17 results on '"Martin, O."'
Search Results
2. The Impact of 68Gallium DOTA PET/CT in Managing Patients With Sporadic and Familial Pancreatic Neuroendocrine Tumours.
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Cuthbertson, Daniel J., Barriuso, Jorge, Lamarca, Angela, Manoharan, Prakash, Westwood, Thomas, Jaffa, Matthew, Fenwick, Stephen W., Nuttall, Christina, Lalloo, Fiona, Prachalias, Andreas, Pizanias, Michail, Wieshmann, Hulya, McNamara, Mairead G., Hubner, Richard, Srirajaskanthan, Raj, Vivian, Gillian, Ramage, John, Weickert, Martin O., Pritchard, D Mark, and Vinjamuri, Sobhan
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COMPUTED tomography ,CROSS-sectional imaging ,ENDOSCOPIC ultrasonography ,PEPTIDE receptors ,HISTOPATHOLOGY ,PANCREATIC tumors ,TUMOR grading ,PANCREATIC surgery - Abstract
Objective: Pancreatic neuroendocrine tumours (panNETs) arise sporadically or as part of a genetic predisposition syndrome. CT/MRI, endoscopic ultrasonography and functional imaging using Octreoscan localise and stage disease. This study aimed to evaluate the complementary role of
68 Gallium (68 Ga)-DOTA PET/CT in managing patients with panNETs. Design: A retrospective study conducted across three tertiary UK NET referral centres. Methods: Demographic, clinical, biochemical, cross-sectional and functional imaging data were collected from patients who had undergone a68 Ga-DOTA PET/CT scan for a suspected panNET. Results: We collected data for 183 patients (97 male): median (SD) age 63 (14.9) years, 89.1 vs. 9.3% (n=163 vs. 17) alive vs. dead (3 data missing), 141 sporadic vs. 42 familial (MEN1, n=36; 85.7%) panNETs. Non-functional vs. functional tumours comprised 73.2 vs. 21.3% (n=134 vs. 39) (10 missing). Histological confirmation was available in 89% of individuals (n=163) but tumour grading (Ki67 classiifcation) was technically possible only in a smaller cohort (n=143): grade 1, 50.3% (n=72); grade 2, 46.2% (n=66) and grade 3, 3.5% (n=5) (40 histopathological classification either not technically feasible or biopsy not perfomed). 60.1% (n=110) were localised, 14.2% (n=26) locally advanced and 23.5% (n=43) metastatic (4 missing). 22468 Ga-DOTA PET/CT scans were performed in total for: diagnosis/staging 40% (n=88), post-operative assessment/clinical surveillance 53% (n=117) and consideration of peptide receptor radionuclide therapy (PRRT) 8% (n=17) (2 missing). PET/CT results confirmed other imaging findings (53%), identified new disease sites (28.5%) and excluded suspected disease (5%). Overall,68 Ga-DOTA PET/CT imaging findings provided additional information in 119 (54%) patients and influenced management in 85 (39%) cases. Conclusion:68 Ga-DOTA PET/CT imaging more accurately stages and guides treatment in patients with sporadic/familial panNETs with newly diagnosed/recurrent disease. [ABSTRACT FROM AUTHOR]- Published
- 2021
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3. Early Metabolic Benefits of Switching Hydrocortisone to Modified Release Hydrocortisone in Adult Adrenal Insufficiency.
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Bannon, Christopher A. M., Border, Daniel, Hanson, Petra, Hattersley, John, Weickert, Martin O., Grossman, Ashley, Randeva, Harpal S., and Barber, Thomas M.
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ADRENAL insufficiency ,HYDROCORTISONE ,FAT ,BODY composition ,ADULTS - Abstract
Purpose: To compare metabolic effects of modified release hydrocortisone (MR-HC) with standard hydrocortisone (HC) therapies in adults with Adrenal Insufficiency (AI). Methods: Adult patients (n = 12) with AI, established on HC therapy, were recruited from Endocrinology clinics at University Hospitals Coventry and Warwickshire (UHCW), UK. Baseline (HC) metabolic assessments included fasting serum HbA1C, lipid and thyroid profiles, accurate measures of body composition (BodPod), and 24-h continuous measures of energy expenditure including Sleeping Metabolic Rate (SMR) using indirect calorimetry within the Human Metabolism Research Unit, UHCW. All participants then switched HC to MR-HC with repeat (MR-HC) metabolic assessments at 3 months. Paired-sample t-tests were used for data comparisons between HC and MR-HC assessments: P-value <0.05 was considered significant. Results: Following exclusion of 2 participants, analyses were based on 10 participants. Compared with baseline HC data, following 3 months of MR-HC therapy mean fat mass reduced significantly by −3.2 kg (95% CI: −6.0 to −0.4). Mean (SD) baseline HC fat mass vs repeat MR-HC fat mass: 31.9 kg (15.2) vs 28.7 kg (12.8) respectively, P = 0.03. Mean SMR increased significantly by +77 kcal/24 h (95% CI: 10–146). Mean (SD) baseline HC SMR vs repeat MR-HC SMR: 1,517 kcal/24 h (301) vs 1,594 kcal/24 h (344) respectively, P = 0.03. Mean body fat percentage reduced significantly by −3.4% (95% CI: −6.5 to −0.2). Other measures of body composition, energy expenditure, and biochemical analytes were equivalent between HC and MR-HC assessments. Conclusions: In adults with AI, switching from standard HC to MR-HC associates with early metabolic benefits of reduced fat mass and increased SMR. [ABSTRACT FROM AUTHOR]
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- 2021
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4. A randomised controlled trial of the impact of structured written and verbal advice by community pharmacists on improving hypertension education and control in patients with high blood pressure.
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Cheema, Ejaz, Sutcliffe, Paul, Weickert, Martin O., and Singer, Donald R. J.
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BLOOD pressure ,COMMUNITY health workers ,CONFIDENCE intervals ,COUNSELING ,DRUG side effects ,HYPERTENSION ,PATIENT education ,QUESTIONNAIRES ,RISK assessment ,VERBAL behavior ,WRITTEN communication ,RANDOMIZED controlled trials ,HEALTH literacy ,PHARMACISTS ,PSYCHOLOGY ,PREVENTION ,ATTITUDE (Psychology) - Abstract
Purpose: This study was aimed to determine whether structured written and verbal education provided to patients by community pharmacists about high blood pressure (BP) and its treatment would be (a) better retained and (b) be associated with improved BP control as compared to patients receiving verbal advice only.Methods: The study was designed as a randomised controlled trial and was conducted in the West Midlands, UK, between January 2014 and June 2014. The primary outcome measures were differences in systolic and diastolic BP from baseline and retention of information about high BP assessed with a questionnaire at 2-, 4- and 26-week follow-up points.Results: A total of 64 adults were included in the study. At the week 26 follow-up, compared to participants in the control group, there was a significant improvement in the knowledge of intervention participants about the risks associated with high BP (p < 0.001) and awareness about potential adverse effects of the new BP medicine (p < 0.001). Similarly, there was a greater and more significant reduction in systolic BP in favour of the intervention group 8 mmHg (95% CI 2.1-13.3 p = 0.009) compared to 6 mmHg (95% CI 0.6-11.7 p = 0.02) in the control group at the week 4 follow-up. However, this greater effect of an intervention on BP was not sustained at the 26-week follow-up. For diastolic BP, there was no added effect of the intervention.Conclusion: This randomised controlled trial suggests that although written advice provided by community pharmacists in comparison to verbal advice was more effective in improving knowledge and understanding of patients about hypertension and its treatment, it did not lead to better blood pressure control. [ABSTRACT FROM AUTHOR]
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- 2018
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5. Growth Trajectories, Breast Size, and Breast-Tissue Composition in a British Prebirth Cohort of Young Women.
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Denholm, Rachel, De Stavola, Bianca, Hipwell, John H., Doran, Simon J., Busana, Marta C., Leach, Martin O., Hawkes, David J., and dos-Santos-Silva, Isabel
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BREAST ,BIRTH weight ,BODY composition ,BODY size ,BODY weight ,BREAST exams ,MAMMOGRAMS ,CONFIDENCE intervals ,DEVELOPMENTAL psychobiology ,LONGITUDINAL method ,MAGNETIC resonance imaging ,MENARCHE ,PUBERTY ,NULLIPARAS ,PHOTON absorptiometry ,ANATOMY - Abstract
Mammographic percent density, the proportion of fibroglandular tissue in the breast, is a strong risk factor for breast cancer, but its determinants in young women are unknown. We examined associations of magnetic resonance imaging (MRI) breast-tissue composition at age 21 years with prospectively collected measurements of body size and composition from birth to early adulthood and markers of puberty (all standardized) in a sample of 500 nulliparous women from a prebirth cohort of children born in Avon, United Kingdom, in 1991-1992 and followed up to 2011-2014. Linear models were fitted to estimate relative change in MRI percent water, which is equivalent to mammographic percent density, associated with a 1-standard-deviation increase in the exposure of interest. In mutually adjusted analyses, MRI percent water was positively associated with birth weight (relative change (RC) = 1.03, 95% confidence interval (CI): 1.00, 1.06) and pubertal height growth (RC = 1.07, 95% CI: 1.02, 1.13) but inversely associated with pubertal weight growth (RC = 0.86, 95% CI: 0.84, 0.89) and changes in dual-energy x-ray absorptiometry percent body fat mass (e.g., for change between ages 11 years and 13.5 years, RC = 0.96, 95% CI: 0.93, 0.99). Ages at the larche and menarche were positively associated with MRI percent water, but these associations did not persist upon adjustment for height and weight growth. These findings support the hypothesis that growth trajectories influence breast-tissue composition in young women, whereas puberty plays no independent role. [ABSTRACT FROM AUTHOR]
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- 2018
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6. How Do People With Diabetes Describe Their Experiences in Primary Care? Evidence From 85,760 Patients With Self-reported Diabetes From the English General Practice Patient Survey.
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Paddison, Charlotte A. M., Saunders, Catherine L., Abel, Gary A., Payne, Rupert A., Adler, Amanda I., Graffy, Jonathan P., and Roland, Martin O.
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PATIENT surveys ,PRIMARY care ,PEOPLE with diabetes ,HEALTH policy ,DIABETES ,MORTALITY ,MEDICAL care - Abstract
OBJECTIVE Developing primary care is an important current health policy goal in the U.S. and England. Information on patients' experience can help to improve the care of people with diabetes. We describe the experiences of people with diabetes in primary care and examine how these experiences vary with increasing comorbidity. RESEARCH DESIGN AND METHODS Using data from 906,578 responders to the 2012 General Practice Patient Survey (England), including 85,760 with self-reported diabetes, we used logistic regressions controlling for age, sex, ethnicity, and socioeconomic status to analyze patient experience using seven items covering three domains of primary care: access, continuity, and communication. RESULTS People with diabetes were significantly more likely to report better experience on six out of seven primary care items than people without diabetes after adjusting for age, sex, ethnicity, and socioeconomic status (adjusted differences 0.88-3.20%; odds ratios [ORs] 1.07-1.18; P < 0.001). Those with diabetes and additional comorbid long-term conditions were more likely to report worse experiences, particularly for access to primary care appointments (patients with diabetes alone compared with patients without diabetes: OR 1.22 [95% CI 1.17-1.28] and patients with diabetes plus three or more conditions compared with patients without diabetes: OR 0.87 [95% CI 0.83-0.91]). CONCLUSIONS People with diabetes in England report primary care experiences that are at least as good as those without diabetes for most domains of care. However, improvements in primary care are needed for diabetes patients with comorbid long-term conditions, including better access to appointments and improved communication. [ABSTRACT FROM AUTHOR]
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- 2015
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7. Influences of organizational features of healthcare settings on clinical decision making: Qualitative results from a cross-national factorial experiment.
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Lutfey, Karen E., Campbell, Stephen M., Marceau, Lisa D., Roland, Martin O., and McKinlay, John B.
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MEDICAL practice ,AUTONOMY (Psychology) ,HEALTH care reform ,INTERVIEWING ,RESEARCH methodology ,CASE studies ,MEDICAL quality control ,MEDICAL care costs ,MEDICALLY uninsured persons ,PRIMARY health care ,PROFESSIONS ,RESEARCH evaluation ,RESEARCH funding ,TIME ,VIDEO recording ,DECISION making in clinical medicine ,QUALITATIVE research ,HEALTH insurance reimbursement ,PRIVATE sector ,CULTURAL values ,SINGLE-payer health care ,DATA analysis software ,PHYSICIANS' attitudes ,DESCRIPTIVE statistics - Abstract
A proliferating literature documents cross-national variation in medical practice and seeks to explain observed differences in terms of the presence of certain kinds of healthcare systems, economic, and cultural differences between countries. Less is known about how providers themselves understand these influences and perceive them as relevant to their clinical work. Using qualitative data from a cross-national factorial experiment in the United States and United Kingdom, we analyze 244 primary care physicians’ explanations of how organizational features of their respective healthcare settings influence the treatment decisions they made for a vignette patient, including affordability of care; within-system quality deficits; and constraints due to patient behavior. While many differences are attributed to financial constraints deriving from two very differently structured healthcare systems, in other ways they are reflections of cultural and historical expectations regarding medical care, or interactions between the two. Implications, including possible challenges to the implementation of universal care in the USA, are discussed. [ABSTRACT FROM PUBLISHER]
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- 2012
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8. A comparison of chronic illness care quality in US and UK family medicine practices prior to pay-for-performance initiatives.
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Crosson, Jesse C., Ohman-Strickland, Pamela A., Campbell, Stephen, Phillips, Robert L., Roland, Martin O., Kontopantelis, Evangelos, Bazemored, Andrew, Balasubramanian, Bijal, and Crabtree, Benjamin F.
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CHRONIC diseases ,FAMILY medicine ,PRIMARY care ,MEDICAL care - Abstract
Background. The Quality and Outcomes Framework (QOF) has contributed to modest improvements in chronic illness care in the UK. US policymakers have proposed similar pay-for-performance (P4P) approaches to improve care. Since previous studies have not compared chronic illness care quality in US and UK primary care practices prior to the QOF, the relative preparedness of practices to respond to P4P incentives is unknown. [ABSTRACT FROM PUBLISHER]
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- 2009
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9. Improvements in quality of clinical care in English general practice 1998-2003: longitudinal observational study.
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Campbell, Stephen M., Roland, Martin O., Middleton, Elizabeth, and Reeves, David
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MEDICAL care , *CHRONIC diseases , *FAMILY medicine , *CORONARY disease , *ASTHMA , *DIABETES , *PATIENTS , *MEDICAL records - Abstract
The article reports on a study to measure changes in quality of care for three major chronic diseases (coronary heart disease, asthma, and type 2 diabetes) between 1998 and 2003 in general care practice in Great Britain. 2300 patients with diabetes, asthma, or coronary heart disease in 1998, and 1495 patients in 2003 participated in the study. The article provides the details of the research and concludes that substantial improvements were seen in quality of care for the three conditions studied between 1998 and 2003, a time of systematic quality improvement initiatives in the NHS. The changes were most marked for coronary heart disease. English general practices could be expected to achieve high clinical quality scores in the initial year of a new contact, which provides financial incentives for high quality care from 2004.
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- 2005
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10. Readers report.
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Schweiker, Richard S., McFarlin, M. M., Hutchinson, Martin O., and Verdier Jr., Leonard D.
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LETTERS to the editor ,JUDGES ,TRUCKING ,BRITISH politics & government, 1964-1979 ,GOVERNMENT policy - Abstract
Several letters to the editor are presented in response to articles in previous issues, including "How Carter will pick all those federal judges," in the December 4, 1978 issue, "Trucking deregulation is moving fast," in the November 27, 1978 issue, and "In defense of Britain," by Peter Jay in the November 20, 1978 issue.
- Published
- 1978
11. Out of hours primary care centres: characteristics of those attending and declining to attend.
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Cragg, David K., Campbell, Stephen M., and Roland, Martin O.
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PRIMARY care ,PATIENTS - Abstract
Examines the number, demography and clinical details of patients supporting and refusing to attend centralized primary care centers for out of hours medical care in Great Britain. Percentage of attendance rate; Dominance of attendance rate in children; Rate of satisfaction with the service. INSET: Key messages.
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- 1994
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12. Synthetic 4D-CT of the thorax for treatment plan adaptation on MR-guided radiotherapy systems.
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Joshua N Freedman, Hannah E Bainbridge, Simeon Nill, David J Collins, Marc Kachelrieß, Martin O Leach, Fiona McDonald, Uwe Oelfke, and Andreas Wetscherek
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LUNG volume ,RADIOTHERAPY treatment planning ,WILCOXON signed-rank test ,THERAPEUTICS ,RADIOTHERAPY ,PHYSIOLOGICAL adaptation - Abstract
MR-guided radiotherapy treatment planning utilises the high soft-tissue contrast of MRI to reduce uncertainty in delineation of the target and organs at risk. Replacing 4D-CT with MRI-derived synthetic 4D-CT would support treatment plan adaptation on hybrid MR-guided radiotherapy systems for inter- and intrafractional differences in anatomy and respiration, whilst mitigating the risk of CT to MRI registration errors. Three methods were devised to calculate synthetic 4D and midposition (time-weighted mean position of the respiratory cycle) CT from 4D-T1w and Dixon MRI. The first approach employed intensity-based segmentation of Dixon MRI for bulk-density assignment (sCT
D ). The second step added spine density information using an atlas of CT and Dixon MRI (sCTDS ). The third iteration used a polynomial function relating Hounsfield units and normalised T1w image intensity to account for variable lung density (sCTDSL ). Motion information in 4D-T1w MRI was applied to generate synthetic CT in midposition and in twenty respiratory phases. For six lung cancer patients, synthetic 4D-CT was validated against 4D-CT in midposition by comparison of Hounsfield units and dose-volume metrics. Dosimetric differences found by comparing sCTD,DS,DSL and CT were evaluated using a Wilcoxon signed-rank test (p = 0.05). Compared to sCTD and sCTDS , planning on sCTDSL significantly reduced absolute dosimetric differences in the planning target volume metrics to less than 98 cGy (1.7% of the prescribed dose) on average. When comparing sCTDSL and CT, average radiodensity differences were within 97 Hounsfield units and dosimetric differences were significant only for the planning target volume D99% metric. All methods produced clinically acceptable results for the organs at risk in accordance with the UK SABR consensus guidelines and the LungTech EORTC phase II trial. The overall good agreement between sCTDSL and CT demonstrates the feasibility of employing synthetic 4D-CT for plan adaptation on hybrid MR-guided radiotherapy systems. [ABSTRACT FROM AUTHOR]- Published
- 2019
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13. PREF-NET: a patient preference and experience study of lanreotide autogel administered in the home versus hospital setting among patients with gastroenteropancreatic neuroendocrine tumours in the UK.
- Author
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Khan MS, Cook K, Weickert MO, Davies L, Pritchard DM, Day M, Shah T, Hull D, Caplin M, Back M, Pommie C, and Higgs K
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- Adult, Humans, Middle Aged, Cross-Sectional Studies, Patient Preference, Quality of Life, Hospitals, United Kingdom, Activities of Daily Living, Neuroendocrine Tumors drug therapy, Peptides, Cyclic, Somatostatin analogs & derivatives
- Abstract
Purpose: PREF-NET reported patients' experience of Somatuline® (lanreotide) Autogel® (LAN) administration at home and in hospital among patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs)., Methods: PREF-NET was a multicentre, cross-sectional study of UK adults (aged ≥ 18 years) with GEP-NETs receiving a stable dose of LAN, which comprised of (1) a quantitative online survey, and (2) qualitative semi-structured interviews conducted with a subgroup of survey respondents. The primary objective was the description of overall patient preference for home versus hospital administration of LAN. Secondary objectives included describing patient-reported opinions on the experience and associated preference for each administration setting, and the impact on healthcare utilisation, societal cost, activities of daily living and health-related quality of life (HRQoL)., Results: In the primary analysis (80 patients; mean age 63.9 years), 98.7% (95% confidence interval [CI]: 96.1-100.0) of patients preferred to receive LAN at home, compared with 1.3% (95% CI: 0.0-3.9) who preferred the hospital setting. Among participants, over half (60.3%) received their injection from a non-healthcare professional. Most patients (79.5% [95% CI: 70.5-88.4]) reported a positive effect on HRQoL after the switch from hospital to home administration. Qualitative interviews (20 patients; mean age 63.6 years) highlighted that patients preferred home administration because it improved overall convenience; saved time and costs; made them feel more comfortable and relaxed, and less stressed; and increased confidence in their ability to self-manage their treatment., Conclusion: Almost all patients preferred to receive LAN treatment at home rather than in hospital with increased convenience and psychological benefits reported as key reasons for this preference., (© 2024. The Author(s).)
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- 2024
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14. Evaluating the sensitivity and specificity of the UK and Dutch growth referral criteria in predicting the diagnosis of pathological short stature.
- Author
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White G, Cosier S, Andrews A, Martin L, Willemsen R, Savage MO, and Storr HL
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- Child, Female, Growth Disorders diagnosis, Humans, Male, Referral and Consultation, United Kingdom, Body Height, Dwarfism
- Abstract
Objective: The aim of this observational study was to evaluate the UK and Dutch referral criteria for short stature to determine their sensitivity and specificity in predicting pathological short stature. Adherence to the recommended panel of investigations was also assessed., Study Design: Retrospective review of medical records to examine the auxological parameters, investigations and diagnosis of subjects referred to two paediatric endocrine clinics at the Royal London Children's Hospital between 2016 and 2021. We analysed: height SD score (HtSDS), height SDS minus target height SDS (Ht-THSDS) and height deflection SDS (HtDefSDS). The UK referral criteria were HtSDS <-2.7, Ht-THSDS >2.0 and HtDefSDS >1.3. The Dutch referral criteria were HtSDS <-2.0, Ht-THSDS >1.6 and HtDefSDS >1.0., Results: Data were available for 143 subjects (72% males) with mean (range) age 8.7 years (0.5-19.9). HtSDS and Ht-THSDS were significantly lower in the pathological stature (n=66) versus the non-pathological stature (n=77) subjects (-2.67±0.82 vs -1.97±0.70; p<0.001 and -2.07±1.02 vs -1.06±0.99; p<0.001, respectively). The sensitivity and specificity to detect pathology was 41% and 83% for the UK criteria (HtSDS <-2.7) compared with 59% and 79% for the Dutch criteria (HtSDS <-2.0), 48% and 83% for UK criteria (Ht-THSDS <-2.0) compared with 74% and 72% for Dutch criteria (Ht-THSDS <-1.6) and 33% and 68% for UK criteria (HtDefSDS >1.3) compared with 44% and 63% for the Dutch criteria (HtDefSDS >1.0). On average, each patient had 88% of the recommended investigations, and 53% had all the recommended testing. New pathology was identified in 36% of subjects., Conclusions: In isolation, the UK auxological referral thresholds have limited sensitivity and specificity for pathological short stature. The combination of HtSDS and Ht-THSDS improved the sensitivity of UK criteria to detect pathology from 41% to 68%. Attention to the child's genetic height potential prior to referral can prevent unnecessary assessments., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2022
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15. Serological responses to COVID-19 Comirnaty booster vaccine, London, United Kingdom, September to December 2021.
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Ireland G, Whitaker H, Ladhani SN, Baawuah F, Subbarao S, Linley E, Warrener L, O'Brien M, Whillock C, Martin O, Moss P, Ramsay ME, Amirthalingam G, and Brown KE
- Subjects
- Humans, London, SARS-CoV-2, United Kingdom, COVID-19, COVID-19 Vaccines
- Abstract
Serum samples were collected pre- and post-booster vaccination with Comirnaty in 626 participants (aged ≥ 50 years) who had received two Comirnaty doses < 30 days apart, two Comirnaty doses ≥ 30 days apart or two Vaxzevria doses ≥ 30 days apart. Irrespective of primary vaccine type or schedule, spike antibody GMTs peaked 2-4 weeks after second dose, fell significantly ≤ 38 weeks later and rose above primary immunisation GMTs 2-4 weeks post-booster. Higher post-booster responses were observed with a longer interval between primary immunisation and boosting.
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- 2022
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16. A nebulised antitumour necrosis factor receptor-1 domain antibody in patients at risk of postoperative lung injury: A randomised, placebo-controlled pilot study.
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Ryan J, Bayliffe AI, McAuley DF, Yeung J, Thickett DR, Howells PA, O'Donnell C, Vassallo AM, Wright TJ, McKie E, Hardes K, Summers C, Shields MO, Powley W, Wilson R, Lazaar AL, Fowler A, and Perkins GD
- Subjects
- Bayes Theorem, Double-Blind Method, Humans, Necrosis, Pilot Projects, Treatment Outcome, United Kingdom, Lung Injury
- Abstract
Background: Tumour necrosis factor receptor 1 (TNFR1) signalling mediates the cell death and inflammatory effects of TNF-α., Objective: The current clinical trial investigated the effects of a nebulised TNFR1 antagonist (GSK2862277) on signs of lung injury in patients undergoing oesophagectomy., Design: Randomised double-blind (sponsor unblind), placebo-controlled, parallel group study., Setting: Eight secondary care centres, the United Kingdom between April 2015 and June 2017., Patients: Thirty-three patients undergoing elective transthoracic oesophagectomy., Interventions: Patients randomly received a single nebulised dose (26 mg) of GSK2862277 (n = 17) or placebo (n = 16), given 1 to 5 h before surgery; 14 and 16, respectively competed the study., Main Outcome Measurements: Physiological and biochemical markers of lung injury, pharmacokinetic and safety endpoints were measured. The primary endpoint was the change from baseline in pulmonary vascular permeability index (PVPI) at completion of surgery, measured using single-indicator transpulmonary thermodilution. Adjusted point estimates and 95% credible intervals (analogous to conventional confidence intervals) were constructed for each treatment using Bayesian statistical models., Results: The mean change (with 95% credible intervals) from baseline in PVPI on completion of surgery was 0.00 (-0.23, 0.39) in the placebo and 0.00 (-0.24, 0.37) in the GSK2862277 treatment groups. There were no significant treatment-related differences in PaO2/FiO2 or Sequential Organ Failure Assessment score. Levels of free soluble TNFR1, Macrophage Inflammatory Protein-1 alpha and total protein were significantly reduced in the bronchoalveolar lavage fluid of patients treated with GSK2862277 (posterior probability of decrease with GSK2862277 vs. placebo:≥0.977; equivalent to P < 0.05). The frequency of adverse events and serious adverse events were distributed evenly across the two treatment arms., Conclusion: Pre-operative treatment with a single 26 mg inhaled dose of GSK2862277 did not result in significantly lower postoperative alveolar capillary leak or extra vascular lung water. Unexpectedly small increases in transpulmonary thermodilution-measured PVPI and extra vascular lung water index at completion of surgery suggest less postoperative lung injury than historically reported, which may have also compromised a clear assessment of efficacy in this trial. GSK2862277 was well tolerated, resulted in expected lung exposure and reduced biomarkers of lung permeability and inflammation., Trial Registration: clinicaltrials.gov: NCT02221037.
- Published
- 2020
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17. Associations between general practice characteristics with use of urgent referrals for suspected cancer and endoscopies: a cross-sectional ecological study.
- Author
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Mendonca SC, Abel GA, Gildea C, McPhail S, Peake MD, Rubin G, Singh H, Hamilton W, Walter FM, Roland MO, and Lyratzopoulos G
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- Adult, Cross-Sectional Studies, Early Detection of Cancer methods, Female, Humans, Male, Middle Aged, Practice Guidelines as Topic, United Kingdom, Endoscopy, General Practice standards, Neoplasms diagnosis, Practice Patterns, Physicians' statistics & numerical data, Referral and Consultation statistics & numerical data
- Abstract
Background: Large variation in measures of diagnostic activity has been described previously between English general practices, but related predictors remain understudied., Objective: To examine associations between general practice population and characteristics, with the use of urgent referrals for suspected cancer, and use of endoscopy., Methods: Cross-sectional observational study of English general practices. We examined practice-level use (/1000 patients/year) of urgent referrals for suspected cancer, gastroscopy, flexible sigmoidoscopy and colonoscopy. We used mixed-effects Poisson regression to examine associations with the sociodemographic profile of practice populations and other practice attributes, including the average age, sex and country of qualification of practice doctors., Results: The sociodemographic characteristics of registered patients explained much of the between-practice variance in use of urgent referrals (32%) and endoscopic investigations (18-25%), all being higher in practices with older and more socioeconomically deprived patients. Practice-level attributes explained a substantial amount of between-practice variance in urgent referral (19%) but little of the variance in endoscopy (3%-4%). Adjusted urgent referral rates were higher in training practices and those with younger GPs. Practices with mean doctor ages of 41 and 57 years (at the 10th/90th centiles of the national distribution) would have urgent referral rates of 24.1 and 19.1/1000 registered patients, P < 0.001., Conclusion: Most between-practice variation in use of urgent referrals and endoscopies seems to reflect health need. Some practice characteristics, such as the mean age of GPs, are associated with appreciable variation in use of urgent referrals, though these associations do not seem strong enough to justify targeted interventions., (© The Author(s) 2018. Published by Oxford University Press.)
- Published
- 2019
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