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Background: Phenantroline is a zinc-chelator that inhibits biological activities of matrix metalloproteinases (MMPs). Over-expression of MMPs can accelerate tissue destruction and disrupt subsequent tissue repair. The effects of phenantroline in two rat models of inflammatory bowel disease (IBD) are evaluated: transmural colitis induced by trinitrobenzensulphonic acid (TNBS) and distal colitis caused by dextran sulphate sodium (DSS). Methods: Transmural colitis was induced by TNBS in two groups of 15 rats each, and distal colitis was induced by DSS in two other groups of 15 rats each. Phenantroline was administered by oral gavage at 20 mg kg[sup -1] day[sup -1] to the test groups, whereas matched control groups received oral vehicle. On the last day of dosing, rats were subjected to intracolonic dialysis under anaesthesia for assessment of luminal eicosanoid release (PGE[sub 2], TXB[sub 2] and LTB[sub 4]) and euthanized. Colons were removed and lesions were blindly scored according to macroscopic and histological scales. Myeloperoxidase (MPO) activity was measured in homogenates of colonic tissue. Results: In the TNBS model, phenantroline treatment significantly reduced colonic strictures; in the DSS model, phenantroline significantly decreased scores of epithelial injury. In both models, the levels of PGE[sub 2], TXB[sub 2] and LTB[sub 4] and tissue MPO were not significantly altered. Conclusions: Although phenantroline did not modify the activity of inflammatory mediators, this compound substantially reduced intestinal injury associated with tissue remodelling. [ABSTRACT FROM AUTHOR]

Bacteria and their products stimulate inflammatory responses. The effects of different antimicrobial regimens (amoxicillin/clavulanic acid, tobramycin, imipenem, vancomycin, metronidazole) were investigated on the course of experimental colitis induced by trinitrobenzenesulphonic acid (TNB) in the rat. On day 7 and 21 after the induction of colitis, matched groups of control and antibiotic treated rats were subjected to colonic dialysis to measure eicosanoid release, and killed for morphological assessment of the colonic lesions (macro and microscopic scores). Stool samples were cultured. Selective antibiotic treatment against Gram positive, Gram negative or anaerobic bacteria had no effect on colonic lesion scores. By contrast, certain broad spectrum antibiotics (amoxicillin/clavulanic acid or the association of imipenem plus vancomycin) significantly reduced macro and microscopic scores. Rats receiving these antibiotics did not develop chronic colitis as shown by the virtual absence of colonic strictures, adhesions, fibrosis, and granulomas. On day 21 after TNB, the intracolonic release of prostaglandin E2, thromboxane B2, and leukotriene B4 was significantly higher in control than in antibiotic treated rats. Control stool cultures showed abundant colony forming units of both aerobic and anaerobic bacteria. Amoxicillin/clavulanic acid and imipenem plus vancomycin induced appreciable reductions in luminal bacteria. In conclusion, certain broad spectrum antibiotics prevent chronic colitis. The normal colonic flora seems to play an important pathogenetic part in the progression of inflammatory colonic lesions to chronicity. [ABSTRACT FROM PUBLISHER]

Eicosanoids are modulators of defensive and inflammatory processes in the gut mucosa, and may be involved in the pathogenesis of chronic inflammatory lesions of the bowel. As omega-3 fatty acids compete with the omega-6 as precursors of eicosanoid synthesis, we compared the effects of dietary supplementation with either sunflower (source of omega-6) or cod liver (source of omega-3) oil on the development of chronic granulomatous lesions in the rat colon. After four weeks on the supplemented diets, plasma omega-6 fatty acid content was significantly higher in the sunflower group, while omega-3 fatty acids predominated in the cod liver group. Inflammatory colitis was then induced by intracolonic administration of trinitrobenzene sulphonic acid. Luminal eicosanoid release, as measured by radioimmunoassay of intracolonic dialysis fluid, increased significantly after the challenge in both groups. Generation of prostaglandin E2 (PGE2) and leucotriene B4 (LTB4) peaked by day 3 and thereafter declined; thromboxane B2 (TXB2), instead, continued to increase from day 3 to 20 in sunflower fed rats, whereas this change was blunted in cod liver animals. The rats were killed 20, 30, or 50 days after the induction of colitis, and the colonic lesions were scored macroscopically (adhesions to surrounding tissues, strictures, ulcerations, and wall thickness) and histologically (ulceration, inflammation, depth of the lesions, and fibrosis). In cod liver animals, the damage score was markedly reduced by day 30, and inflammation and ulceration were almost absent by day 50. In conclusion, a fish oil diet prevents the increase in thromboxane in the chronic state of inflammation and shortens the course of the colonic disease by diminishing both the severity of the lesions and their progression to chronicity. [ABSTRACT FROM PUBLISHER]

To assess the diagnostic usefulness of temporal artery biopsy in temporal arteritis (TA) and establish clinical features capable of predicting its positivity we have retrospectively studied the biopsy specimens and the clinical features of 103 patients who had undergone temporal artery biopsy. Temporal artery biopsy reached a positive predictive value of 90.2% with respect to the final diagnosis based on the criteria proposed by Ellis and Ralston and the clinical course. The simultaneous presence of recent onset headache, jaw claudication, and abnormalities of the temporal arteries on physical examination had a specificity of 94.8% with respect to the histological diagnosis and of 100% with respect to final diagnosis. The presence of any of these clinical features, though of little specificity (34.4%), had a sensitivity of 100% with respect to histological diagnosis, selecting a group of patients in whom temporal artery biopsy has more discriminative value. [ABSTRACT FROM PUBLISHER]

Hepatic lesions were studied for the first time in 13 cases of boutonneuse fever (Mediterranean exanthematous fever). The glutamic-oxalacetic transaminases were raised in eight patients, the glutamic-pyruvic transaminases showed an increase in 10 patients, alkaline phosphatases in seven of the 10 patients investigated, and conjugate bilirubin showed moderate increases in three patients. Five patients were studied histologically; this study showed lesions of a granulomatous type, similar to those described in Q fever, in three patients, fatty degeneration with marked alcoholism in another patient, and a normal liver in the last patient. Two of the three patients with granulomatous lesions showed a moderate increase in alkaline phosphatases. After this report boutonneuse fever must be included among the infectious conditions that can produce granulomas within the liver. [ABSTRACT FROM PUBLISHER]

Background: Monitoring and evaluation of prostate cancer (PCa) screening is key to ensure that the programme achieves the desired objectives. Utilizing a set of prioritized, feasible and harmonized key performance indicators (KPIs) is crucial for this purpose. We describe the methodology used to identify the PCa screening KPIs and the outcome of this process within the scope of the EU-funded PRostate cancer Awareness and Initiative for Screening in the EU (PRAISE-U) project. Feasibility of implementing these KPIs will be evaluated in the five pilots set up at multiple sites in the EU (Spain-2 sites, Poland, Ireland, Lithuania)., Methods: The indicators were developed following a structured methodology involving the following steps: (i) Development of a specific conceptual framework for PCa screening is adapted from the existing risk-based algorithms and modified to guide the selection and mapping of indicators (from identification of population eligible for screening to the decision for treatment or follow-up), (ii) Scoping review of literature (coverage from 1971 to June 2023) to identify existing performance indicators for PCa screening to adapt to the new framework with redefining the indicators, where necessary, (iii) Survey among experts (October-November 2023) to select the indicators fulfilling pre-determined criteria such as accuracy of definition and calculation, importance, and feasibility, and (iv) Deliberations among experts to list the finalized set of indicators, held in December 2023., Findings: A total of 63 KPIs were selected for review using the step-wise methodology as described earlier. Following the review, survey, and deliberations, 21 KPIs were finalized to be piloted in the PRAISE-U project. The resulting 21 KPIs cover the different phases of the screening programme, including invitation, screening test, risk stratification, diagnosis, and also on treatment, harms, and impact. Each KPI has been defined with agreed numerator and denominator., Interpretation: Continuous monitoring of PCa screening programmes using the KPIs will serve as a powerful tool for optimizing service delivery, programme improvement, comparison per screening site, and ultimately contributing to a better benefit to harm ratio. The KPIs will be implemented in five pilot sites identified to be included in the PRAISE-U project aiming to identify an evidence-based scalable model for risk adapted PCa screening for Europe., Funding: This project has received funding from the EU4Health program under grant agreement 101101217, co-funded by the European Union., Competing Interests: None declared., (© 2024 World Health Organization.)

Background: Periodontitis is a chronic inflammatory non-communicable disease (NCD) characterised by the destruction of the tooth-supporting apparatus (periodontium), including alveolar bone, the presence of periodontal pockets, and bleeding on probing., Objectives: To outline, for family doctors, the implications of the association between periodontal and systemic diseases; to explore the role of family doctors in managing periodontitis as an ubiquitous non-communicable disease (NCD)., Methods: The consensus reports of previous focused collaborative workshops between WONCA Europe and the European Federation of Periodontology (using previously undertaken systematic reviews), and a specifically commissioned systematic review formed the technical papers to underpin discussions. Working groups prepared proposals independently, and the proposals were subsequently discussed and approved at plenary meetings., Results: Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease, obstructive sleep apnoea, and COVID-19 complications. Treatment of periodontitis has been associated with improvements in systemic health outcomes. The article also presents evidence gaps. Oral health care professionals (OHPs) and family doctors should collaborate in managing these conditions, including implementing strategies for early case detection of periodontitis in primary medical care centres and of systemic NCDs in oral/dental care settings. There is a need to raise awareness of periodontal diseases, their consequences, and the associated risk factors amongst family doctors., Conclusion: Closer collaboration between OHPs and family doctors is important in the early case detection and management of NCDs like cardiovascular diseases, diabetes mellitus, and respiratory diseases. Strategies for early case detection/prevention of NCDs, including periodontitis, should be developed for family doctors, other health professionals (OHPs), and healthcare funders. Evidence-based information on the reported associations between periodontitis and other NCDs should be made available to family doctors, OHPs, healthcare funders, patients, and the general population.

In 2022, the European Commission updated its recommendation on cancer screening, inviting the Member States (MSs) to explore the feasibility of stepwise implementation of population-based screening for prostate cancer (PCa). In line with this recommendation, the PRAISE-U (Prostate Cancer Awareness and Initiative for Screening in the European Union (EU)) project was initiated. As part of the PRAISE-U, we aim to understand the current practice towards early detection in the EU MSs, the barriers to implementing or planning population-based screening programmes, and potential solutions to overcome these barriers., Methods: We adapted the Barriers to Effective Screening Tool (BEST) survey to the PCa context. However, it has not been validated in this context. We translated it into all spoken languages in the EU27 and disseminated it to different stakeholders across the EU using a snowballing approach., Results: We received 410 responses from 55 countries, of which 301 (73%) were from the 27 EU MSs. The most represented stakeholder group was urologists (218 (54%)), followed by general practitioners (GPs) (83 (21%)), patient representatives (35 (9%)), policy stakeholders (27 (7%)), researchers (23 (6%)), oncologists, pathologists, radiologists, nurses, and others (16 (4%)) and one industry representative. Among all respondents, 286 (69%) reported the absence of a population-based screening programme, mainly attributed to resource limitations and a lack of political and medical society support. Out of these 286 respondents, 196 (69%) indicated that opportunistic screening is being applied in their country, and 199 (70%) expressed their support for population-based screening programmes (which was highest amongst patient representatives and urologists and lowest amongst GPs and policy stakeholders). The highest scored barriers were lack of political support, insufficient operational resources, and inadequate participation. Suggested solutions to overcome these included awareness campaigns, consensus meetings, political lobbying and European guidelines (to overcome political support barriers), compatible IT systems (to overcome operational barriers), and easy access (to overcome participation barriers)., Conclusions: Participants have noted the presence of opportunistic screening, and particularly urologists and patient representatives expressed their support for the establishment of a population-based PCa screening programme. Nevertheless, successful implementation of population-based screening programmes is complex; it requires political and medical society support, operational resources and capacity, awareness campaigns, as well as the development of protocols, guidelines, and legal frameworks.

Introduction: Disease-modifying therapies (DMTs) for Alzheimer's disease (AD) will increase diagnostic demand. A non-invasive blood-based biomarker (BBBM) test for detection of amyloid-β pathology may reduce diagnostic barriers and facilitate DMT initiation., Objective: To explore heterogeneity in AD care pathways and potential role of BBBM tests., Methods: Survey of 213 healthcare professionals/payers in US/China/UK/Germany/Spain/France and two advisory boards (US/Europe)., Results: Current diagnostic pathways are heterogeneous, meaning many AD patients are missed while low-risk patients undergo unnecessary procedures. Confirmatory amyloid testing (cerebrospinal fluid biomarkers/positron emission tomography) is utilized in few patients, resulting in diagnostic/treatment delays. A high negative-predictive-value test could streamline the diagnostic pathway by reducing unnecessary procedures in low-risk patients; supporting confirmatory testing where needed. Imminent approval of DMTs will increase need for fast and reliable AD diagnostic tests., Discussion: An easy-to-use, accurate, non-invasive BBBM test for amyloid pathology could guide diagnostic procedures or referral, streamlining early diagnosis and DMT initiation., Highlights: This study explored AD care pathways and how BBBM may meet diagnostic demandsCurrent diagnostic pathways are heterogeneous, with country and setting variationsMany AD patients are missed, while low-risk patients undergo unnecessary proceduresAn easy-to-use, accurate, non-invasive BBBM test for amyloid pathology is neededThis test could streamline early diagnosis of amyloid pathology and DMT initiation., Competing Interests: W.M.vd.F., A.U.M., N.B., R.B., M.S., J.V., D.C., and J.J.L. received honoraria to participate in the advisory boards described in this manuscript organized by Roche Diagnostics. J.J.L. serves as a consultant for Roche Diagnostics. WMF serves as a consultant to Roche Diagnostics. I.S. and M.C. are full‐time employees of Roche Diagnostics International Ltd. I.S. also a shareholder of Roche Diagnostics International Ltd., (© 2023 Roche Diagnostics International Ltd and The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Aim: To explore the implications for dentists and family doctors of the association between periodontal and systemic diseases and the role of dentists and family doctors in managing non-communicable diseases (NCDs) and promoting healthy lifestyles., Materials and Methods: The consensus reports of the previous Focused Workshops on the associations between periodontitis and diabetes (2017) and periodontitis and cardiovascular diseases (2019) formed the technical reviews to underpin discussions on both topics. For the association with respiratory diseases, a systematic review was specifically commissioned for the Workshop discussions. Working groups prepared proposals independently, and then the proposals were discussed and approved at plenary meetings., Results: Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea and COVID-19 complications. Dentists and family doctors should collaborate in managing NCDs, implementing strategies for early detection of periodontitis in primary care centres and of cardiovascular diseases or diabetes in dental settings. Family doctors should be informed about periodontal diseases and their consequences, and oral health professionals (OHPs) should be informed about the relevance of NCDs and the associated risk factors., Conclusions: Closer collaboration between OHPs and family doctors is important in the early detection and management of NCDs and in promoting healthy lifestyles. Pathways for early case detection of periodontitis in family medicine practices and of NCDs in dental practices should be developed and evaluated., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

COVID-19 outbreak has significantly changed all aspects of general practice in Europe. This article focuses on the academic challenges for the discipline, mainly in the field of education, research, and quality assurance. The efforts of the European Region of the World Organisation of National Colleges, Academies, and Academic Associations of General Practitioners/Family Physicians (WONCA Europe) to support academic sustainability of the discipline in the time of pandemic are presented. Medical education was affected by the pandemic, threatening both its productivity and quality. Emerging new educational methods might be promising, but the results of their rapid implementation remain uncertain. A relatively small number of publications related to COVID-19 and general practice is available in the medical literature. There is a shortage of original data from general practice settings. This contrasts with the crucial role of GPs in fighting a pandemic. COVID-19 outbreak has opened widely new research areas, which should be explored by GPs. Maintaining the quality of care and safety of all patients during the COVID-19 pandemic is the utmost priority. Many of them suffer from poor access or inadequate management of their problems. Rapid implementation of telemedicine brought both threats and opportunities. The COVID-19 pandemic also challenged doctors' safety and well-being. These aspects will require discussion and remedy to prevent deterioration of the quality of primary care. WONCA Europe is making a multi-faceted effort to support GPs in difficult times of the pandemic. It is ready to support future efforts to uphold the integrity of family medicine as an academic discipline.

Introduction: The article describes evaluation of the first year of implementation of a process-management project and a quality-improvement programme linked to economic incentives carried out at CAPSE (Consortium of Primary Healthcare of Eixample, Barcelona City, Catalonia, Spain)., Objective: To evaluate the changes and to describe the experience of a variable payment scheme linked to quality objectives in two primary healthcare centres in Spain., Method: Data from a variable payment scheme for professionals, where the variable payment consisted of three parts, were analysed. The three areas included in the variable payment were the results of management by objectives, performance evaluation, and participation in a quality-improvement programme. Parallel to this the actions of continuous quality improvement that had been proposed during 2006 were described and evaluated., Results: Participation among personnel in the quality-improvement programme was high, including 96% of doctors and 100% of nurses. Seventy-two improvement actions were proposed and accepted; 56% of the improvement actions took place within the established period of time, 18% did not finish within the deadline and 26% could not be accomplished for various reasons., Discussion: The following areas needing improving were detected: process-management training for healthcare professionals, process orientation to the patients, the need to develop a communication plan, the selection of process and outcomes indicators, appropriate use of information systems and the time spent in implementation of the quality-improvement programme., Conclusion: Our preliminary results are encouraging. More studies and comparison of similar experiences are required before widespread use of this system can be recommended.

Objective: Polyethylene glycol (PEG) has been suggested to protect against pathogen colonization by improving colonic barrier function. We aimed to establish whether PEG 4000 affects colonic barrier function and the development of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats., Materials and Methods: PEG was included in the drinking water for a period of 48 h before intracolonic administration of TNBS., Results and Discussion: PEG increased colonic surface hydrophobicity and diminished luminal bacterial load. Moreover, PEG markedly reduced mucosal damage and inflammation induced by TNBS. This protection effect appeared to be independent of its laxative properties since the laxatives mannitol or senna extracts had no effect on TNBS colitis. Using everted colonic sacs, pretreatment with PEG produced a lasting reduction in epithelial permeability to mannitol and dextran-70 K that correlated with decreased surface hydrophobicity., Conclusion: Our results suggest that the protective effect of PEG on TNBS colitis is associated with reinforcement of the epithelial barrier.

Objectives: Preliminary studies suggested that octreotide may be therapeutic in bleeding angiodysplasia. Our aim was to investigate the efficacy of long-term octreotide therapy in the prevention of rebleeding from gastrointestinal angiodysplasia., Methods: A cohort of 32 patients diagnosed with bleeding from angiodysplasia was treated with octreotide 50 mu 12 h subcutaneously for a 1-2 yr period. This cohort was compared with an external control group (38 patients who had received placebo [1 tablet/day] in a concurrent randomized clinical trial for the same period., Results: Two patients of the octreotide group were lost to follow-up. Treatment failure occurred in seven of 30 (23%) patients in the octreotide group and in 17 of 35 (48%) in the placebo group (three dropouts before first visit) (P= 0.043). The actuarial probability of remaining free of rebleeding at 1 and 2 yr of follow-up was 77% and 68%, respectively, for the octreotide group and 55% and 36%, respectively, for the placebo group (log rank P= 0.030). Multivariate proportional hazards-regression analysis showed that octreotide therapy and previous bleeding episodes were positive and negative predictors of efficacy, respectively. No significant differences between the groups were observed according to number of bleeding episodes (0.4 +/- 0.7 vs 0.9 +/- 1.5, P= 0.070) and transfusion requirements (1.1 +/- 2.6 vs 0.7 +/- 1.5 units); however, iron requirements were lower in the octreotide than in the placebo group (22 +/- 62 vs 166 +/- 267 units; P < 0.001). Likewise, major adverse events (1 vs 1) and mortality (0 vs 1) were similar between groups., Conclusions: This study suggests that octreotide treatment may be beneficial in preventing rebleeding from gastrointestinal angiodysplasia.

Nitric oxide (NO) is implicated in the pathophysiology of intestinal inflammation. Intestinal mast cells may amplify inflammatory response and mucosal injury in inflammatory bowel disease. Our aim was to examine the role of NO and intestinal mast cells by investigating the effects of NO synthase (NOS) inhibitors and a mast cell stabilizer during induction of dextran sulfate sodium (DSS) colitis. Colitis was induced by 4% DSS in drinking water, in rats pretreated with L-NAME or aminoguanidine. In another set of experiments, we investigated the effect of ketotifen in this setting. Inhibition of NO by L-NAME worsened DSS-induced inflammation, however, aminoguanidine had no effect. On the other hand, ketotifen abolished the deleterious effects of L-NAME on colonic inflammation, suggesting that hyperactivation of mast cells by NOS inhibition amplifies mucosal injury induced by DSS. Our results suggest that constitutive isoforms of NOS prevent mast cell activation.