How do general practitioners recognize the definition of multimorbidity? A European qualitative study

Background: Multimorbidity is a challenging concept for general practice. An EGPRN working group has published a comprehensive definition of the concept of multimorbidity. As multimorbidity could be a way to explore complexity in general practice, it was of importance to explore whether European general practitioners (GPs) recognize this concept and whether they would change it.

Objectives: To investigate whether European GPs recognize the EGPRN concept of multimorbidity and whether they would change it.

Methods: Focus group meetings and semi-structured interviews as data collection techniques with a purposive sample of practicing GPs from every country. Data collection continued until saturation was reached in every country. The analysis was undertaken using a grounded theory based method. In each national team, four independent researchers, working blind and pooling data, carried out the analysis. To ensure the internationalization of the data, an international team of 10 researchers pooled the axial and selective coding of all national teams to check the concept and highlight emerging themes.

Results: The maximal variation and saturation of the sample were reached in all countries with 211 selected GPs. The EGPRN definition was recognized in all countries. Two additional ideas emerged, the use of Wonca’s core competencies of general practice, and the dynamics of the doctor–patient relationship for detecting and managing multimorbidity and patient’s complexity.

Conclusion: European GPs recognized and enhanced the EGPRN concept of multimorbidity. These results open new perspectives regarding the management of complexity using the concept of multimorbidity in general practice.

Key Messages

• European general practitioners recognize the EGPRN enhanced, comprehensive concept of multimorbidity.

• They add the use of Wonca’s core competencies and the patient–doctor relationship dynamics for detecting and managing multimorbidity.

• The EGPRN concept of multimorbidity leads to new perspectives for the management of complexity.

     

Modulation of the Effect of Endothelin-3 on Blood Pressure by Atrial Natriuretic Peptide in Conscious Spontaneously Hypertensive (SHR) and Normotensive (WKY) Rats

Endothelin (ET) exerts direct vasoconstrictory effects and stimulates release of vasoactive substances. It has been demonstrated that ET stimulates the release of atrial natriuretic peptide (ANP) both under in vitro and in vivo conditions. The present study aimed at elucidating whether the cardiovascular effects of endothelin-3 (ET-3) in normotensive (WKY) and spontaneously hypertensive (SHR) rats are modulated by ANP. The experiments were performed on 17 conscious WKY and 17 SHR rats. The effects of i.v. administration of 1 μg of ET-3 on blood pressure (BP) and heart rate (HR) were investigated under control conditions and during ANP infusion (0.3 μg/kg/min). In both strains ET-3 elicited a transient significant hypotensive effect followed by an increase in BP. BP fall was significantly greater and pressor effect significantly smaller in SHR than in WKY. In WKY, but not in SHR rats, both hypotensive and pressor phases were significantly attenuated during ANP administration. The results are evidence of differential involvement of endogenous blood pressure regulating factors in the cardiovascular effects of ET-3 in WKY and SHR rats during ANP infusion.     

Primary amenorrhea in a young Polish woman with complete androgen insensitivity syndrome and Sertoli-Leydig cell tumor: identification of a new androgen receptor gene mutation and evidence of aromatase hyperactivity and apoptosis dysregulation within the tumor.

Primary amenorrhea in 46,XY females can be due to complete androgen insensitivity syndrome (CAIS), pure gonadal dysgenesis, 17-hydroxysteroid dehydrogenase deficiency, or mixed gonadal dysgenesis. The present paper describes a new de novo non-sense mutation in exon 1 (K141Z) of the androgen receptor gene (AR) and the expression in CAIS testis of aromatase, estrogen receptors, as well as proliferation- and apoptosis-associated proteins. CAIS is a rare disease characterized by absent virilization in 46,XY individuals and the development of a female phenotype despite normal or even elevated androgen levels. CAIS is usually caused by a mutation in AR, which leads to organ resistance to androgens. Testicular tumors such as Sertoli-Leydig cell tumor often develop in patients with CAIS. The immunohistochemical findings in the testes of our CAIS patient suggest that the high expression of aromatase and other molecular changes in the testis may be responsible for pubertal breast development and the increased risk of testicular tumor.     

Retinal explant culture: A platform to investigate human neuro‐retina

The retina is the tissue responsible for light detection, in which retinal neurons convert light energy into electrical signals to be transported towards the visual cortex. Damage of retinal neurons leads to neuronal cell death and retinal pathologies, compromising visual acuity and eventually leading to irreversible blindness. Models of retinal neurodegeneration include 2D systems like cell lines, disassociated cultures and co‐cultures, and 3D models like organoids, organotypic retinal cultures and animal models. Of these, ex vivo human retinal cultures are arguably the most suitable models for translational research as they retain complex inter‐cellular interactions of the retina and precisely mimic in‐situ responses. In this review, we summarize the distinguishing features of the human retina which are important to preserve in experimental culture, the historical development of human retinal culture systems, the factors affecting ex vivo human retinal culture and the applications and challenges associated with current methods of human retinal explant culture.     

Catabolism of glycoconjugates in chronic otitis media with cholesteatoma.

Chronic ear disease with cholesteatoma is characterized by an intrusion of keratinizing stratified squamous epithelium into the middle ear manifesting bone resorption at the interface of the perimatrix. The aim of our study was to investigate the markers of a catabolic process associated with several chronic inflammatory states. We assessed the level of catabolism of glycoconjugates in assays of cholesteatoma extracts, quantifying two lysosomal exoglycosidases: alpha-mannosidase (alpha-MAN) and beta-galactosidase (beta-GAL). Cholesteatomas (n = 15) and normal adult postauricular skin served as controls (n = 15) were collected from the patients during surgery owing to chronic otitis media. To assess exoglycosidase activity, release of p-nitrophenol from p-nitrophenol derivatives of alpha-mannose and beta-galactose was used. In 13 of 15 specimens, we observed significantly higher activity of investigated enzymes in cholesteatoma tissue compared with control tissue (postauricular skin). The mean activity of alpha-MAN from the cholesteatoma cells was 1.76 +/- 1.10 nkat/g wet tissue and 0.61 +/- 0.21 nkat/g wet tissue in the control probes. The mean activity of beta-GAL from the cholesteatoma cells was 1.77 +/- 1.07 nkat/g wet tissue and 0.87 +/- 0.20 nkat/g wet tissue in the control probes. Catabolic reactions involving glycoproteins, glycolipids, and proteoglycans may play a role in cholesteatoma-related bone resorption. The present data indicating that the lysosomal exoglycosidases alpha-MAN and beta-GAL are significantly and consistently elevated suggest the need to further correlations assessment between levels of alpha-MAN and beta-GAL and cholesteatoma behavior. Further research should also evaluate the relative importance of these particular exoglycosidases in manifesting bone resorption in considering the spectrum of identified inflammatory mediators.     

Triple-site biventricular pacing in patients undergoing cardiac resynchronization therapy: a feasibility study.

AIMS: To evaluate implantation safety and efficiency of triple-site (double left-single right) cardiac resynchronization therapy (CRT) and to assess the outcome of this procedure. METHODS AND RESULTS: Twenty-six patients with New York Heart Association (NYHA) class III-IV, left ventricular ejection fraction (EF) < or = 35%, and QRS > or = 120 ms underwent triple-site CRT. Procedural course and complications were analysed. NYHA class, QRS duration, echocardiographic parameters, peak oxygen consumption (VO(2)max), and 6 min walking distance (6MWD) were assessed at baseline and after 3 months. Responders were defined by survival, by no re-hospitalization for heart failure, and by >10% EF, VO(2)max, and 6MWD increase. Implantation was successful in 22 patients (84.6%). Procedure duration (199.1 min) and fluoroscopy time (38.7 min) were higher than in standard procedures. Two clinically silent coronary sinus dissections occurred intra-operatively; one phrenic nerve stimulation and one pocket infection were observed during follow-up. After 3 months of CRT, a significant reduction (P < 0.05) of NYHA class, increment of VO(2)max, 6MWD, EF, and improvement of indices of dyssynchrony were observed. Response rate in the studied group was 95.4%. CONCLUSION: Triple-site resynchronization appears to be a safe and efficient treatment method, with high response rate. Further studies are needed to evaluate the role of this pacing mode in CRT.     

Pure word deafness in a patient with bilateral ischemic stroke in the superior temporal gyrus (STG)

ABSTRACT

Introduction

Pure word deafness is a rare neurological disorder linked with an inability to comprehend speech. The precise localization of damage is still unclear.