Review article: rethinking the “ladder” approach to reflux-like symptom management in the era of PPI “resistance”: a multidisciplinary perspective

Background: Despite widespread adoption of potent acid suppression treatment with proton pump inhibitors (PPI) for reflux-like symptoms, persistent symptoms are commonly reported in primary care and community studies. Aims: This multidisciplinary review critically evaluates how the management of reflux-like symptoms could better reflect their multifactorial pathophysiology. Methods: A panel of experts (from general practice, gastroenterology and gastropsychology) attended a series of workshops to review current management and propose a framework for the provision of more individualised care. Results: It was agreed that the perceptual (as well as the physiological) causes of reflux-like symptoms should be considered at the start of management, not as a last resort when all else has failed. A short course of PPI is a pragmatic approach to address reflux-like symptoms, but equally important is counselling about the gut-brain axis and provision of symptom-specific behavioural interventions for those who show signs of somatisation, hypervigilance or co-existing disorders of gut-brain interaction. Other low-harm interventions such as lifestyle and dietary advice, should also be better integrated into care at an early stage. Multidisciplinary care management programmes (including dietary, weight loss, exercise and behavioural intervention) should be developed to promote greater self-management and take advantage of the general shift toward the use of remotely accessed health care resources. Conclusions: Management of reflux-like symptoms should be adapted to reflect the advances in knowledge about the multifactorial aetiology of these symptoms, addressing both acid-related and behavioural components early in management. The time has come to treat the patient, not the “disease”

Anti-Inflammatory Nutrition and Successful Ageing in Elderly Individuals: The Multinational MEDIS Study

Abstract BACKGROUND: The role of diet and inflammation in successful ageing is not transparent, and as such, is still being investigated. The aim of the present work was to evaluate the inflammatory potential of dietary habits in the successful ageing of a random sample of older adults living in the Mediterranean basin and who participated in the MEDIS (MEDiterranean ISlands) study. METHODS: During 2005-2016, 3,128 older adults (aged 65-100 years) from 24 Mediterranean islands and the rural Mani region (Peloponnesus) of Greece were enrolled in the study. A multidimensional successful ageing index consisting of 10 components was employed. A validated and reproducible Food Frequency Questionnaire (FFQ) was used to evaluate the dietary habits of the older adults. A nutrition anti-inflammatory (NAI) score based on the participants' specific dietary habits was assessed. RESULTS: Participants with high NAI scores (proinflammatory nutrition) had a higher prevalence of hypercholesterolemia and lower levels of successful ageing. After adjusting for several confounders, the NAI score was associated with successful ageing (-0.03, 95% CI -0.5 to -0.006). Stratified analysis by gender and advanced age revealed heterogeneity in the NAI score, predicting successful ageing. CONCLUSIONS: The inflammatory potential of nutrition was reported as an important factor for successful ageing, suggesting that further research is needed on the role of anti- and proinflammatory dietary habits in healthy and successful ageing

Measuring the burden of herpes zoster and post herpetic neuralgia within primary care in rural Crete, Greece

<p>Abstract</p> <p>Background</p> <p>Research has indicated that general practitioners (GPs) have good clinical judgment in regards to diagnosing and managing herpes zoster (HZ) within clinical practice in a country with limited resources for primary care and general practice. The objective of the current study was to assess the burden of HZ and post herpetic neuralgia (PHN) within rural general practices in Crete, Greece.</p> <p>Methods</p> <p>The current study took place within a rural setting in Crete, Greece during the period of November 2007 to November 2009 within the catchment area in which the Cretan Rural Practice-based Research Network is operating. In total 19 GP's from 14 health care units in rural Crete were invited to participate, covering a total turnover patient population of approximately 25, 000 subjects. For the purpose of this study an electronic record database was constructed and used as the main tool for monitoring HZ and PHN incidence. Stress related data was also collected with the use of the Short Anxiety Screening Test (SAST).</p> <p>Results</p> <p>The crude incidence rate of HZ was 1.4/1000 patients/year throughout the entire network of health centers and satellite practices, while among satellite practices alone it was calculated at 1.3/1000 patients/year. Additionally, the standardised incidence density within satellite practices was calculated at 1.6/1000 patients/year. In regards to the stress associated with HZ and PHN, the latter were found to have lower levels of anxiety, as assessed through the SAST score (17.4 ± 3.9 vs. 21.1 ± 5.7; <it>p </it>= 0.029).</p> <p>Conclusions</p> <p>The implementation of an electronic surveillance system was feasible so as to measure the burden of HZ and PHN within the rural general practice setting in Crete.</p

Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Is car use related with successful aging of older adults? Results from the multinational Mediterranean islands study

Purpose The aim of the present work was to evaluate the relation between car use and the level of successful aging of a random sample of older adults living in the Mediterranean basin. Methods During 2005–2011, 2749 older (aged 65–100 years) from 22 islands and the rural Mani region (Peloponnesus) of Greece were voluntarily enrolled in the Mediterranean islands cross-sectional study. Sociodemographics, medical conditions, and dietary and lifestyle habits were derived throughout standard procedures. Car use was recorded with a standard binary question. A successful aging index ranging from 0–10 was used. Results Older adults who used a car on regular basis had significantly higher levels of successful aging, as well as less prevalence of obesity and hypertension while were more physically active (P < .001). After adjusting for several confounders car use was still positively related with elderly islander's successful aging level (beta coefficient [95% confidence interval]: 0.65 [0.54–0.77]). Conclusions In conclusion, the activity of car use seems to be an indicator of quality of life among older adults, as measured through successful aging

Lifestyle determinants of healthy ageing in a Mediterranean population: The multinational MEDIS study.

BACKGROUND: To evaluate modifiable, lifestyle risk factors of cardiovascular disease (CVD) among older adults, across ageing, in the Mediterranean area. METHODS: During 2005-2017, 3131 individuals from 26 Mediterranean islands of 5 countries, ≥65 years of age, were voluntarily enrolled. Anthropometrical, clinical and socio-demographic characteristics, dietary habits, lifestyle parameters were measured through standard procedures. Analyses were performed by year and across consecutive age groups of the participants. RESULTS: A decrease in the prevalence of current smoking (p < 0.001), engagement in physical activities (p = 0.001) and participation in social events (p = 0.001) for every year increase in age was found. Moderate alcohol drinking increased through ageing (p = 0.008), whereas adherence to Mediterranean diet remained stable, but adequate (p = 0.90). Trend analysis also revealed that a quadratic (U-shape) function better characterized the association between ageing and total cardiometabolic risk factors burden (p for trend <0.001). CONCLUSIONS: The gaps in the understanding of factors affecting longevity and healthy ageing remain; public health authorities and stakeholders should focus on the lifestyle determinants of healthy ageing, that seems to be an effective mean for improving older peoples' health