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Clinical Chemistry and Laboratory... Jul 2024Analytical performance specifications (APS) are typically established through one of three models: (i) outcome studies, (ii) biological variation (BV), or (iii)...
Analytical performance specifications (APS) are typically established through one of three models: (i) outcome studies, (ii) biological variation (BV), or (iii) state-of-the-art. Presently, The APS can, for most measurands that have a stable concentration, be based on BV. BV based APS, defined for imprecision, bias, total allowable error and allowable measurement uncertainty, are applied to many different processes in the laboratory. When calculating APS, it is important to consider the different APS formulae, for what setting they are to be applied and if they are suitable for the intended purpose. In this opinion paper, we elucidate the background, limitations, strengths, and potential intended applications of the different BV based APS formulas. When using BV data to set APS, it is important to consider that all formulae are contingent on accurate and relevant BV estimates. During the last decade, efficient procedures have been established to obtain reliable BV estimates that are presented in the EFLM biological variation database. The database publishes detailed BV data for numerous measurands, global BV estimates derived from meta-analysis of quality-assured studies of similar study design and automatic calculation of BV based APS.
Topics: Humans; Biological Variation, Population
PubMed: 38501489
DOI: 10.1515/cclm-2024-0108 -
Clinical Liver Disease 2024
Review
Diagnosis and management of protoporphyria-related liver dysfunction in erythropoietic protoporphyria and x-linked protoporphyria: A patient-friendly summary of the 2023 evidence-based consensus guidelines.
PubMed: 38487349
DOI: 10.1097/CLD.0000000000000133 -
BMJ Open Mar 2024haemochromatosis genetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant...
OBJECTIVES
haemochromatosis genetic variants have an uncertain clinical penetrance, especially to older ages and in undiagnosed groups. We estimated p.C282Y and p.H63D variant cumulative incidence of multiple clinical outcomes in a large community cohort.
DESIGN
Prospective cohort study.
SETTING
22 assessment centres across England, Scotland, and Wales in the UK Biobank (2006-2010).
PARTICIPANTS
451 270 participants genetically similar to the 1000 Genomes European reference population, with a mean of 13.3-year follow-up through hospital inpatient, cancer registries and death certificate data.
MAIN OUTCOME MEASURES
Cox proportional HRs of incident clinical outcomes and mortality in those with p.C282Y/p.H63D mutations compared with those with no variants, stratified by sex and adjusted for age, assessment centre and genetic stratification. Cumulative incidences were estimated from age 40 years to 80 years.
RESULTS
12.1% of p.C282Y+/+ males had baseline (mean age 57 years) haemochromatosis diagnoses, with a cumulative incidence of 56.4% at age 80 years. 33.1% died vs 25.4% without variants (HR 1.29, 95% CI: 1.12 to 1.48, p=4.7×10); 27.9% vs 17.1% had joint replacements, 20.3% vs 8.3% had liver disease, and there were excess delirium, dementia, and Parkinson's disease but not depression. Associations, including excess mortality, were similar in the group undiagnosed with haemochromatosis. 3.4% of women with p.C282Y+/+ had baseline haemochromatosis diagnoses, with a cumulative incidence of 40.5% at age 80 years. There were excess incident liver disease (8.9% vs 6.8%; HR 1.62, 95% CI: 1.27 to 2.05, p=7.8×10), joint replacements and delirium, with similar results in the undiagnosed. p.C282Y/p.H63D and p.H63D+/+ men or women had no statistically significant excess fatigue or depression at baseline and no excess incident outcomes.
CONCLUSIONS
Male and female p.C282Y homozygotes experienced greater excess morbidity than previously documented, including those undiagnosed with haemochromatosis in the community. As haemochromatosis diagnosis rates were low at baseline despite treatment being considered effective, trials of screening to identify people with p.C282Y homozygosity early appear justified.
Topics: Adult; Aged, 80 and over; Female; Humans; Male; Middle Aged; Biological Specimen Banks; Delirium; Genotype; Hemochromatosis; Hemochromatosis Protein; Histocompatibility Antigens Class I; Homozygote; Liver Diseases; Mutation; Prospective Studies; UK Biobank; Aged
PubMed: 38479735
DOI: 10.1136/bmjopen-2023-081926 -
Internal Medicine (Tokyo, Japan) Mar 2024Hereditary coproporphyria (HCP) is caused by a partial deficiency of coproporphyrinogen oxidase during heme biosynthesis. Givosiran is approved for the treatment of...
Hereditary coproporphyria (HCP) is caused by a partial deficiency of coproporphyrinogen oxidase during heme biosynthesis. Givosiran is approved for the treatment of acute hepatic porphyria. We herein report the case of a 47-year-old woman with HCP. Monthly givosiran administration improved her subjective symptoms and reduced her δ-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels to the normal range. However, givosiran was discontinued after six months due to a decreased renal function. The patient's ALA and PBG levels remained within the normal ranges, and her HCP-related symptoms resolved more than 2 years after the discontinuation of givosiran.
PubMed: 38462517
DOI: 10.2169/internalmedicine.3284-23 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Nov 2023Erythropoietic protoporphyria (EPP) is an inherited metabolic disease caused by the deficiency in ferrochelatase (FECH) encoded by the gene, and it is inherited in an...
Erythropoietic protoporphyria (EPP) is an inherited metabolic disease caused by the deficiency in ferrochelatase (FECH) encoded by the gene, and it is inherited in an autosomal recessive manner. EPP usually produces acute pain photosensitivity after exposure to sunlight in infancy or early childhood, and liver failure is the most serious associated complication. This article reported an adult female case of EPP complicated with thyrotoxicosis and liver dysfunction which is a rare condition. The patient's liver function improved after liver protection treatment, her thyroid function returned to normal, and her EPP symptoms improved significantly. Moreover, the c.286C>T gene mutation may be the pathogenic locus of EPP. For patients with abnormal liver function, the possibility of EPP should be considered after the common causes are excluded, and gene detection should be done to confirm the diagnosis in time. When EPP is associated with thyrotoxicosis and liver dysfunction, priority may be given to hepatoprotective therapy.
Topics: Humans; Child, Preschool; Female; Adult; Protoporphyria, Erythropoietic; Thyrotoxicosis; Liver Failure; Mutation
PubMed: 38432869
DOI: 10.11817/j.issn.1672-7347.2023.230242 -
Medicina (Kaunas, Lithuania) Jan 2024Endogenous endophthalmitis (ECE) is a rare but sight-threatening disease. Patients with ECE present with various clinical signs and symptoms, which can complicate the...
Endogenous endophthalmitis (ECE) is a rare but sight-threatening disease. Patients with ECE present with various clinical signs and symptoms, which can complicate the diagnosis. The aim of this report was to demonstrate the outcomes of treatment and to diagnose macular complications caused by intraocular inflammation. A 41-year-old woman with a history of acute intermittent porphyria presented with a progressive vision loss in her left eye. Left-eye OCT revealed findings consistent with a fungal etiology, which was confirmed by the culture of swabs collected from a central vein catheter. The outcomes of intravenous fluconazole treatment were not satisfactory, and the patient developed recurrent attacks of porphyria, suggesting a porphyrogenic effect of systemic antifungal therapy. Repeated intravitreal injections with amphotericin B led to a gradual regression of inflammatory lesions. However, follow-up examinations revealed active macular neovascularization (MNV) on both OCT and OCTA scans. The patient was administered intravitreal bevacizumab. At the 11th month of follow-up, OCT and OCTA scans showed significant inflammatory lesions regression with macula scarring, and no MNV activity was detected. This case highlights the importance of OCT and OCTA as valuable noninvasive imaging techniques for the identification of ECE, the monitoring of its clinical course, and the diagnosis of macular complications.
Topics: Humans; Female; Adult; Follow-Up Studies; Tomography, Optical Coherence; Fluorescein Angiography; Choroidal Neovascularization; Endophthalmitis; Candida
PubMed: 38399495
DOI: 10.3390/medicina60020207 -
Patient Related Outcome Measures 2024Erythropoietic protoporphyria (EPP), a rare inherited disorder, presents in early childhood with severe, painful phototoxicity, with significant impacts on...
Development and Content Validation of Novel Patient-Reported Outcome Measures to Assess Disease Severity and Change in Patients with Erythropoietic Protoporphyria: The EPP Impact Questionnaire (EPIQ).
PURPOSE
Erythropoietic protoporphyria (EPP), a rare inherited disorder, presents in early childhood with severe, painful phototoxicity, with significant impacts on health-related quality of life (HRQoL). Previous studies have not captured all concepts important to patients. Therefore, this study sought to develop a novel, comprehensive, and content valid patient-reported outcome (PRO) measure to assess the efficacy of new therapies.
PATIENTS AND METHODS
Qualitative interviews were conducted with EPP participants and clinical experts to obtain views on concepts relevant to patients. Results informed the development of novel PROs, which were debriefed during subsequent combined concept elicitation and cognitive debriefing interviews.
RESULTS
Twenty-three interviews were conducted with 17 adults and 6 adolescents with EPP. Concept elicitation revealed that participants experienced many symptoms with significant variability. The most common were burning, pain, swelling, and tingling. Tingling was the most common prodromal symptom, while burning was the most bothersome, and pain was the worst full reaction symptom. Participants reported being negatively impacted in their ability to do daily activities, and social and emotional functioning. Many reported impacted ability to work and be productive at their job. Participants reviewed and completed the newly developed PRO measures assessing full reactions and ability to do activities, as well as items to assess severity and change in severity of prodromal symptoms, full reactions, and EPP overall. All measures were found to be comprehensive, clear, and relevant.
CONCLUSION
PRO measures are needed to assess important aspects of HRQoL and evaluate therapeutic response. These PRO measures are unique in assessing overall severity and change in EPP.
PubMed: 38375415
DOI: 10.2147/PROM.S438892 -
Cureus Jan 2024Chronic kidney disease (CKD) is a progressive disease and has multiple clinical manifestations; when CKD reaches the end stage, at least one cutaneous manifestation... (Review)
Review
Chronic kidney disease (CKD) is a progressive disease and has multiple clinical manifestations; when CKD reaches the end stage, at least one cutaneous manifestation appears due to some increased toxin levels or a constant proinflammatory state. Nonspecific manifestations include pruritus, xerosis, pigmentation disorders, acquired ichthyosis, purpuric spots, and nail disorders. Some specific manifestations are bullous dermatoses, acquired perforating dermatoses (APD), eruptive xanthoma, access site infections, calcifying disorders, and nephrogenic systemic fibrosis (NSF). All these cutaneous changes negatively impact patients; early recognition and diagnosis of these dermatoses will make a difference in their quality of treatment. Exploring a patient's skin is fundamental to suspect some diseases and increased toxin levels; pruritus occurs when uremic toxins are raised, and nail disorders are associated with hypoalbuminemia. This review provides the clinician with information on the clinical manifestations that occur in CKD, including epidemiology, pathophysiology, clinical manifestations, diagnosis, histopathology, treatment, and life impact of the dermatoses in CKD.
PubMed: 38352109
DOI: 10.7759/cureus.52253 -
Clinica Chimica Acta; International... Mar 2024Knowledge of biological variation (BV) of hormones is essential for interpretation of laboratory tests and for diagnostics of endocrinological and reproductive diseases....
The European biological variation study (EuBIVAS): Biological variation data for testosterone, follicle stimulating hormone, prolactin, luteinizing hormone and dehydroepiandrosterone sulfate in men.
BACKGROUND
Knowledge of biological variation (BV) of hormones is essential for interpretation of laboratory tests and for diagnostics of endocrinological and reproductive diseases. There is a lack of robust BV data for many hormones in men.
METHODS
We used serum samples collected weekly over 10 weeks from the European Biological Variation Study (EuBIVAS) to determine BV of testosterone, follicle-stimulating hormone (FSH), prolactin, luteinizing hormone (LH) and dehydroepiandrosterone sulfate (DHEA-S) in 38 men. We derived within-subject (CV) and between-subject (CV) BV estimates by CV-ANOVA after trend, outlier, and homogeneity analysis and calculated reference change values, index of individuality (II), and analytical performance specifications.
RESULTS
The CV estimates were 10 % for testosterone, 8 % for FSH, 13 % for prolactin, 22 % for LH, and 9 % for DHEA-S, respectively. The IIs ranged between 0.14 for FSH to 0.66 for LH, indicating high individuality.
CONCLUSIONS
In this study, we have used samples from the highly powered EuBIVAS study to derive BV estimates for testosterone, FSH, prolactin, LH and DHEA-S in men. Our data confirm previously published BV estimates of testosterone, FSH and LH. For prolactin and DHEA-S BV data for men are reported for the first time.
Topics: Male; Humans; Follicle Stimulating Hormone; Luteinizing Hormone; Prolactin; Testosterone; Dehydroepiandrosterone Sulfate
PubMed: 38341016
DOI: 10.1016/j.cca.2024.117806