoskeletal tissues such as tendons. This study aimed to investigate the association between DOT and the metabolic healing response, patient reported outcome and the rate of post-operative complications after acute Achilles tendon injury.METHODS: Observational cohort, cross-sectional study with observers blinded to patient grouping. A total of two-hundred and fifty-six prospectively randomized patients (210 men, 46 women; mean age 41 years) with an acute total Achilles tendon rupture all operated on with uniform anaesthetic and surgical technique were retrospectively assessed. At 2 weeks post-operatively, six metabolites were quantified using microdialysis. At 3, 6 and 12 months, patient-reported pain, walking ability and physical activity were examined using self-reported questionnaires, Achilles tendon total rupture score, foot and ankle outcome score and physical activity scale. At 12 months, functional outcome was assessed using the heel-rise test. Complications, such as deep venous thrombosis, infections and re-operations, were recorded throughout the study.RESULTS: Patients who underwent longer DOT exhibited higher levels of glutamate (p = 0.026) and glycerol (p = 0.023) at 2 weeks. At the 1-year follow-up, longer DOT was associated with significantly less loss in physical activity (p = 0.003), less pain (p = 0.009), less walking limitations (p = 0.022) and better functional outcome (p = 0.014). DOT did not significantly correlate with the rate of adverse events, such as deep venous thrombosis, infections or reruptures. Higher glutamate levels were associated with less loss in physical activity (p = 0.017). All correlations were confirmed by multiple linear regressions taking confounding factors into consideration.CONCLUSION: The results from this study suggest a previously unknown mechanism, increased metabolic response associated with longer DOT, which may improve patient outcome after Achilles tendon rupture surgery. Allowing for a higher amount of traumatized tissue, as reflected by up-regulation of glycerol in patients with longer DOT, may prove to be an important surgical tip for stimulation of repair of hypometabolic soft tissue injuries, such as Achilles tendon ruptures.II.

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