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Informing and Empowering Patients and Clinicians to Make Evidence-Supported Outcome-Based Decisions in Relation to SGLT2 Inhibitor Therapies: The Use of the Novel Years of Drug administration (YoDa) Concept.
No full textThe American Diabetes Association guidelines for the management of type 2 diabetes mellitus recommends treating patients with atherosclerotic cardiovascular diseases, heart failure or diabetic kidney disease with sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists, irrespective of the baseline HbA1c, to reduce adverse renal and cardiovascular outcomes. Initiation of such therapies have a significant cost impact on health economies. Cost of gain in quality-adjusted life-years is normally used for cost effectiveness for a particular drug. In the absence of head-to-head comparisons, prescribers may go for the cheapest option, which may not necessarily be the right decision. We propose using the calculated 'YoDa' (Years of Drug administration) as an easily comparable metric between the drug accrual cost and clinical outcomes. YoDa is calculated as a product of numbers needed to treat and the median duration in years that the trial ran over, to accrue the positive clinical outcomes. Clinical phenotyping of the patient to the specific inclusion and exclusion criteria of relevant clinical trials could guide the clinician to choose the most appropriate therapy. We also propose a series of steps or 'deliberations', which a clinician should consider in making a final choice of sodium-glucose co-transporter-2 inhibitor therapy. A comprehensive summary of the sodium-glucose co-transporter-2 inhibitor trials, clinical phenotyping and YoDa calculations for various significant clinical outcomes could assist making evidence-based, patient-individualised and cost-effective management plans for diabetes care. Informing and Empowering Patients and Clinicians to Make Evidence-Supported Outcome-Based Decisions in Relation to SGLT2 Inhibitor Therapies: The Use of The Novel Years of Drug administration (YoDa) Concept
Adult North Star Network (ANSN): Consensus Document for Therapists Working with Adults with Duchenne Muscular Dystrophy (DMD) - Therapy Guidelines.
No full textCombined Perioperative Lapatinib and Trastuzumab in Early HER2-Positive Breast Cancer Identifies Early Responders: Randomized UK EPHOS-B Trial Long-Term Results.
No full textBACKGROUND
EPHOS-B aimed to determine whether perioperative anti-HER2 therapy inhibited proliferation and/or increased apoptosis in HER2-positive breast cancer.
PATIENTS AND METHODS
This randomized phase II, two-part, multicenter trial included newly diagnosed women with HER2-positive invasive breast cancer due to undergo surgery. Patients were randomized to: part 1 (1:2:2), no treatment (control), trastuzumab or lapatinib; part 2 (1:1:2) control, trastuzumab, or lapatinib and trastuzumab combination. Treatment was given for 11 days presurgery. Coprimary endpoints were change in Ki67 and apoptosis between baseline and surgery tumor samples (biologic response: ≥30% change). Central pathology review scored residual cancer burden (RCB). Relapse-free survival (RFS) explored long-term effects.
RESULTS
Between November 2010 and September 2015, 257 patients were randomized (part 1: control 22, trastuzumab 57, lapatinib 51; part 2: control 29, trastuzumab 32, combination 66). Ki67 response was evaluable for 223 patients: in part 1 Ki67 response occurred in 29/44 (66%) lapatinib versus 18/49 (37%) trastuzumab ( = 0.007) and 1/22 (5%) control ( < 0.0001); in part 2 in 36/49 (74%) combination versus 14/31 (45%) trastuzumab ( = 0.02) and 2/28 (7%) control ( < 0.0001). No significant increase in apoptosis after 11 days was seen in treatment groups. Six patients achieved complete pathologic response (pCR, RCB0) and 13 RCB1, all but two in the combination group. After 6 years median follow-up, 28 (11%) had recurrence and 19 (7%) died. No recurrences or deaths were observed among patients who achieved a pCR. Ki67% falls ≥50% associated with fewer recurrences ( = 0.002).
CONCLUSIONS
Early response after short duration anti-HER2 dual therapy identifies cancers dependent on the HER2 pathway providing a strategy for exploring risk-adapted individualized treatment de-escalation
The effect of end-ischaemic normothermic machine perfusion on donor hepatic artery endothelial integrity.
No full textBACKGROUND
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
Population screening for liver fibrosis: Toward early diagnosis and intervention for chronic liver diseases.
No full textCirrhosis, highly prevalent worldwide, develops after years of hepatic inflammation triggering progressive fibrosis. Currently, the main etiologies of cirrhosis are non-alcoholic fatty liver disease and alcohol-related liver disease, although chronic hepatitis B and C infections are still major etiological factors in some areas of the world. Recent studies have shown that liver fibrosis can be assessed with relatively high accuracy noninvasively by serological tests, transient elastography, and radiological methods. These modalities may be utilized for screening for liver fibrosis in at-risk populations. Thus far, a limited number of population-based studies using noninvasive tests in different areas of the world indicate that a significant percentage of subjects without known liver disease (around 5% in general populations and a higher rate -18% to 27%-in populations with risk factors for liver disease) have significant undetected liver fibrosis or established cirrhosis. Larger international studies are required to show the harms and benefits before concluding that screening for liver fibrosis should be applied to populations at risk for chronic liver diseases. Screening for liver fibrosis has the potential for changing the current approach from diagnosing chronic liver diseases late when patients have already developed complications of cirrhosis to diagnosing liver fibrosis in asymptomatic subjects providing the opportunity of preventing disease progression
Metaphors that shape parents' perceptions of effective communication with healthcare practitioners following child death: a qualitative UK study.
No full textOBJECTIVES
To offer an interpretation of bereaved parents' evaluations of communication with healthcare practitioners (HCPs) surrounding the death of a child.
DESIGN
Interpretative qualitative study employing thematic and linguistic analyses of metaphor embedded in interview data.
SETTING
England and Scotland.
PARTICIPANTS
24 bereaved parents (21 women, 3 men).
METHODS
Participants were recruited through the True Colours Trust website and mailing list, similar UK charities and word of mouth. Following interviews in person or via video-conferencing platforms (Skype/Zoom), transcripts first underwent thematic and subsequently linguistic analyses supported by NVivo. A focused analysis of metaphors used by the parents was undertaken to allow in-depth interpretation of how they conceptualised their experiences.
RESULTS
The findings illuminate the ways parents experienced communication with HCPs surrounding the death of a child. Key findings from this study suggest that good communication with HCPs following the death of a child should acknowledge parental identity (and that of their child as an individual) and offer opportunities for them to enact this; taking account their emotional and physical experiences; and accommodate their altered experiences of time.
CONCLUSIONS
This study suggests that HCPs when communicating with bereaved parents need to recognise, and seek to comprehend, the ways in which the loss impacts on an individual's identity as a parent, the 'physical' nature of the emotions that can be unleashed and the ways in which the death of a child can alter their metaphorical conceptions of time
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
Functional outcome measures in young, steroid-naïve boys with Duchenne muscular dystrophy.
No full textThe purpose of this study was to quantitate motor performance in 196 genetically confirmed steroid-naïve boys with Duchenne muscular dystrophy (DMD), to evaluate the test-retest reliability of measures of motor performance in young DMD boys, and to assess correlations among the different functional outcomes including timed tests. Boys aged 4-7 years were recruited in the FOR-DMD study, a comparative effectiveness study of different steroid regimens in DMD. Eligible boys had to be able to rise from the floor independently and to perform pulmonary function testing consistently. The boys were evaluated with standardized assessments at the screening and baseline visits at 32 sites in 5 countries (US, UK, Canada, Italy, Germany). Assessments included timed rise from floor, timed 10 m walk/run, six-minute walk distance, North Star Ambulatory Assessment (NSAA) and forced vital capacity (FVC). Mean age at baseline was 5.9 years (range 4.1-8.1 years). Test-retest reliability was high for functional assessments, regardless of time lag between assessments (up to 90 days) and for the majority of age groups. Correlations were strong among the functional measures and timed tests, less so with FVC. Physiotherapy measures are reliable in a young, steroid-naïve population and rise from floor velocity appears to be a sensitive measure of strength in this population
The Impact of Atrial Fibrillation on Outcomes of Peripheral Arterial Disease: Analysis of Routinely Collected Primary Care Data.
No full textBACKGROUND
The combination of peripheral arterial disease and atrial fibrillation is linked with high risk of mortality and stroke. This study aims to investigate the impact of atrial fibrillation on patients with diagnosed peripheral arterial disease.
METHODS
This is a retrospective study using The Health Improvement Network database, which contains prospectively collected data from participating primary care practices. Patients with a new diagnosis of peripheral arterial disease between January 8, 1995 and January 5, 2017 were identified in the database alongside relevant demographic information, clinical history, and medications. Every patient in the dataset with peripheral arterial disease and baseline atrial fibrillation (case) was matched to a patient without atrial fibrillation (control) with similar characteristics using propensity score matching. Cox-regression analysis was performed and hazard ratios (HR) calculated for the outcomes of death, stroke, ischemic heart disease, heart failure, and major amputation.
RESULTS
Prevalence of atrial fibrillation in this cohort was 10.2%. All patients with peripheral arterial disease and atrial fibrillation (n = 5685) were matched with 5685 patients without atrial fibrillation but otherwise similar characteristics. After multivariate analysis, atrial fibrillation was independently associated with mortality (HR 1.18; 95% confidence interval [CI], 1.12-1.26; P < .01), cerebrovascular events (HR 1.35; 95% CI, 1.17-1.57; P < .01), and heart failure (HR 1.87; 95% CI, 1.62-2.15; P < .01), but not with ischemic heart disease or limb loss.
CONCLUSION
In peripheral arterial disease patients, atrial fibrillation is a risk factor for mortality, stroke, and heart failure. This emphasizes the need for proactive surveillance and holistic management of these patients