Recent Submissions

  • Temporary keratoprosthesis and primary corneal graft for ocular trauma: A systematic review and meta-analysis.

    McMaster, David; Halliday, Sophia; Bapty, James; McClellan, Scott F; Miller, Sarah C; Justin, Grant A; Agrawal, Rupesh; Hoskin, Annette K; Cavuoto, Kara; Leong, James; et al. (Elsevier Science, 2024-09-28)
    Purpose: When severe retinal and corneal injury occur together, a temporary keratoprosthesis (TKP) is often a last resort to allow posterior segment visualization to enable vitreoretinal surgery, followed by a penetrating keratoplasty (PKP) which can restore corneal clarity in a single operation. We aimed to assess visual outcomes following combined PKP and vitreoretinal surgery with the use of a TKP for cases of ocular trauma. Design: A systematic literature review was performed following PRISMA guidelines (PROSPERO registration number: CRD42023423518). Methods: CENTRAL, MEDLINE, Embase, ISRCTN registry, and ClinicalTrials.gov were searched from inception to 27 April 2023. Randomized and nonrandomized studies assessing visual outcomes after combined vitreoretinal surgery and PKP with the use of a TKP after ocular trauma were eligible for inclusion. Outcomes included change in best corrected visual acuity, corneal graft survival and retinal reattachment at final follow up. Proportional meta-analysis was used to estimate the overall rate of the primary outcomes. Risk of bias for nonrandomized studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist for case series. Results: A total of 19 studies met inclusion criteria reporting a total of 352 eyes. All studies were retrospective and nonrandomized with follow up times ranging from 6 to 91 months, with at least 79% of outcomes reported after 6 months. After combined surgery the rate of corneal graft survival was 52% (95% CI 0.41-0.62; I2 60%) successful retinal attachment was 79% (95% CI 0.73-0.84; I2 0%). and improved visual acuity, when compared to no change or decrease in visual acuity, was 45% (95% CI 0.32-0.59; I2 66%). Conclusion: Patients with severe injury affecting the anterior and posterior segments have very limited treatment options. This systematic review found that when combined vitreoretinal surgery and PKP with a TKP are performed, approximately half of corneal grafts survive, anatomically successful retinal reattachment is likely, and a similar proportion of patients benefit in terms of improved visual acuity, compared to their preoperative function. This systematic review of the available literature may help inform surgeons of the benefits of using a TKP for cases of ocular trauma.
  • Understanding the intensive care unit experience of patients and relatives at the end-of-life during the Coronavirus disease 2019 pandemic.

    Eskell, Matthew; Thompson, Jamie; Powell, Ohema; Torlinski, Tomasz; Mullhi, Randeep; Torlinski, Tomasz; Mullhi, Randeep; Anaesthetics; Medical and Dental (Sage, 2022-06-15)
    The coronavirus disease 2019 (COVID-19) pandemic has had a significant impact on patients and relatives' experiences of end-of-life care, as well as changing the provision of these services in intensive care units (ICUs) across the world. Established methods for assisting relatives through the grieving process have required modification due to the unique features and circumstances surrounding deaths from this disease. This mixed-methods study from the United Kingdom (UK) aims to review data from patients who died in a large ICU (the unit had a capacity for more than 100 ventilated patients), over the course of approximately 1 year. The inpatient noting of these patients was reviewed specifically for details of visiting practices, chaplaincy support, and patient positioning (prone vs supine) prior to death. Using this data, recommendations are made to improve end-of-life care services. To allow relatives the opportunity to attend the ICU, there is a need for early recognition of patients approaching the end of life. Clear explanations of the need for prone positioning and increased access to chaplaincy services were also identified.
  • Understanding the burden of interstitial lung disease post-COVID-19: the UK Interstitial Lung Disease-Long COVID Study (UKILD-Long COVID).

    Wild, Jim M; Porter, Joanna C; Molyneaux, Philip L; George, Peter M; Stewart, Iain; Allen, Richard James; Aul, Raminder; Baillie, John Kenneth; Barratt, Shaney L; Beirne, Paul; et al. (BMJ Publishing Group Ltd & British Thoracic Society, 2021-09)
    Introduction: The COVID-19 pandemic has led to over 100 million cases worldwide. The UK has had over 4 million cases, 400 000 hospital admissions and 100 000 deaths. Many patients with COVID-19 suffer long-term symptoms, predominantly breathlessness and fatigue whether hospitalised or not. Early data suggest potentially severe long-term consequence of COVID-19 is development of long COVID-19-related interstitial lung disease (LC-ILD). Methods and analysis: The UK Interstitial Lung Disease Consortium (UKILD) will undertake longitudinal observational studies of patients with suspected ILD following COVID-19. The primary objective is to determine ILD prevalence at 12 months following infection and whether clinically severe infection correlates with severity of ILD. Secondary objectives will determine the clinical, genetic, epigenetic and biochemical factors that determine the trajectory of recovery or progression of ILD. Data will be obtained through linkage to the Post-Hospitalisation COVID platform study and community studies. Additional substudies will conduct deep phenotyping. The Xenon MRI investigation of Alveolar dysfunction Substudy will conduct longitudinal xenon alveolar gas transfer and proton perfusion MRI. The POST COVID-19 interstitial lung DiseasE substudy will conduct clinically indicated bronchoalveolar lavage with matched whole blood sampling. Assessments include exploratory single cell RNA and lung microbiomics analysis, gene expression and epigenetic assessment. Ethics and dissemination: All contributing studies have been granted appropriate ethical approvals. Results from this study will be disseminated through peer-reviewed journals. Conclusion: This study will ensure the extent and consequences of LC-ILD are established and enable strategies to mitigate progression of LC-ILD.
  • The authors reply.

    Chotalia, Minesh; Ali, Muzzammil; Alderman, Joseph E; Kalla, Manish; Parekh, Dhruv; Bangash, Mansoor; Patel, Jaimin; Ali, Muzzammil; Kalla, Manish; Parekh, Dhruv; et al. (Lippincott Williams & Wilkins, 2022-02-01)
    No abstract available
  • The epidemiology of epidermolysis bullosa in England and Wales: data from the national epidermolysis bullosa database.

    Petrof, Gabriela; Papanikolaou, Maria; Martinez, Anna E; Mellerio, Jemima E; McGrath, John A; Bardhan, Ajoy; Harper, Natasha; Heagerty, Adrian; Ogboli, Malobi; Chiswell, Christopher; et al. (Oxford University Press, 2022-03-31)
    Background: The National Health Service (NHS) epidermolysis bullosa (EB) service, established in 2002, offers comprehensive, free care to all patients in England and Wales. Objectives: To quantify prevalence, incidence and mortality of EB in England and Wales. Methods: Demographic data for patients in England and Wales were collected on a secure electronic database, prospectively from January 2002 to April 2021 and retrospectively for cases prior to 2002. Vital status was verified using central NHS data. Results: By March 2021, 2594 individuals were registered, of whom 2361 were living, which yielded a prevalence of 34·8 per million of the population for all EB types [EB simplex (EBS) 17 per million, dystrophic EB (DEB) 10·7 per million, junctional EB (JEB) 1 per million and Kindler EB 0·3 per million]. We recorded 1200 babies with EB born since 2002. The average incidence per million live births for EBS, DEB, JEB and Kindler EB was 32·5, 26·1, 8·9 and 0·9, respectively (total incidence for all types of EB was 67·8 per million). Birth rates fell progressively over the 19-year period for JEB-severe (JEB-S) (r = -0·56) and recessive DEB-severe (r = -0·44) and also for milder types of EB. We observed longer survival in JEB-S over the 19-year period (r2 = 0·18) with a median survival of 12·7 months over the past 5 years. Conclusions: In this study, we provide the first accurate epidemiological data for EB in England and Wales. We believe the observed reduction in birth incidence of severe types of EB reflects an uptake of genetic counselling advice, whereas the reduction in milder types may be due to delayed presentation. A potential small trend towards longer survival of babies with JEB-S may reflect improved multidisciplinary care.
  • The effect of end-ischaemic normothermic machine perfusion on donor hepatic artery endothelial integrity.

    Attard, J; Sneiders, D; Laing, R; Boteon, Y; Mergental, H; Isaac, J; Mirza, D F; Afford, S; Hartog, H; Neil, D A H; et al. (Springer Verlag, 2022-01-09)
    Background: Ex vivo normothermic machine liver perfusion (NMLP) involves artificial cannulation of vessels and generation of flow pressures. This could lead to shear stress-induced endothelial damage, predisposing to vascular complications, or improved preservation of donor artery quality. This study aims to assess the spatial donor hepatic artery (HA) endothelial quality downstream of the cannulation site after end-ischaemic NMLP. Methods: Remnant HA segments from the coeliac trunk up to the gastroduodenal artery branching were obtained after NMLP (n = 15) and after static cold storage (SCS) preservation (n = 15). Specimens were fixed in 10% neutral buffered formalin and sectioned at pre-determined anatomical sites downstream of the coeliac trunk. CD31 immunohistostaining was used to assess endothelial integrity by a 5-point ordinal scale (grade 0: intact endothelial lining, grade 5: complete denudation). Endothelial integrity after SCS was used as a control for the state of the endothelium at commencement of NMP. Results: In the SCS specimens, regardless of the anatomical site, near complete endothelial denudation was present throughout the HA (median scores 4.5-5). After NMLP, significantly less endothelial loss in the distal HA was present compared to SCS grafts (NMLP vs. SCS: median grade 3 vs. 4.5; p = 0.042). In NMLP specimens, near complete endothelial denudation was present at the cannulation site in all cases (median grade: 5), with significantly less loss of the endothelial lining the further from the cannulation site (proximal vs. distal, median grade 5 vs. 3; p = 0.005). Conclusion: Loss of endothelial lining throughout the HA after SCS and at the cannulation site after NMLP suggests extensive damage related to surgical handling and preservation injury. Gradual improved endothelial lining along more distal sites of the HA after NMLP indicates potential for re-endothelialisation. The regenerative effect of NMLP on artery quality seems to occur to a greater extent further from the cannulation site. Therefore, arterial cannulation for machine perfusion of liver grafts should ideally be as proximal as possible on the coeliac trunk or aortic patch, while the site of anastomosis should preferentially be attempted distal on the common HA.
  • The EASL-Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality.

    Karlsen, Tom H; Sheron, Nick; Zelber-Sagi, Shira; Carrieri, Patrizia; Dusheiko, Geoffrey; Bugianesi, Elisabetta; Pryke, Rachel; Hutchinson, Sharon J; Sangro, Bruno; Martin, Natasha K; et al. (Elsevier, 2021-12-02)
    No abstract available
  • The association between overweight/obesity and double diabetes in adults with type 1 diabetes; a cross-sectional study.

    Cantley, Nathan Wp; Lonnen, Kathryn; Kyrou, Ioannis; Tahrani, Abd A; Kahal, Hassan (BioMed Central, 2021-09-16)
    Background: Double Diabetes (DD), type 1 diabetes (T1DM) + insulin resistance (IR), is associated with increased risk of micro/macro-vascular complications and mortality. Obesity can contribute to the development of DD. This study explored the prevalence of overweight/obesity and their association with DD in adults with T1DM. Methods: Cross-sectional study of consecutive adults with T1DM attending diabetes clinics in a secondary care hospital (January-November 2019). Estimated glucose disposal rate (eGDR) was used as a marker of IR, and an eGDR < 8 was used to identify individuals with DD. Results: One hundred seven adults with T1DM were included; female/male: 51/56; age [median (inter-quartile range): 30.0 (23-51) years]; BMI 25.4 (22.8-30.0) kg/m2. Overweight/obesity prevalence was 57/107 (53.3 %) [overweight: 30/107 (28 %); obesity: 27/107 (25.2 %)]. Compared to those with normal BMI, individuals with T1DM and overweight/obesity had longer diabetes duration; higher total daily insulin dose; and higher DD prevalence: 48/57 (84.2 %) vs. 14/50 (28 %) (p < 0.01); with similar HbA1c. BMI correlated with total daily insulin dose (rho = 0.55; p < 0.01). Individuals with DD were older, had longer duration of diabetes, higher HbA1c, and more adverse lipid profile and microalbuminuria compared to those without DD. Conclusions: Overweight/obesity is very common in adults with T1DM, and is associated with double diabetes. BMI is positively associated with total insulin dose. Double diabetes is associated with adverse cardiovascular risk profile and is also common in lean individuals with T1DM. Further research is needed to examine the impact of overweight/obesity in people with T1DM and whether weight loss in this population can improve diabetes-related outcomes.
  • Patient-completed online "follow-up form" to assess continuation of anti-CGRP(r) antibody therapy in patients with chronic migraine: a pilot study

    Stuart, Sarah; Gregg, Stephanie; Ware, Sally; Koonalintip, Prut; Wakerley, Benjamin R; Stuart, Sarah; Gregg, Stephanie; Ware, Sally; Wakerley, Benjamin; Nursing; et al. (Elsevier, 2024-10-24)
    Background: The introduction of new drugs that target the Calcitonin Gene-Related Peptide (CGRP) system has provided significant hope for patients with otherwise treatment-resistant migraine, but also resulted in significant capacity issues at the point of delivery, as patients require follow-up at certain timepoints. Aim: Pilot a patient-completed "follow-up form" (FuF) to replace direct patient contact at the time of 1-year treatment review in patients receiving anti-CGRP (receptor (r)) antibody therapy for chronic migraine. Methods: Patients with chronic migraine already receiving anti-CGRP(r) antibody therapy and due for 1-year review were contacted by telephone and recruited into the study. Patients completed a simple online form, which mirrored questions asked at 1-year follow-up, and a patient satisfaction survey. Results: Thirty-nine (78 %) of 50 patients completed the FuF, which resulted in further telephone contact in 3 (8 %) patients. Over 90 % strongly agreed that the FuF was easy to understand and complete. 80 % strongly agreed that they felt confident in decision making regarding continuation or cessation of anti-CGRP(r) antibody therapy. Overall, 88 % rated their experience of the online form as "Excellent" and 12 % as "Good". Conclusions: Within our headache service, we have demonstrated that an appropriately designed online patient-completed form has the potential to replace direct patient contact at 1-year review in patients already receiving anti-CGRP(r) antibody therapy for chronic migraine.
  • Diagnostic performance of deep learning for infectious keratitis: a systematic review and meta-analysis

    Ong, Zun Zheng; Sadek, Youssef; Qureshi, Riaz; Liu, Su-Hsun; Li, Tianjing; Liu, Xiaoxuan; Takwoingi, Yemisi; Sounderajah, Viknesh; Ashrafian, Hutan; Ting, Daniel S W; et al. (The Lancet, 2024-10-18)
    Background: Infectious keratitis (IK) is the leading cause of corneal blindness globally. Deep learning (DL) is an emerging tool for medical diagnosis, though its value in IK is unclear. We aimed to assess the diagnostic accuracy of DL for IK and its comparative accuracy with ophthalmologists. Methods: In this systematic review and meta-analysis, we searched EMBASE, MEDLINE, and clinical registries for studies related to DL for IK published between 1974 and July 16, 2024. We performed meta-analyses using bivariate models to estimate summary sensitivities and specificities. This systematic review was registered with PROSPERO (CRD42022348596). Findings: Of 963 studies identified, 35 studies (136,401 corneal images from >56,011 patients) were included. Most studies had low risk of bias (68.6%) and low applicability concern (91.4%) in all domains of QUADAS-2, except the index test domain. Against the reference standard of expert consensus and/or microbiological results (seven external validation studies; 10,675 images), the summary estimates (95% CI) for sensitivity and specificity of DL for IK were 86.2% (71.6-93.9) and 96.3% (91.5-98.5). From 28 internal validation studies (16,059 images), summary estimates for sensitivity and specificity were 91.6% (86.8-94.8) and 90.7% (84.8-94.5). Based on seven studies (4007 images), DL and ophthalmologists had comparable summary sensitivity [89.2% (82.2-93.6) versus 82.2% (71.5-89.5); P = 0.20] and specificity [(93.2% (85.5-97.0) versus 89.6% (78.8-95.2); P = 0.45]. Interpretation: DL models may have good diagnostic accuracy for IK and comparable performance to ophthalmologists. These findings should be interpreted with caution due to the image-based analysis that did not account for potential correlation within individuals, relatively homogeneous population studies, lack of pre-specification of DL thresholds, and limited external validation. Future studies should improve their reporting, data diversity, external validation, transparency, and explainability to increase the reliability and generalisability of DL models for clinical deployment.
  • Reply: RASopathy syndrome: Do not overlook mitral valve anomalies!

    Naneishvili, Tamara; Yuan, Mengshi; Mansour, Mohamed; Moody, William E; Steeds, Richard P; Yuan, Mengshi; Mansour, Mohamed; Moody, William; Steeds, Rick; Cardiology; et al. (Elsevier, 2024-10-02)
    No abstract available
  • Unresected screen-detected ductal carcinoma in situ: Outcomes of 311 women in the Forget-Me-Not 2 study.

    Maxwell, Anthony J; Hilton, Bridget; Clements, Karen; Dodwell, David; Dulson-Cox, Joanne; Kearins, Olive; Kirwan, Cliona; Litherland, Janet; Mylvaganam, Senthurun; Provenzano, Elena; et al. (Elsevier, 2022-01-04)
    Background and aim: The natural history of ductal carcinoma in situ (DCIS) is poorly understood. The aim of this cohort study was to determine the outcomes of women who had no surgery for screen-detected DCIS in the 6 months following diagnosis. Methods: English breast screening databases were retrospectively searched for women diagnosed with DCIS without invasive cancer at screening and who had no record of surgery within 6 months of diagnosis. These were cross-referenced with cancer registry data. Details of the potentially eligible women were sent to the relevant breast screening units for verification and for completion of data forms detailing clinical, radiological and pathological findings, non-surgical treatment and subsequent clinical course. Results: Data for 311 eligible women (median age 62 years) were available. 60 women developed invasive cancer, 56 ipsilateral and 4 contralateral. Ipsilateral invasion risk increased approximately linearly with time for at least 10 years. The 10-year cumulative risk of ipsilateral invasion was 9% (95% CI 4-21%), 39% (24-58%) and 36% (24-50%) for low, intermediate and high grade DCIS respectively and was higher in younger women, in those with larger DCIS lesions and in those with microinvasion. Most invasive cancers that developed were grade 2 or 3. Conclusion: The findings suggest that active surveillance may be a reasonable alternative to surgery in patients with low grade DCIS but that women with intermediate or high grade disease should continue to be offered surgery. This highlights the importance of reproducible grading of DCIS to ensure patients receive appropriate treatment.
  • Upregulation of C/EBPα inhibits suppressive activity of myeloid cells and potentiates antitumor response in mice and patients with cancerr.

    Hashimoto, Ayumi; Sarker, Debashis; Reebye, Vikash; Jarvis, Sheba; Sodergren, Mikael H; Kossenkov, Andrew; Sanseviero, Emilio; Raulf, Nina; Vasara, Jenni; Andrikakou, Pinelopi; et al. (American Association for Cancer Research, 2021-08-18)
    Purpose: To evaluate the mechanisms of how therapeutic upregulation of the transcription factor, CCAAT/enhancer-binding protein alpha (C/EBPα), prevents tumor progression in patients with advanced hepatocellular carcinoma (HCC) and in different mouse tumor models. Experimental design: We conducted a phase I trial in 36 patients with HCC (NCT02716012) who received sorafenib as part of their standard care, and were given therapeutic C/EBPα small activating RNA (saRNA; MTL-CEBPA) as either neoadjuvant or adjuvant treatment. In the preclinical setting, the effects of MTL-CEBPA were assessed in several mouse models, including BNL-1ME liver cancer, Lewis lung carcinoma (LLC), and colon adenocarcinoma (MC38). Results: MTL-CEBPA treatment caused radiologic regression of tumors in 26.7% of HCC patients with an underlying viral etiology with 3 complete responders. MTL-CEBPA treatment in those patients caused a marked decrease in peripheral blood monocytic myeloid-derived suppressor cell (M-MDSC) numbers and an overall reduction in the numbers of protumoral M2 tumor-associated macrophages (TAM). Gene and protein analysis of patient leukocytes following treatment showed CEBPA activation affected regulation of factors involved in immune-suppressive activity. To corroborate this observation, treatment of all the mouse tumor models with MTL-CEBPA led to a reversal in the suppressive activity of M-MDSCs and TAMs, but not polymorphonuclear MDSCs (PMN-MDSC). The antitumor effects of MTL-CEBPA in these tumor models showed dependency on T cells. This was accentuated when MTL-CEBPA was combined with checkpoint inhibitors or with PMN-MDSC-targeted immunotherapy. Conclusions: This report demonstrates that therapeutic upregulation of the transcription factor C/EBPα causes inactivation of immune-suppressive myeloid cells with potent antitumor responses across different tumor models and in cancer patients. MTL-CEBPA is currently being investigated in combination with pembrolizumab in a phase I/Ib multicenter clinical study (NCT04105335).
  • Early intervention in patients with asymptomatic severe aortic stenosis and myocardial fibrosis: the EVOLVED randomized clinical trial

    Loganath, Krithika; Craig, Neil J; Everett, Russell J; Bing, Rong; Tsampasian, Vasiliki; Molek, Patrycja; Botezatu, Simona; Aslam, Saadia; Lewis, Steff; Graham, Catriona; et al. (American Medical Association, 2024-10-28)
    Importance: Development of myocardial fibrosis in patients with aortic stenosis precedes left ventricular decompensation and is associated with an adverse long-term prognosis. Objective: To investigate whether early valve intervention reduced the incidence of all-cause death or unplanned aortic stenosis-related hospitalization in asymptomatic patients with severe aortic stenosis and myocardial fibrosis. Design, setting, and participants: This prospective, randomized, open-label, masked end point trial was conducted between August 2017 and October 2022 at 24 cardiac centers across the UK and Australia. Asymptomatic patients with severe aortic stenosis and myocardial fibrosis were included. The final date of follow-up was July 26, 2024. Intervention: Early valve intervention with transcatheter or surgical aortic valve replacement or guideline-directed conservative management. Main outcomes and measures: The primary outcome was a composite of all-cause death or unplanned aortic stenosis-related hospitalization in a time-to-first-event intention-to-treat analysis. There were 9 secondary outcomes, including the components of the primary outcome and symptom status at 12 months. Results: The trial enrolled 224 eligible patients (mean [SD] age, 73 [9] years; 63 women [28%]; mean [SD] aortic valve peak velocity of 4.3 [0.5] m/s) of the originally planned sample size of 356 patients. The primary end point occurred in 20 of 113 patients (18%) in the early intervention group and 25 of 111 patients (23%) in the guideline-directed conservative management group (hazard ratio, 0.79 [95% CI, 0.44-1.43]; P = .44; between-group difference, -4.82% [95% CI, -15.31% to 5.66%]). Of 9 prespecified secondary end points, 7 showed no significant difference. All-cause death occurred in 16 of 113 patients (14%) in the early intervention group and 14 of 111 (13%) in the guideline-directed group (hazard ratio, 1.22 [95% CI, 0.59-2.51]) and unplanned aortic stenosis hospitalization occurred in 7 of 113 patients (6%) and 19 of 111 patients (17%), respectively (hazard ratio, 0.37 [95% CI, 0.16-0.88]). Early intervention was associated with a lower 12-month rate of New York Heart Association class II-IV symptoms than guideline-directed conservative management (21 [19.7%] vs 39 [37.9%]; odds ratio, 0.37 [95% CI, 0.20-0.70]). Conclusions and relevance: In asymptomatic patients with severe aortic stenosis and myocardial fibrosis, early aortic valve intervention had no demonstrable effect on all-cause death or unplanned aortic stenosis-related hospitalization. The trial had a wide 95% CI around the primary end point, with further research needed to confirm these findings. Trial registration: ClinicalTrials.gov Identifier: NCT03094143.
  • Asthma control in severe asthma and occupational exposures to inhalable asthmagens

    Walters, Gareth I; Reilly, Christopher; Le Moual, Nicole; Huntley, Christopher C; Hussein, Hanan; Marsh, Julie; Bahron, Ali; Krishna, Mamidipudi Thirumala; Mansur, Adel H; Walters, Gareth I; et al. (BMJ Publishing Group LtdBritish Thoracic Society, 2024-09-30)
    Introduction: Work-related asthma accounts for ≥25% of asthma in working-age populations, though the relationship between work exposures and symptoms is frequently missed, leading to poor health and employment outcomes. We hypothesised that inhalable exposures at work are associated with poor asthma control in severe asthma (SA). Methods: We searched the Birmingham (UK) Regional NHS SA Service clinical database (n=1453 records; 1 March 2004 to 1 March 2021) and undertook a cross-sectional study using baseline data collected at diagnosis. We included all employed patients aged 16-64 with documented current occupation (n=504), and collected socio-demographic, general health and asthma-specific data, including Asthma Control Questionnaire 7 (ACQ7) score. The Occupational Asthma Specific Job-Exposure Matrix (OAsJEM) was employed to determine the likelihood of exposure to respiratory sensitisers, irritants, cleaning agents and detergents; associations between exposures and ACQ7 were investigated using binary and multinomial regression. Results: Frequently reported occupations were care assistants (7%) and nurses (6%); 197/504 (39%) patients were exposed to an asthmagen, including respiratory sensitisers (30%), airway irritants (38%) and cleaning products/disinfectants (29%). ACQ7 score was available for 372/504 (74%) patients, of whom 14% had adequate control (ACQ7=0-1.5). After adjustment for major confounders there were no significant associations between inhaled asthmagens and ACQ7 score (either as binary or multinomial outcomes). Conclusion: JEM-determined workplace exposures to inhaled asthmagens are not associated with asthma control in SA; 29-39% of patients may have current exposure to workplace asthmagens. Routine collection of lifetime occupational data including current job role and level of exposure, in the national asthma registry, would give further insights into this relationship.
  • Functionality loss due to COVID-19 hospitalisation in older adults recovers with inpatient rehabilitation: A systematic review and meta-analysis

    Lapo, Henrique Monteiro; Sardeli, Amanda Veiga; Mariano, Lilian Oliveira; Howroyd, Fiona Jayne; Sokoll, Paulo Roberto; Sapey, Elizabeth; Chacon-Mikahil, Mara Patrícia Traina; Howroyd, Fiona; Physiotherapy; Allied Health Professional; et al. (Elsevier Science Publishers, 2024-11-05)
    Introduction: Older adults are more likely to acquire the severe manifestation of COVID-19 and the hospitalised survivors experience significant functionality loss. Thus, we aimed to identify the level of functionality in older adults hospitalised due to COVID-19, and the effect of inpatient rehabilitation upon functional recovery. Methods: A search was performed on July 2024, across five databases to retrieve studies assessing functionality in patients during COVID-19 hospitalisation, with or without rehabilitation. Results: At admission, higher functionality was significant higher for survivors than non survivors (standardized mean difference (SMD): 0.83 [0.56; 1.09]). The effect of inpatient rehabilitation on functionality was tested among 38 arms across studies. Inpatient rehabilitation improved functionality SMD across all indexes (1.47 [1.18; 1.77], P ≤ 0.001), with greatest effect in the patients >70y (2.84 [1.74, 3.93], P = 0.006), compared to their counterparts. Conclusion: Hospitalisation due to COVID-19 reduced functionality to a higher extent in older adults above 70 years. Inpatient rehabilitation was effective to improve functionality in both age groups. Protocol registration: PROSPERO CRD42021278619.
  • Impact of the preservation of residual kidney function on hemodialysis survival: results from the BISTRO trial

    Belcher, John; Coyle, David; Lindley, Elizabeth J; Keane, David; Caskey, Fergus J; Dasgupta, Indranil; Davenport, Andrew; Farrington, Ken; Mitra, Sandip; Ormandy, Paula; et al. (Wolters Kluwer HealthAmerican Society of Nephrology, 2024-10-10)
    Background: Preservation of residual kidney function (RKF) in dialysis patients has been associated with improved survival. RKF in the BISTRO trial was relatively well preserved and here we describe its association with survival during the trial and extended follow-up. Methods: RKF, measured as the average urea and creatinine clearance (GFR) or 24-hour urine volume was assessed at baseline, one, two and three months and three-monthly up to 2 years in incident haemodialysis patients. Time to event survival data or competing events (transplantation, modality change) were obtained for 50 months post enrolment via data linkage with the UK Renal Registry. Cox proportional hazards regression survival models, including those incorporating change in GFR from baseline as a time-varying variable and joint regression models for longitudinal and survival data (longitudinal models for GFR or urine volume) were used to explore the relationship of RKF preservation with survival. Analyses were adjusted for age, sex, comorbidity and ethnicity. Results: 2919 measures of RKF were made in 387 patients from 32 UK dialysis units. Higher age and comorbidity score associated with increased mortality in all models. Baseline GFR reduced the risk of death (Hazard Ratio: 0.918 95%CI: 0.844, 0.999) per ml/min/1.73m2. A greater fall in GFR and urine volume from baseline was associated with a non-significant increased risk of death as visualised on spline plots. In the joint survival models higher GFR (adjusted HR: 0.88 95%CI 0.80, 0.97) or urine volume (adjusted HR: 0.75 95%CI 0.57, 0.95 per L) at any time point associated with better survival. Conclusions: Lower RKF during the first two years of haemodialysis is associated with an increased death risk for up to 50 months following dialysis initiation. This adds to a growing body of evidence that interventions to preserve RKF should be developed and tested in clinical trials.
  • Reply to: Hypothermic cardiac arrest: Criteria for extracorporeal cardiopulmonary resuscitation

    Alenazi, Amani; Couper, Keith; Couper, Keith; Research and Development; Medical and Dental; University of Warwick; King Saud Bin Abdulaziz University for Health Sciences; King Abdullah International Medical Research Centre; University Hospitals Birmingham NHS Foundation Trust (ElsevierNorth-Holland Biomedical Press, 2024-10-19)
    No abstract available
  • Incidence of carotid wall irregularities in acute ischemic stroke patients: a descriptive analysis

    Nair, Aparnna Unnikrishnan; Ramanathan, Nitin; Gnanasekaran, Pritika; Srirangam, Rama Krishna; Vinay, Shanmukha; Sekar, Kishore; Subburam, Sairam; Gaurdian, Monica; Sharma, Yagyavalkya; Pascal, Shoraf; et al. (Cureus, 2024-10-01)
    Background: Carotid wall abnormalities are significant predictors of cardiovascular events, including ischemic stroke. Identifying the clinical and biochemical risk factors associated with these abnormalities can aid in early intervention and prevention strategies. This study aimed to assess the association between lipid profiles, age, gender, smoking habits, hypertension, and carotid wall abnormalities in patients. Methodology: A cross-sectional study was conducted on 60 patients, evaluating their clinical and biochemical profiles, including lipid levels, age, gender, smoking status, and the presence of hypertension. Carotid intima-media thickness was measured using ultrasound to identify carotid wall abnormalities. The data were analyzed to determine the associations between these factors and the presence of carotid wall abnormalities. Results: Carotid wall abnormalities were present in 78.3% (n = 47) of the patients. Individuals with carotid wall irregularities exhibited markedly elevated total cholesterol concentrations (175 ± 35.0 mg/dl) compared to those without abnormalities (150 ± 31.0 mg/dl) (p = 0.007). The mean age was 64.0 ± 8.0 years in the abnormality group versus 56.0 ± 5.0 years in the non-abnormality group (p = 0.008). Males constituted 80.0% of the abnormality group, compared to 46.7% in the non-abnormality group (p = 0.03). This higher prevalence of carotid wall abnormalities in males could be related to gender-specific risk factors, such as higher rates of smoking and hypertension, both of which were more common in the abnormality group and are known contributors to vascular changes. Smoking (70% vs. 20%, p = 0.0005) and hypertension (85% vs. 40%, p = 0.0005) were significantly more prevalent in individuals with carotid wall abnormalities. Conclusions This study highlights the significant association between elevated total cholesterol, older age, male gender, smoking, and hypertension with carotid wall abnormalities. These findings emphasize the importance of early detection and management of these risk factors to prevent the progression of carotid atherosclerosis and reduce the risk of ischemic stroke and other cardiovascular events.
  • 1-year health outcomes associated with systemic corticosteroids for COVID-19: a longitudinal cohort study

    Leavy, Olivia C; Russell, Richard J; Harrison, Ewen M; Lone, Nazir I; Kerr, Steven; Docherty, Annemarie B; Sheikh, Aziz; Richardson, Matthew; Elneima, Omer; Greening, Neil J; et al. (European Respiratory Society, 2024-09-30)
    Background: In patients with coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) 1 year after discharge. Methods: Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies (Post-hospitalisation COVID-19 and the International Severe Acute Respiratory and emerging Infection Consortium). HRQoL, assessed by the EuroQol-Five Dimensions-Five Levels utility index (EQ-5D-5L UI), pre-hospital and 1 year after discharge were compared between those receiving corticosteroids or not after propensity weighting for treatment. Secondary outcomes included patient-reported recovery, physical and mental health status, and measures of organ impairment. Sensitivity analyses were undertaken to account for survival and selection bias. Findings: Of the 1888 participants included in the primary analysis, 1149 received corticosteroids. There was no between-group difference in EQ-5D-5L UI at 1 year (mean difference 0.004, 95% CI -0.026-0.034). A similar reduction in EQ-5D-5L UI was seen at 1 year between corticosteroid exposed and nonexposed groups (mean±sd change -0.12±0.22 versus -0.11±0.22). Overall, there were no differences in secondary outcome measures. After sensitivity analyses modelled using a cohort of 109 318 patients admitted to hospital with COVID-19, EQ-5D-5L UI at 1 year remained similar between the two groups. Interpretation: Systemic corticosteroids for acute COVID-19 have no impact on the large reduction in HRQoL 1 year after hospital discharge. Treatments to address the persistent reduction in HRQoL are urgently needed.

View more