Internet and social media for health-related information and communication in health care: preferences of the Dutch general population.

BACKGROUND: Health care is increasingly featured by the use of Web 2.0 communication and collaborative technologies that are reshaping the way patients and professionals interact. These technologies or tools can be used for a variety of purposes: to instantly debate issues, discover news, analyze research, network with peers, crowd-source information, seek support, and provide advice. Not all tools are implemented successfully; in many cases, the nonusage attrition rates are high. Little is known about the preferences of the Dutch general population regarding the use of the Internet and social media in health care. OBJECTIVE: To determine the preferences of the general population in the Netherlands regarding the use of the Internet and social media in health care. METHODS: A cross-sectional survey was disseminated via a popular Dutch online social network. Respondents were asked where they searched for health-related information, how they qualified the value of different sources, and their preferences regarding online communication with health care providers. Results were weighed for the Dutch population based on gender, age, and level of education using official statistics. Numbers and percentages or means and standard deviations were presented for different subgroups. One-way ANOVA was used to test for statistical differences. RESULTS: The survey was completed by 635 respondents. The Internet was found to be the number one source for health-related information (82.7%), closely followed by information provided by health care professionals (71.1%). Approximately one-third (32.3%) of the Dutch population search for ratings of health care providers. The most popular information topics were side effects of medication (62.5%) and symptoms (59.7%). Approximately one-quarter of the Dutch population prefer to communicate with a health care provider via social media (25.4%), and 21.2% would like to communicate via a webcam. CONCLUSIONS: The Internet is the main source of health-related information for the Dutch population. One in 4 persons wants to communicate with their physician via social media channels and it is expected that this number will further increase. Health care providers should explore new ways of communicating online and should facilitate ways for patients to connect with them. Future research should aim at comparing different patient groups and diseases, describing best practices, and determining cost-effectiveness.

SERT and TPH-1 mRNA expression are reduced in irritable bowel syndrome patients regardless of visceral sensitivity state in large intestine.

Colorectal visceral hypersensitivity has been demonstrated in a subset of irritable bowel syndrome (IBS) patients. Serine protease and serotonergic signaling modulate gastrointestinal visceral sensitivity. We evaluated whether altered mucosal serine protease and serotonergic pathway components are related to rectal visceral hypersensitivity in IBS patients. Colorectal mucosal biopsies of 23 IBS patients and 15 controls were collected. Gene transcripts of protease-activated receptor (PAR)-2, trypsinogen IV, tryptophan hydroxylase (TPH)-1, and serotonin reuptake transporter (SERT) were quantified using real-time polymerase chain reaction. Substance P and 5-HT contents were measured by ELISA. The number of enterochromaffin cells, mast cells, and intraepithelial lymphocytes was determined using immunohistochemistry. Rectal visceral sensitivity was determined in IBS patients using barostat programmed for phasic ascending distension. Rectal hypersensitivity (+) and (-) IBS patients showed lower TPH-1 and SERT mRNA levels in the rectum compared with controls (P ≤ 0.05). Rectal hypersensitivity (+) IBS patients (n = 12) showed lower TPH-1 mRNA level in the sigmoid compared with controls (P = 0.015). No significant differences were observed in PAR-2 and trypsinogen IV expression between controls and IBS patients. Rectal substance P content was increased in IBS patients compared with controls (P = 0.045). No significant differences were found in transcript levels, cell counts, and substance P and 5-HT contents between rectal hypersensitivity (+) and (-) IBS patients. In conclusion, regardless of visceral hypersensitivity state, several serotonergic signaling components are altered in IBS patients.

In gastroesophageal reflux disease, differential gene expression in the duodenum points towards enhanced chylomicron production and secretion.

BACKGROUND: Duodenal signaling affects esophageal motility and perception, both pathophysiological factors in gastroesophageal reflux disease (GERD). Duodenal gene expression abnormalities, contributing to altered esophageal sensorimotor function, have not been reported to date. AIM: To identify differentially expressed genes in GERD patients' duodenum. METHODS: Twenty GERD patients (total 24-h acid exposure 6-12%, SAP ≥95%) and ten healthy controls (HC) were included. Two weeks prior to duodenal biopsy collection, ten patients discontinued proton pump inhibitor (PPI) treatment and ten took maximum dose PPI. RNA was profiled on an Affymetrix Human Genome U133 Plus 2.0 array (Affymetrix, Santa Clara, CA, USA). Genes exhibiting a fold change ≥ 1.4 (t test p value <1E-4) were considered differentially expressed. A subset of 21 differentially expressed genes was selected for confirmatory TaqMan low-density array RT-PCR. Mucosal apolipoprotein A-IV (apoA-IV) and cholecystokinin (CCK) concentrations were determined by ELISA and RIA, respectively. RESULTS: In GERD patients off PPI, 23 up- and 23 down-regulated genes relative to HC were found. In GERD patients on PPI, 33 and five genes were higher, respectively, lower expressed. The majority of up-regulated genes were associated with lipid absorption, particularly triglyceride resynthesis and intracellular vesicular transport, rate-limiting processes for chylomicron production and secretion. Differential expression of 11 genes was confirmed by RT-PCR. Mucosal apoA-IV and CCK concentrations (signaling proteins released upon chylomicron secretion) were similar in GERD patients and HC. CONCLUSIONS: The identified mRNA expression differences suggest that in GERD patients' duodenum, the chylomicron production and secretion potential is elevated, and may underlie a mechanism by which postprandial duodenal signaling contributes to GERD symptom generation.

Use of social media by Western European hospitals: longitudinal study.

BACKGROUND: Patients increasingly use social media to communicate. Their stories could support quality improvements in participatory health care and could support patient-centered care. Active use of social media by health care institutions could also speed up communication and information provision to patients and their families, thus increasing quality even more. Hospitals seem to be becoming aware of the benefits social media could offer. Data from the United States show that hospitals increasingly use social media, but it is unknown whether and how Western European hospitals use social media. OBJECTIVE: To identify to what extent Western European hospitals use social media. METHODS: In this longitudinal study, we explored the use of social media by hospitals in 12 Western European countries through an Internet search. We collected data for each country during the following three time periods: April to August 2009, August to December 2010, and April to July 2011. RESULTS: We included 873 hospitals from 12 Western European countries, of which 732 were general hospitals and 141 were university hospitals. The number of included hospitals per country ranged from 6 in Luxembourg to 347 in Germany. We found hospitals using social media in all countries. The use of social media increased significantly over time, especially for YouTube (n = 19, 2% to n = 172, 19.7%), LinkedIn (n =179, 20.5% to n = 278, 31.8%), and Facebook (n = 85, 10% to n = 585, 67.0%). Differences in social media usage between the included countries were significant. CONCLUSIONS: Social media awareness in Western European hospitals is growing, as well as its use. Social media usage differs significantly between countries. Except for the Netherlands and the United Kingdom, the group of hospitals that is using social media remains small. Usage of LinkedIn for recruitment shows the awareness of the potential of social media. Future research is needed to investigate how social media lead to improved health care.

Serotonin receptor 3A polymorphism c.-42C > T is associated with severe dyspepsia.

BACKGROUND: The association between anxiety and depression related traits and dyspepsia may reflect a common genetic predisposition. Furthermore, genetic factors may contribute to the risk of having increased visceral sensitivity, which has been implicated in dyspeptic symptom generation. Serotonin (5-HT) modulates visceral sensitivity by its action on 5-HT3 receptors. Interestingly, a functional polymorphism in HTR3A, encoding the 5-HT3 receptor A subunit, has been reported to be associated with depression and anxiety related traits. A functional polymorphism in the serotonin transporter (5-HTT), which terminates serotonergic signalling, was also found associated with these psychiatric comorbidities and increased visceral sensitivity in irritable bowel syndrome, which coexistence is associated with higher dyspeptic symptom severity. We investigated the association between these functional polymorphisms and dyspeptic symptom severity. METHODS: Data from 592 unrelated, Caucasian, primary care patients with dyspepsia participating in a randomised clinical trial comparing step-up and step-down antacid drug treatment (The DIAMOND trial) were analysed. Patients were genotyped for HTR3A c.-42C > T SNP and the 44 bp insertion/deletion polymorphism in the 5-HTT promoter (5-HTTLPR). Intensity of 8 dyspeptic symptoms at baseline was assessed using a validated questionnaire (0 = none; 6 = very severe). Sum score ≥20 was defined severe dyspepsia. RESULTS: HTR3A c.-42T allele carriers were more prevalent in patients with severe dyspepsia (OR 1.50, 95% CI 1.06-2.20). This association appeared to be stronger in females (OR 2.05, 95% CI 1.25-3.39) and patients homozygous for the long (L) variant of the 5-HTTLPR genotype (OR 2.00, 95% CI 1.01-3.94). Females with 5-HTTLPR LL genotype showed the strongest association (OR = 3.50, 95% CI = 1.37-8.90). CONCLUSIONS: The HTR3A c.-42T allele is associated with severe dyspeptic symptoms. The stronger association among patients carrying the 5-HTTLPR L allele suggests an additive effect of the two polymorphisms. These results support the hypothesis that diminished 5-HT3 mediated antinociception predisposes to increased visceral sensitivity of the gastrointestinal tract. Moreover, the HTR3A c.-42C > T and 5-HTTLPR polymorphisms likely represent predisposing genetic variants in common to psychiatric morbidity and dyspepsia.

Intestinal permeability in irritable bowel syndrome patients: effects of NSAIDs.

Intestinal permeability and the effect of NSAIDs on permeability were investigated in 14 irritable bowel syndrome (IBS) patients and 15 healthy subjects. In the study, 24-h urinary recoveries of orally administered polyethylene glycols (PEGs 400, 1500, and 4000) were not significantly different in healthy subjects and IBS patients before or after NSAID ingestion. Lactulose mannitol ratios in healthy subjects and IBS patients were not significantly different. Only time-dependent monitoring of PEG excretion showed that NSAIDs enhanced intestinal permeability for PEG 4000 in healthy subjects (P = 0.050) and for PEGs 400, 1500, and 4000 in IBS patients (P = 0.012, P = 0.041, and P = 0.012, respectively). These results show that intestinal permeability in IBS patients is not different from that in healthy subjects; NSAIDs compromise intestinal permeability in IBS patients to a greater extent than in healthy subjects, which suggests that IBS is associated with an altered response of the intestinal barrier to noxious agents.

Diabetes mellitus and gastric emptying: questions and issues in clinical practice.

It is long known that both type 1 and type 2 diabetes can be associated with changes in gastric emptying; a number of publications have linked diabetes to delayed gastric emptying of variable severity and often with poor relationship to gastrointestinal symptomatology. In contrast, more recent studies have reported accelerated gastric emptying when adjusted for glucose concentration in patients with diabetes, indicating a reciprocal relationship between gastric emptying and ambient glucose concentrations. This review proposes that gastroparesis or gastroparesis diabeticorum, a severe condition characterized by a significant impairment of gastric emptying accompanied by severe nausea, vomiting, and malnutrition, is often overdiagnosed and not well contrasted with delays in gastric emptying. The article offers a clinically relevant definition of gastroparesis that should help differentiate this rare condition from (often asymptomatic) delays in gastric emptying. The fact that delayed gastric emptying can also be observed in non-diabetic individuals under experimental conditions in which hyperglycaemia is artificially induced suggests that a delay in gastric emptying rate when blood glucose concentrations are high is actually an appropriate physiological response to hyperglycaemia, slowing further increases in blood glucose. The article discusses the strengths and weaknesses of various methodologies for assessing gastric emptying, especially with respect to the diabetes population, and reviews newer diabetes therapies that decelerate the rate of gastric emptying. These therapies may be a beneficial tool in managing postprandial hyperglycaemia because they attenuate rapid surges in glucose concentrations by slowing the delivery of meal-derived glucose.

Increased intragastric pressure gradients are involved in the occurrence of acid reflux in gastroesophageal reflux disease.

OBJECTIVE: Increased pressure gradients across the esophagogastric junction (DeltaEGJp) play a role in gastroesophageal flow during TLESR. The aim of this study was to further explore DeltaEGJp in patients with gastroesophageal reflux disease (GERD) and controls. MATERIAL AND METHODS: Twenty GERD patients were studied along with 20 control subjects. High resolution manometry and pH recording were performed 1 h before and 2 h after a liquid meal (500 ml/300 kcal). DeltaEGJp was calculated at the start of a TLESR and at 180, 60, and 10 s before TLESR. RESULTS: DeltaEGJp at the start of a TLESR and at 180, 60, and 10 s before TLESR was markedly increased in GERD patients compared with that in control subjects (9.9 mmHg and 7.5 mmHg, respectively; p<0.05). Whilst intragastric pressure gradients in GERD patients were increased compared with those in controls (4.6 mmHg and 2.5 mmHg, respectively; p<0.01), intraesophageal pressure gradients were similar in both groups. Furthermore, in controls, first- and second-hour postprandial intragastric pressures were decreased compared with in fasting periods (1.9 +/- 0.4 mmHg and 2.1 +/- 0.4 mmHg versus 3.5 +/- 0.4 mmHg; p<0.05), while this was not observed in GERD patients. CONCLUSIONS: In GERD patients, DeltaEGJp is greater than that in controls both before and during TLESR. This phenomenon is caused by increased intragastric pressure and might contribute to increased rates of acid reflux during TLESR in GERD patients.

Functional dyspepsia and irritable bowel syndrome in patients with achalasia and its association with non-cardiac chest pain and a decreased health-related quality of life.

OBJECTIVE: In patients with achalasia, little is known about symptoms of the gastrointestinal tract other than the esophagus. The purpose of this study was to determine the prevalence of two functional disorders, functional dyspepsia (FD) and irritable bowel syndrome (IBS), in a group of treated achalasia patients and to assess the additional impact of these disorders on health-related quality of life (HRQoL). MATERIAL AND METHODS: Questionnaires assessing the Rome II criteria for FD and IBS together with the Eckardt clinical symptom score and RAND-36 were sent to 171 treated achalasia patients. RESULTS: Of these patients, 76.6% returned their questionnaires. In the group of achalasia patients, 23% fulfilled the criteria for FD (Dutch general population 13-14%), and 21% fulfilled the criteria for IBS (Dutch general population 1-6%). The prevalence of frequent chest pain (at least weekly) was higher in patients with FD and/or IBS than in those without these symptoms (54.2% versus 28.2%; p=0.004). Female patients with achalasia and with frequent chest pain showed a higher probability of fulfilling the FD and/or IBS criteria (adjusted OR 2.90 (1.18-7.14) and 3.35 (1.4-8.1), respectively; both with p <0.05). Patients fulfilling the FD and/or IBS criteria scored a lower HRQoL on the RAND-36 subscales--pain, social functioning, and vitality--as compared with patients not fulfilling these criteria (p <0.006). CONCLUSIONS; Symptoms of FD and IBS in patients with treated achalasia are common and have a negative impact on HRQoL. Therefore, this has to be included in the standard evaluation of achalasia patients. The association with chest pain suggests a mutual underlying mechanism.

Gastroesophageal pressure gradients in gastroesophageal reflux disease: relations with hiatal hernia, body mass index, and esophageal acid exposure.

OBJECTIVES: The roles of intragastric pressure (IGP), intraesophageal pressure (IEP), gastroesophageal pressure gradient (GEPG), and body mass index (BMI) in the pathophysiology of gastroesophageal reflux disease (GERD) and hiatal hernia (HH) are only partly understood. METHODS: In total, 149 GERD patients underwent stationary esophageal manometry, 24-h pH-metry, and endoscopy. RESULTS: One hundred three patients had HH. Linear regression analysis showed that each kilogram per square meter of BMI caused a 0.047-kPa increase in inspiratory IGP (95% confidence interval [CI] 0.026-0.067) and a 0.031-kPa increase in inspiratory GEPG (95% CI 0.007-0.055). Each kilogram per square meter of BMI caused expiratory IGP to increase with 0.043 kPa (95% CI 0.025-0.060) and expiratory IEP with 0.052 kPa (95% CI 0.027-0.077). Each added year of age caused inspiratory IEP to decrease by 0.008 kPa (95% CI -0.015-0.001) and inspiratory GEPG to increase by 0.008 kPa (95% CI 0.000-0.015). In binary logistic regression analysis, HH was predicted by inspiratory and expiratory IGP (odds ratio [OR] 2.93 and 2.62, respectively), inspiratory and expiratory GEPG (OR 3.19 and 2.68, respectively), and BMI (OR 1.72/5 kg/m(2)). In linear regression analysis, HH caused an average 5.09% increase in supine acid exposure (95% CI 0.96-9.22) and an average 3.46% increase in total acid exposure (95% CI 0.82-6.09). Each added year of age caused an average 0.10% increase in upright acid exposure and a 0.09% increase in total acid exposure (95% CI 0.00-0.20 and 0.00-0.18). CONCLUSIONS: BMI predicts IGP, inspiratory GEPG, and expiratory IEP. Age predicts inspiratory IEP and GEPG. Presence of HH is predicted by IGP, GEPG, and BMI. GEPG is not associated with acid exposure.

Critical evaluation of diagnosing bacterial overgrowth in the proximal small intestine.

BACKGROUND: Clinical small bowel bacterial overgrowth (SBBO) syndrome can be objectified by bacterial overgrowth tests. As direct culture of jejunal aspirates has disadvantages, noninvasive tests such as breath tests (BTs) are used. Major drawback of lactulose BT might be rapid lactulose transit to the colon. We evaluated diagnosing bacterial overgrowth using experimental and standard BT, and culture and molecular-based methods. STUDY: Bacterial overgrowth was analyzed in 11 controls and 15 SBBO predisposed subjects. During experimental breath testing, an occlusive balloon limited lactulose to the small intestine. Jejunal fluid was analyzed using culture and molecular-based methods. Bacterial overgrowth was diagnosed on the basis of 20 ppm hydrogen or methane increase above baseline within 90 minutes or more than 10 CFU/mL excluding lactobacilli and streptococci and furthermore using all published definitions. RESULTS: Experimental and standard BT showed no changes in timing of hydrogen excretion between controls and SBBO subjects. Using standard BT, 3/11 controls and 8/15 SBBO subjects were bacterial overgrowth positive. Total counts showed no significant differences between controls and SBBO subjects using culture and molecular-based methods. Bacterial overgrowth was diagnosed in 0/9 controls and 4/12 SBBO subjects using culture-based methods. Other definitions used in literature revealed no significant differences between controls and SBBO subjects. CONCLUSIONS: In a small group of subjects, the experimental BT did not improve the ability of lactulose BT to diagnose bacterial overgrowth. Culturing showed less bacterial overgrowth in controls compared with BT. Remarkably, current diagnostic criteria do not seem to be accurate in discriminating between SBBO subjects and controls.

Reliability of oesophageal pH recording for the detection of gastro-oesophageal reflux.

OBJECTIVE: Despite the new gold standard oesophageal impedance monitoring, pH monitoring is still used frequently for detection of gastro-oesophageal reflux (GOR). Besides drops in pH from above to below pH4, drops of > or =1 unit are also used as a marker for GOR. In this study the objective was to investigate the accuracy of drops in pH for detection of GOR, using impedance monitoring as the gold standard. MATERIAL AND METHODS: Nineteen GORD patients (9 M, 55+/-11 years) underwent combined 24-h pH-impedance recording off acid-suppressive therapy. All drops in pH > or =0.5 pH units, with a duration > or =4 s, reaching the nadir pH within 5 s after onset were included. Reflux events detected with impedance monitoring were taken as the reference. RESULTS: In total, 2221 drops in pH were found; 47% were acid (nadir pH <4), 47% weakly acidic (nadir pH between pH7 and 4) and 5% were superimposed (pH drop starting below pH4). The sensitivities of acid, weakly acidic and superimposed pH drops > or =1 were 91%, 28%, 24%, respectively, and the percentages of false-positive reflux episodes were 20, 56 and 54, respectively. Acid reflux with a cut-off > or =0.5 and < or =3.3 had a moderate-to-good sensitivity (94-70%) and low false-positive percentages (23-13%). In contrast, weakly acidic and superimposed reflux showed greater false-positive than true-positive percentages for all cut-off values. CONCLUSIONS: Compared to impedance monitoring, detection of reflux with pH monitoring is clearly inferior. When drops in pH > or =1 are used irrespective of nadir pH as an indicator of reflux episodes, the number of reflux episodes is overestimated. Decreases from above to below 4 with cut-offs between > or =0.5 and < or =3.3 are the most indicative of true reflux episodes.

C-reactive protein levels during a relapse of Crohn's disease are associated with the clinical course of the disease.

AIM: To explore if C-reactive protein (CRP) levels might serve as a prognostic factor with respect to the clinical course of Crohn's disease and might be useful for classification. METHODS: In this retrospective cohort study we enrolled 94 patients from the inflammatory bowel disease (IBD) database of the University Medical Centre Utrecht. CRP levels during relapse were correlated with the number of relapses per year. Severity of relapses was based on endoscopic reports and prednisone use. Furthermore, patients were categorized in a low or high CRP group based on their CRP response during relapse and demographic and clinical features were compared. RESULTS: Overall, a positive correlation between CRP levels, number of relapses, and severity of relapse was found (respectively rs = 0.31, P < 0.01 and rs = 0.50, P < 0.001). Employing a cut-off level of 15 mg/L, the index CRP level was found to discriminate patients with respect to the number of relapses per year, as well as for severity of relapses (respectively 0.25 +/- 0.16 vs 0.36 +/- 0.24, P < 0.05 and 4.4 +/- 1.2 vs 3.2 +/- 1.1 on a 10-point visual analogue scale, P < 0.001 for the high CRP and low CRP groups respectively). In addition, the high CRP group showed more cumulative days of prednisone use per year (107 +/- 95 vs 58 +/- 48, P < 0.05), as well as a better response to infliximab (93 % vs 33 %, P = 0.06). CONCLUSION: A higher CRP level during relapse seems to be associated with a more severe clinical course of disease.

Serotonin synthesis and uptake in symptomatic patients with Crohn's disease in remission.

BACKGROUND & AIMS: Symptoms resembling irritable bowel syndrome (IBS) are reported frequently in Crohn's disease (CD) patients in remission. Studies of the mucosal content of serotonin, which is a pivotal neurotransmitter in the gut, suggest that serotonin availability is altered in IBS patients. We aimed to study the role of serotonin in the generation of IBS-like symptoms in CD patients in remission. METHODS: Ileal and colonic biopsy specimens were obtained from 20 CD patients in remission, 10 with and 10 without IBS-like symptoms, and 11 healthy controls. Enterochromaffin cells were counted, and messenger RNA expression levels of tryptophan hydroxylase (TpH)-1 and serotonin reuptake transporter were determined. RESULTS: The levels of mucosal serotonin reuptake transporter expression were significantly higher in the ileum than in the colon, in all groups studied (P < .02). When the ileum and colon were analyzed separately, TpH-1 expression in the colon of CD patients with IBS-like symptoms was found to be significantly higher compared with the 2 other studied groups (controls, P < .005; CD patients without IBS-like symptoms, P < .01). The number of enterochromaffin cells per gland was comparable for the patient groups in the ileum and colon. CONCLUSIONS: CD patients in remission who experience IBS-like symptoms have increased mucosal TpH-1 levels in the colon, suggesting that increased serotonin biosynthesis in the colon plays a role in the generation of the symptoms.

What predicts mucosal inflammation in Crohn's disease patients?

A number of disease-specific instruments have been created over the last 30 years to assess disease activity in Crohn's disease (CD). These disease activity indices are constituted of clinical and laboratory parameters and their role in predicting disease activity and the course of disease has been reviewed various times. Currently, the severity of mucosal inflammation, assessed by endoscopy, is considered the gold standard for disease activity in CD. In the present review the most frequently used endoscopic disease activity indices and the correlation between mucosal inflammation and clinical disease activity indices, quality of life questionnaires, and biochemical markers is critically appraised. We conclude that no clinical disease activity index or single laboratory parameter of inflammation reliably predicts the mucosal inflammatory disease activity. A new, easy-to-use and robust activity index predicting mucosal inflammation is highly needed to assess the response to investigational drugs in trials and the effect of therapeutical interventions in clinical practice.

Pragmatic trials in primary care. Methodological challenges and solutions demonstrated by the DIAMOND-study.

BACKGROUND: Pragmatic randomised controlled trials are often used in primary care to evaluate the effect of a treatment strategy. In these trials it is difficult to achieve both high internal validity and high generalisability. This article will discuss several methodological challenges in designing and conducting a pragmatic primary care based randomised controlled trial, based on our experiences in the DIAMOND-study and will discuss the rationale behind the choices we made. From the successes as well as the problems we experienced the quality of future pragmatic trials may benefit. DISCUSSION: The first challenge concerned choosing the clinically most relevant interventions to compare and enable blinded comparison, since two interventions had very different appearances. By adding treatment steps to one treatment arm and adding placebo to both treatment arms both internal and external validity were optimized. Nevertheless, although blinding is essential for a high internal validity, it should be warily considered in a pragmatic trial because it decreases external validity. Choosing and recruiting a representative selection of participants was the second challenge. We succeeded in retrieving a representative relatively large patient sample by carefully choosing (few) inclusion and exclusion criteria, by random selection, by paying much attention to participant recruitment and taking the participant's reasons to participate into account. Good and regular contact with the GPs and patients was to our opinion essential. The third challenge was to choose the primary outcome, which needed to reflect effectiveness of the treatment in every day practice. We also designed our protocol to follow every day practice as much as possible, although standardized treatment is usually preferred in trials. The aim of this was our fourth challenge: to limit the number of protocol deviations and increase external validity. SUMMARY: It is challenging to design and conduct a pragmatic trial. Thanks to thorough preparation, we were able to collect highly valid data. To our opinion, a critical deliberation of where on the pragmatic--explanatory spectrum you want your trial to be on forehand, in combination with consulting publications especially on patient recruitment procedures, has been helpful in conducting a successful trial.

Crohn's disease, fatigue, and infliximab: is there a role for cytokines in the pathogenesis of fatigue?

AIM: To study the effect of infliximab on fatigue in relation to cytokine levels in Crohn's disease (CD) patients. METHODS: Fourteen CD patients were blinded for treatment and received placebo at baseline, and infliximab 2 wk later, with a follow-up of 4 wk. Blood samples were drawn on a regular basis, and questionnaires on fatigue, depression, quality of life, and clinical disease activity were completed at regular intervals. RESULTS: After placebo infusion, fatigue scores decreased within 3 d (3.5 points +/- 1.1, P

Evaluation of gallbladder motility: comparison of two-dimensional and three-dimensional ultrasonography.

Since impaired gallbladder emptying contributes to gallstone formation, the evaluation of gallbladder motility requires accurate methodology. Recently developed 3-dimensional ultrasonography may take into account various gallbladder shapes more accurately than conventional 2-dimensional ultrasonography. Therefore, volumes of water-filled balloons of various sizes were determined in vitro by 2-dimensional ultrasonography with the sum of cylinders method and by 3-dimensional ultrasonography. Also, in 15 gallstone patients and 6 healthy volunteers, fasting gallbladder volumes and postprandial motility were determined by both methods. Volumes of water-filled balloons as measured by both methods correlated strongly with true volumes (R= 0.93 for 2-dimensional and R = 0.98 for 3- dimensional ultrasonography). Gallbladder volumes measured by both methods were also correlated (R = 0.66, P <0.001). In gallstone patients, 3-dimensional ultrasonography yielded smaller gallbladder volumes than 2-dimensional ultrasonography (P = 0.007), but not in healthy subjects. With both methods, gallstone patients exhibited decreased postprandial gallbladder motility compared to healthy subjects. In conclusion, gallbladder volume measurements by 3-dimensional and 2-dimensional ultrasonography are strongly correlated.Nevertheless, in gallstone patients, gallbladder volumes by 3-dimensional ultrasonography tend to be smaller than by 2-dimensional ultrasonography, possibly due to interference of gallstones with the volume measurement.

Small bowel motility affects glucose absorption in a healthy man.

OBJECTIVE: To investigate the relationship between duodenojejunal motor activity and glucose absorption and to evaluate the effect of modification of duodenojejunal motility on glucose absorption by using the prokinetic drug cisapride. RESEARCH DESIGN AND METHODS: We examined seven healthy males, mean age 22 years, who were treated with cisapride 10 mg t.i.d. and placebo during 3 days in a randomized order, with a 2-week time interval. Duodenojejunal manometry was performed after each treatment on the morning of day 3, using an 18-lumen catheter. A liquid nutrient (3 kcal/min) was administered intraduodenally for 30 min, followed by a bolus of the glucose analog 3-O-methylglucose (3-OMG). Plasma 3-OMG concentrations were measured to assess absorption kinetics. RESULTS: The area under the 3-OMG concentration curve in the first 30 min after infusion was related to the number of antegrade propagated pressure waves (r = 0.49, P < 0.05), but not to the peak concentration, time to peak, and absorption fraction. The mean amplitude of pressure waves was higher during cisapride than placebo (P < 0.05), but the reoccurrence of interdigestive motility, numbers of pressure waves, and propagated pressure waves, as well as 3-OMG absorption characteristics, were not significantly different between the two treatments. During both treatments >60% of antegrade propagated pressure waves were propagated over a very short distance (1.5 cm). CONCLUSIONS: Glucose absorption in the human small intestine is related to short-traveling propagated intestinal contractile activity. Cisapride increases the amplitude of pressure waves, but does not affect the organization of pressure waves or the absorption of 3-OMG.