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Evaluating Patient Safety And Ease Of Use Of A Novel Connection-Assist Device For Peritoneal Dialysis.
No full textIntroduction
It is estimated that there are currently over 3 million patients receiving dialysis treatment worldwide. With effective pre-dialysis counselling, a majority of patients choose the home-based therapy peritoneal dialysis (PD) but only approximately 11% of prevalent dialysis patients use this modality. Connection-assist devices can overcome the challenges posed by decreased manual dexterity and/or visual acuity, and can allow more patients to be treated with home-based therapies. As part of the CE marking authorization, a connection device has been evaluated for safety and ease of use in a usability study.
Methods
Fifteen patients and nine carers volunteered in this study, ranging from 23 to 86 years in age and from 0.3 to 24 years in experience in the PD therapy. The operating cycle consisted of eight tasks, each having several handling steps. The data analysis focused on the task effectiveness and the subjects' subjective feedback from the NASA task load index (N-TLX) questionnaire and semi-structured interviews.
Results
Of 1248 handling steps performed in total, 38 use errors were observed and discussed with the subjects. This equates to 97% of all handling steps being performed safely and easily. In all six dimensions of the N-TLX, more than 50 percent of subjects rated the task load 50 points or less on the scale. Regarding the handling of the device, 13 of 15 of the patients and 8 of 9 of the carers gave positive feedback.
Discussion
Safety and ease of use was demonstrated by evaluating task effectiveness (97% SU), interviews and N-TLX. Additionally the study provided valuable individual user feedback, which will inform the final design of the system for PD. The majority of patients and carers gave positive feedback regarding use and handling of this connection device. Innovative connection devices in general promise to reduce the barriers to using this home-based dialysis treatment
Osler Centenary Papers: William Osler in medical education.
No full textWilliam Osler combined many excellent characteristics of a clinical educator being a scientific scholar, a motivational speaker and writer and a proficient physician. As we celebrate his life a century on, many of his educational ideals are as pertinent today as they were in those Victorian times. Osler's contributions to modern medicine go beyond his legacy of quotable aphorisms to a doctor, educator and leader whose proponent use of bedside teaching, careful clinical methods, and clinicopathological correlation was a great inspiration for students and junior doctors. He was also a great advocate of patient-centred care-listening to and closely observing his patients, an important message for modern medicine as the reliance on investigations strains modern healthcare systems. This review of Osler's contribution to medical education summarises his development as an educator and provides reflection on his influences to modern clinical education
Instrument-based tests for quantifying aqueous humour protein levels in uveitis: a systematic review protocol.
No full textBACKGROUND
Inflammation in anterior uveitis is characterised by breakdown of the blood-ocular barrier, which allows leakage of blood constituents of higher molecular weight into the aqueous humour. In routine clinical care, increase in aqueous protein levels can be observed at the slit lamp as 'flare' and the severity can be graded using various clinical grading systems, of which the Standardization of Uveitis Nomenclature (SUN) grading system is most commonly used. Alternative instrument-based technologies are available, which can detect aqueous protein levels in an objective and quantifiable way. This review will identify instruments capable of measuring anterior chamber inflammation in this way, their level of reliability, and how well the measurements correlate with clinical grading and/or actual aqueous protein concentration.
METHODS
Standard systematic review methodology will be used to identify, select and extract data from studies that report the use of any instrument-based technology in the assessment of aqueous protein levels. Searches will be conducted through bibliographic databases (MEDLINE, EMBASE and Cochrane Library), clinical trial registries and the grey literature. No restrictions will be placed on language or year of publication. The outcomes of interest are the level of correlation between identified instrument-based test measurements, clinical grading and/or actual aqueous protein concentration, as well as the reliability of each index test identified. Study quality assessment will be based on QUADAS2. Correlation and reliability outcomes will be pooled and meta-analysed if appropriate.
DISCUSSION
The assessment of inflammation in anterior chamber protein levels currently relies on crude and subjective clinical examination. The findings of this review will identify non-invasive technologies which show good correlation with actual protein concentration, which could be used in routine clinical practice for objective monitoring of AC inflammation.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42017084167. Study screening stage has just been completed
Effect of Thoracoscopic Talc Poudrage vs Talc Slurry via Chest Tube on Pleurodesis Failure Rate Among Patients With Malignant Pleural Effusions: A Randomized Clinical Trial.
No full textImportance
Malignant pleural effusion (MPE) is challenging to manage. Talc pleurodesis is a common and effective treatment. There are no reliable data, however, regarding the optimal method for talc delivery, leading to differences in practice and recommendations.
Objective
To test the hypothesis that administration of talc poudrage during thoracoscopy with local anesthesia is more effective than talc slurry delivered via chest tube in successfully inducing pleurodesis.
Design, Setting, and Participants
Open-label, randomized clinical trial conducted at 17 UK hospitals. A total of 330 participants were enrolled from August 2012 to April 2018 and followed up until October 2018. Patients were eligible if they were older than 18 years, had a confirmed diagnosis of MPE, and could undergo thoracoscopy with local anesthesia. Patients were excluded if they required a thoracoscopy for diagnostic purposes or had evidence of nonexpandable lung.
Interventions
Patients randomized to the talc poudrage group (n = 166) received 4 g of talc poudrage during thoracoscopy while under moderate sedation, while patients randomized to the control group (n = 164) underwent bedside chest tube insertion with local anesthesia followed by administration of 4 g of sterile talc slurry.
Main Outcomes and Measures
The primary outcome was pleurodesis failure up to 90 days after randomization. Secondary outcomes included pleurodesis failure at 30 and 180 days; time to pleurodesis failure; number of nights spent in the hospital over 90 days; patient-reported thoracic pain and dyspnea at 7, 30, 90, and 180 days; health-related quality of life at 30, 90, and 180 days; all-cause mortality; and percentage of opacification on chest radiograph at drain removal and at 30, 90, and 180 days.
Results
Among 330 patients who were randomized (mean age, 68 years; 181 [55%] women), 320 (97%) were included in the primary outcome analysis. At 90 days, the pleurodesis failure rate was 36 of 161 patients (22%) in the talc poudrage group and 38 of 159 (24%) in the talc slurry group (adjusted odds ratio, 0.91 [95% CI, 0.54-1.55]; P = .74; difference, -1.8% [95% CI, -10.7% to 7.2%]). No statistically significant differences were noted in any of the 24 prespecified secondary outcomes.
Conclusions and Relevance
Among patients with malignant pleural effusion, thoracoscopic talc poudrage, compared with talc slurry delivered via chest tube, resulted in no significant difference in the rate of pleurodesis failure at 90 days. However, the study may have been underpowered to detect small but potentially important differences.
Trial Registration
ISRCTN Identifier: ISRCTN47845793
Endovascular repair of acute juxtarenal and thoracoabdominal aortic aneurysms with surgeon-modified fenestrated endografts.
No full textOBJECTIVE
The objective of this study was to report the short- and medium-term outcome of surgeon-modified fenestrated endovascular aneurysm repair (SM-FEVAR) for acute complex aortic aneurysms.
METHODS
Interrogation of a prospectively maintained database identified consecutive patients who underwent SM-FEVAR for acute complex aortic aneurysms (including mycotic aneurysms treated with rifampicin-soaked endografts) in a single institution between October 2009 and November 2018.
RESULTS
A total of 54 patients (37 men; median age, 73 years [range, 50-85 years]; aneurysm diameter, 76 mm [interquartile range, 58-90 mm]) with acute thoracoabdominal aortic aneurysms (n = 50; 40 symptomatic, 10 ruptured; 19 extent I-III, 31 extent IV) or symptomatic type IA endoleaks after infrarenal endovascular aneurysm repair (n = 4) underwent SM-FEVAR. Seven of the patients had adjunct chimney and periscope stent grafts or surgical bypasses. A total of 187 vessels (mean, 3.4 [range, 1-5] per patient) were targeted for preservation; nine occluded intraoperatively or within 30 days. The 30-day/in-hospital mortality was 16.7% (n = 9; symptomatic, 7.4%; rupture, 50%) and fell significantly from 29.6% (n = 8) in the first 27 patients to 3.7% (n = 1) in the most recent 27 patients (P = .0243). Spinal cord ischemia occurred in one patient (1.9%) who died within 30 days. No survivors required permanent renal dialysis. Estimated survival at 12 and 24 months was 73.2% (standard error [SE], 6.2%). Eight patients underwent 12 late aorta- or graft-related reinterventions. Estimated freedom from reintervention at 12 months and 24 months was 87.9% (SE, 5.2%) and 81.6% (SE, 6.4%), respectively.
CONCLUSIONS
In patients with acute complex aneurysms, SM-FEVAR provides a customized solution that is associated with good medium-term survival and durability. The knowledge and skills to perform safe SM-FEVAR should be within the capabilities of high-volume specialist aortic centers
Impact of graft-versus-lymphoma effect on outcomes after reduced intensity conditioned-alemtuzumab allogeneic haematopoietic stem cell transplantation for patients with mature lymphoid malignancies.
No full textAllogeneic haematopoietic stem cell transplant (allo-HSCT) offers potentially curative therapy for patients with relapsed/refractory lymphoid malignancies. Reduced-intensity conditioning (RIC) with Alemtuzumab reduces transplant-related mortality and graft-versus-host disease (GvHD), but may be associated with increased risk of relapse. With the aim of studying the effect of GVHD and donor lymphocyte infusions (DLI) on relapse, we performed a retrospective study of 288 patients (57% non-Hodgkin lymphoma, 24% Hodgkin lymphoma and 19% chronic lymphocytic leukaemia; 58% were relapsed/refractory) who underwent RIC-Alemtuzumab-HSCT between 2000 and 2012. Median follow-up time for survivors was 64 months. Five-year overall survival, relapse incidence, GvHD/relapse-free survival and non-relapse mortality were 47%, 33%, 37% and 28% respectively. Cumulative incidence of grade II-IV acute and extensive chronic GvHD was 22% and 21% at 100 days and 5 years respectively. On multivariate analysis, presence of GvHD (P = 0·03) and unrelated donor type (P = 0·03) were protective of relapse. 62/288 patients received DLI for either mixed donor chimerism (prophylactic DLI, n = 37) or clinical relapse (therapeutic DLI, n = 25). Prophylactic and therapeutic DLI successfully converted the patient to full or stable mixed donor chimerism in 78% and 56% of patients respectively. These data demonstrate good long-term outcomes and support the concept of the graft-vs-lymphoma effect as a key protective factor against relapse following RIC-Alemtuzumab allo-HSCT for patients with mature lymphoid malignancies
Long-Term Ibrutinib Therapy Reverses CD8 T Cell Exhaustion in B Cell Chronic Lymphocytic Leukaemia.
No full textChronic Lymphocytic Leukaemia (CLL) is associated with immune suppression and susceptibility to infection. CD8 T cell numbers are increased and demonstrate elevated expression of PD-1 and impaired function. The mechanisms driving these features of exhaustion are uncertain but are likely to include chronic immune recognition of tumor and/or infectious agents. We investigated the number, phenotype and function of total and virus-specific CD8+ T cells in 65 patients with CLL and 14 patients undergoing long-term ibrutinib therapy (median 21 months). Ibrutinib substantially reduced the number of both CD3+ T cells and CD8+ T cells. Importantly, this was associated with a reduction in PD-1 expression on CD8+ T cells (median 28 vs. 24%; = 0.042) and 3.5 fold increase in cytokine production following mitogen stimulation. The influence of ibrutinib on antigen-specific CD8+ T cell function was assessed by HLA-peptide tetramers and revealed increased IFNγ and TNFα cytokine responses following stimulation with CMV or EBV peptides together with a 55% reduction in the frequency of "inflated" virus-specific CD8+ T cells. These findings reveal that long-term ibrutinib therapy is associated with substantial reversal of T cell exhaustion in B-CLL and is likely to contribute to the reduced infection risk seen in association with this agent
Coupling between cerebral blood flow and cerebral blood volume: Contributions of different vascular compartments.
No full textA better understanding of the coupling between changes in cerebral blood flow (CBF) and cerebral blood volume (CBV) is vital for furthering our understanding of the BOLD response. The aim of this study was to measure CBF-CBV coupling in different vascular compartments during neural activation. Three haemodynamic parameters were measured during a visual stimulus. Look-Locker flow-sensitive alternating inversion recovery was used to measure changes in CBF and arterial CBV (CBV ) using sequence parameters optimized for each contrast. Changes in total CBV (CBV ) were measured using a gadolinium-based contrast agent technique. Haemodynamic changes were extracted from a region of interest based on voxels that were activated in the CBF experiments. The CBF-CBV coupling constant α was measured as 0.16 ± 0.14 and the CBF-CBV coupling constant α was measured as 0.65 ± 0.24. Using a two-compartment model of the vasculature (arterial and venous), the change in venous CBV (CBV ) was predicted for an assumed value of baseline arterial and venous blood volume. These results will enhance the accuracy and reliability of applications that rely on models of the BOLD response, such as calibrated BOLD
Efficacy of venetoclax monotherapy in patients with relapsed chronic lymphocytic leukaemia in the post-BCR inhibitor setting: a UK wide analysis.
No full textVenetoclax is a BCL2 inhibitor with activity in relapsed/refractory (R/R) chronic lymphocytic leukaemia (CLL). We conducted a multi-centre retrospective analysis of 105 R/R CLL patients who received venetoclax pre-National Health Service commissioning. The median age was 67 years and median prior lines was 3 (range: 1-15). 48% had TP53 disruption. At ≥2 lines, 60% received a Bruton Tyrosine Kinase inhibitor (BTKi) and no prior phosphoinositide 3-kinase inhibitor (Pi3Ki), 25% received a Pi3Ki and no prior BTKi, and 10% received both. Patients discontinued B cell receptor inhibitor (BCRi) because of toxicity in 44% and progression in 54%. Tumour lysis syndrome risk was low, intermediate or high in 27%, 25%, and 48% respectively. Overall response was 88% (30% complete response [CR]). The overall response rate was 85% (CR 23%) in BTKi-exposed patients, 92% (CR 38%) in Pi3Ki-exposed patients and 80% (CR 20%) in both (P = 0·59). With a median follow-up of 15·6 months, 1-year progression-free survival was 65·0% and 1-year overall survival was 75·1%. Dose reduction or temporary interruption did not result in an inferior progression-free or discontinuation-free survival. Risk of progression or death after stopping a prior BCRi for progression was double compared to those stopping for other reasons (predominantly toxicity) (Hazard Ratio 2·01 P = 0·05). Venetoclax is active and well tolerated in R/R CLL post ≥1 BCRi. Reason(s) for stopping BCRi influences venetoclax outcomes