5366 research outputs found
Sort by
International perspectives on suboptimal patient-reported outcome trial design and reporting in cancer clinical trials: A qualitative study.
No full textPURPOSE
Evidence suggests that the patient-reported outcome (PRO) content of cancer trial protocols is frequently inadequate and non-reporting of PRO findings is widespread. This qualitative study examined the factors influencing suboptimal PRO protocol content, implementation, and reporting, and use of PRO data during clinical interactions.
METHODS
Semi-structured interviews were conducted with four stakeholder groups: (1) trialists and chief investigators; (2) people with lived experience of cancer; (3) international experts in PRO cancer trial design; (4) journal editors, funding panelists, and regulatory agencies. Data were analyzed using directed thematic analysis with an iterative coding frame.
RESULTS
Forty-four interviews were undertaken. Several factors were identified that could influenced effective integration of PROs into trials and subsequent findings. Participants described (1) late inclusion of PROs in trial design; (2) PROs being considered a lower priority outcome compared to survival; (3) trialists' reluctance to collect or report PROs due to participant burden, missing data, and perceived reticence of journals to publish; (4) lack of staff training. Strategies to address these included training research personnel and improved communication with site staff and patients regarding the value of PROs. Examples of good practice were identified.
CONCLUSION
Misconceptions relating to PRO methodology and its use may undermine their planning, collection, and reporting. There is a role for funding, regulatory, methodological, and journalistic institutions to address perceptions around the value of PROs, their position within the trial outcomes hierarchy, that PRO training and guidance is available, signposted, and readily accessible, with accompanying measures to ensure compliance with international best practice guidelines
Flares in patients with systemic lupus erythematosus.
No full textOBJECTIVE
SLE is characterized by relapses and remissions. We aimed to describe the frequency, type and time to flare in a cohort of SLE patients.
METHODS
SLE patients with one or more 'A' or 'B' BILAG-2004 systems meeting flare criteria ('new' or 'worse' items) and requiring an increase in immunosuppression were recruited from nine UK centres and assessed at baseline and monthly for 9 months. Subsequent flares were defined as: severe (any 'A' irrespective of number of 'B' flares), moderate (two or more 'B' without any 'A' flares) and mild (one 'B').
RESULTS
Of the 100 patients, 94% were female, 61% White Caucasians, mean age (s.d.) was 40.7 years (12.7) and mean disease duration (s.d.) was 9.3 years (8.1). A total of 195 flares re-occurred in 76 patients over 781 monthly assessments (flare rate of 0.25/patient-month). There were 37 severe flares, 32 moderate flares and 126 mild flares. By 1 month, 22% had a mild/moderate/severe flare and 22% had a severe flare by 7 months. The median time to any 'A' or 'B' flare was 4 months. Severe/moderate flares tended to be in the system(s) affected at baseline, whereas mild flares could affect any system.
CONCLUSION
. In a population with active SLE we observed an ongoing rate of flares from early in the follow-up period with moderate-severe flares being due to an inability to fully control the disease. This real-world population study demonstrates the limitations of current treatments and provides a useful reference population from which to inform future clinical trial design
Outcome of femoral-popliteal bypass procedures in different ethnic groups in England: A retrospective analysis of Hospital Episode Statistics.
No full textBACKGROUND
Previous studies, mainly from the United States, have reported worse outcomes from lower limb bypass procedures in ethnic minority populations. Limited nationwide data are available from ethnic minority populations from Europe. The aim of this study is to investigate outcomes from lower limb bypass procedures in ethnic minorities from England.
METHODS
We enquired the "Hospital Episode Statistics" database, using ICD-10 codes to identify all cases of femoral-popliteal bypass operations from English NHS Hospitals from 01/01/2006 to 31/12/2015. Every case was followed up for 2 years for subsequent events. The primary outcomes were mortality and major leg amputation. Patients were broadly categorised according to Black, Asian and White ethnicity. Chi-square test was used to the ethnic groups and odds ratios (OR) were calculated using White ethnic group with the largest numbers of participants as a reference category.
RESULTS
In the examined 10-year period, 20825 femoral-popliteal bypass procedures (250 of Black, 167 of Asian, and 20.408 of White ethnicity) were recorded. Thirty-day and 2-year mortality were 2.8% and 16.8% with no significant ethnic differences. Patients of Black ethnicity had higher risk of limb loss compared to Whites (23.2% vs 15.6%, OR =1.63, 95% confidence interval (CI) 1.21-2.19, p<0.01). There was no significant difference in amputation rates between Asians and Whites (16.2% vs 15.6%, p=0.94).
CONCLUSION
Patients of Black ethnicity are at higher risk of limb loss after a femoropopliteal bypass procedure. Further research is needed to identify the causes of this discrepancy
Hypophosphatasia.
No full textHypophosphatasia (HPP) is a group of inherited disorders characterised by the impaired mineralisation of bones and/or teeth and low serum alkaline phosphatase (ALP) activity. It is caused by a mutation in the ALPL gene encoding the tissue-non-specific isoenzyme of ALP (TNSALP) resulting in a loss of function. The disease is highly heterogenous in its clinical expression ranging from stillbirth without mineralised bone to the mild form of late adult onset with symptoms and signs such as musculoskeletal pain, arthropathy, lower-extremity fractures, premature loss of teeth or an incidental finding of reduced serum ALP activity. A classification based on the age at diagnosis and the presence or absence of bone symptoms was historically used: perinatal, prenatal benign, infantile, childhood, adult and odontohypophosphatasia. These subtypes are known to have overlapping signs and complications. Three forms of HPP distinguishable by their genetic characteristics have been described: severe, moderate and mild. Severe forms of HPP (perinatal and infantile severe) are recessively inherited, whereas moderate HPP may be dominantly or recessively inherited. The biochemical hallmark of HPP is persistently low serum ALP for age and increase in natural substrates of TNSALP, pyridoxal 5'-phosphate and phosphoethanolamine supported by radiological findings. The diagnosis is confirmed by ALPL sequencing. A multidisciplinary team of experts is essential for the effective management. Calcium restriction is recommended in infants/children to manage hypercalcaemia. A targeted enzyme replacement therapy for HPP has become available and correct diagnosis is crucial to allow early treatment
Machine learning-based radiomic evaluation of treatment response prediction in glioblastoma.
No full textAIM
To investigate machine learning based models combining clinical, radiomic, and molecular information to distinguish between early true progression (tPD) and pseudoprogression (psPD) in patients with glioblastoma.
MATERIALS AND METHODS
A retrospective analysis was undertaken of 76 patients (46 tPD, 30 psPD) with early enhancing disease following chemoradiotherapy for glioblastoma. Outcome was determined on follow-up until 6 months post-chemoradiotherapy. Models comprised clinical characteristics, O-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and 307 quantitative imaging features extracted from enhancing disease and perilesional oedema masks on early post-chemoradiotherapy contrast-enhanced T1-weighted imaging, T2-weighted imaging (T2WI), and apparent diffusion coefficient (ADC) maps. Feature selection was performed within bootstrapped cross-validated recursive feature elimination with a random forest algorithm. Naive Bayes five-fold cross-validation was used to validate the final model.
RESULTS
Top selected features included age, MGMT promoter methylation status, two shape-based features from the enhancing disease mask, three radiomic features from the enhancing disease mask on ADC, and one radiomic feature from the perilesional oedema mask on T2WI. The final model had an area under the receiver operating characteristics curve (AUC) of 0.80, sensitivity 78.2%, specificity 66.7%, and accuracy of 73.7%.
CONCLUSION
Incorporating a machine learning-based approach using quantitative radiomic features from standard-of-care magnetic resonance imaging (MRI), in combination with clinical characteristics and MGMT promoter methylation status has a complementary effect and improves model performance for early prediction of glioblastoma treatment response
The natural history of glycogen storage disease type Ib in England: A multisite survey.
No full textGlycogen storage disease type Ib (GSDIb) is characterized by hepatomegaly and fasting hypoglycaemia as well as neutropaenia and recurrent infections. We conducted a retrospective observational study on a cohort of patients with GSDIb across England. A total of 35 patients, with a median age of 9.1 years (range 1-39 years), were included in the study. We examined the genotype and phenotype of all patients and reported 14 novel alleles. The phenotype of GSDIb in England involves a short fasting tolerance that extends into adulthood and a high prevalence of gastrointestinal symptoms. Growth is difficult to manage and neutropaenia and recurrent infections persist throughout life. Liver transplantation was performed in nine patients, which normalized fasting tolerance but did not correct neutropaenia. This is the first natural history study on the cohort of GSDIb patients in England
Lactic acidosis, hypoglycaemia and eosinophilia: novel markers of antibody mediated rejection causing graft ischaemia.
No full textHistorically, minimal significance has been given to the humoral immune response after liver transplantation and, despite antibodies against HLA antigens being present in 10-20% of patients awaiting transplant, the incidence of antibody mediated rejection (AMR) after ABO compatible (ABO-C) liver transplantation is low (1).Donor Specific Antibodies (DSA) can lead to early graft loss (2), but most patients awaiting liver transplant are not screened for HLA sensitisation and serum DSA measurement are only undertaken if AMR is suspected. We describe two cases of AMR occurring within one week of ABO-C liver transplantation with previously unreported biochemical and histological characteristics
Trainee doctors' experiences of learning and well-being while working in intensive care during the COVID-19 pandemic: a qualitative study using appreciative inquiry.
No full textOBJECTIVES
Concern about trainee work-related well-being has been raised in recent years and is the subject of several reviews, reports and research studies. This study aimed to understand the experiences of trainees working in a large intensive care unit during the first surge of the COVID-19 pandemic from an educational and operational perspective in order to highlight what worked and what could be improved.
DESIGN
A qualitative study using peer-to-peer semistructured interviews, developed using appreciative inquiry methodology, was conducted during July 2020. Responses were analysed using a thematic analysis technique.
SETTING
A large, tertiary intensive care unit in the UK.
PARTICIPANTS
All trainees in anaesthesia and intensive care working on the intensive care unit during the first surge were invited to participate.
RESULTS
Forty interviews were conducted and four over-arching themes were identified. These were: feeling safe and supported; physical demands; the emotional burden of caring; and a sense of fulfilment, value and personal development. Positive aspects of the organisational response to the pandemic included communication, personal protective equipment supply, team working and well-being support. Suggestions for improvement focused on rest facilities, rota patterns and hierarchies, creating opportunities for reflection and ensuring continued educational and training opportunities despite operational demands.
CONCLUSIONS
Trainees described opportunities for learning and fulfilment, as well as challenges, in working through a pandemic. Trainees described their needs and how well these were met during the pandemic. Ideas for improvement most frequently related to basic needs including safety and fatigue, but suggestions also related to supporting learning and development. The appreciative inquiry methodology of the project facilitated effective reflection on positive aspects of trainee experiences
Is it safe to perform elective orthopaedic surgery with high community rates of COVID-19? An observational cohort study.
No full textINTRODUCTION
During the first wave of the COVID-19 pandemic, University Hospitals Birmingham NHS Foundation trust was able to recommence elective orthopaedic surgery using private hospitals procured by the NHS as COVID-19 free 'green' sites. We report on the safety of elective orthopaedic surgery with high rates of community transmission.
METHODS
We conducted an observational cohort study on consecutive NHS patients attending three private hospitals between 4 May 2020 and 16 June 2020. Patients attended preoperative assessment, including coronavirus disease (COVID-19) symptom screening, were instructed to self-isolate for 14 days and had a negative COVID-19 swab within 72 hours of surgery. Patient age, American Society of Anesthesiologists (ASA) grade, body mass index, surgery performed, type of anaesthetic and length of stay were collected. Our primary outcome was a positive COVID-19 swab, secondary outcomes were COVID-19 symptoms, readmission, surgical complications and mortality.
RESULTS
Between 4 May 2020 and 16 June 2020, 191 patients were admitted to three private hospitals for elective surgery; 121 (67%) patients underwent general or regional anaesthetic, 179 patients were ASA grades 1 or 2 (94%) and 12 (6%) were ASA 3. In total, 187 (98%) patients were successfully contacted at 30 days postoperative and no COVID-19 symptoms, positive COVID-19 swabs or mortality or were recorded. One patient was readmitted following a pulmonary embolism and two patients were treated as outpatients for a deep vein thrombosis and a superficial infection.
CONCLUSION
With 'green pathways' elective orthopaedic surgery can safely be performed while rates of COVID-19 in the community are high