Heart of England: HEFT Repository
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Clinical practice guidelines for management of hyperglycaemia in adults with diabetic kidney disease.
No full textA significant percentage of people with diabetes develop chronic kidney disease and diabetes is also a leading cause of end-stage kidney disease (ESKD). The term diabetic kidney disease (DKD) includes both diabetic nephropathy (DN) and diabetes mellitus and chronic kidney disease (DM CKD). DKD is associated with high morbidity and mortality, which are predominantly related to cardiovascular disease. Hyperglycaemia is a modifiable risk factor for cardiovascular complications and progression of DKD. Recent clinical trials of people with DKD have demonstrated improvement in clinical outcomes with sodium glucose co-transporter-2 (SGLT-2) inhibitors. SGLT-2 inhibitors have significantly reduced progression of DKD and onset of ESKD and these reno-protective effects are independent of glucose lowering. At the time of this update Canagliflozin and Dapagliflozin have been approved for delaying the progression of DKD. The Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) Diabetic Kidney Disease Clinical Speciality Group have undertaken a literature review and critical appraisal of the available evidence to inform clinical practice guidelines for management of hyperglycaemia in adults with DKD. This 2021 guidance is for the variety of clinicians who treat people with DKD, including GPs and specialists in diabetes, cardiology and nephrology
Addressing the clinical unmet needs in primary Sjögren's Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts.
No full textFor many decades, the clinical unmet needs of primary Sjögren's Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-art data analytics services to address the pSS clinical unmet needs, including the development of lymphoma classification models and the identification of biomarkers for lymphomagenesis. The users of the platform have been able to successfully interlink, curate, and harmonize 21 regional, national, and international European cohorts of 7,551 pSS patients with respect to the ethical and legal issues for data sharing. Federated AI algorithms were trained across the harmonized databases, with reduced execution time complexity, yielding robust lymphoma classification models with 85% accuracy, 81.25% sensitivity, 85.4% specificity along with 5 biomarkers for lymphoma development. To our knowledge, this is the first GDPR compliant platform that provides federated AI services to address the pSS clinical unmet needs
Lipopolysaccharide induces acute lung injury and alveolar hemorrhage in association with the cytokine storm, coagulopathy and AT1R/JAK/STAT augmentation in a rat model that mimics moderate and severe Covid-19 pathology.
No full textProgress in the study of Covid-19 disease in rodents has been hampered by the lack of angiotensin converting enzyme 2 (ACE2; virus entry route to the target cell) affinities for the virus spike proteins across species. Therefore, we sought to determine whether a modified protocol of lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in rats can mimic both cell- signaling pathways as well as severe disease phenotypes of Covid-19 disease. Rats were injected via intra-tracheal (IT) instillation with either 15 mg/kg of LPS (model group) or saline (control group) before being sacrificed after 3 days. A severe acute respiratory syndrome (SARS)-like effect was observed in the model group as demonstrated by the development of a "cytokine storm" (> 2.7 fold increase in blood levels of IL-6, IL-17A, GM-CSF, and TNF-α), high blood ferritin, demonstrable coagulopathy, including elevated D-dimer (approximately 10-fold increase), PAI-1, PT, and APTT (p 4 fold increase). Chest imaging revealed bilateral small patchy opacities of the lungs. Severe lung injury was noted by the presence of both, alveolar collapse and hemorrhage, desquamation of epithelial cells in the airway lumen, infiltration of inflammatory cells (CD45+ leukocytes), widespread thickening of the inter-alveolar septa, and ultrastructural alterations similar to Covid-19. Thus, these findings demonstrate that IT injection of 15 mg/kg LPS into rats, induced an AT1R/JAK/STAT-mediated cytokine storm with resultant pneumonia and coagulopathy that was commensurate with moderate and severe Covid-19 disease noted in humans
Single stage versus two-stage orthoplastic management of bone infection.
No full textINTRODUCTION
Bone infection cases with major soft tissue loss have conventionally been treated with a staged orthoplastic approach, addressing the infection first followed by definitive management to achieve bony stability and soft tissue cover. In the last few decades, specialist centers have advocated for single stage bony stabilization with soft tissue coverage. We aimed to investigate the outcomes of patients that underwent a single stage versus a two-stage orthoplastic intervention.
METHODS
Using an existing 2009-2019 database from a single major trauma centre, we identified all adults with a diagnosis of fracture related infection (FRI) or osteomyelitis (OM). The primary outcome was resolution of infection. Secondary outcomes included time to bony union, amputation, failure of orthopaedic fixation, mortality, and return to theatre.
RESULTS
A total of 96 patients were included. 71 patients (74%) underwent a single stage procedure; out of which 61 were FRI. 25 patients (26%) underwent a two-stage procedure; out of which 24 were FRI. The average follow up for the single stage and two-stage cohorts was 32.1 and 30.3 months, respectively. Resolution of infection without the need for an amputation was achieved in 67 (94.4%) patients in the single stage cohort and in 23 (92%) patients in the two-stage cohort. When compared to the two-stage group, the single stage cohort had less recurrence of infection (9.9% versus 12%, p = 0.72), lower rates of amputation (8.5% versus 12%, p = 0.69), lower rates of failure of orthopaedic fixation (11.1% versus 13%, p = 0.82), but higher average time to bony union (15.25 months versus 12.35, p = 0.42). The differences were not statistically significant. A total of 37 patients (52.1%) had an unplanned return to theatre in the single stage compared to 12 (48%) in the two-stage cohort. In subgroup analysis of FRI cases, open fractures had a longer time to bony union when compared to closed fractures (19.7 versus 11.6 months, p = 0.01). No mortality was observed in both cohorts.
CONCLUSIONS
The single stage orthoplastic approach to bone infection is effective if planned carefully with clinical outcomes comparable to the two-stage approach. Further research should examine factors associated with unplanned return to theatre and any variation in treatment of bone infection across regions
Effect of Noninvasive Respiratory Strategies on Intubation or Mortality Among Patients With Acute Hypoxemic Respiratory Failure and COVID-19: The RECOVERY-RS Randomized Clinical Trial.
No full textImportance
Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been recommended for acute hypoxemic respiratory failure in patients with COVID-19. Uncertainty exists regarding the effectiveness and safety of these noninvasive respiratory strategies.
Objective
To determine whether either CPAP or HFNO, compared with conventional oxygen therapy, improves clinical outcomes in hospitalized patients with COVID-19-related acute hypoxemic respiratory failure.
Design, Setting, and Participants
A parallel group, adaptive, randomized clinical trial of 1273 hospitalized adults with COVID-19-related acute hypoxemic respiratory failure. The trial was conducted between April 6, 2020, and May 3, 2021, across 48 acute care hospitals in the UK and Jersey. Final follow-up occurred on June 20, 2021.
Interventions
Adult patients were randomized to receive CPAP (n = 380), HFNO (n = 418), or conventional oxygen therapy (n = 475).
Main Outcomes and Measures
The primary outcome was a composite of tracheal intubation or mortality within 30 days.
Results
The trial was stopped prematurely due to declining COVID-19 case numbers in the UK and the end of the funded recruitment period. Of the 1273 randomized patients (mean age, 57.4 [95% CI, 56.7 to 58.1] years; 66% male; 65% White race), primary outcome data were available for 1260. Crossover between interventions occurred in 17.1% of participants (15.3% in the CPAP group, 11.5% in the HFNO group, and 23.6% in the conventional oxygen therapy group). The requirement for tracheal intubation or mortality within 30 days was significantly lower with CPAP (36.3%; 137 of 377 participants) vs conventional oxygen therapy (44.4%; 158 of 356 participants) (absolute difference, -8% [95% CI, -15% to -1%], P = .03), but was not significantly different with HFNO (44.3%; 184 of 415 participants) vs conventional oxygen therapy (45.1%; 166 of 368 participants) (absolute difference, -1% [95% CI, -8% to 6%], P = .83). Adverse events occurred in 34.2% (130/380) of participants in the CPAP group, 20.6% (86/418) in the HFNO group, and 13.9% (66/475) in the conventional oxygen therapy group.
Conclusions and Relevance
Among patients with acute hypoxemic respiratory failure due to COVID-19, an initial strategy of CPAP significantly reduced the risk of tracheal intubation or mortality compared with conventional oxygen therapy, but there was no significant difference between an initial strategy of HFNO compared with conventional oxygen therapy. The study may have been underpowered for the comparison of HFNO vs conventional oxygen therapy, and early study termination and crossover among the groups should be considered when interpreting the findings.
Trial Registration
isrctn.org Identifier: ISRCTN16912075
Applying a COVID Virtual Ward model, assessing patient outcomes and staff workload.
No full textA COVID virtual ward (CVW) is recommended by NHS England, but 'usual care' outcomes have not been reported. A retrospective study of all adults with COVID-19 attending Queen Elizabeth Hospital Birmingham between 01/06/2020-31/01/2021, assessed against CVW criteria and followed for 28 days. Of 2301 COVID-19 patients, 571(25%) would have met CVW criteria. Of these, 325(57%) were discharged after review and 246(43%) admitted. Of admitted patients who met CVW criteria, 81% required hospital-supported therapies; 11% died. Of the 325 discharged, 13% re-presented, 9% with COVID-related symptoms, 2% required intensive care admission, and one died (0.3%). In this comparison, discharging patients without a CVW did not lead to more re-presentations, re-admissions, ITU escalations or deaths compared to published outcomes for hospitals with a CVW
Contemporary challenges in the diagnosis and management of chronic inflammatory demyelinating polyneuropathy.
No full textINTRODUCTION
Despite extensive research, multiple inter-related diagnostic and management challenges remain for chronic inflammatory demyelinating polyneuropathy (CIDP).
AREAS COVERED
A literature review was performed on diagnosis and treatment in CIDP. The clinical features and disease course were evaluated. Investigative techniques, including electrophysiology, cerebrospinal fluid examination, neuropathology, imaging and neuroimmunology, were considered in relation to technical aspects, sensitivity, specificity, availability and cost. Available evidenced-based treatments and those with possible efficacy despite lack of evidence, were considered, as well as current methods for evaluation of treatment effects.
EXPERT OPINION
CIDP remains a clinical diagnosis, supported first and foremost by electrophysiology. Other investigative techniques have limited impact. Most patients with CIDP respond to available first-line treatments and immunosuppression may be efficacious in those who do not. Consideration of the natural history and of the high reported remission rate, of under-recognised associated disabling features, of treatment administration modalities and assessment methods, require enhanced attention
The risk of mental illness in people living with HIV in the UK: a propensity score-matched cohort study.
No full textBACKGROUND
Prevalence of mental illness is higher in people living with HIV than in the general population, but the incidence of composite mental illness and its components is unclear. We aimed to identify the risk of incident mental illness along with individual conditions of depression, anxiety, and severe mental illness in people living with HIV in the UK.
METHODS
Data for this population-based cohort were extracted from the IQVIA Medical Research Database, a nationally representative UK-based database of primary care electronic health records. We included adults (aged ≥18 years) living with HIV, matched with adults without HIV using propensity score matching (1:1 ratio). The primary outcome was composite mental illness comprising a diagnosis of depression, anxiety, or severe mental illness. Secondary outcomes were individual mental health conditions. Cox proportional hazard regression models were used to compare the risk of each outcome between people with and without HIV. Each model excluded those with the outcome at baseline. Individuals were followed up prospectively. The study period was from Jan 1, 2000, to Jan 1, 2020.
FINDINGS
Of 7167 people living with HIV without mental illness at baseline, 586 developed a mental illness (incidence rate 19·6 per 1000 person-years) compared with 418 of 7167 people without HIV (incidence rate 12·1 per 1000 person-years), resulting in an adjusted hazard ratio (HR) of 1·63 (95% CI 1·44-1·85). People living with HIV had higher incidence rates for depression (15·4 per 1000 person-years), anxiety (7·2 per 1000 person-years), and severe mental illness (1·6 per 1000 person-years) compared with people without HIV (7·9, 5·0, and 0·6 per 1000 person-years, respectively), with adjusted HRs of 1·94 (95% CI 1·68-2·24) for depression, 1·38 (1·15-1·66) for anxiety, and 2·18 (1·41-3·39) for severe mental illness.
INTERPRETATION
People living with HIV have an increased risk for developing composite mental illness, depression, anxiety, and severe mental illness compared with people without HIV. People living with HIV should be regularly screened for mental illness; however, there is a strong need to improve prevention of mental illness in people living with HIV and for more outreach programmes to ensure that no groups of people living with HIV are being underdiagnosed.
FUNDING
None
Evaluating semantic similarity methods for comparison of text-derived phenotype profiles.
No full textBACKGROUND
Semantic similarity is a valuable tool for analysis in biomedicine. When applied to phenotype profiles derived from clinical text, they have the capacity to enable and enhance 'patient-like me' analyses, automated coding, differential diagnosis, and outcome prediction. While a large body of work exists exploring the use of semantic similarity for multiple tasks, including protein interaction prediction, and rare disease differential diagnosis, there is less work exploring comparison of patient phenotype profiles for clinical tasks. Moreover, there are no experimental explorations of optimal parameters or better methods in the area.
METHODS
We develop a platform for reproducible benchmarking and comparison of experimental conditions for patient phentoype similarity. Using the platform, we evaluate the task of ranking shared primary diagnosis from uncurated phenotype profiles derived from all text narrative associated with admissions in the medical information mart for intensive care (MIMIC-III).
RESULTS
300 semantic similarity configurations were evaluated, as well as one embedding-based approach. On average, measures that did not make use of an external information content measure performed slightly better, however the best-performing configurations when measured by area under receiver operating characteristic curve and Top Ten Accuracy used term-specificity and annotation-frequency measures.
CONCLUSION
We identified and interpreted the performance of a large number of semantic similarity configurations for the task of classifying diagnosis from text-derived phenotype profiles in one setting. We also provided a basis for further research on other settings and related tasks in the area