Exenatide modulates visual cortex responses.

BACKGROUND: Increasing evidence suggests that metabolism affects brain physiology. Here, we examine the effect of GLP-1 on simple visual-evoked functional Magnetic Resonance Imaging (fMRI) responses in cortical areas. METHODS: Lean (n = 10) and nondiabetic obese (n = 10) subjects received exenatide (a GLP-1 agonist) or saline infusion, and fMRI responses to visual stimuli (food and nonfood images) were recorded. We analysed the effect of exenatide on fMRI signals across the cortical surface with special reference to the visual areas. We evaluated the effects of exenatide on the raw fMRI signal and on the fMRI signal change during visual stimulation (vs rest). RESULTS: In line with previous studies, we find that exenatide eliminates the preference for food (over nonfood) images present under saline infusion in high-level visual cortex (temporal pole). In addition, we find that exenatide (vs saline) also modulates the response of early visual areas, enhancing responses to both food and nonfood images in several extrastriate occipital areas, similarly in obese and lean participants. Unexpectedly, exenatide increased fMRI raw signals (signal intensity during rest periods without stimulation) in a large occipital region, which were negatively correlated to BMI. CONCLUSIONS: In both lean and obese individuals, exenatide affects neural processing in visual cortex, both in early visual areas and in higher order areas. This effect may contribute to the known effect of GLP1 analogues on food-related behaviour.

Consensus-building on developing dysphagia competence: a North West of England perspective.

BACKGROUND: Dysphagia has been an increasing area of practice for speech and language therapists (SLTs) for over 20 years, and throughout that period there has been debate about how practical skills in dysphagia can best be developed. The implementation of the new Royal College of Speech and Language Therapists (RCSLT) framework was considered from a regional perspective seeking to establish consensus across different speech and language therapy settings. AIM: To explore practical solutions to the development of dysphagia competency in new graduates whilst acknowledging the wide variation in staffing and clinical dysphagia experience across the geographical and clinical landscape in the North West of England. METHODS & PROCEDURES: A four-phase study involved a literature search; interviews with experts in the field of dysphagia; a survey to identify current practice; and a two-round Delphi process. OUTCOMES & RESULTS: Five themes emerged for dysphagia competency development: development of practical skills; supervision; clinical excellence networks; workforce planning; and postgraduate formal training. Challenges, and solutions to these, were identified through the phases of the study. A model for dysphagia competency development relevant to the North West context was achieved by consensus. CONCLUSIONS & IMPLICATIONS: There are many practical ways of developing dysphagia competency. The themes and model generated provide constructive support to services in adopting the most appropriate methods for their own settings.

Dysphagia: its nature, assessment and management.

Dysphagia impacts on the health and quality of life of individuals and contributes to the cost of health care. This paper summarises current literature regarding the nature, assessment and management of acquired oro-pharyngeal dysphagia in older adults. It examines the aetiology, prevalence and consequences of dysphagia, as well as issues regarding medication administration. Assessment of dysphagia is explored in terms of multidisciplinary screening, speech and language therapist clinical swallowing evaluation and instrumental assessment.

Agreement between patient's description of abdominal symptoms of possible upper gastrointestinal cancer and general practitioner consultation notes: a qualitative analysis of video-recorded UK primary care consultation data.

INTRODUCTION: Abdominal symptoms are common in primary care but infrequently might be due to an upper gastrointestinal (UGI) cancer. Patients' descriptions may differ from medical terminology used by general practitioners (GPs). This may affect how information about abdominal symptoms possibly due to an UGI cancer are documented, creating potential missed opportunities for timely investigation. OBJECTIVES: To explore how abdominal symptoms are communicated during primary care consultations, and identify characteristics of patients' descriptions that underpin variation in the accuracy and completeness with which they are documented in medical records. METHODS AND ANALYSIS: Primary care consultation video recordings, transcripts and medical records from an existing dataset were screened for adults reporting abdominal symptoms. We conducted a qualitative content analysis to capture alignments (medical record entries matching patient verbal and non-verbal descriptions) and misalignments (symptom information omitted or differing from patient descriptions). Categories were informed by the Calgary-Cambridge guide's 'gathering information' domains and patterns in descriptions explored. RESULTS: Our sample included 28 consultations (28 patients with 18 GPs): 10 categories of different clinical features of abdominal symptoms were discussed. The information GPs documented about these features commonly did not match what patients described, with misalignments more common than alignments (67 vs 43 instances, respectively). Misalignments often featured patients using vague descriptors, figurative speech, lengthy explanations and broad hand gestures. Alignments were characterised by patients using well-defined terms, succinct descriptions and precise gestures for symptoms with an exact location. Abdominal sensations reported as 'pain' were almost always documented compared with expressions of 'discomfort'. CONCLUSIONS: Abdominal symptoms that are well defined or communicated as 'pain' may be more salient to GPs than those expressed vaguely or as 'discomfort'. Variable documentation of abdominal symptoms in medical records may have implications for the development of clinical decision support systems and decisions to investigate possible UGI cancer.

Understanding symptom appraisal and help-seeking in people with symptoms suggestive of pancreatic cancer: a qualitative study.

OBJECTIVE: Pancreatic cancer has poor survival rates due to non-specific symptoms leading to later diagnosis. Understanding how patients interpret their symptoms could inform approaches to earlier diagnosis. This study sought to explore symptom appraisal and help-seeking among patients referred to secondary care for symptoms suggestive of pancreatic cancer. DESIGN: Qualitative analysis of semistructured in-depth interviews. Data were analysed iteratively and thematically, informed by the Model of Pathways to Treatment. PARTICIPANTS AND SETTING: Pancreatic cancer occurs rarely in younger adults, therefore patients aged ≥40 years were recruited from nine hospitals after being referred to hospital with symptoms suggestive of pancreatic cancer; all were participants in a cohort study. Interviews were conducted soon after referral, and where possible, before diagnosis. RESULTS: Twenty-six interviews were conducted (cancer n=13 (pancreas n=9, other intra-abdominal n=4), non-cancer conditions n=13; age range 48-84 years; 14 women). Time from first symptoms to first presentation to healthcare ranged from 1 day to 270 days, median 21 days. We identified three main themes. Initial symptom appraisal usually began with intermittent, non-specific symptoms such as tiredness or appetite changes, attributed to diet and lifestyle, existing gastrointestinal conditions or side effects of medication. Responses to initial symptom appraisal included changes in meal type or frequency, or self-medication. Symptom changes such as alterations in appetite and enjoyment of food or weight loss usually prompted further appraisal. Triggers to seek help included a change or worsening of symptoms, particularly pain, which was often a 'tipping point'. Help-seeking was often encouraged by others. We found no differences in symptom appraisal and help-seeking between people diagnosed with cancer and those with other conditions. CONCLUSIONS: Greater public and healthcare professional awareness of the combinations of subtle and intermittent symptoms, and their evolving nature, is needed to prompt timelier help-seeking and investigation among people with symptoms of pancreatic cancer.

Symptoms and patient factors associated with diagnostic intervals for pancreatic cancer (SYMPTOM pancreatic study): a prospective cohort study.

BACKGROUND: Pancreatic cancer is the tenth most common cancer in the UK; however, outcomes are poor, in part due to late diagnosis. We aimed to identify symptoms and other clinical and sociodemographic factors associated with pancreatic cancer diagnosis and diagnostic intervals. METHODS: We did this prospective cohort study at seven hospitals in two regions in England. We recruited participants aged 40 years or older who were referred for suspicion of pancreatic cancer. Data were collected by use of a patient questionnaire and primary care and hospital records. Descriptive and regression analyses were done to examine associations between symptoms and patient factors with the total diagnostic interval (time from onset of the first symptom to the date of diagnosis), comprising patient interval (time from first symptom to first presentation) and health system interval (time from first presentation to diagnosis). FINDINGS: We recruited 391 participants between Jan 1, 2011, and Dec 31, 2014 (24% response rate). 119 (30%) participants were diagnosed with pancreatic cancer (41 [34%] had metastatic disease), 47 (12%) with other cancers, and 225 (58%) with no cancer. 212 (54%) patients had multiple first symptoms whereas 161 (41%) patients had a solitary first symptom. In this referred population, no initial symptoms were reported more frequently by patients with cancer than by those with no cancer. Several subsequent symptoms predicted pancreatic cancer: jaundice (51 [49%] of 105 patients with pancreatic cancer vs 25 [12%] of 211 patients with no cancer; p<0·0001), fatigue (48/95 [51%] vs 40/155 [26%]; p=0·0001), change in bowel habit (36/87 [41%] vs 28/175 [16%]; p<0·0001), weight loss (55/100 [55%] vs 41/184 [22%]; p<0·0001), and decreased appetite (41/86 [48%] vs 41/156 [26%]; p=0·0011). There was no difference in any interval between patients with pancreatic cancer and those with no cancer (total diagnostic interval: median 117 days [IQR 57-234] vs 131 days [IQR 66-284]; p=0·32; patient interval 18 days [0-37] vs 15 days [1-62]; p=0·22; health system interval 76 days [28-161] vs 79 days [30-156]; p=0·68). Total diagnostic intervals were shorter when jaundice (hazard ratio [HR] 1·38, 95% CI 1·07-1·78; p=0·013) and decreased appetite (1·42, 1·11-1·82; p=0·0058) were reported as symptoms, and longer in patients presenting with indigestion (0·71, 0·56-0·89; p=0·0033), back pain (0·77, 0·59-0·99; p=0·040), diabetes (0·71, 0·52-0·97; p=0·029), and self-reported anxiety or depression, or both (0·67, 0·49-0·91; p=0·011). Health system intervals were likewise longer with indigestion (0·74, 0·58-0·95; p=0·0018), back pain (0·76, 0·58-0·99; p=0·044), diabetes (0·63, 0·45-0·89; p=0·0082), and self-reported anxiety or depression, or both (0·63, 0·46-0·88; p=0·0064), but were shorter with male sex (1·41, 1·1-1·81; p=0·0072) and decreased appetite (1·56, 1·19-2·06; p=0·0015). Weight loss was associated with longer patient intervals (HR 0·69, 95% CI 0·54-0·89; p=0·0047). INTERPRETATION: Although we identified no initial symptoms that differentiated people diagnosed with pancreatic cancer from those without pancreatic cancer, key additional symptoms might signal the disease. Health-care professionals should be vigilant to the possibility of pancreatic cancer in patients with evolving gastrointestinal and systemic symptoms, particularly in those with diabetes or mental health comorbidities. FUNDING: National Institute for Health Research and Pancreatic Cancer Action.

Discordance Between Central (Brain) and Pancreatic Action of Exenatide in Lean and Obese Subjects.

OBJECTIVE: This study examined the effect of exenatide on brain activity measured by functional (f)MRI and on insulin secretion in lean and obese normal-glucose-tolerant individuals. RESEARCH DESIGN AND METHODS: The brain fMRI signal in response to high-calorie-content food pictures was measured with and without intravenous exenatide infusion in 10 lean and 10 obese healthy volunteers. Insulin secretion was measured with a two-step (+100 and +200 mg/dL) hyperglycemic clamp with exenatide and with saline infusion. RESULTS: The brain fMRI signal in response to food pictures in amygdala, insula, hippocampus, and frontal cortex was significantly greater in obese versus lean individuals. Intravenous exenatide significantly inhibited the fMRI signal in response to food pictures in obese individuals but did not affect the brain fMRI signal in lean subjects. Conversely, exenatide infusion caused an 18.5-fold increase in insulin secretion in lean individuals compared with an 8.8-fold increase in obese subjects. No significant correlation was observed between inhibition of the brain fMRI signal and increase in insulin secretion during exenatide infusion. CONCLUSIONS: Exenatide causes greater augmentation in insulin secretion in lean compared with obese individuals but inhibits the brain response to food pictures only in obese individuals.

The importance of quantifying inherent variability when interpreting stable isotope field data.

Stable isotope data are often used to assess diet, trophic level, trophic niche width and the extent of omnivory. Notwithstanding ongoing discussions about the value of these approaches, variations in isotopic signatures among individuals depend on inherent variability as well as differences in feeding habitats. Remarkably, the relative contributions of diet variation and inherent variability to differences in delta(15)N and delta(13)C among individuals have not been quantified for the same species at the same life history stages, and inherent variability has been ignored or assumed. We quantified inherent variability in delta(13)C and delta(15)N among individuals of a marine fish (the European sea bass, Dicentrarchus labrax) reared in a controlled environment on a diet of constant isotopic composition and compared it with variability in delta(13)C and delta(15)N among individuals from wild bass populations. The analysis showed that inherent variability among reared individuals on a controlled diet was equivalent to a large proportion of the observed variability among wild individuals and, therefore, that inherent variability should be measured to establish baseline variability in wild populations before any assumptions are made about the influence of diet. Given that inherent variability is known to be dependent on species, life history stage and the environment, our results show that it should be quantified on a case-by-case basis if diet studies are intended to provide absolute assessments of dietary habits.