Why several truths can be true

In this paper, we offer a perspective on complementarity, acknowledging that it is not possible for human perception and cognition to grasp reality with unambiguous concepts or theories. Therefore, multiple concepts and perspectives are valid when they are not exaggerated beyond reasonable limits and do not claim exclusive validity. We recommend a humble stance enabling respectful dialogue between different perspectives in medical science and practice.

• KEY POINTS

• No single perspective in clinical or scientific medicine can exhaustively explain medical phenomena.

• Scientific attitude is characterised by a willingness to look for objections against what we prefer as truths.

• Complementarity or unifying contradictions are concepts that allow for humility and pluralism in clinical and scientific medicine.

     

Ephrin-A1 binding to CD4+ T lymphocytes stimulates migration and induces tyrosine phosphorylation of PYK2

Eph receptors, the largest subfamily of receptor tyrosine kinases, and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, shape, and mobility. Here we demonstrate that CD4+ T lymphocytes express the EphA1 and EphA4 receptors and that these cells bind the ligand ephrin-A1. Further we show ephrin-A1 expression in vivo on high endothelial venule (HEV) endothelial cells. Ephrin-A1 binding to CD4+ T cells stimulates both stromal cell-derived factor 1alpha (SDF-1alpha)- and macrophage inflammatory protein 3beta (MIP3beta)-mediated chemotaxis. In line with the increased chemotactic response, increased actin polymerization is observed in particular with the combination of ephrin-A1 and SDF-1alpha. Signaling through EphA receptors induces intracellular tyrosine phosphorylation. In particular, proline-rich tyrosine kinase 2 (PYK2) is phosphorylated on tyrosine residues 402 and 580. Ephrin-A1-induced chemotaxis and intracellular tyrosine phosphorylation, including EphA1 and Pyk2, was inhibited by Tyrphostin-A9. In conclusion, ligand engagement of EphA receptors on CD4+ T cells stimulates chemotaxis, induces intracellular tyrosine phosphorylation, and affects actin polymerization. This, together with our finding that ephrin-A1 is expressed by HEV endothelial cells, suggests a role for Eph receptors in transendothelial migration.     

Plantar flexion training primes peripheral arterial disease patients for improvements in cardiac function

This study investigated if initial calf muscle training immediately followed by whole body training improved aerobic power and cardiovascular function in peripheral arterial disease (PAD) patients. The training group (n = 10) pursued 8 weeks of high aerobic intensity plantar flexion interval training continued by 8 weeks of high aerobic intensity treadmill training. The control group (n = 11) received advice according to exercise guidelines. Treadmill VO_2peak and time to exhaustion increased significantly with 16.8 and 23.4% during the plantar flexion training period while no changes occurred in heart stroke volume (SV). Following treadmill training, SV increased with 25.1% while treadmill VO_2peak and time to exhaustion increased 9.9 and 16.1%. Plantar flexion training was effective for increasing treadmill VO_2peak and time to exhaustion in PAD patients and amplified the effects of the additional treadmill training, as SV increased and treadmill VO_2peak and time to exhaustion improved further. This study suggests that calf muscle training prime PAD patients for cardiovascular adaptations when applying whole body exercise.     

Genetic epidemiology of BRCA mutations--family history detects less than 50% of the mutation carriers

Ten BRCA mutations were demonstrated to be frequent in the Norwegian population. We present maps verifying the uneven distribution of prevalences according to municipality. We tested incident breast cancer cases treated in Mid-Norway from 1999 onwards for these mutations. Uptake of testing was 97% and 2.5% were demonstrated to be mutation carriers. Ten (77%) were outside families previously known to carry a mutation. Ten (77%) did not meet clinical criteria to be selected for mutation testing. We tested incident ovarian cancer cases in South-West Norway from 2001 onwards. Uptake of testing was 80% and 23% were mutation carriers. Twenty-one (88%) were outside families previously known. Twelve (67%) did not meet clinical criteria to be selected for testing. All patients with mutation collaborated actively to give our offer of predictive genetic testing to their relatives. No complaint on the activity was received.     

Sport as a vehicle for health promotion – an analysis of Norwegian policy documents

In contemporary western society, there has been an increasing focus on physical activity as a vehicle for promoting health. How physical activity is promoted and organized varies across countries. This article focuses on the Norwegian system, which is characterized by voluntary sport being organized during leisure time, and all being federated under the Norwegian Olympic Committee and Confederation of Sports (NOC). Guided by the field concept of Bourdieu, historical works and contemporary sport policy documents are analyzed in order to explore how health is considered within the sport context. The conclusion is that health is both facilitated and constrained in the sport field. The voluntary dominance of the sport field makes it sustainable in relation to providing physical activity. However, the voluntary dominance of the sport field also makes it vulnerable and unpredictable in relation to implementing state sport and/or health policy. The state cannot in any way be assured to achieve its health objectives through the sport field.     

Release of netilmicin and vancomycin from cancellous bone

First, we studied the effect of the following variables used for netilmicin- and vancomycin-impregnation of cancellous bone: a) antibiotic concentration of the impregnation fluid, b) time used for impregnation, c) pH of the impregnation fluid, d) the degree of bone morselizing and e) antibiotic combination. An increase in the antibiotic concentration of the impregnation fluid increased the amount of antibiotics released from bone. In addition, the amount of vancomycin eluted was also dependent on the time used for impregnation. The fraction of the total amount of netilmicin and vancomycin released after 24 h was 80% and 30%, respectively. More netilmicin and vancomycin were eluted from bone impregnated with antibiotics at pH 7 than the amount eluted from bone impregnated at pH 3. More netilmicin was eluted from fine morselized bone than from coarse morselized bone. By combining netilmicin and vancomycin in the impregnation fluid, the release of vancomycin was reduced. Secondly, we analyzed if the release of antibiotics from bone was complete: 99.9% of the total amount of netilmicin adsorbed to the bone was released by elution during 6 weeks. Finally, after implantation of netilmicin-impregnated bone in rabbit femur condyle, we measured netilmicin and vancomycin in serum: peak serum values of netilmicin were 4.2 (3.7-4.7) mg/L 2-3 h postoperatively.     

Determinants of adherence to recommendations for depressed elderly patients in primary care: A multi-methods study

Objective. It is logical that tailoring implementation strategies to address identified determinants of adherence to clinical practice guidelines should improve adherence. This study aimed to identify and prioritize determinants of adherence to six recommendations for elderly patients with depression. Design and setting. Group and individual interviews and a survey were conducted in Norway. Method. Individual and group interviews with healthcare professionals and patients, and a mailed survey of healthcare professionals. A generic checklist of determinants of practice was used to categorize suggested determinants. Participants. Physicians and nurses from primary and specialist care, psychologists, researchers, and patients. Main outcome measures. Determinants of adherence to recommendations for depressed elderly patients in primary care. Results. A total of 352 determinants were identified, of which 99 were prioritized. The most frequently identified factors had to do with dissemination of guidelines, general practitioners’ time constraints, the low prioritization of elderly patients with depression, and the patients’ or relatives’ wish for medication. Approximately three-quarters of the determinants were from three of the seven domains in the generic checklist: individual healthcare professional factors, patient factors, and incentives and resources. The survey did not provide useful information due to a low response rate and a lack of responses to open-ended questions. Implications. The list of prioritized determinants can inform the design of interventions to implement recommendations for elderly patients with depression. The importance of the determinants that were identified may vary across communities, practices. and patients. Interventions that address important determinants are necessary to improve practice.Key Words: Depression, determinants of practice, elderly patients, general practice, Norway, primary care, tailored implementation

• Multiple factors might impede or facilitate general practitioners’ (GPs’) adherence to guidelines for the care of depressed elderly patients. Interviews and a survey were conducted to identify and prioritize such determinants of adherence.
• Factors related to dissemination of guidelines, GPs’ time constraints, and the lack of priority given to elderly patients with depression were the most frequently suggested barriers to adherence.
• Other determinants were individual healthcare professional factors (e.g. their knowledge and skills), patient factors (e.g. their beliefs and preferences), incentives, and the availability of necessary resources.

     

Adherence to clinical guidelines for Barrett’s esophagus

Abstract

Background and aim: Clinical guidelines recommend endoscopy surveillance at given intervals or endoscopic therapy for Barrett’s esophagus with low-grade dysplasia (LGD) and high-grade dysplasia (HGD). Whether these guidelines are followed in clinical practice is unknown and was assessed in this study.

Methods: This nationwide Swedish cohort study included patients with Barrett’s esophagus with histologically verified LGD or HGD from 50 centers in 2006–2013. These patients were followed up using nationwide registers. Adherence to clinical guidelines was explored. Eight potential risk factors for deviation from guidelines were assessed using multivariable logistic regression, providing adjusted odds ratios (OR) with 95% confidence intervals (95%CI).

Results: Among 211 patients with Barrett’s esophagus (mean age 67.0 years, standard deviation 9.7 years, 81% male), 71% had LGD and 29% had HGD. During median 3.9 years of follow-up, 84% underwent a follow-up endoscopy, 17% received endoscopic therapy and 8% underwent esophagectomy. The clinical management deviated from guidelines in 60% of all patients (69% in LGD and 39% in HGD), which was mainly due to under-surveillance (86%). Risk factors for deviation from guidelines were LGD compared to HGD (OR 3.4, 95%CI 1.7–6.8), longer Barrett’s segment length (OR 2.0, 95%CI 1.0–3.9, comparing ≥3?cm with <3?cm), and treatment at gastroenterology compared to surgery departments (OR 2.3, 95%CI 1.2–4.4). Age, sex, calendar period and university hospital status were not associated with deviation from surveillance guidelines.

Conclusions: Adherence to guidelines for dysplastic Barrett’s esophagus is poor, particularly for LGD. Efforts to implement clinical guideline recommendations are needed.