Exploring why European primary care physicians sometimes do not think of, or act on, a possible cancer diagnosis. A qualitative study.

BACKGROUND: While primary care physicians (PCPs) play a key role in cancer detection, they can find cancer diagnosis challenging, and some patients have considerable delays between presentation and onward referral. AIM: To explore European PCPs' experiences and views on cases where they considered that they had been slow to think of, or act on, a possible cancer diagnosis. DESIGN & SETTING: A multicentre European qualitative study, based on an online survey with open-ended questions, asking PCPs for their narratives about cases when they had missed a diagnosis of cancer. METHOD: Using maximum variation sampling, PCPs in 23 European countries were asked to describe what happened in a case where they were slow to think of a cancer diagnosis, and for their views on why it happened. Thematic analysis was used to analyse the data. RESULTS: A total of 158 PCPs completed the questionnaire. The main themes were as follows: patients' descriptions did not suggest cancer; distracting factors reduced PCPs' cancer suspicions; patients' hesitancy delayed the diagnosis; system factors not facilitating timely diagnosis; PCPs felt that they had acted wrongly; and problems with communicating adequately. CONCLUSION: The study identified six overarching themes that need to be addressed. Doing so should reduce morbidity and mortality in the small proportion of patients who have a significant, avoidable delay in their cancer diagnosis. The 'Swiss cheese' model of accident causation showed how the themes related to each other.

The fractured lens: a controversial revision of the International Classification of Primary Care.

Background: The International Classification of Primary Care (ICPC) has represented the international standard reduction for measuring the content of primary care for over 30 years. In the process of its third revision, its authors, the Wonca International Classification Committee (WICC), delegated a major part of the technical work to a purposely formed Consortium. However, in the process of such revision, standard classification principles and rules have been inconsistently applied with the result that ICPC-3 has been published with major errors and an inconsistent structure. Objectives: To formally describe and critically appraise the revision process of ICPC-3. Methods: The formal review of ICPC-3 performed by an expert group within WICC and commissioned by the Executive Council of Wonca Europe is presented in abridged form. Results: ICPC-3 as currently presented introduces major departures from formal classification principles and rules, besides other major errors and inconsistencies, all of which are listed and described. Conclusion: Major changes in ICPC-3 defy categorisation and conceptualisation standards. ICPC-3 now represents an untested departure from international standard presentations, without a formal academic base. The direct inclusion of measures of functioning in a classification of reasons for encounter and health problems fails to address the dichotomy of these domains, the boundaries of and relationships between which are not satisfactorily resolved by the system. Analysis of ICPC-3 data will require the development and implementation of alternative, as yet undefined, models of the relationships between disease and health. By including different domains without resolving ambiguity, and by splitting function from other body systems, ICPC-3 becomes an internally fractured instrument.

Translation of the working alliance inventory short revised into Italian using a Delphi procedure and a forward-backward translation.

Introduction: Enhancing treatment adherence, especially for chronic diseases, can be achieved through therapeutic alliance, potentially elevating the quality of care. An instrument to evaluate the therapeutic alliance could be beneficial in routine clinical settings, educational environments, and extensive research efforts at national and European levels. In this study, we translated therapist and patient versions of the Working Alliance Inventory Short Revised (WAI-SR) into Italian. Methodology: An email-based Delphi method was employed for the English-to-Italian translation, incorporating a forward-backward process. The initial translation team comprised two Italian family physicians proficient in English, a linguist, and a psychiatrist. The forward translation was then reviewed by 18 Italian family physicians through a Delphi process and was subjected to a backward translation by two Italian English teachers. A cultural correspondence was subsequently identified to adjust translations within a national and international framework. Results: All 18 experts fully engaged in the Delphi process, and consensus was achieved by the second Delphi round. A cultural check checked for discrepancies regarding linguistic consistency with other translations and found no difference. Conclusion: This Italian translation of the WAI-SR is expected to support Italian family physicians aiming to enhance their clinical practice and therapeutic outcomes. It could also be a valuable tool for Italian medical students to foster therapeutic relationships and improve their communication skills.

What factors empower general practitioners for early cancer diagnosis? A 20-country European Delphi Study.

BACKGROUND: Some symptoms are recognised as red flags for cancer, causing the General Practitioner (GP) to refer the patient for investigation without delay. However, many early symptoms of cancer are vague and unspecific, and in these cases, a delay in referral risks a diagnosis of cancer that is too late. Empowering GPs in their management of patients that may have cancer is likely to lead to more timely cancer diagnoses. AIM: To identify the factors that affect European GPs' empowerment in making an early diagnosis of cancer. METHODS: This was a Delphi study involving GPs in 20 European countries. We presented GPs with 52 statements representing factors that could empower GPs to increase the number of early cancer diagnoses. Over three Delphi rounds, we asked GPs to indicate the clinical relevance of each statement on a Likert scale.The final list of statements indicated those that were considered by consensus to be the most relevant. RESULTS: In total, 53 GPs from 20 European countries completed the Delphi process, out of the 68 GPs who completed round one. Twelve statements satisfied the pre-defined criteria for relevance. Five of the statements related to screening and four to the primary/secondary care interface. The other selected statements concerned information technology (IT) and GPs' working conditions. Statements relating to training, skills and working efficiency were not considered priority areas. CONCLUSION: GPs consider that system factors relating to screening, the primary-secondary care interface, IT and their working conditions are key to enhancing their empowerment in patients that could have cancer. These findings provide the basis for seeking actions and policies that will support GPs in their efforts to achieve timely cancer diagnosis.

How are reasons for encounter associated with influenza-like illness and acute respiratory infection diagnoses and interventions? A cohort study in eight Italian general practice populations.

BACKGROUND: Influenza-like illness (ILI) and Acute Respiratory Infections (ARI) are a considerable health problem in Europe. Most diagnoses are made by family physicians (FPs) and based on symptoms and clinical signs rather than on diagnostic testing. The International Classification of Primary Care (ICPC) advocates that FPs record patients' 'Reasons for Encounters' (RfEs) as they are presented to them. This study analyses the association of patients' RfEs with FPs' diagnoses of ILI and ARI diagnoses and FPs' management of those patients. METHODS: Cohort study of practice populations. Over a 4-month period during the winter season 2013-14, eight FPs recorded ILI and ARI patients' RfEs and how they were managed. FPs recorded details of their patients using the ICPC format, collecting data in an Episode of Care (EoC) structure. RESULTS: There were 688 patients diagnosed as having ILI; between them they presented with a total of 2,153 RfEs, most commonly fever (79.7%), cough (59.7%) and pain (33.0%). The 848 patients with ARI presented with a total of 1,647 RfEs, most commonly cough (50.4%), throat symptoms (25.9%) and fever (19.9%). For patients with ILI, 37.0% of actions were related to medication for respiratory symptoms; this figure was 38.4% for patients with ARI. FPs referred six patients to specialists or hospitals (0.39% of all patients diagnosed with ILI and ARI). CONCLUSIONS: In this study of patients with ILI and ARI, less than half received a prescription from their FPs, and the illnesses were mainly managed in primary care, with few patients' needing referral. The ICPC classification allowed a standardised data collection system, providing documentary evidence of the management of those diseases.

Primary care practitioners' diagnostic action when the patient may have cancer: an exploratory vignette study in 20 European countries.

OBJECTIVES: Cancer survival rates vary widely between European countries, with differences in timeliness of diagnosis thought to be one key reason. There is little evidence on the way in which different healthcare systems influence primary care practitioners' (PCPs) referral decisions in patients who could have cancer.This study aimed to explore PCPs' diagnostic actions (whether or not they perform a key diagnostic test and/or refer to a specialist) in patients with symptoms that could be due to cancer and how they vary across European countries. DESIGN: A primary care survey. PCPs were given vignettes describing patients with symptoms that could indicate cancer and asked how they would manage these patients. The likelihood of taking immediate diagnostic action (a diagnostic test and/or referral) in the different participating countries was analysed. Comparisons between the likelihood of taking immediate diagnostic action and physician characteristics were calculated. SETTING: Centres in 20 European countries with widely varying cancer survival rates. PARTICIPANTS: A total of 2086 PCPs answered the survey question, with a median of 72 PCPs per country. RESULTS: PCPs' likelihood of immediate diagnostic action at the first consultation varied from 50% to 82% between countries. PCPs who were more experienced were more likely to take immediate diagnostic action than their peers. CONCLUSION: When given vignettes of patients with a low but significant possibility of cancer, more than half of PCPs across Europe would take diagnostic action, most often by ordering diagnostic tests. However, there are substantial between-country variations.

In vitro dexamethasone treatment does not induce alternative ATM transcripts in cells from Ataxia-Telangiectasia patients.

Short term treatment with low doses of glucocorticoid analogues has been shown to ameliorate neurological symptoms in Ataxia-Telangiectasia (A-T), a rare autosomal recessive multisystem disease that mainly affects the cerebellum, immune system, and lungs. Molecular mechanisms underlying this clinical observation are unclear. We aimed at evaluating the effect of dexamethasone on the induction of alternative ATM transcripts (ATMdexa1). We showed that dexamethasone cannot induce an alternative ATM transcript in control and A-T lymphoblasts and primary fibroblasts, or in an ATM-knockout HeLa cell line. We also demonstrated that some of the reported readouts associated with ATMdexa1 are due to cellular artifacts and the direct induction of γH2AX by dexamethasone via DNA-PK. Finally, we suggest caution in interpreting dexamethasone effects in vitro for the results to be translated into a rational use of the drug in A-T patients.

Unburdening dementia - a basic social process grounded theory based on a primary care physician survey from 25 countries.

OBJECTIVE: To explore dementia management from a primary care physician perspective. DESIGN: One-page seven-item multiple choice questionnaire; free text space for every item; final narrative question of a dementia case story. Inductive explorative grounded theory analysis. Derived results in cluster analyses. Appropriateness of dementia drugs assessed by tertiary care specialist. SETTING: Twenty-five European General Practice Research Network member countries. SUBJECTS: Four hundred and forty-five key informant primary care physician respondents of which 106 presented 155 case stories. MAIN OUTCOME MEASURES: Processes and typologies of dementia management. Proportion of case stories with drug treatment and treatment according to guidelines. RESULTS: Unburdening dementia - a basic social process - explained physicians' dementia management according to a grounded theory analysis using both qualitative and quantitative data. Unburdening starts with Recognizing the dementia burden by Burden Identification and Burden Assessment followed by Burden Relief. Drugs to relieve the dementia burden were reported for 130 of 155 patients; acetylcholinesterase inhibitors or memantine treatment in 89 of 155 patients - 60% appropriate according to guidelines and 40% outside of guidelines. More Central and Northern primary care physicians were allowed to prescribe, and more were engaged in dementia management than Eastern and Mediterranean physicians according to cluster analyses. Physicians typically identified and assessed the dementia burden and then tried to relieve it, commonly by drug prescriptions, but also by community health and home help services, mentioned in more than half of the case stories. CONCLUSIONS: Primary care physician dementia management was explained by an Unburdening process with the goal to relieve the dementia burden, mainly by drugs often prescribed outside of guideline indications. Implications: Unique data about dementia management by European primary care physicians to inform appropriate stakeholders. Key points Dementia as a syndrome of cognitive and functional decline and behavioural and psychological symptoms causes a tremendous burden on patients, their families, and society. •We found that a basic social process of Unburdening dementia explained dementia management according to case stories and survey comments from primary care physicians in 25 countries. •First, Burden Recognition by Identification and Assessment and then Burden Relief - often by drugs. •Prescribing physicians repeatedly broadened guideline indications for dementia drugs. The more physicians were allowed to prescribe dementia drugs, the more they were responsible for the dementia work-up. Our study provides unique data about dementia management in European primary care for the benefit of national and international stakeholders.

How European primary care practitioners think the timeliness of cancer diagnosis can be improved: a thematic analysis.

BACKGROUND: National European cancer survival rates vary widely. Prolonged diagnostic intervals are thought to be a key factor in explaining these variations. Primary care practitioners (PCPs) frequently play a crucial role during initial cancer diagnosis; their knowledge could be used to improve the planning of more effective approaches to earlier cancer diagnosis. OBJECTIVES: This study sought the views of PCPs from across Europe on how they thought the timeliness of cancer diagnosis could be improved. DESIGN: In an online survey, a final open-ended question asked PCPs how they thought the speed of diagnosis of cancer in primary care could be improved. Thematic analysis was used to analyse the data. SETTING: A primary care study, with participating centres in 20 European countries. PARTICIPANTS: A total of 1352 PCPs answered the final survey question, with a median of 48 per country. RESULTS: The main themes identified were: patient-related factors, including health education; care provider-related factors, including continuing medical education; improving communication and interprofessional partnership, particularly between primary and secondary care; factors relating to health system organisation and policies, including improving access to healthcare; easier primary care access to diagnostic tests; and use of information technology. Re-allocation of funding to support timely diagnosis was seen as an issue affecting all of these. CONCLUSIONS: To achieve more timely cancer diagnosis, health systems need to facilitate earlier patient presentation through education and better access to care, have well-educated clinicians with good access to investigations and better information technology, and adequate primary care cancer diagnostic pathway funding.

Abnormal neutrophil signature in the blood and pancreas of presymptomatic and symptomatic type 1 diabetes.

BACKGROUND: Neutrophils and their inflammatory mediators are key pathogenic components in multiple autoimmune diseases, while their role in human type 1 diabetes (T1D), a disease that progresses sequentially through identifiable stages prior to the clinical onset, is not well understood. We previously reported that the number of circulating neutrophils is reduced in patients with T1D and in presymptomatic at-risk subjects. The aim of the present work was to identify possible changes in circulating and pancreas-residing neutrophils throughout the disease course to better elucidate neutrophil involvement in human T1D. METHODS: Data collected from 389 subjects at risk of developing T1D, and enrolled in 4 distinct studies performed by TrialNet, were analyzed with comprehensive statistical approaches to determine whether the number of circulating neutrophils correlates with pancreas function. To obtain a broad analysis of pancreas-infiltrating neutrophils throughout all disease stages, pancreas sections collected worldwide from 4 different cohorts (i.e., nPOD, DiViD, Siena, and Exeter) were analyzed by immunohistochemistry and immunofluorescence. Finally, circulating neutrophils were purified from unrelated nondiabetic subjects and donors at various T1D stages and their transcriptomic signature was determined by RNA sequencing. RESULTS: Here, we show that the decline in ß cell function is greatest in individuals with the lowest peripheral neutrophil numbers. Neutrophils infiltrate the pancreas prior to the onset of symptoms and they continue to do so as the disease progresses. Of interest, a fraction of these pancreas-infiltrating neutrophils also extrudes neutrophil extracellular traps (NETs), suggesting a tissue-specific pathogenic role. Whole-transcriptome analysis of purified blood neutrophils revealed a unique molecular signature that is distinguished by an overabundance of IFN-associated genes; despite being healthy, said signature is already present in T1D-autoantibody-negative at-risk subjects. CONCLUSIONS: These results reveal an unexpected abnormality in neutrophil disposition both in the circulation and in the pancreas of presymptomatic and symptomatic T1D subjects, implying that targeting neutrophils might represent a previously unrecognized therapeutic modality. FUNDING: Juvenile Diabetes Research Foundation (JDRF), NIH, Diabetes UK.

Identifying important health system factors that influence primary care practitioners' referrals for cancer suspicion: a European cross-sectional survey.

OBJECTIVES: Cancer survival and stage of disease at diagnosis and treatment vary widely across Europe. These differences may be partly due to variations in access to investigations and specialists. However, evidence to explain how different national health systems influence primary care practitioners' (PCPs') referral decisions is lacking.This study analyses health system factors potentially influencing PCPs' referral decision-making when consulting with patients who may have cancer, and how these vary between European countries. DESIGN: Based on a content-validity consensus, a list of 45 items relating to a PCP's decisions to refer patients with potential cancer symptoms for further investigation was reduced to 20 items. An online questionnaire with the 20 items was answered by PCPs on a five-point Likert scale, indicating how much each item affected their own decision-making in patients that could have cancer. An exploratory factor analysis identified the factors underlying PCPs' referral decision-making. SETTING: A primary care study; 25 participating centres in 20 European countries. PARTICIPANTS: 1830 PCPs completed the survey. The median response rate for participating centres was 20.7%. OUTCOME MEASURES: The factors derived from items related to PCPs' referral decision-making. Mean factor scores were produced for each country, allowing comparisons. RESULTS: Factor analysis identified five underlying factors: PCPs' ability to refer; degree of direct patient access to secondary care; PCPs' perceptions of being under pressure; expectations of PCPs' role; and extent to which PCPs believe that quality comes before cost in their health systems. These accounted for 47.4% of the observed variance between individual responses. CONCLUSIONS: Five healthcare system factors influencing PCPs' referral decision-making in 20 European countries were identified. The factors varied considerably between European countries. Knowledge of these factors could assist development of health service policies to produce better cancer outcomes, and inform future research to compare national cancer diagnostic pathways and outcomes.

High miR-100 expression is associated with aggressive features and modulates TORC1 complex activation in lung carcinoids.

PURPOSE: Mammalian target of rapamycin (mTOR) is a promising therapeutic target in advanced lung carcinoid patients. However, the mechanisms of mTOR modulation and of responsiveness to mTOR inhibitors are largely unclear. Our aim was to analyze the expression and functional role of specific miRNAs in lung carcinoids as an alternative mechanism targeting mTOR pathway. EXPERIMENTAL DESIGN: Seven miRNAs, selected by bioinformatic tools and literature search, were analyzed in 142 lung neuroendocrine neoplasms (92 carcinoids and a control group of 50 high grade neuroendocrine carcinomas), and compared with mTOR mRNA expression and clinical/pathological parameters. Tissue results were validated in vitro in two lung carcinoid cell lines by specific RNA interference and biological/pharmacological tests. RESULTS: Tissutal expression of five miRNAs (miR-99b, miR-100, miR-155, miR-193a-3p, miR-193a-5p) was inversely correlated with mTOR mRNA expression, supporting their role in the negative regulation of mTOR transcription. High expression of miR-100, miR-193a-3p and miR-193a-5p was associated with aggressive features and, for the former two, with shorter time to progression. In H727 and UMC11 lung carcinoid cells, miR-100 modulated mTOR RNA and TORC1 complex protein expression, positively promoted cell migration and negatively influenced cell proliferation. Moreover, miR-100 directly influenced responsiveness of H727 and UMC11 cells to rapamycin. CONCLUSIONS: MiR-100 actively participates to the regulation of mTOR expression in lung carcinoids and represents a novel candidate prognostic biomarker for this tumor type; moreover, inhibition of its expression is associated to increased responsiveness to mTOR inhibitors and might represent a novel strategy to sensitize lung carcinoids to these target agents.

CD38 promotes pristane-induced chronic inflammation and increases susceptibility to experimental lupus by an apoptosis-driven and TRPM2-dependent mechanism.

In this study, we investigated the role of CD38 in a pristane-induced murine model of lupus. CD38-deficient (Cd38-/-) but not ART2-deficient (Art2-/-) mice developed less severe lupus compared to wild type (WT) mice, and their protective phenotype consisted of (i) decreased IFN-I-stimulated gene expression, (ii) decreased numbers of peritoneal CCR2hiLy6Chi inflammatory monocytes, TNF-α-producing Ly6G+ neutrophils and Ly6Clo monocytes/macrophages, (iii) decreased production of anti-single-stranded DNA and anti-nRNP autoantibodies, and (iv) ameliorated glomerulonephritis. Cd38-/- pristane-elicited peritoneal exudate cells had defective CCL2 and TNF-α secretion following TLR7 stimulation. However, Tnf-α and Cxcl12 gene expression in Cd38-/- bone marrow (BM) cells was intact, suggesting a CD38-independent TLR7/TNF-α/CXCL12 axis in the BM. Chemotactic responses of Cd38-/- Ly6Chi monocytes and Ly6G+ neutrophils were not impaired. However, Cd38-/- Ly6Chi monocytes and Ly6Clo monocytes/macrophages had defective apoptosis-mediated cell death. Importantly, mice lacking the cation channel TRPM2 (Trpm2-/-) exhibited very similar protection, with decreased numbers of PECs, and apoptotic Ly6Chi monocytes and Ly6Clo monocytes/macrophages compared to WT mice. These findings reveal a new role for CD38 in promoting aberrant inflammation and lupus-like autoimmunity via an apoptosis-driven mechanism. Furthermore, given the implications of CD38 in the activation of TRPM2, our data suggest that CD38 modulation of pristane-induced apoptosis is TRPM2-dependent.

Human canonical CD157/Bst1 is an alternatively spliced isoform masking a previously unidentified primate-specific exon included in a novel transcript.

CD157/Bst1 is a dual-function receptor and ß-NAD+-metabolizing ectoenzyme of the ADP-ribosyl cyclase family. Expressed in human peripheral blood neutrophils and monocytes, CD157 interacts with extracellular matrix components and regulates leukocyte diapedesis via integrin-mediated signalling in inflammation. CD157 also regulates cell migration and is a marker of adverse prognosis in epithelial ovarian cancer and pleural mesothelioma. One form of CD157 is known to date: the canonical sequence of 318 aa from a 9-exon transcript encoded by BST1 on human chromosome 4. Here we describe a second BST1 transcript, consisting of 10 exons, in human neutrophils. This transcript includes an unreported exon, exon 1b, located between exons 1 and 2 of BST1. Inclusion of exon 1b in frame yields CD157-002, a novel proteoform of 333 aa: exclusion of exon 1b by alternative splicing generates canonical CD157, the dominant proteoform in neutrophils and other tissues analysed here. In comparative functional analyses, both proteoforms were indistinguishable in cell surface localization, specific mAb binding, and behaviour in cell adhesion and migration. However, NAD glycohydrolase activity was detected in canonical CD157 alone. Comparative phylogenetics indicate that exon 1b is a genomic innovation acquired during primate evolution, pointing to the importance of alternative splicing for CD157 function.

Postherpetic neuralgia, diabetic neuropathy, and trigeminal neuralgia - Chronic peripheral neuropathic pain in 58,480 rural Italian primary care patients.

INTRODUCTION: Chronic peripheral neuropathic pain (CPNP) is a condition due to peripheral nervous system diseases or injury, but its prevalence is unknown in Italian primary care. AIM: The aim of this study is to assess the prevalence of CPNP in a rural primary care area in Northern Italy. MATERIALS AND METHODS: A multicenter audit study was carried out in a rural area in Northern Italy with 113 participating general practitioners (GPs) seeing 58,480 patients >18 years during 3 months. Patients who for any reason attended GPs' surgeries and had symptoms suggestive of neuropathic pain (NP) were given the NP diagnostic questionnaire "Douleur Neuropathique en 4 Questions" (DN4) and recorded their pain level on a visual analog scale (VAS). RESULTS: Chronic NP was established by a DN4 score of ≥4 and a VAS pain score of ≥40 mm for >6 months together with a clinical diagnosis in 448 (254 women and 194 men) out of 58,480 patients giving a prevalence of 0.77%. 179 patients (0.31%) had diabetes neuropathy, 142 (0.24%) had postherpetic pain, 41 (0.07%) had trigeminal neuralgia, 27 (0.05%) had NP postinjury, 27 (0.05%) had NP caused by nerve entrapments, 11 (0.02%) had NP triggered by systemic diseases, and 21 (0.04%) had NP of unknown etiology. CONCLUSIONS: The prevalence of CPNP in this population of primary care attenders in a rural area in Northern Italy was 0.77%. Diabetes neuropathy (0.31%) and postherpetic pain (0.24%) were the two most common subgroups of NP, followed by trigeminal neuralgia (0.07%).

Exploring dementia management attitudes in primary care: a key informant survey to primary care physicians in 25 European countries.

BACKGROUND: Strategies for the involvement of primary care in the management of patients with presumed or diagnosed dementia are heterogeneous across Europe. We wanted to explore attitudes of primary care physicians (PCPs) when managing dementia: (i) the most popular cognitive tests, (ii) who had the right to initiate or continue cholinesterase inhibitor or memantine treatment, and (iii) the relationship between the permissiveness of these rules/guidelines and PCP's approach in the dementia investigations and assessment. METHODS: Key informant survey. SETTING: Primary care practices across 25 European countries. SUBJECTS: Four hundred forty-five PCPs responded to a self-administered questionnaire. Two-step cluster analysis was performed using characteristics of the informants and the responses to the survey. MAIN OUTCOME MEASURES: Two by two contingency tables with odds ratios and 95% confidence intervals were used to assess the association between categorical variables. A multinomial logistic regression model was used to assess the association of multiple variables (age class, gender, and perceived prescription rules) with the PCPs' attitude of "trying to establish a diagnosis of dementia on their own." RESULTS: Discrepancies between rules/guidelines and attitudes to dementia management was found in many countries. There was a strong association between the authorization to prescribe dementia drugs and pursuing dementia diagnostic work-up (odds ratio, 3.45; 95% CI 2.28-5.23). CONCLUSIONS: Differing regulations about who does what in dementia management seemed to affect PCP's engagement in dementia investigations and assessment. PCPs who were allowed to prescribe dementia drugs also claimed higher engagement in dementia work-up than PCPs who were not allowed to prescribe.

INFORMEG, a new evaluation system for family medicine trainees: feasibility in an Italian rural setting.

INTRODUCTION: In Italy the course to become a general practitioner (GP) lasts 3 years and includes both theoretical and practical study. Different from the theoretical part, until recently the practical activity has not been assessed at all. The Emilia Romagna Regional Health Authority has developed a special program called INFORMEG (Management of Tutoring during the Triennial Specific Training in General Practice), aimed at assessing primary doctor trainees' practical skills. INFORMEG includes a list of pre-defined cases of specific diseases, conditions or health problem, a web application and a smartphone app, aimed at assisting trainee self-management and helping the tutor in the assessment of trainee performance. The Emilia Romagna Regional Health Authority divided the pre-defined cases into three categories (A, B and C) according to their relevance to a trainee's education and coded them using the International Classification of Primary Care (ICPC). The aim of this project report is to illustrate the implementation of INFORMEG in a rural setting. METHODS: Program evaluation took place from 2 May to 31 October 2013 during GPs' routine clinical activities. The following steps were accomplished during every meeting: (1) consultation recording; (2) identification of the reason for the encounter (RfE); (3) classification of the diagnostic procedure(s) performed (diagnostic/therapeutic/test results/administrative/advice); (4) classification of special procedures called 'practical clinical skills' and (5) elaboration of the final diagnosis after the encounter. RESULTS: The number of cases of specific disease or condition encountered by the trainee were 98 for type A, 57 for type B and 22 for type C. A total of 605 RfEs were collected: 376 for type A cases, 147 for type B cases and 82 for type C cases. A total of 976 procedures were performed during the 6 months: 590 procedures for the type A cases, 271 for type B and 115 for type C. CONCLUSIONS: The pre-selected health problems were almost all addressed, thus confirming the good degree of representativeness of these clinical cases even in a rural setting. The ICPC coding helped the trainee in the construction of the case according to the logical process of family medicine. Two things to amend in INFORMEG are the absence of common arrhythmic conditions such as atrial fibrillation and the absence of means to assess the patient-trainee relationship.

Is a practice-based rural research network feasible in Europe?

Research in family medicine is a well-established entity nationally and internationally, covering all aspects of primary care including remote and isolated practices. However, due to limited capacity and resources in rural family medicine, its potential is not fully exploited yet. An idea to foster European rural primary care research by establishing a practice-based research network has been recently put forward by several members of the European Rural and Isolated Practitioners Association (EURIPA) and the European General Practice Research Network (EGPRN). Two workshops on why, and how to design a practice-based research network among rural family practices in Europe were conducted at two international meetings. This paper revisits the definition of practice-based research in family medicine, reflects on the current situation in Europe regarding the research in rural family practice, and discusses a rationale for practice-based research in rural family medicine. A SWOT analysis was used as the main tool to analyse the current situation in Europe regarding the research in rural family practice at both meetings. The key messages gained from these meetings may be employed by the Wonca Working Party on research, the International Federation of Primary Care Research Network and the EGPRN that seek to introduce a practice-based research approach. The cooperation and collaboration between EURIPA and EGPRN creates a fertile ground to discuss further the prospect of a European practice-based rural family medicine research network, and to draw on the joint experience.

Adult-onset autosomal recessive ataxia associated with neuronal ceroid lipofuscinosis type 5 gene (CLN5) mutations.

Autosomal recessive inherited ataxias are a growing group of genetic disorders. We report two Italian siblings presenting in their mid-50s with difficulty in walking, dysarthria and progressive cognitive decline. Visual loss, ascribed to glaucoma, manifested a few years before the other symptoms. Brain MRI showed severe cerebellar atrophy, prevalent in the vermis, with marked cortical atrophy of both hemispheres. Exome sequencing identified a novel homozygous mutation (c.935G > A;p.Ser312Asn) in the ceroid neuronal lipofuscinosis type 5 gene (CLN5). Bioinformatics predictions and in vitro studies showed that the mutation was deleterious and likely affects ER-lysosome protein trafficking. Our findings support CLN5 hypomorphic mutations cause autosomal recessive cerebellar ataxia, confirming other reports showing CLN mutations are associated with adult-onset neurodegenerative disorders. We suggest CLN genes should be considered in the molecular analyses of patients presenting with adult-onset autosomal recessive cerebellar ataxia.