Untreated, hypoparathyroidism (hypoPT) is a state of hypocalcemia with inappropriately low plasma parathyroid hormone (PTH) levels and hyperphosphatemia. PTH administration normalizes plasma calcium and phosphate levels and reduces the doses of calcium and active vitamin D analogues needed. To develop an evidence-based clinical algorithm to monitor hypoPT patients treated with recombinant human PTH (rhPTH ) injected subcutaneously in the thigh, we performed a 24-hour monitoring study of pharmacokinetic and pharmacodynamic effects in a group of 38 patients who had completed a 6-month randomized study on effects of treatment with a fixed rhPTH(1-84) dose of 100 mg/d or similar placebo as an add-on to conventional treatment. PTH levels rose immediately, reaching a median peak level of 26.5 (interquartile range [IQR], 20.1-42.5) pmol/L 15 minutes following injection. Thereafter, levels gradually decreased until reaching predosing levels after 16 hours, with a plasma half-life of 2.2 (1.7-2.5) hours. rhPTH (1-84) changed the diurnal rhythms of ionized calcium levels and 1,25-dihydroxyvitamin D (1,25[OH] 2 D) levels, with rising levels following injection. Ionized calcium peaked after 7.0 (5.0-10.0) hours. Asymptomatic hypercalcemia was present in 71% of the rhPTH(1-84)-treated patients. Compared with placebo, 24-hour urinary calcium, phosphate, and magnesium did not change, although the diurnal variation in renal excretion rates changed significantly in response to treatment. In conclusion, as a safety precaution, we recommend occasionally measuring calcium levels at approximately 7 hours after administration in order to reveal episodes of hypercalcemia. A 100-mg daily dose of rhPTH(1-84) appears to be too high in some patients, suggesting a need for a device allowing for individual dose adjustments.
Chronic inflammatory diseases (CIDs), including Crohn’s disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome. This report describes the establishment of a cohort that aims to obtain this information. Clinical data including lifestyle and treatment response and biological specimens (blood, faeces, urine, and, in IBD patients, intestinal biopsies) are sampled prior to and while on TNF inhibitor therapy. Both hypothesis-driven and data-driven analyses will be performed according to pre-specified protocols including pathway analyses resulting from candidate gene expression analyses and global approaches (e.g., metabolomics, metagenomics, proteomics). The final purpose is to improve the lives of patients suffering from CIDs, by providing tools facilitating treatment selection and dietary recommendations likely to improve the clinical outcome.
IntroductionChronic inflammatory diseases (CIDs) are frequently treated with biological medications, specifically tumour necrosis factor inhibitors (TNFi)). These medications inhibit the pro-inflammatory molecule TNF alpha, which has been strongly implicated in the aetiology of these diseases. Up to one-third of patients do not, however, respond to biologics, and lifestyle factors are assumed to affect treatment outcomes. Little is known about the effects of dietary lifestyle as a prognostic factor that may enable personalised medicine. The primary outcome of this multidisciplinary collaborative study will be to identify dietary lifestyle factors that support optimal treatment outcomes.Methods and analysisThis prospective cohort study will enrol 320 patients with CID who are prescribed a TNFi between June 2017 and March 2019. Included among the patients with CID will be patients with inflammatory bowel disease (Crohn’s disease and ulcerative colitis), rheumatic disorders (rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis), inflammatory skin diseases (psoriasis, hidradenitis suppurativa) and non-infectious uveitis. At baseline (pretreatment), patient characteristics will be assessed using patient-reported outcome measures, clinical assessments of disease activity, quality of life and lifestyle, in addition to registry data on comorbidity and concomitant medication(s). In accordance with current Danish standards, follow-up will be conducted 14–16 weeks after treatment initiation. For each disease, evaluation of successful treatment response will be based on established primary and secondary endpoints, including disease-specific core outcome sets. The major outcome of the analyses will be to detect variability in treatment effectiveness between patients with different lifestyle characteristics.Ethics and disseminationThe principle goal of this project is to improve the quality of life of patients suffering from CID by providing evidence to support dietary and other lifestyle recommendations that may improve clinical outcomes. The study is approved by the Ethics Committee (S-20160124) and the Danish Data Protecting Agency (2008-58-035). Study findings will be disseminated through peer-reviewed journals, patient associations and presentations at international conferences.Trial registration numberNCT03173144; Pre-results.
BackgroundAchilles tendinopathy is a painful inflammatory condition characterized by swelling, stiffness and reduced function of the Achilles tendon. Kager’s fat pad is an adipose tissue located in the area anterior to the Achilles tendon. Observations reveal a close physical interplay between Kager’s fat pad and its surrounding structures during movement of the ankle, suggesting that Kager’s fat pad may stabilize and protect the mechanical function of the ankle joint.AimThe aim of this study was to characterize whether Achilles tendinopathy was accompanied by changes in expression of inflammatory markers and metabolic enzymes in Kager’s fat pad.MethodsA biopsy was taken from Kager’s fat pad from 31 patients with chronic Achilles tendinopathy and from 13 healthy individuals. Gene expression was measured by reverse transcription-quantitative PCR. Focus was on genes related to inflammation and lipid metabolism.ResultsExpression of the majority of analyzed inflammatory marker genes was increased in patients with Achilles tendinopathy compared to that in healthy controls. Expression patterns of the patient group were consistent with reduced lipolysis and increased fatty acid β-oxidation. In the fat pad, the pain-signaling neuropeptide substance P was found to be present in one third of the subjects in the Achilles tendinopathy group but in none of the healthy controls.ConclusionGene expression changes in Achilles tendinopathy patient samples were consistent with Kager’s fat pad being more inflamed than in the healthy control group. Additionally, the results indicate an altered lipid metabolism in Kager’s fat pad of Achilles tendinopathy patients.
ObjectivesThe objectives of this study were to asses (1) inter-rater and intrarater reliability of ultrasound imaging in patients with hip osteoarthritis, and (2) agreement between ultrasound and X-ray findings of hip osteoarthritis using validated Outcome Measures in Rheumatology ultrasound definitions for pathology.DesignAn inter-rater and intrarater reliability study.SettingA single-centre study conducted at a regional hospital.Participants50 patients >39 years of age referred for radiography due to hip pain and suspected hip osteoarthritis were included. Exclusion criteria were previous hip surgery in the painful hip, suspected fracture or malignant changes in the hip.InterventionBilateral ultrasound examinations (n=92) were performed continuously by two experienced operators blinded to clinical information and other imaging findings. After 4–6 weeks, one operator reassessed the images. X-rays were assessed by a third imaging specialist.Primary and secondary outcome measuresInter-rater and intrarater reliability and agreement between ultrasound imaging and X-ray were assessed using Cohen’s ordinal kappa statistics for binary categorical variables and weighted kappa for ordered categorical variables.ResultsKappa values (κ) for inter-rater reliability were 0.9 and 0.8 for hip effusion/synovitis and osteoarthritis grading, respectively. For acetabular and femoral osteophytes, femoral cartilage changes and labrum changes κ ranged from 0.4 to 0.7. Intrarater reliability had κ equal or higher compared with inter-rater reliability. Agreement between ultrasound and X-ray findings ranged from κ=0.2 to κ=0.5.ConclusionThis study demonstrated substantial to almost perfect reliability on the most common ultrasound findings related to hip osteoarthritis and osteoarthritis grading. Agreement on the grade of osteoarthritis between ultrasound and X-ray was moderate. Overall, these results support ultrasound imaging as a reliable tool in the assessment of hip osteoarthritis.
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