Status and perspectives of biomarker validation for diagnosis, stratification, and treatment.

OBJECTIVES: The aim of this study was to discuss the status of and perspective for biomarker validation in view of the challenges imposed on national healthcare systems due to an increasing number of citizens with chronic diseases and new expensive drugs with effects that are sometimes poorly documented. The demand for a paradigm shift toward stratification of patients or even 'personalized medicine' (PM) is rising, and the implementation of such novel strategies has the potential to increase patient outcomes and cost efficiency of treatments. The implementation of PM depends on relevant and reliable biomarkers correlated to disease states, prognosis, or effect of treatment. Beyond biomarkers of disease, personalized prevention strategies (such as individualized nutrition guidance) are likely to depend on novel biomarkers. STUDY DESIGN: We discuss the current status of the use of biomarkers and the need for standardization and integration of biomarkers based on multi-omics approaches. METHODS: We present representative cases from laboratory medicine, oncology, and nutrition, where present and emerging biomarkers have or may present opportunities for PM or prevention. RESULTS: Biomarkers vary greatly in complexity, from single genomic mutations to metagenomic analyses of the composition of the gut microbiota and comprehensive analyses of metabolites, metabolomics. Using biomarkers for decision-making has previously often relied on measurements of single biomolecules. The current development now moves toward the use of multiple biomarkers requiring the use of machine learning or artificial intelligence. Still, the usefulness of biomarkers is often challenged by suboptimal validation, and the discovery of new biomarkers moves much faster than standardization efforts. To reap the potential benefits of personalization of treatment and prevention, healthcare systems and regulatory authorities need to focus on validation and standardization of biomarkers. CONCLUSION: There is a great public health need for better understanding of the usefulness, but also limitations, of biomarkers among policy makers, clinicians, and scientists, and efforts securing effective validation are key to the future use of novel sets of complex biomarkers.

Avian mite dermatitis: Diagnostic challenges and unmet needs.

The avian mite Dermanyssus gallinae (poultry red mite, PRM) is of major economic and veterinary importance for the poultry and egg industry worldwide. The accumulating reports on the opportunistic nonavian feeding of D. gallinae raise concerns on PRM host expansion. However, the consequent threats to human health remain largely unclear. PRM infestation in humans is usually manifested as a local or generalized noncharacteristic skin reaction referred to as gamasoidosis. This report presents the current state of the art and the new developments on PRM-associated dermatitis, sharing neither the authors' personal experience nor focusing on differential diagnosis. Specifically, it reflects the outcome of the critical assessment of the available literature by European medical and veterinary experts in the field under the "One Health" approach.

Clues for early detection of autoimmune Addison's disease - myths and realities.

BACKGROUND: Early detection of autoimmune Addison's disease (AAD) is important as delay in diagnosis may result in a life-threatening adrenal crisis and death. The classical clinical picture of untreated AAD is well-described, but methodical investigations are scarce. OBJECTIVE: Perform a retrospective audit of patient records with the aim of identifying biochemical markers for early diagnosis of AAD. MATERIAL AND METHODS: A multicentre retrospective study including 272 patients diagnosed with AAD at hospitals in Norway and Sweden during 1978-2016. Scrutiny of medical records provided patient data and laboratory values. RESULTS: Low sodium occurred in 207 of 247 (84%), but only one-third had elevated potassium. Other common nonendocrine tests were largely normal. TSH was elevated in 79 of 153 patients, and hypoglycaemia was found in 10%. Thirty-three per cent were diagnosed subsequent to adrenal crisis, in whom electrolyte disturbances were significantly more pronounced (P < 0.001). Serum cortisol was consistently decreased (median 62 nmol L-1 [1-668]) and significantly lower in individuals with adrenal crisis (38 nmol L-1 [2-442]) than in those without (81 nmol L-1 [1-668], P < 0.001). CONCLUSION: The most consistent biochemical finding of untreated AAD was low sodium independent of the degree of glucocorticoid deficiency. Half of the patients had elevated TSH levels. Only a minority presented with marked hyperkalaemia or other nonhormonal abnormalities. Thus, unexplained low sodium and/or elevated TSH should prompt consideration of an undiagnosed AAD, and on clinical suspicion bring about assay of cortisol and ACTH. Presence of 21-hydroxylase autoantibodies confirms autoimmune aetiology. Anticipating additional abnormalities in routine blood tests may delay diagnosis.

Positive correlation between Aeromonas salmonicida vaccine antigen concentration and protection in vaccinated rainbow trout Oncorhynchus mykiss evaluated by a tail fin infection model.

Rainbow trout, Oncorhynchus mykiss (Walbaum), are able to raise a protective immune response against Aeromonas salmonicida subsp. salmonicida (AS) following injection vaccination with commercial vaccines containing formalin-killed bacteria, but the protection is often suboptimal under Danish mariculture conditions. We elucidated whether protection can be improved by increasing the concentration of antigen (formalin-killed bacteria) in the vaccine. Rainbow trout juveniles were vaccinated by intraperitoneal (i.p.) injection with a bacterin of Aeromonas salmonicida subsp. salmonicida strain 090710-1/23 in combination with Vibrio anguillarum serotypes O1 and O2a supplemented with an oil adjuvant. Three concentrations of AS antigens were applied. Fish were subsequently challenged with the homologous bacterial strain administered by perforation of the tail fin epidermis and 60-s contact with live A. salmonicida bacteria. The infection method proved to be efficient and could differentiate efficacies of different vaccines. It was shown that protection and antibody production in exposed fish were positively correlated to the AS antigen concentration in the vaccine.

Patient knowledge of anticoagulant treatment does not correlate with treatment quality.

OBJECTIVES: The objectives of this study were to investigate whether patient knowledge is a predictor of treatment stability in anticoagulant clinic patients and to evaluate the correlation between the patients' subjective assessment of own knowledge and their score on a validated knowledge assessment instrument. STUDY DESIGN: This is a prospective study where international normalized ratio (INR) stability was followed up 6 months after knowledge assessment. METHODS: We analyzed data of 42 consecutive patients new to vitamin-K antagonist (VKA) treatment and 64 experienced patients from an anticoagulant clinic offering patient education. The patients filled out a VKA knowledge assessment questionnaire with 24 items under standardized conditions, and simultaneously, they were asked about their subjective knowledge. Subsequently, time in range of INR (TIR) was collected for each patient. RESULTS: Out of the 106 patients, 52 had 18 or more correct answers (>75%), defined as a 'satisfactory level' of objective knowledge. The average TIR was 73%, and treatment stability was significantly higher in experienced patients than new patients. We found no correlation between objective knowledge and TIR (Spearman rho = -0.03, P = 0.78). Most patients (77%) reported a high subjective knowledge of VKA, but no correlation was found between objective and subjective knowledge (Spearman rho = 0.129, P = 0.19). CONCLUSION: We observed that many patients had a low level of knowledge of VKA, despite high treatment stability and patient education. The patient's own assessment of knowledge was not found to predict objective knowledge, which could have implications for selection of patients for self-test or self-management of treatment.

Short-term effects of liraglutide on kidney function and vasoactive hormones in type 2 diabetes: a randomized clinical trial.

AIMS: To investigate the effects of a single dose of 1.2 mg liraglutide, a once-daily glucagon-like peptide-1 (GLP-1) receptor agonist, on key renal variables in patients with type 2 diabetes. METHODS: The study was a placebo-controlled, double-blind, crossover trial in 11 male patients with type 2 diabetes. Measurements included (51) Cr-EDTA plasma clearance estimated glomerular filtration rate (GFR) and MRI-based renal blood flow (RBF), tissue perfusion and oxygenation. RESULTS: Liraglutide had no effect on GFR [95% confidence interval (CI) -6.8 to 3.6 ml/min/1.73 m(2) ] or on RBF (95% CI -39 to 30 ml/min) and did not change local renal blood perfusion or oxygenation. The fractional excretion of lithium increased by 14% (p = 0.01) and sodium clearance tended to increase (p = 0.06). Liraglutide increased diastolic and systolic blood pressure (3 and 6 mm Hg) and heart rate (2 beats per min; all p < 0.05). Angiotensin II (ANG II) concentration decreased by 21% (p = 0.02), but there were no effects on other renin-angiotensin system components, atrial natriuretic peptides (ANPs), methanephrines or excretion of catecholamines. CONCLUSIONS: Short-term liraglutide treatment did not affect renal haemodynamics but decreased the proximal tubular sodium reabsorption. Blood pressure increased with short-term as opposed to long-term treatment. Catecholamine levels were unchanged and the results did not support a GLP-1-ANP axis. ANG II levels decreased, which may contribute to renal protection by GLP-1 receptor agonists.

Attitudinal changes toward exercise in mexican american women.

BACKGROUND: This experimental study was designed to examine the attitude changes and exercise adherence of a group of sedentary minority women. METHOD: Fifty sedentary Mexican American women participated in a 9-month, biweekly education and exercise program that was preceded by a 6-month program initiation composed of weekly interactions to facilitate trust between participants and researchers. RESULTS: Compared to Mexican American and Caucasian control groups, the experimental participants displayed significant changes in scores on the Exercise Benefits and Barriers Scales (EBBS) at three, six, and nine months. Adherence to the physical activity program was 84%. At pre-test, the Mexican American participants and controls displayed significantly lower EBBS scores than the Caucasian controls. CONCLUSIONS: The results of this study are examined in light of existing reports on the facilitation of attitudes toward exercise, exercise adherence and health promotion particularly in regard to understanding the barriers to physical activity for minorities. The findings of this study are particularly important given the paucity of research about health promotion for individuals who belong to minority groups.

Hallucinogenic mushroom use by Danish students: pattern of consumption.

A survey among Danish students revealed that 33 (7.2%) of the respondents had experience with hallucinogenic mushrooms (HM). Afterwards these students answered an extended questionnaire about habits and pattern of consumption. It seems that mushroom use is experimental and may be due to risk-seeking behaviour but is mostly recreational and restricted to a few events. Age over 25 years and male sex were statistically related to a higher lifetime consumption rate of HM. The age of first time users was significantly lower for marijuana than for HM. Only 15 of the respondents wanted to continue use. Most of them were males and they had significantly more friends with HM experience than those who would not continue. We recommend that surveys of drug abuse include questions concerning HM to monitor the trends and extent of HM abuse.

[Consumption of psilocybin-containing hallucinogenic mushrooms by young people]. / Unges brug af hallucinogene psilocybinholdige svampe.

The aim of this questionnaire survey was to investigate the extent of hallucinogenic mushroom consumption among students from a high school in the county of Aarhus, Denmark and among students at the University of Aarhus and students from the Danish school of journalism in Aarhus, Denmark. 3% of the high school students had used psilocybine-containing mushrooms as a hallucinogen. Only 1% had experience with LSD. Of the students at the University of Aarhus, and students from the Danish school of journalism in Aarhus, 333 persons (83%) returned the anonymous questionnaire. 9% had experience with hallucinogenic psilocybine containing mushrooms while only 2% had LSD experience. The use of hallucinogenic mushrooms was surprisingly high. This suggest that mushrooms are the most commonly used hallucinogenic substance in Denmark and that the use has exceeded that of LSD. Compared to non-users mushrooms users had significant more friends with mushroom experience. Furthermore, the study shows that the intention to use mushroom is commoner in persons who have friends with HPS experience. We find that the use of mushroom takes place in minor groups known to each other. Compared to non-users, mushroom-users are significant more experienced with marijuana and other substances. Unfortunately, our data do not permit us to show whether mushroom users are more inclined to try other drugs or whether persons with a high drug experience use mushrooms as well. Further investigation on the subject is recommended.

[Pain and dysesthesias in the mastectomy scar]. / Cikatricielle smerter og dysaestesier efter ablatio mammae.

With the object of investigating the occurrence of pain and dysaesthesiae in the scar following mastectomy, 120 were interviewed by a standard questionnaire in a prospective study. These women had commenced postoperative control or treatment in the Department of Oncology in the University Hospital of Aarhus consecutively during a one-year period. One hundred and ten of these women were interviewed again one year later. In 92% of the patients with scar pain and dysaesthesiae, these appeared within the first three months postoperatively. At the first interview, 42 patients (35%) had scar pain and 15 of these (13%) experienced constant scar pain. One year later, 25 patients (23%) still had scar pain and 13 patients (12%) had experienced persistent scar pain throughout the entire year. Two of the patients (8%) with scar pain had constant pain while, at the second interview, 14 patients (56%) reported that the scar pain lasted for seconds. Twenty-seven patients (23%) had dysaesthesiae at the first interview while 29 patients experienced these continually one year after operation. Both the intensity and the duration of the scar pain diminished with the elapse of time. This held also true where dysaesthesiae were concerned but was not so marked.

Intraocular pressure in the first days after implantation of posterior chamber lenses with the use of sodium hyaluronate (Healon).

Intraocular pressure (IOP) was measured before and 6, 24, 48 and 72 h after extracapsular cataract extraction with implantation of a posterior chambers lens in 3 groups of patients. Group I (30 patients): Sodium hyaluronate (Healon) was used during anterior capsulotomy and lens implantation and was aspirated at the end of surgery. Group II (22 patients): Healon as in group I + 500 mg acetazolamide at the end of surgery. Group III (17 patients): BSS and/or air was used instead of Healon during surgery. In all groups statistically significant rises in IOP after 6 h were followed by significant falls in the remaining post-operative period. The rise and subsequent fall in IOP was significantly greater in group I than in group III. Acetazolamide in group II did not prevent excessive rises in IOP. Aspiration probably shortens the period of Healon-induced hypertension. We recommend a meticulous aspiration of Healon at the end of surgery.