Effect of Oral CNSA-001 (sepiapterin,PTC923) on gastric accommodation in women with diabetic gastroparesis: A randomized,placebo-controlled,Phase 2 trial

AimsDiabetic gastroparesis may be associated with impaired nitric oxide metabolism and reduced tetrahydrobiopterin (BH₄) synthesis. Oral treatment with CNSA-001 (sepiapterin, currently known as PTC923) increased BH₄ levels in humans in a previous study. This Phase 2 study evaluated CNSA-001 in women with diabetic gastroparesis.MethodsNon-pregnant diabetic women with moderate/severe symptomatic gastroparesis, delayed gastric emptying, and impaired gastric accommodation (nutrient satiety testing) were randomized to 10 mg/kg BID CNSA-001 or matching placebo for 14 days. The primary endpoint was change in gastric accommodation (maximal tolerated liquid meal volume) at 14- and 28-days' follow-up.ResultsGastric accommodation improved in CNSA-001-treated vs. placebo-treated subjects at 28 days (least squares mean [LSM] difference: 98 [95% CI 36 to 161], p = 0.0042). Subjects' ratings of bloating, fullness, nausea, and pain were lower vs. baseline in the CNSA-001 group at 14 and 28 days, though these improvements were not observed consistently in placebo-treated subjects. There were no significant group differences in upper gastrointestinal symptom scores, and in gastric emptying breath test parameters. CNSA-001 was well tolerated, with no withdrawals for adverse events.ConclusionsCNSA-001 improved gastric accommodation in women with diabetic gastroparesis. Further evaluation of CNSA-001 in gastroparesis is warranted; ClinicalTrials.gov number, NCT03712124.     

Prevalence of symptoms suggestive of gastroparesis in a cohort of patients with diabetes mellitus

AimsTo estimate the prevalence of symptoms suggestive of gastroparesis and their association to clinical and demographic data in a large population of patients with diabetes mellitus and in the general population in Israel.MethodsA cross-sectional survey of type 2 diabetic patients treated in community settings was performed. All patients and controls completed a demographic questionnaire as well as the Gastroparesis Cardinal Symptom Index (GCSI). Data regarding disease duration, medications, complications, recent blood glucose and HbA1C levels, were also collected.ResultsA total of 382 patients and 88 healthy volunteers were included. Patients and controls were aged 63.07 ± 10.63 and 58.69 ± 10.73 years respectively with a BMI of 30.45 ± 8.15 and 25.64 ± 4.25 kg/m² respectively. Compared to controls, more patients with diabetes complained of nausea (24.8% vs. 4.5%, p < 0.0001), post-prandial fullness (44.6% vs. 26.1%, p = 0.001), bloating (48.8% vs. 36.4%, p = 0.035) and stomach or belly visibly larger after a meal (53% vs. 29.5%, p < 0.0001). In multivariate analysis, symptoms were associated with female sex, BMI, blood glucose, HbA1C, metformin treatment and disease duration.ConclusionsThe prevalence of symptoms suggestive of gastroparesis among patients with diabetes mellitus in Israel is high and is independently associated with female sex and metformin therapy.     

Acute phase homocysteine related to severity and outcome of atherothrombotic stroke

BackgroundHomocysteine (HCY) is associated with risk of stroke, but whether HCY affects stroke severity and prognosis remains controversial. We hypothesized HCY has an impact on atherothrombosis and this prospective study was aimed to explore the association between acute phase HCY with stroke severity and outcome in patients with atherothrombosis.MethodsPatients < 72 h after symptom onset were categorized by the modified Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification and those typed as atherothrombosis were included. Neurologic function was assessed with National Institute of Health Stroke Score (NIHSS) < 72 h after symptom onset and Modified Rankin Scale (mRS) and Barthel Index (BI) 6-month, 12-month and 18-month poststroke respectively. HCY was recorded < 72 h after symptom onset. Participants were divided into hHCY (HCY > 15 μmol/l) and nhHCY (HCY ≤ 15 μmol/l). The correlation between HCY and mRS was analyzed.Results125 of 130 participants without HCY interventional therapy completed the 18-month follow-up. There was no difference in demographics, histories of hypertension, diabetes mellitus, coronary heart disease, previous cerebral vascular event, and plasma low-density lipoprotein between hHCY and nhHCY. NIHSS, mRS were significantly higher and BI was significantly lower in hHCY than in nhHCY. The 18-month recurrence rate in hHCY (21.0%) was significantly higher than that in nhHCY (6.8%). Spearman correlation analysis revealed correlation between HCY and mRS (p = 0.000). By ordinal logistic regression, HCY was an independent predictor of 18-month mRS (odds ratio 1.08, 95% confidence interval 1.04–1.13, p = 0.000).ConclusionsAcute phase elevated HCY correlated with severity and prognosis in patients with atherothrombotic stroke.     

13C-octanoic acid breath test (OBT) with a new test meal (EXPIROGer®): Toward standardization for testing gastric emptying of solids

BackgroundStandardization of the ¹³C-octanoic acid breath test is still lacking.AimTo evaluate the accuracy of the ¹³C-octanoic acid breath test using a new standardized ready-to-eat, gluten-, glucose-, and lactose-free muffin.MethodsHealthy subjects were recruited and sorted by sex and age. Patients with diabetic gastroparesis and untreated celiac disease with known gastric motility disorders were also tested with the new labelled muffin. Expired breath ¹³CO₂ was analysed and t_1/2 was calculated.ResultsOverall, 131 healthy subjects were enrolled. The reference range of t_1/2 was 88 ± 29 min with the value of 146 min as the upper limit of normal range. No significant difference in t_1/2 was found among subjects sorted by sex or age. The within-subject variability of t_1/2 was 17%. Mean (±standard deviation) t_1/2 values were 179 ± 50 min in patients with diabetic gastroparesis (n = 8) and 151 ± 20 min in those with untreated celiac disease (n = 11) (p ≤ 0.001 vs controls).ConclusionsA new standardized test meal simplifies the execution of the ¹³C-octanoic acid breath test, is not influenced by sex or age, has low intra-individual variability, is palatable, does not cause side effects, and is able to evaluate gastric emptying in both patients and healthy controls. Moreover, it can be used in subjects with lactose intolerance, diabetes, and celiac disease.     

Switching from carvedilol to bisoprolol ameliorates adverse effects in heart failure patients with dizziness or hypotension

BackgroundTreatment with carvedilol is an established primary therapy for patients with heart failure (HF). However, its most common adverse effects, dizziness and hypotension, often discourage continuation or dosage increase. The aim of this study was to examine whether switching to bisoprolol from carvedilol would help to avoid adverse symptoms and signs related to carvedilol administration.Methods and subjectsData were retrospectively collected from 23 patients with HF [age 57 ± 18 years, left ventricular ejection fraction (LVEF) 33 ± 15%] who could not increase the dosage of carvedilol because of dizziness or hypotension, defined as systolic blood pressure < 90 mmHg. Before and immediately after, and 6 months after switching to bisoprolol, we examined symptoms, vital signs, laboratory data, and New York Heart Association functional class. Furthermore, left ventricular (LV) dimension and ejection fraction (EF) were evaluated in 19 patients using echocardiography.ResultsAll 13 patients with dizziness (100%) and 9 of 16 with hypotension (56%) were relieved of adverse symptoms or signs. The mean dose of carvedilol before switching was 5.60 ± 3.43 mg. Immediately after the switch, the mean dose of bisoprolol was 1.84 ± 1.08 mg and then increased to 3.13 ± 1.74 mg after 6 months (p < 0.01). At 6-month follow-up examinations, LV function determined by LVEF was significantly improved, which was accompanied by increased exercise tolerance.ConclusionSwitching from carvedilol to bisoprolol may help with continuation of β-blocker treatment as well as dosage increase in HF patients with adverse symptoms or signs, allowing them to reach the target dose.     

Motilin concentrations in relation to gastro intestinal dysmotility in diabetes mellitus

AimDysmotility in the upper gastro intestinal (GI) tract are common problems in diabetics. Many peptides are involved in the regulation of the motility. The aim of this study was to examine whether plasma levels of motilin were related to dysfunction in the oesophagus and stomach in a well-defined diabetic patient group.MethodsNineteen patients with symptoms from the GI tract who had been examined with oesophageal manometry, gastric emptying scintigraphy and deep-breathing test were included. They received a fat-rich meal, after which blood samples were collected and analysed for motilin concentrations.ResultsSymptoms of abdominal fullness and gastro oesophageal reflux significantly associated with delayed gastric emptying, whereas no symptom correlated to oesophageal dysmotility. Plasma levels of motilin were increased after the fat-rich meal (p = 0.000), with no difference between the groups. Abnormal manometry was characterized by aperistalsis and/or simultaneous contractions. The percentage of simultaneous contractions correlated to basic and peak motilin values (r_s = 0.898, p = 0.006 and r_s = 0.842, p = 0.017, respectively). Gastric emptying did not influence motilin concentrations.ConclusionPlasma motilin concentrations vary with abnormalities of oesophageal motility in diabetics, but not with abnormalities of gastric emptying.     

Audit of digestive complaints and psychopathological traits in patients with eating disorders: A prospective study

BackgroundEsophago-gastrointestinal symptoms are frequently reported by patients with eating disorders. Scanty data exist on the relationship between psychopathological traits and digestive complaints.AimsTo prospectively analyze (i) prevalence of digestive symptoms; (ii) psychopathological traits; (iii) relationship between symptom scores and psychopathological profiles.MethodsPsychopathological and digestive symptom questionnaires were completed at baseline, at discharge, at 1 and 6 months’ follow-up in 48 consecutive patients (85.4% female, median age, 15 years) hospitalized for eating disorders.ResultsThe most frequently reported symptoms were postprandial fullness (96%) and abdominal distention (90%). Pooled esophageal (4; IQR 0–14) and gastrointestinal (34; IQR 19–53) symptoms significantly decreased at 6 months’ follow-up (1; IQR 0–3 and 10; IQR 4–34; p < 0.0001 and p < 0.005, respectively). Pooled gastrointestinal symptoms significantly correlated with hypochondriasis (r = 0.42, p < 0.01). Both esophageal and gastrointestinal symptoms improved in patients with normal values of hypochondriasis and hysteria scales (p < 0.05 and p < 0.005, respectively) compared to those with pathological traits.ConclusionsDigestive symptoms are frequently reported by patients with eating disorders with their expression and outcome being influenced by psychopathological profiles. Hypochondriasis and hysteria traits are predictive factors for symptomatic improvement.     

Prevalence and real clinical impact of Cupressus sempervirens and Juniperus communis sensitisations in Tuscan “Maremma”, Italy

ObjectiveThe aim was to evaluate the impact of Cupressus sempervirens (Cs) and Juniperus communis (Jc) sensitisations in “Maremma” in southern Tuscany.Methods811 consecutive outpatients (357 F – 57.86%; age: 36.9 ± 16.6) with suspected allergic respiratory symptoms underwent skin prick tests (SPT) for common allergens and for Cs and Jc.ResultsSPT resulted negative in 295 (36.37%) subjects. A Cs/Jc sensitisation was found in 294 (36.25%): 289 (98.3%) were sensitised to Cs whereas 198 (67.34%) to Jc. There was a co-sensitisation between Cs and Jc in 193 (65.6%) subjects. Cs/Jc mono-sensitisation was found in 39 (13.6%) subjects. A higher number (p < 0.0001) of Cs/Jc sensitised subjects reported winter (131–44.55%) and spring (124–42.2%) symptoms compared to Cs/Jc non-sensitised and non-allergic subjects. Most Cs/Jc sensitised subjects reported rhinitis and conjunctivitis (p < 0.0001), whereas only few reported coughing and asthma (p < 0.01). The most frequent co-sensitisation was with grass, olive and other trees in Cs/Jc subjects (p < 0.001). Those who reported winter symptoms, likely influenced by Cupressaceae, rhinitis was the main symptom whereas asthma was less frequent. Cs/Jc sensitisation resulted to be a risk factor (OR: 1.73 [CI95% 1.18–2.55]) for rhinitis whereas the probability of being asthmatic was reduced (OR: 0.62 [CI95% 0.44–0.85]).ConclusionThe prevalence of Cs/Jc sensitisation is about 36% in “Maremma”. However, only in 44% of the patients, Cs/Jc seem to cause typical winter symptoms. Rhinitis is the predominant symptom, whereas asthma is less frequent. Testing Cupressaceae sensitisation using Jc pollen extract, rather than Cs, may result to be less sensitive.     

Factors Associated with Symptom Response to Pyloric Injection of Botulinum Toxin in a Large Series of Gastroparesis Patients

Case series report symptom reductions after pyloric botulinum toxin injection in gastroparesis, but small controlled trials show no benefit. Factors that enhance response to therapy are undefined. A retrospective analysis of 179 gastroparetics undergoing pyloric botulinum toxin injection from 2001 to 2007 assessed responses relating to drug dosing, demographic factors, comorbidities, and gastric function. Overall, there was a decrease in gastroparetic symptoms 1–4 months after pyloric botulinum toxin injection in 92 patients (51.4%). Increasing the botulinum toxin dose significantly improved clinical responses of patients who provided information on symptoms after therapy (100 units: 54.2%; 200 units: 76.7%; P = 0.02). Other factors that improved response to botulinum toxin included female gender, age <50 years, and nondiabetic nonpostsurgical etiology (all P < 0.05). Eighty-seven patients received 307 follow-up injections. A clinical response to a second injection was observed in 73.4% of evaluable patients. In conclusion, responses to pyloric botulinum toxin depended on dose and were maintained on repeat injection. Subgroup analyses defined subgroups likely to benefit. These findings provide the foundation for large, controlled trials of high-dose botulinum toxin in selected gastroparesis subsets.     

Ability to predict six-month mortality and inter-tool agreement between four nutritional assessment instruments in the SAFES cohort

AimTo measure the ability to predict 6-month mortality of several different instruments for evaluating nutrition, and to compare agreement between results obtained with these different instruments.MethodsProspective, multi-centre cohort study, including subjects aged 75 years or older, admitted to hospital through the emergency room. The predictive capacity of the different nutrition instruments (namely: Mini Nutritional Assessment (MNA), Geriatric Nutritional Risk Index (GNRI), body mass index (BMI) and albuminemia) were tested using a Cox model after adjustment for socio-demographic and clinical variables. Agreement between these four instruments was assessed by calculating Cohen's Kappa coefficient.ResultsIn total, 1306 subjects were included in the cohort, average age 85 ± 6 years. The crude death rate at 6 months was 24.4%. Prevalence of malnutrition varied from 24 to 59%. All the nutrition instruments evaluated were significantly related to survival; the strongest associations with mortality were observed with GNRI (hazard ratio [HR] = 1.65; 95% CI =  1.31–2.06) and MNA (HR = 1.64; 95% CI = 1.27–2.03). Agreement between indicators was moderate to poor.ConclusionThe GNRI and the MNA appear to be the most useful tools for detecting malnutrition in elderly patients admitted via the emergency room.     

Prevalence of gastroparesis-related symptoms in an unselected cohort of patients with Type 1 diabetes

BackgroundThe prevalence of diabetic gastroparesis is not well defined because of discrepancy between objective measurements, i.e. gastric emptying time, and symptoms experienced by patients. Furthermore most studies have been performed on small selected cohorts.ObjectiveTo determine the prevalence of clinical symptoms of diabetic gastroparesis in a large unselected cohort of out-patients with Type 1 diabetes.Methods1028 patients with Type 1 diabetes attending a specialized diabetes clinic were mailed a validated questionnaire; “patient assessment of upper gastrointestinal disorders-symptom severity index”, in which a subset of questions measures symptoms of gastroparesis (GCSI; Gastroparesis Cardinal Symptom Index). Response rate was 74.4% (n = 765). All patients were classified according to presence or absence of late diabetic complications and clinical and paraclinical data were obtained.ResultsA GCSI Total Score ≥ 1.90 signified definite symptoms of gastroparesis (n = 102) and patient charts were investigated for concomitant illness and/or medication influencing gastric emptying. In 30 patients an alternative etiology was revealed, leaving 72 (9.8%) patients with symptoms related to diabetic gastroparesis. Only 8 patients were previously diagnosed. HbA_1c levels were significantly higher in patients with diabetic gastroparesis (8.4 ± 1.3 vs. 8.2 ± 1.2 respectively, p = 0.02). Furthermore, patients with diabetic gastroparesis had more retinopathy (p = 0.006) and peripheral polyneuropathy (16.7% vs. 6.7%, p < 0.001) and there was a trend for diabetic nephropathy being more common (p = 0.08).ConclusionsSymptoms of diabetic gastroparesis affect approximately 10% of patients with Type 1 diabetes in a specialized diabetes clinic and are associated with poor glycemic control and other late diabetic complications.     

Factors affecting quality of life of asthma patients in Spain: The importance of patient education

ObjectivesAssessment of demographic and clinical factors that have an impact on the quality of life (QoL) of patients with asthma in Spain.Patients and methodsMulticenter, prospective, observational, cohort study, conducted in 40 Spanish Pneumology Units during a 12-month period. Data on sociodemographic, clinical variables, asthma treatment and QoL were collected in a case report form.Results536 patients (64.6% women, mean age: 54) were recruited. Reported QoL was better for patients from Northern and Central Spain as compared with those from the South and the East (p < 0.001), students and employed patients as compared with housewives and unemployed (p < 0.01), for those who had received asthma information (p < 0.01), for those with milder daytime symptoms (p < 0.01) and for patients with higher level of education (p < 0.05).ConclusionsAmong the factors that have a significant effect on patients’ QoL only symptom control and patient education on asthma control are modifiable. Therefore, all the strategies should be tailored to improve such factors when managing asthma patients.     

Calcium and vitamin D modulate postprandial vascular function: A pilot dose–response study

BackgroundCalcium and vitamin D may modulate postprandial endothelial function.Subjects and MethodsSeven lean, young males completed a single blind randomized crossover design where they consumed three breakfast meals containing varying calcium and vitamin D (meal 1 ～200 mg/15 IU, meal 2 ～450 mg/140 IU, and meal 3 ～700 mg/265 IU). Stiffness index (SI), reflective index (RI) and pulse rate (PR) were serially assessed from the digital volume pulse by photoplethysmography (Pulse Trace PT-1000, Micro Medical, UK).ResultsIncremental areas under the curve over 3 h (Δ) were analyzed by repeated measures ANOVA. ΔPTH was significantly less suppressed with meal A than with meal B and C (P = 0.003). In contrast, ΔRI was significantly more suppressed following meal A than with either meal B or C (P = 0.021). ΔSI did not change with meal ingestion and there was no difference in the rise of Δglucose, Δinsulin and ΔPR between meals.ConclusionHigher calcium and vitamin D at breakfast prevented the fall in postprandial vascular tone without changes in glucose or insulin.     

A study to explore the factors related to treatment seeking delay among adults diagnosed with acute myocardial infarction at KMCH,Coimbatore

ObjectiveThe main aim of the study was to explore the factors causing delay in seeking treatment among adult patients diagnosed with CAAs acute myocardial infarction (AMI) and compare the factors between timely and late treatment seeking groups.MethodA total of 93 subjects were included in the study diagnosed with AMI interviewed within 48 h of hospitalization. Data were collected from onset of symptoms to arrival at hospital on demography, clinical profile, clinical factors, cognitive factors and social support factors. Subjects were categorized in two study groups i.e. timely treatment seeking group (<120 min from onset of symptoms) and delayed treatment seeking group (>120 min from onset of symptoms).ResultsThe minimum and maximum time took by subjects to seek treatment was 10 and 5450 min, respectively. The mean pain score of subjects who sought delayed treatment (2.2619) is less than those who sought timely treatment (3.3725). The mean knowledge score (12.2754), mean symptom perception (3.6667), mean perceived seriousness (4.7647) is more in subjects who sought timely treatment than those who sought delayed treatment (5.7381), (1.3095), (1.8333) respectively. The mean family support score (57.4492), mean non-family support score (24.902), mean social support score (48.3002) is more in timely treatment group than in delayed treatment seeking group (42.6829), (4.7619), (29.2138) respectively.ConclusionDecreased pain, knowledge about AMI, symptom perception, perceived seriousness respectively and inadequate family & non-family support i.e. social support were the factors related to treatment seeking delay among adults diagnosed with AMI.     

Psychosocial sequelae following cardiac arrest

BackgroundCardiac arrest (CA) leads to cerebral hypoxia resulting in multifactorial brain injury. Cognitive impairment and a higher degree of depressive symptoms are the most frequently described mental health problems after CA. The aim of the present study is to characterize psychosocial sequelae of CA.MethodsThe study population included 113 subjects. 62 patients after CA were matched to 51 healthy controls according to demographic characteristics and premorbid intelligence level. Cognitive test (MoCA), inventories of depressive (BDI-II) and anxiety symptoms (STAI) and midlife crisis scale (MCS) were administrated to study participants.ResultsThe analysis showed that CA patients have a decreased level of cognitive performance (p = 0.016) and a higher degree of state anxiety symptoms (p = 0.023). There was no significant difference between CA patients and control subjects in the degree of depressive (p = 0.435) and trait anxiety symptoms (p = 0.542). Ex-post facto analysis based on logistic regression indicated that the strongest predictors of being classified as having had a cardiac arrest was male gender and state anxiety (OR = 4.45 and 0.50). Discriminant function analysis showed that group prediction was sensitive to age, cognitive performance, and state anxiety (λ = 0.81, p = 0.028).ConclusionsOur results show that CA has significant cognitive and neuropsychiatric sequelae. The integration of psychosocial care and neuropsychiatric treatment into the complex medical care of CA patients seems to be justified.     

Effects of the regular consumption of wholemeal wheat foods on cardiovascular risk factors in healthy people

Background and aimThe intake of wholemeal foods is consistently associated with reduced risk of type 2 diabetes and cardiovascular diseases in epidemiological studies, although the mechanisms of this association are unclear. Here we aim to compare in healthy subjects the metabolic effects of a diet rich in wholemeal wheat foods versus one based on the same products in refined form.Methods and resultsFifteen healthy individuals (12 M/3 F), mean age 54.5 ± 7.6 years, BMI 27.4 ± 3.0 kg/m² (mean ± SD), participated in a randomized sequential crossover study. After 2 weeks run-in, participants were randomly assigned to two isoenergetic diets with similar macronutrient composition, one rich in wholemeal wheat foods and the other with the same foods but in refined form (cereal fibre 23.1 vs. 9.8 g/day). After the two treatment periods (each lasting 3 weeks) plasma glucose and lipid metabolism, antioxidant activity, acetic acid, magnesium, adipokines, incretins and high-sensitivity C-reactive protein (hs-CRP) were measured at fasting and for 4 h after a standard test meal (kcal 1103, protein 12%, CHO 53%, fat 35%) based on wholemeal or refined wheat foods, respectively. After the two diets there were no differences in fasting nor in postprandial plasma parameter responses; only glucose was slightly but significantly lower at 240 min after the refined wheat food meal compared to the wholemeal wheat food meal. Conversely, after the wholemeal diet both total (?4.3%; p < 0.03) and LDL (?4.9%; p < 0.04) cholesterol levels were lower than after the refined wheat diet at fasting.ConclusionsConsumption of wholemeal wheat foods for 3 weeks reduces significantly fasting plasma cholesterol as well as LDL cholesterol levels in healthy individuals without major effects on glucose and insulin metabolism, antioxidant status and sub-clinical inflammation markers.     

Peak-time determination of post-meal glucose excursions in insulin-treated diabetic patients

ObjectiveThis study aimed to determine the optimal time to measure peak blood glucose values to find the best approach for self-monitoring blood glucose after a meal.Design and methodsFor this retrospective analysis, 69 ambulatory continuous glucose-monitoring system (CGMS) profiles were obtained from 75 consecutive insulin-treated patients with diabetes. The parameters measured were the peak post-meal blood glucose values, peak time, and rates of increase and decrease to and from the zenith of the resulting curves.ResultsThe mean peak time after breakfast was 72 ± 23 min, which was reached in less than 90 min in 80% of the patients. The apparent glucose rate of increase from pre-meal to the maximum postprandial value was 1.23 ± 0.76 mg/dL/min, while the glucose rate of decrease was 0.82 ± 0.70 mg/dL/min. Peak time correlated with the amplitude of postprandial excursions, but not with the peak glucose value. Also, peak times were similar after breakfast, lunch and dinner, and in type 1 and type 2 diabetic patients.ConclusionTo best assess peak postprandial glucose levels, the optimal time for blood glucose monitoring is about 1 h and 15 min after the start of the meal, albeit with wide interpatient variability. Nevertheless, 80% of post-meal blood glucose peaks were observed at less than 90 min after the start of the meal.     

The effects of paroxetine and amitriptyline on the upper esophageal sphincter (UES) pressure and its natural history in globus pharyngeus

BackgroundAntidepressant agents have been shown to be an effective and safe treatment method for patients with globus. However, there are few clinical trials dedicated to studying the effects of antidepressant agents on the natural history and upper oesophageal sphincter (UES) pressure of treated globus patients.AimsTo evaluate the effect of paroxetine and amitriptyline to prevent relapses in patients with globus, the simultaneous relationship between changes in UES pressure and improvement of globus symptoms were measured.MethodsGlobus patients were randomised into amitriptyline, paroxetine and lansoprazole groups for a 6-week treatment period, and follow-up was extended to 12 additional months. Efficacy was evaluated in terms of the Glasgow-Edinburgh Throat Scale (GETS), and UES pressure was measured by standard oesophageal manometry.ResultsParoxetine therapy resulted in a higher withdrawal rate due to symptom relapse (15.9% vs 44.1%, P = 0.01; 15.9% vs 64.7, P = 0.001) than amitriptyline and lansoprazole. Furthermore, globus symptoms were alleviated with the decrease of UES pressure after paroxetine and amitriptyline treatment (r = 0.620, P = 0.02; r = 0.575, P = 0.03)ConclusionsThis follow-up study indicates that paroxetine may alter the natural history of globus and can effectively be used for the long-term management of patients with the disease. Apart from the clinical benefits, paroxetine and amitriptyline can potentially decrease UES pressure.     

The relationship between gastro-oesophageal reflux disease and asthma during childhood

BackgroundThe relationship between GERD and asthma is complex. It is not yet clear whether GERD is an accompanying finding or a cause of asthma, or even if it is an aggravating factor. The aim of this study was to determine the frequency of asthma and allergic diseases in patients who underwent 24-h pH monitoring for a suspicion of GERD, including a comparison between subjects with and without GERD.MethodSubjects who were evaluated by 24 h ambulatory intraoesophageal pH monitoring were investigated for the presence of asthma and allergic disorders. All participants were subjected to a skin prick test and a complete blood count and serum levels of specific IgE.ResultsA total of 204 subjects (49.5% male) with a mean age of 7.8 ± 4.3 years were enrolled. A diagnosis of GERD was made in 78 (38.2%) subjects after 24 h pH monitoring. The frequency of asthma in subjects with GERD was 20.5% compared to 25.4% in subjects without GERD (p = 0.424). Subjects with GERD presenting with respiratory symptoms have higher incidence of asthma compared to subjects with GERD presenting with gastrointestinal symptoms (35.3% and 5.3% respectively; p = 0.001).ConclusionAlthough, patients with and without GERD had comparable frequencies of asthma, our findings suggest that subjects who present with respiratory symptoms suggestive of GERD should also be evaluated for the presence of an underlying asthma.     

Asymptomatic systolic and diastolic dysfunction in patients with risk factors referred for echocardiography. The DAVES study by the Italian Society of Cardiovascular Echography

ObjectivesThis study aims to determine the prevalence of left ventricular dysfunction in subjects without signs and symptoms of heart failure referred for echocardiography essentially for the presence of one or more cardiovascular risk factors.Materials and methodsThe DAVES study (Disfunzione Asintomatica del Ventricolo Sinistro, left ventricular asymptomatic dysfunction) is a multicenter cross-sectional observational study based on echocardiography. Among 16,099 screened subjects from 75 Centers, we enrolled 3,537 subjects without signs or symptoms of heart failure. The prevalence of depressed left ventricular systolic (left ventricular ejection fraction ≤ 50%) and diastolic function was analyzed.ResultsThe overall prevalence of asymptomatic left ventricular systolic dysfunction was 9.4%, while diastolic dysfunction was detected in 39.1% of subjects. The rate of systolic and diastolic dysfunction increased proportionally to the number of cardiovascular risk factors (1 or ≥ 5 risk factors), ranging from 8.1% to 27.1% and from 37.5% to 45.0%, respectively. At multivariate analysis, independent variables predictive for systolic dysfunction were male gender (p < 0.001), family history of cardiovascular disease (p = 0.002) and diabetes (p = 0.027); while for diastolic dysfunction they were age (p < 0.001), hypertension (p < 0.001) and diabetes (p < 0.05).ConclusionsIn a large sample of subjects without symptoms of heart failure referred to echocardiography, we found a significant prevalence of left ventricular systolic and diastolic dysfunction, both related to the number of cardiovascular risk factors.