Comparison of two endoscope channel cleaning approaches to remove cyclic build-up biofilm.

INTRODUCTION: Biofilm contributes significantly to bacterial persistence in endoscope channels. Enhanced cleaning methods capable of removing biofilm from all endoscope channels are required to decrease infection risk to patients. This head-to-head study compared cyclic build-up biofilm removal of an automated endoscope channel cleaner (AECC) with standard manual cleaning according to instructions for use (IFU) in polytetrafluorethylene channels. METHODS: Cyclic build-up biofilm was grown in 1.4-mm (representing air/water and auxiliary channels) and 3.7-mm (representing suction/ biopsy channels) inner diameter polytetrafluorethylene channels. All channels were tested for residual total organic carbon, protein, and viable bacteria. Internationally recognized ISO 15883-5:2021 alert levels were used as cleaning benchmarks for protein (3 µg/cm2) and total organic carbon (6 µg/cm2). RESULTS: The automated cleaner significantly outperformed manual cleaning for all markers assessed (protein, total organic carbon, viable bacteria) in 1.4-mm and 3.7-mm channels representing air/water/auxiliary and suction/biopsy channels, respectively. Manual cleaning failed to remove biofilm from the air/water and auxiliary channels. According to the IFU, these channels are not brushed, suggesting a potential root cause for a portion of the numerous endoscopy-associated infections reported in the literature. CONCLUSION: AECC shows potential to deliver enhanced cleaning over current practice to all endoscope channels and may thereby address infection risk.

Variation in General Dentists' Patterns of Sealant Use in Children with Elevated Caries Risk.

INTRODUCTION: Strong evidence supports use of dental sealants to prevent tooth decay, and professional guidelines recommend use in children with elevated caries risk. However, not all children indicated for sealants receive this preventive intervention, even when they use routine dental care. OBJECTIVE: The aim of this study was to explore the extent to which dentists' use of sealants varied in pediatric patients with elevated caries risk. METHODS: Claims and enrollment data from a private dental program were used to identify a cohort of 6- to 17-y-olds with elevated caries risk (N = 27,677) and general dentists (N = 818) who provided services to the children. Children were identified as having elevated caries risk based on history of restorative treatment over a 5-y period (2010-2014). The 2 outcomes of interest were whether a dentist provided any sealants to children with elevated risk and, if so, the extent to which these were used during a 2-y observation period (2013-2014). A 2-stage hurdle model was used for multivariable analysis to identify dentist characteristics associated with sealant use. RESULTS: Over the observation period, 13.3% (n = 109) of dentists did not provide any sealants to their elevated risk patients from the study cohort. Logistic regression found that female dentists were significantly more likely to have used sealants (odds ratio = 2.27); dentist age and practice in an isolated small rural town were negatively associated with any sealant use. However, among dentists who did place sealants (n = 709), female dentists, older dentists, dentists in solo practice, and those working full-time were significantly more likely to provide sealants to a child. Overall, substantial variation in practitioners' use of sealants was observed. CONCLUSION: This is the first study to explore provider-level variation in sealant use, representing a critical step in future efforts to increase routine use of sealants by dentists and eliminate oral health disparities. KNOWLEDGE TRANSFER STATEMENT: Findings from this study can be used to design targeted policy and behavioral interventions to increase sealant use by general dentists. This study provides foundational evidence for future research that explores motivation and barriers to routine use of preventive dental interventions by clinicians.

Exploring psychological mechanisms of clinical response to an internet-delivered psychological pain management program.

BACKGROUND: The evidence for Internet-delivered pain management programs for chronic pain is growing, but there is little empirical understanding of how they effect change. Understanding mechanisms of clinical response to these programs could inform their effective development and delivery. METHODS: A large sample (n = 396) from a previous randomized controlled trial of a validated internet-delivered psychological pain management program, the Pain Course, was used to examine the influence of three potential psychological mechanisms (pain acceptance, pain self-efficacy, fear of movement/re-injury) on treatment-related change in disability, depression, anxiety and average pain. Analyses involved generalized estimating equation models for clinical outcomes that adjusted for co-occurring change in psychological variables. This was paired with cross-lagged analysis to assess for evidence of causality. Analyses involved two time points, pre-treatment and post-treatment. RESULTS: Changes in pain-acceptance were strongly associated with changes in three (depression, anxiety and average pain) of the four clinical outcomes. Changes in self-efficacy were also strongly associated with two (anxiety and average pain) clinical outcomes. These findings suggest that participants were unlikely to improve in these clinical outcomes without also experiencing increases in their pain self-efficacy and pain acceptance. However, there was no clear evidence from cross-lagged analyses to currently support these psychological variables as direct mechanisms of clinical improvements. There was only statistical evidence to suggest higher levels of self-efficacy moderated improvements in depression. CONCLUSIONS: The findings suggest that, while clinical improvements are closely associated with improvements in pain acceptance and self-efficacy, these psychological variables may not drive the treatment effects observed. SIGNIFICANCE: This study employed robust statistical techniques to assess the psychological mechanisms of an established internet-delivered pain management program. While clinical improvements (e.g. depression, anxiety, pain) were closely associated with improvements in psychological variables (e.g. pain self-efficacy and pain acceptance), these variables do not appear to be treatment mechanisms.

Rydberg-Dressed Magneto-optical Trap.

We propose and demonstrate the laser cooling and trapping of Rydberg-dressed Sr atoms. By off-resonantly coupling the excited state of a narrow (7 kHz) cooling transition to a high-lying Rydberg state, we transfer Rydberg properties such as enhanced electric polarizability to a stable magneto-optical trap operating at <1 µK. Simulations show that it is possible to reach a regime where the long-range interaction between Rydberg-dressed atoms becomes comparable to the kinetic energy, opening a route to combining laser cooling with tunable long-range interactions.

The Effects of Medical Well Baby Visits in Promoting Earlier First Dental Visits for Children.

The objective of the study was to assess the effects of medical well baby visits in promoting earlier first dental visits. We analyzed Iowa Medicaid claims data (2000-2013). The sample included 4 cohorts of children born in 2000, 2003, 2007, or 2010 and enrolled in Medicaid from birth (N = 38,211). Children were followed for 3 y. The independent variables were cohort year and medical well baby visit frequency during 3 time periods (birth to age 10 mo, ages 11-19 mo, ages 20-36 mo). We used survival analyses to estimate first dental visit rates. First dental visit rates improved significantly from 2000 to 2013, with children in latter cohorts having significantly earlier first dental visits. Children with more medical well baby visits before age 11 mo had significantly delayed first dental visit rates than children with fewer medical well baby visits. The opposite was observed for children with more medical well baby visits between ages 11 to 19 mo and ages 20 to 36 mo. First dental visit rates for Medicaid-enrolled children have improved, but there continues to be a need for early interventions to improve age 1 dental visits and other preventive oral health behaviors. Knowledge Transfer Statement: The results of this study can be used by policy makers when developing strategies to improve access to dental care for young children in Medicaid. With consideration to promoting earlier preventive dental visits for publicly insured children, this study could lead to early interventions and improved health outcomes.

The cost of a patient activation intervention for achieving successful outcomes: results from the PAADRN randomized controlled trial.

In a large, pragmatic clinical trial, we calculated the costs of achieving four successful patient-centered outcomes using a tailored patient activation DXA result letter accompanied by a bone health brochure. The cost to achieve one successful outcome (e.g., a 0.5 standard deviation improvement in care satisfaction) ranged from $127.41 to $222.75. INTRODUCTION: Pragmatic randomized controlled trials (RCTs) should focus on patient-centered outcomes and report the costs for achieving those outcomes. We calculated per person incremental intervention costs, the number-needed-to-treat (NNT), and incremental per patient costs (cost per NNT) for four patient-centered outcomes in a direct-to-patient bone healthcare intervention. METHODS: The Patient Activation after DXA Result Notification (PAADRN) pragmatic RCT enrolled 7749 patients presenting for DXA at three health centers between February 2012 and August 2014. Interviews occurred at baseline and 52 weeks post-DXA. Intervention subjects received an individually tailored DXA result letter accompanied by an educational bone health brochure 4 weeks post-DXA, while the usual care subjects did not. Outcomes focused on patients (a) correctly identifying their results, (b) contacting their providers, (c) discussing their results with their providers, and (d) satisfaction with their bone healthcare. NNTs were determined using intention-to-treat linear probability models, per person incremental intervention costs were calculated, and costs per NNT were computed. RESULTS: Mean age was 66.6 years old, 83.8% were women, and 75.3% were non-Hispanic whites. The incremental per patient cost (costs per NNT) to increase the ability of a patient to (a) correctly identify their DXA result was $171.07; (b) contact their provider about their DXA result was $222.75; (c) discuss their DXA result with their provider was $193.55; and (d) achieve a 0.5 SD improvement in satisfaction with their bone healthcare was $127.41. CONCLUSION: An individually tailored DXA result letter accompanied by an educational brochure can improve four patient-centered outcomes at a modest cost. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT01507662.

The effects of a patient activation intervention on smoking and excessive drinking cessations: results from the PAADRN randomized controlled trial.

Patients may exhibit risky bone health behaviors. In a large pragmatic clinical trial, we tested whether a tailored patient activation DXA result letter accompanied by a bone health brochure led to smoking and excessive drinking cessations. The intervention did not, however, alter these risky bone health behaviors. INTRODUCTION: Besides dual-energy x-ray absorptiometry (DXA) screening and pharmacotherapy when indicated, beneficial bone health behaviors including proper calcium and vitamin D intake and weight-bearing and muscle-strengthening exercise should be encouraged. Similarly, risky bone health behaviors like smoking and excessive drinking should be discouraged. We examined whether a direct-to-patient activation intervention led to smoking and excessive drinking cessations. METHODS: The Patient Activation after DXA Result Notification (PAADRN) pragmatic clinical trial enrolled 7749 patients between February 2012 and August 2014. Interviews occurred at baseline and 12 and 52 weeks later. Intervention subjects were mailed an individually tailored DXA results letter accompanied by a bone health educational brochure 4 weeks post-DXA. Usual care subjects were not sent these materials. Smoking and excessive drinking were assessed by self-report at each interview. Intention-to-treat linear probability models were used. RESULTS: Mean age was 66.6 years, 83.8% were women, and 75.3% were Non-Hispanic-Whites. Smoking was reported at baseline by 7.6% of the intervention group vs. 7.7% of the usual care group (p = 0.873). Excessive drinking was reported at baseline by 6.5% of the intervention group vs. 6.5% of the usual care group (p = 0.968). Intention-to-treat analyses indicated no significant differences between the intervention vs. usual care groups at either 12 or 52 weeks post-DXA (all p values ≥ 0.346). CONCLUSION: An individually tailored DXA result letter accompanied by an educational brochure did not lead to smoking or excessive drinking cessations in patients who received DXA. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT01507662.

Cortisol levels in hair are altered in irritable bowel syndrome - A case control study in primary care.

OBJECTIVE: Stress is an important component in the pathophysiology of irritable bowel syndrome (IBS). Long term Hypothalamus Pituitary Adrenal (HPA)-axis activity can be studied by measuring hair cortisol concentrations (HCC). Some previous studies have indicated a dysregulated HPA-axis in IBS patients, but cortisol levels in hair have not yet been studied. We investigated whether HCC and self-reported stress differentiate IBS patients from controls. METHODS: In a cross-sectional study within 10 Swedish Primary Health Care Centers we compared patients in working age with active IBS to patients without GI complaints. The participants donated hair samples and completed questionnaires including a scale of self-reported perceived stress (PSS). 169 Rome III-fulfilling IBS patients and 316 non-IBS patients were available for final analyses. RESULTS: IBS patients had significantly lower HCC, median=16.3pg/mg, IQR=26.9pg/mg, compared to non-IBS patients, median=22.8pg/mg, IQR=29.1pg/mg. There was also a difference in the distribution of HCC quintiles between the two groups, with 30.2% IBS patients and 14.2% of non-IBS patients in the lowest quintile of HCC. PSS was higher among IBS patients with a mean (SD) total score of 25.3 (8.0) compared to controls 21.4, (7.5). Quintiles of HCC and PSS stayed significantly but very weakly related to IBS (B=-0.332, Std error=0.146, p<0.005) in multivariable analyses. CONCLUSION: This study suggests a possible suppression of the HPA-axis activity in a considerable portion of IBS patients.

The epidemiology of irritable bowel syndrome: Symptom development over a 3-year period in Denmark. A prospective, population-based cohort study.

BACKGROUND: We aimed to explore the natural history of irritable bowel syndrome (IBS) in Denmark over 3 years by studying development of IBS symptoms and associated factors. METHODS: A cohort study was carried out using a web panel representative of the Danish general population 18-50 years. The survey, including a questionnaire based on the Rome III criteria for IBS, was conducted in January 2010, January 2011, and March 2013. KEY RESULTS: The prevalence of IBS was 15.4% (920/5986). The incidence was 10.3%, and was three times higher for persons with unspecific gastrointestinal (GI) symptoms compared to asymptomatic persons. Of respondents with IBS symptoms in both 2010 and 2011, 69% (131/191) also reported symptoms of IBS in 2013, which was significantly more compared to respondents with IBS symptoms in 2010 reporting to be asymptomatic or having unspecific GI symptoms in 2011 (20% and 39%, respectively, P<.001). Being diagnosed with IBS predicted fulfilling the criteria for IBS 3 years later (OR: 2.59, 95% CI: 1.11-6.10). Fulfilling criteria for IBS after 1 year also led to a high risk of IBS symptoms 3 years later in asymptomatic persons and persons with unspecific symptoms at baseline. CONCLUSIONS & INFERENCES: The vast majority of persons fulfilling criteria for IBS report GI symptoms after one and 3 years. Fulfilling IBS criteria after 1 year led to a high risk of reporting IBS symptoms after 3 years. In the general population having an IBS diagnosis predicts persistently fulfilling the Rome III criteria for IBS 3 years later.

Predictors of bone mineral density testing among older women on Medicare.

Although dual-energy X-ray absorptiometry (DXA) is recommended for all women ≥65 and is covered by Medicare, 40 % of women on Medicare report never having had a DXA. In a longitudinal cohort of 3492 women followed for two decades, we identified several risk factors that should be targeted to improve DXA testing rates. INTRODUCTION: DXA is used to measure bone mineral density, screen for osteoporosis, and assess fracture risk. DXA is recommended for all women ≥65 years old. Although Medicare covers DXA every 24 months for women, about 40 % report never having had a DXA test, and little is known from prospective cohort studies about which subgroups of women have low use rates and should be targeted for interventions. Our objective was to identify predictors of DXA use in a nationally representative cohort of women on Medicare. METHODS: We used baseline and biennial follow-up survey data (1993-2012) for 3492 women ≥70 years old from the nationally representative closed cohort known as the Survey on Assets and Health Dynamics among the Oldest Old (AHEAD). The survey data for these women were then linked to their Medicare claims (1991-2012), yielding 17,345 person years of observation. DXA tests were identified from the Medicare claims, and Cox proportional hazard regression models were used with both fixed and time-dependent predictors from the survey interviews including demographic characteristics, socioeconomic factors, health status, health habits, and the living environment. RESULTS: DXA use was positively associated with being Hispanic American, better cognition, higher income, having arthritis, using other preventative services, and living in Florida or other southern states. DXA use was negatively associated with age, being African-American, being overweight or obese, having mobility limitations, and smoking. CONCLUSIONS: Interventions to increase DXA use should target the characteristics that were observed here to be negatively associated with such screening.

Patient-activation and guideline-concordant pharmacological treatment after bone density testing: the PAADRN randomized controlled trial.

Patients often do not know or understand their bone density test results, and pharmacological treatment rates are low. In a clinical trial of 7749 patients, we used a tailored patient-activation result letter accompanied by a bone health brochure to improve appropriate pharmacological treatment. Treatment rates, however, did not improve. INTRODUCTION: Patients often do not know or understand their dual-energy x-ray absorptiometry (DXA) test results, which may lead to suboptimal care. We tested whether usual care augmented by a tailored patient-activation DXA result letter accompanied by an educational brochure would improve guideline-concordant pharmacological treatment compared to usual care only. METHODS: We conducted a randomized, controlled, double-blinded, pragmatic clinical trial at three health care centers in the USA. We randomized 7749 patients ≥50 years old and presenting for DXA between February 2012 and August 2014. The primary clinical endpoint at 12 and 52 weeks post-DXA was receiving guideline-concordant pharmacological treatment. We also examined four of the steps along the pathway from DXA testing to that clinical endpoint, including (1) receiving and (2) understanding their DXA results and (3) having subsequent contact with their provider and (4) discussing their results and options. RESULTS: Mean age was 66.6 years, 83.8 % were women, and 75.3 % were non-Hispanic whites. Intention-to-treat analyses revealed that guideline-concordant pharmacological treatment was not improved at either 12 weeks (65.1 vs. 64.3 %, p = 0.506) or 52 weeks (65.2 vs. 63.8 %, p = 0.250) post-DXA, even though patients in the intervention group were more likely (all p < 0.001) to recall receiving their DXA results letter at 12 weeks, correctly identify their results at 12 and 52 weeks, have contact with their provider at 52 weeks, and have discussed their results with their provider at 12 and 52 weeks. CONCLUSION: A tailored DXA result letter and educational brochure failed to improve guideline-concordant care in patients who received DXA.

Autonomic nervous system function predicts the inflammatory response over three years in newly diagnosed ulcerative colitis patients.

BACKGROUND: The autonomic nervous system (ANS) modulates intestinal inflammation in animal models. Human evidence confirming such modulating influence is limited. We aimed to investigate whether ANS function is associated with inflammatory parameters at disease onset, and whether it predicts the evolution of inflammation in patients with ulcerative colitis (UC). METHODS: We prospectively monitored 51 patients from onset of UC for 3 years. Upon remission of the onset flare, ANS activity was assessed by heart rate variability analysis and compared with healthy controls. Inflammatory parameters in blood, stool, and colonic biopsies obtained at onset and during follow-up visits were analyzed. Generalized linear models were used to test cross-sectional associations between ANS activity and inflammatory parameters at onset; linear mixed models were used to test whether ANS function at onset predicted the evolution of inflammation over the following 3 years. KEY RESULTS: Sympathovagal balance was different in UC patients compared to healthy controls, and cross-sectional associated with higher levels of systemic (erythrocyte sedimentation rate [ESR], CRP, TNF-α, IFN-γ) and mucosal inflammation (interleukin-8, IFN-γ) at onset. Conversely, a negative cross-sectional association with parasympathetic activity was found for ESR & TNF-α. Longitudinally, parasympathetic activity at onset predicted systemic (ESR, WBC), but not mucosal inflammation during follow-up. CONCLUSIONS & INFERENCES: This study further strengthens the association between the ANS system and intestinal inflammation previously found in animal models and recently in patients with inflammatory bowel disease. These results may have important implications for the pathogenesis and treatment of UC.

Liver-related mortality in countries of the developed world: an ecological study approach to explain the variability.

BACKGROUND: Liver-related mortality varies across developed nations. AIM: To assess the relative role of various risk factors in relation to liver-related mortality in an ecological study approach. METHODS: Data for liver-related mortality, prevalence data for hepatitis B and C, human immunodeficiency virus (HIV), alcohol consumption per capita, Type 2 Diabetes mellitus (T2DM), overweight and obesity were extracted from peer-reviewed publications or WHO databases for different developed countries. As potential other risk-modifying factors, purchase power parity (PPP)-adjusted gross domestic product (GDP) per capita and health expenditure per capita were assessed. As an environmental 'hygiene factor', we also assessed the effect of the prevalence of Helicobacter pylori. Only countries with a PPP-adjusted GDP greater than $20 000 and valid information for at least 8 risk modifiers were included. Univariate and multivariate analyses were utilised to quantify the contribution to the variability in liver-related mortality. RESULTS: The proportion of chronic liver diseases (CLD)-related mortality ranged from 0.73-2.40% [mean 1.56%, 95% CI (1.43-1.69)] of all deaths. Univariately, CLD-related mortality was significantly associated with Hepatitis B prevalence, alcohol consumption, PPP-adjusted GDP (all P < 0.05) and potentially H. pylori prevalence (P = 0.055). Other investigated factors, including hepatitis C, did not yield significance. Backward elimination suggested hepatitis B, alcohol consumption and PPP-adjusted GDP as risk factors (explaining 66.3% of the variability). CONCLUSION: Hepatitis B infection, alcohol consumption and GDP, but not hepatitis C or other factors, explain most of the variance of liver-related mortality.

The influence of image valence on visual attention and perception of risk in drivers.

Currently there is little research into the relationship between emotion and driving in the context of advertising and distraction. Research that has looked into this also has methodological limitations that could be affecting the results rather than emotional processing (Trick et al., 2012). The current study investigated the relationship between image valence and risk perception, eye movements and physiological reactions. Participants watched hazard perception clips which had emotional images from the international affective picture system overlaid onto them. They rated how hazardous or safe they felt, whilst eye movements, galvanic skin response and heart rate were recorded. Results suggested that participants were more aware of potential hazards when a neutral image had been shown, in comparison to positive and negative valenced images; that is, participants showed higher subjective ratings of risk, larger physiological responses and marginally longer fixation durations when viewing a hazard after a neutral image, but this effect was attenuated after emotional images. It appears that emotional images reduce sensitivity to potential hazards, and we suggest that future studies could apply these findings to higher fidelity paradigms such as driving simulators.

Increased prevalence of autoimmune diseases in functional gastrointestinal disorders: case-control study of 23471 primary care patients.

BACKGROUND: There is increasing evidence that impaired mucosal defence mechanisms are implicated in the pathogenesis of the functional gastrointestinal disorders (FGIDs), allowing inappropriate immune activation. AIM: To test the hypothesis that an excess of autoimmune disorders among sufferers, using a large primary care database to examine this. METHODS: Cases were diagnosed with FGIDs - irritable bowel syndrome (IBS), functional dyspepsia (FD), chronic idiopathic constipation (CIC), and multiple FGIDs. Controls were those without FGIDs. Prevalence of autoimmune disorders was compared between cases and controls using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We included 23,471 patients (mean age 51.4 years, 66.1% female). Prevalence of autoimmune disorders was greater among all FGIDs, compared with controls without. In those with FD (OR 1.35; 95% CI 1.12-1.63), CIC (OR 1.75; 95% CI 1.11-2.75), or multiple FGIDs (OR 1.49; 95% CI 1.25-1.77) this was statistically significant after controlling for age and gender. Rheumatological autoimmune disorders were significantly more frequent in those with FD (OR 1.44; 95% CI 1.15-1.80), CIC (OR 1.84; 95% CI 1.08-3.13), or multiple FGIDs (OR 1.53; 95% CI 1.24-1.88), after controlling for age and gender. However, endocrine autoimmune disorders were no more frequent in those with FGIDs, after controlling for age and gender. CONCLUSIONS: In a large sample of primary care patients, there was a significantly higher prevalence of autoimmune disorders among those with FD, CIC, or multiple FGIDs not explained by differences in age or gender. We were unable to control for concomitant drug use, which may partly explain this association.

The overlap of atopy and functional gastrointestinal disorders among 23,471 patients in primary care.

BACKGROUND: Activation of the immune system has been demonstrated in atopy and functional gastrointestinal disorders (FGIDs). Previous data from our group have suggested a connection between immune dysregulation, FGIDs and mood disorders. AIM: To investigate if these data translate to clinical practice and examine connections from the perspective of FGIDs to determine whether atopy and FGIDs are connected via mood disorders. METHODS: Evidence of irritable bowel syndrome (IBS), functional dyspepsia (FD) and constipation was sought from the medical records of 30,000 primary care records over a minimum 5 year period. The same records yielded diagnoses of four atopic conditions (asthma, eczema, allergic rhinitis/hay fever and conjunctivitis). RESULTS: Atopic conditions were found in excess among all FGID groups considered when compared with controls. In the groups with IBS alone (OR = 1.43, 1.29-1.58), FD alone (OR = 1.41, 1.26-1.58) and those with multiple FGIDs (OR = 1.92, 1.75-2.12) there was elevated prevalence of asthma compared with controls without a FGID. Across disorders the excess was generally highest among patients diagnosed with multiple FGIDs (rhinitis/hay fever OR = 3.74, 3.32-4.20; conjunctivitis OR = 3.00, 2.49-3.62) and was only partly explained by a common association between both FGIDs and atopic conditions with mood disorders, although not for every atopic/FGID combination (rhinitis/hay fever OR = 2.60, 2.29-2.96, conjunctivitis OR = 2.34, 1.90-2.87). CONCLUSIONS: Irritable bowel syndrome, functional dyspepsia and constipation share an association with atopy that is only partly explained via a common connection with mood disorders. These data have important implications for understanding both the pathophysiology of functional gastrointestinal disorders and development of new treatments.