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1.  Irritable bowel syndrome: The evolution of multi-dimensional looking and multidisciplinary treatments 
Irritable bowel syndrome (IBS) is common in the society. Among the putative pathogeneses, gut dysmotility results in pain and disturbed defecation. The latter is probably caused by the effect of abnormal gut water secretion. The interaction between abnormal gas accumulation, abdominal pain and bloating remains controversial. Visceral hypersensitivity and its modification along with the central transmission are the characteristics of IBS patients. The identification of biologic markers based on genetic polymorphisms is undetermined. Imbalanced gut microbiota may alter epithelial permeability to activate nociceptive sensory pathways which in turn lead to IBS. Certain food constituents may exacerbate bowel symptoms. The impact of adult and childhood abuses on IBS is underestimated. Using the concept of biopsychosocial dysfunction can integrate multidimensional pathogeneses. Antispasmodics plus stool consistency modifiers to treat the major symptoms and defecation are the first-line drug treatment. New drugs targeting receptors governing bowel motility, sensation and secretion can be considered, but clinicians must be aware of their potential serious side effects. Psychiatric drugs and modalities may be the final options for treating intractable subjects. Probiotics of multi-species preparations are safe and worth to be considered for the treatment. Antibiotics are promising but their long-term safety and effectiveness are unknown. Diet therapy including exclusion of certain food constituents is an economic measure. Using relatively safe complementary and alternative medicines (CAMs) may be optional to those patients who failed classical treatment. In conclusion, IBS is a heterogeneous disorder with multidimensional pathogeneses. Personalized medicines with multidisciplinary approaches using different classes of drugs, psychiatric measures, probiotics and antibiotics, dietary therapy, and finally CAMs, can be considered.
doi:10.3748/wjg.v20.i10.2499
PMCID: PMC3949260  PMID: 24627587
Antispasmodics; Biopsychosocial dysfunction; Comorbidity; Genetics; Irritable bowel syndrome; Microbiota; Probiotics; Visceral hyperalgesia
2.  Therapeutic Roles of Curcumin: Lessons Learned from Clinical Trials 
The AAPS Journal  2012;15(1):195-218.
Extensive research over the past half century has shown that curcumin (diferuloylmethane), a component of the golden spice turmeric (Curcuma longa), can modulate multiple cell signaling pathways. Extensive clinical trials over the past quarter century have addressed the pharmacokinetics, safety, and efficacy of this nutraceutical against numerous diseases in humans. Some promising effects have been observed in patients with various pro-inflammatory diseases including cancer, cardiovascular disease, arthritis, uveitis, ulcerative proctitis, Crohn’s disease, ulcerative colitis, irritable bowel disease, tropical pancreatitis, peptic ulcer, gastric ulcer, idiopathic orbital inflammatory pseudotumor, oral lichen planus, gastric inflammation, vitiligo, psoriasis, acute coronary syndrome, atherosclerosis, diabetes, diabetic nephropathy, diabetic microangiopathy, lupus nephritis, renal conditions, acquired immunodeficiency syndrome, β-thalassemia, biliary dyskinesia, Dejerine-Sottas disease, cholecystitis, and chronic bacterial prostatitis. Curcumin has also shown protection against hepatic conditions, chronic arsenic exposure, and alcohol intoxication. Dose-escalating studies have indicated the safety of curcumin at doses as high as 12 g/day over 3 months. Curcumin’s pleiotropic activities emanate from its ability to modulate numerous signaling molecules such as pro-inflammatory cytokines, apoptotic proteins, NF–κB, cyclooxygenase-2, 5-LOX, STAT3, C-reactive protein, prostaglandin E2, prostate-specific antigen, adhesion molecules, phosphorylase kinase, transforming growth factor-β, triglyceride, ET-1, creatinine, HO-1, AST, and ALT in human participants. In clinical trials, curcumin has been used either alone or in combination with other agents. Various formulations of curcumin, including nanoparticles, liposomal encapsulation, emulsions, capsules, tablets, and powder, have been examined. In this review, we discuss in detail the various human diseases in which the effect of curcumin has been investigated.
doi:10.1208/s12248-012-9432-8
PMCID: PMC3535097  PMID: 23143785
clinical trial; curcumin; human diseases; inflammation; safety
3.  Biopsychosocial Model of Irritable Bowel Syndrome 
Irritable bowel syndrome (IBS) is a common chronic disorder seen in gastroenterology and primary care practice. It is characterized by recurrent abdominal pain or discomfort associated with disturbed bowel function. It is a heterogeneous disorder with varying treatments, and in this regard physicians sometimes struggle with finding the optimal approach to management of patients with IBS. This disorder induces high health care costs and variably reduces health-related quality of life. IBS is in the class of functional gastrointestinal disorders, and results from dysregulation of central and enteric nervous system interactions. Psychosocial factors are closely related to their gut physiology, associated cognitions, symptom manifestations and illness behavior. Therefore, it is important for the physician to recognize the psychosocial issues of patients with IBS and in addition to build a good patient-physician relationship in order to optimize treatment. This review focuses on the interaction between psychological and physiological factors associated with IBS by using a biopsychosocial model. In this article, we describe (1) the predisposing psychological features seen in early life; (2) the psychological factors associated with life stress, the symptom presentation, and their associated coping patterns; (3) gut pathophysiology with emphasis on disturbances in motility, visceral hypersensitivity and brain-gut interactions; and finally (4) the clinical outcomes and effective treatments including psychotherapeutic methods.
doi:10.5056/jnm.2011.17.2.131
PMCID: PMC3093004  PMID: 21602989
Irritable bowel syndrome; Pathophysiology; Psychology
4.  A new model of care collaboration for community-dwelling elders: findings and lessons learned from the NORC-health care linkage evaluation 
Purpose
Providing care for older individuals with chronic illnesses in the community requires a model of service delivery that takes into account both physical health and social health needs. However, packaging care in this way does not fit into existing service or reimbursement structures in the US, and there are few financial incentives that encourage service coordination. Lack of coordinated care can negatively affect access to high quality, appropriate care, putting seniors' physical and mental health and quality of life at risk, as well as their ability to stay in the community. Supportive Social Programs (SSPs), operating in Naturally Occurring Retirement Communities (NORCs), attempt to increase access to care and enhance care quality for aging residents through outreach and service facilitation. Since their inception in 1986, NORC-SSPs have partnered with local health care providers to address both individual and community-wide health issues; however, each sector continues to operate along functional lines, and on a reactive basis. This article presents findings from an evaluation conducted from 2002 to 2006 looking at the feasibility, quality and outcomes of linking health and social services through innovative NORC-SSP and health organization partnerships.
Methods
Four NORC-SSPs participated in the study by finding a health care provider to collaborate on addressing health conditions that could benefit from a biopsychosocial approach. Each site focused on a specific population, a specific condition or problem, and created different linkages to address the target problem. Using a case study approach, incorporating both qualitative and quantitative methods, this evaluation sought to answer the following two primary questions: 1) have the participating sites created viable linkages between the participating organizations that did not exist prior to the study; and, 2) to what extent have the linkages resulted in improvements in clinical and other health and social outcomes?
Results
Findings suggest that immediate outcomes were widely achieved across sites: knowledge of other sector providers' capabilities and services increased; communication across providers increased; identification of target population increased; and, awareness of risks, symptoms and healthy behaviors among clients/patients increased. Furthermore, intermediate outcomes were also widely achieved: shared care planning increased across providers; continuity of care was enhanced; disease management improved; and self care among clients improved. Finally, several linkage partnerships were also able to demonstrate improvements in distal outcomes: falls risk decreased; clinical indicators for diabetes management improved; and inappropriate hospitalizations decreased.
Discussion
Using simple, familiar and relatively low-tech approaches to sharing critical patient information among collaborating organizations, inter-sector linkages were successfully established at all four sites. Seven critical success factors emerged that increase the likelihood that linkages will be implemented, effective and sustained: 1) careful goal selection; 2) meaningful collaboration; 3) appropriate role for clients; 4) realistic interventions; 5) realistic expectations for implementation environment; 6) continuous focus on outcomes; and, 7) stable leadership. A considerable amount of literature speaks to the importance of organizational partnerships to improve community health; however, findings from this evaluation suggest that less complex, more focused, micro-level collaborations can also make a difference, extending the feasibility that organizations will enter into such endeavors.
PMCID: PMC2807089
older people; integrated care models; linkage
5.  A new model of care collaboration for community-dwelling elders: findings and lessons learned from the NORC-Health Care linkage evaluation 
Introduction and background
Few financial incentives in the United States encourage coordination across the health and social care systems. Supportive Service Programs (SSPs), operating in Naturally Occurring Retirement Communities (NORCs), attempt to increase access to care and enhance care quality for aging residents. This article presents findings from an evaluation conducted from 2004 to 2006 looking at the feasibility, quality and outcomes of linking health and social services through innovative NORC-SSP and health organization micro-collaborations.
Methods
Four NORC-SSPs participated in the study by finding a health care organization or community-based physicians to collaborate with on addressing health conditions that could benefit from a biopsychosocial approach. Each site focused on a specific population, addressed a specific condition or problem, and created different linkages to address the target problem. Using a case study approach, incorporating both qualitative and quantitative methods, this evaluation sought to answer the following two primary questions: 1) Have the participating sites created viable linkages between their organizations that did not exist prior to the study; and, 2) To what extent have the linkages resulted in improvements in clinical and other health and social outcomes?
Results
Findings suggest that immediate outcomes were widely achieved across sites: knowledge of other sector providers’ capabilities and services increased; communication across providers increased; identification of target population increased; and, awareness of risks, symptoms and health seeking behaviors among clients/patients increased. Furthermore, intermediate outcomes were also widely achieved: shared care planning, continuity of care, disease management and self care among clients improved. Evidence of improvements in distal outcomes was also found.
Discussion
Using simple, familiar and relatively low-tech approaches to sharing critical patient information among collaborating organizations, inter-sector linkages were successfully established at all four sites. Seven critical success factors emerged that increase the likelihood that linkages will be implemented, effective and sustained: 1) careful goal selection; 2) meaningful collaboration; 3) appropriate role for patients/clients; 4) realistic interventions; 5) realistic expectations for implementation environment; 6) continuous focus on outcomes; and, 7) stable leadership. Focused, micro-level collaborations have the potential to improve care, increasing the chance that organizations will undertake such endeavors.
PMCID: PMC3107066  PMID: 21637704
collaboration; linkage; aging; chronic illness; community-based
6.  Predictors of Patient-Assessed Illness Severity in Irritable Bowel Syndrome 
Background
Conceptual models suggest that “irritable bowel syndrome (IBS) severity” is a multidimensional outcome that is related to, yet distinct from, health-related quality of life (HRQOL). Existing severity questionnaires are largely based on physician rather than patient-based ratings. Since severity is a patient-centered outcome, it is essential that future instruments are based on patients' self-perceptions of severity. We measured patient-derived predictors of severity in a large cohort of IBS patients.
Methods
We performed a cross-sectional analysis in 755 IBS patients recruited at a university-based center. Subjects completed a bowel symptom questionnaire, SCL-90, and SF-36. The main outcome was patient-assessed “overall severity of gastrointestinal symptoms,” as measured on a 0–20 scale (20 = most severe). We first developed a conceptual model of IBS, and then performed bivariate analyses to identify biopsychosocial predictors of severity. We then entered significant predictors into a multivariable model to measure the independent association of each predictor with severity.
Results
Six factors predicted severity: (a) abdominal pain rating (P < 0.001); (b) belief that “something serious is wrong with body” (P < 0.001); (c) straining with defecation (P = 0.001); (d) myalgias (P = 0.02); (e) urgency with defecation (P = 0.03); and (f) bloating (P = 0.05). Severity correlated highly with HRQOL in bivariate, but not multivariate, analysis.
Conclusion
Patient-derived severity in IBS is related to, yet distinct from, generic HRQOL. IBS severity is predicted by abdominal pain, bloating, straining, urgency, myalgias, and disease-related concern. These symptoms fall along both poles of the “brain-gut axis,” indicating that a full assessment of patient severity must include a balanced biopsychosocial history.
doi:10.1111/j.1572-0241.2008.01997.x
PMCID: PMC2949074  PMID: 18637089
7.  Irritable Bowel Syndrome Is Positively Related to Metabolic Syndrome: A Population-Based Cross-Sectional Study 
PLoS ONE  2014;9(11):e112289.
Irritable bowel syndrome is a common gastrointestinal disorder that may affect dietary pattern, food digestion, and nutrient absorption. The nutrition-related factors are closely related to metabolic syndrome, implying that irritable bowel syndrome may be a potential risk factor for metabolic syndrome. However, few epidemiological studies are available which are related to this potential link. The purpose of this study is to determine whether irritable bowel syndrome is related to metabolic syndrome among middle-aged people. We designed a cross-sectional study of 1,096 subjects to evaluate the relationship between irritable bowel syndrome and metabolic syndrome and its components. Diagnosis of irritable bowel syndrome was based on the Japanese version of the Rome III Questionnaire. Metabolic syndrome was defined according to the criteria of the American Heart Association scientific statements of 2009. Dietary consumption was assessed via a validated food frequency questionnaire. Principal-components analysis was used to derive 3 major dietary patterns: “Japanese”, “sweets-fruits”, and “Izakaya (Japanese Pub) “from 39 food groups. The prevalence of irritable bowel syndrome and metabolic syndrome were 19.4% and 14.6%, respectively. No significant relationship was found between the dietary pattern factor score tertiles and irritable bowel syndrome. After adjustment for potential confounders (including dietary pattern), the odds ratio (95% confidence interval) of having metabolic syndrome and elevated triglycerides for subjects with irritable bowel syndrome as compared with non-irritable bowel syndrome are 2.01(1.13–3.55) and 1.50(1.03–2.18), respectively. Irritable bowel syndrome is significantly related to metabolic syndrome and it components. This study is the first to show that irritable bowel syndrome was significantly related to a higher prevalence of metabolic syndrome and elevated triglycerides among an adult population. The findings suggest that the treatment of irritable bowel syndrome may be a potentially beneficial factor for the prevention of metabolic syndrome. Further study is needed to clarify this association.
doi:10.1371/journal.pone.0112289
PMCID: PMC4226513  PMID: 25383869
8.  Psychopharmacological Treatment and Psychological Interventions in Irritable Bowel Syndrome 
Irritable bowel syndrome (IBS) accounts for 25% of gastroenterology output practice, making it one of the most common disorders in this practice. Psychological and social factors may affect the development of this chronic disorder. Furthermore, psychiatric symptoms and psychiatric diseases are highly prevalent in this condition, but the approach to treating these is not always straightforward. As emphasized in the biopsychosocial model of IBS, with regard to the modulatory role of stress-related brain-gut interactions and association of the disease with psychological factors and emotional state, it proves useful to encourage psychopharmacological treatments and psychosocial therapies, both aiming at reducing stress perception. The aim of this paper is to analyze the effectiveness of psychopharmacological treatment and psychological interventions on irritable bowel syndrome.
doi:10.1155/2012/486067
PMCID: PMC3432371  PMID: 22956940
9.  Diagnostic value of the Manning criteria in irritable bowel syndrome. 
Gut  1990;31(1):77-81.
Because unexplained 'functional symptoms' are a major cause of referral to gastroenterologists, the efficiency of the medical history to lead to a positive diagnosis of irritable bowel syndrome, without resorting to the use of expensive tests, remains a key question. Whilst the six criteria of Manning et al are widely used, data on their validity in discriminating irritable bowel syndrome from healthy controls, irritable bowel syndrome from non-ulcer dyspepsia and especially among irritable bowel syndrome subgroups, are not available. To evaluate this, we studied 361 outpatients who completed a bowel disease questionnaire, which objectively measured Manning's (and other) criteria. The group included 82 patients with irritable bowel syndrome, 33 with non-ulcer dyspepsia, 101 with organic gastrointestinal disease, and 145 healthy controls. Diagnoses were based on a full and independent clinical evaluation, not on responses to the bowel disease questionnaire. Reliability was assessed by a test-retest procedure. All six of the individual Manning criteria were found to be reliable (median kappa = 0.79). Based on a logistic regression analysis of the discriminatory value of Manning's criteria, as the number of positive criteria increased, so did the predicted probability of irritable bowel syndrome. This predictive value was highest in younger patients and in females. The Manning criteria discriminated irritable bowel syndrome from organic gastrointestinal disease and from all non-irritable bowel syndrome gastrointestinal disease with a sensitivity of 58% and 42%, and a specificity of 74% and 85%, respectively. Stools that were often loose and watery provided an additional independent criterion for distinguishing irritable bowel syndrome from non-irritable bowel syndrome. Thus, symptoms can be used to diagnose irritable bowel syndrome positively, but Manning's criteria are not highly sensitive.
PMCID: PMC1378344  PMID: 2318433
10.  Using gene expression data to identify certain gastro-intestinal diseases 
Background
Inflammatory bowel diseases, ulcerative colitis and Crohn’s disease are considered to be of autoimmune origin, but the etiology of irritable bowel syndrome remains elusive. Furthermore, classifying patients into irritable bowel syndrome and inflammatory bowel diseases can be difficult without invasive testing and holds important treatment implications. Our aim was to assess the ability of gene expression profiling in blood to differentiate among these subject groups.
Methods
Transcript levels of a total of 45 genes in blood were determined by quantitative real-time polymerase chain reaction (RT-PCR). We applied three separate analytic approaches; one utilized a scoring system derived from combinations of ratios of expression levels of two genes and two different support vector machines.
Results
All methods discriminated different subject cohorts, irritable bowel syndrome from control, inflammatory bowel disease from control, irritable bowel syndrome from inflammatory bowel disease, and ulcerative colitis from Crohn’s disease, with high degrees of sensitivity and specificity.
Conclusions
These results suggest these approaches may provide clinically useful prediction of the presence of these gastro-intestinal diseases and syndromes.
doi:10.1186/2043-9113-2-20
PMCID: PMC3599448  PMID: 23171526
11.  Irritable bowel syndrome in children: Pathogenesis, diagnosis and evidence-based treatment 
Irritable bowel syndrome (IBS) is the commonest cause of recurrent abdominal pain (RAP) in children in both more developed and developing parts of the world. It is defined by the Rome III criteria for functional gastrointestinal disorders. It is characterized by abdominal pain that is improved by defecation and whose onset is associated with a change in stool form and or frequency and is not explained by structural or biochemical abnormalities. It is estimated that 10%-15% of older children and adolescents suffer from IBS. IBS can be considered to be a brain-gut disorder possibly due to complex interaction between environmental and hereditary factors. The diagnosis of IBS is made based on the Rome III criteria together with ruling out organic causes of RAP in children such as inflammatory bowel disease and celiac disease. Once the diagnosis of IBS is made, it is important to explain to the parents (and children) that there is no serious underlying disease. This reassurance may be effective treatment in a large number of cases. Lifestyle modifications, stress management, dietary interventions and probiotics may be beneficial in some cases. Although there is limited evidence for efficacy of pharmacological therapies such as antispasmodics and antidiarrheals; these have a role in severe cases. Biopsychosocial therapies have shown encouraging results in initial trials but are beset by limited availability. Further research is necessary to understand the pathophysiology and provide specific focused therapies.
doi:10.3748/wjg.v20.i20.6013
PMCID: PMC4033441  PMID: 24876724
Recurrent abdominal pain; Irritable bowel syndrome; Brain-gut disorder; Lifestyle modifications; Biopsychosocial therapies; Children; Rome III criteria
12.  Complementary and alternative medicine for treatment of irritable bowel syndrome 
Canadian Family Physician  2009;55(2):143-148.
Abstract
OBJECTIVE
To review the evidence supporting selected complementary and alternative medicine approaches used in the treatment of irritable bowel syndrome (IBS).
QUALITY OF EVIDENCE
MEDLINE (from January 1966), EMBASE (from January 1980), and the Cochrane Database of Systematic Reviews were searched until March 2008, combining the terms irritable bowel syndrome or irritable colon with complementary therapies, alternative medicine, acupuncture, fiber, peppermint oil, herbal, traditional, yoga, massage, meditation, mind, relaxation, probiotic, hypnotherapy, psychotherapy, cognitive therapy, or behavior therapy. Results were screened to include only clinical trials, systematic reviews, and meta-analyses. Level I evidence was available for most interventions.
MAIN MESSAGE
Soluble fibre improves constipation and global IBS symptoms. Peppermint oil alleviates IBS symptoms, including abdominal pain. Probiotic trials show overall benefit for IBS but there is little evidence supporting the use of any specific strain. Hypnotherapy and cognitive-behavioural therapy are also effective therapeutic options for appropriate patients. Certain herbal formulas are supported by limited evidence, but safety is a potential concern. All interventions are supported by systematic reviews or meta-analyses.
CONCLUSION
Several complementary and alternative therapies can be recommended as part of an evidence-based approach to the treatment of IBS; these might provide patients with satisfactory relief and improve the therapeutic alliance.
PMCID: PMC2642499  PMID: 19221071
13.  Irritable bowel syndrome 
Clinical Evidence  2010;2010:0410.
Introduction
The prevalence of irritable bowel syndrome (IBS) varies depending on the criteria used to diagnose it, but it ranges from about 5% to 20%. IBS is associated with abnormal gastrointestinal motor function and enhanced visceral perception, as well as psychosocial and genetic factors. People with IBS often have other bodily and psychiatric symptoms, and have an increased likelihood of having unnecessary surgery compared with people without IBS.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with IBS? We searched: Medline, Embase, The Cochrane Library, and other important databases up to July 2009 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 18 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: 5HT3 receptor antagonists (alosetron and ramosetron); 5HT4 receptor agonists (tegaserod); antidepressants (tricyclic antidepressants and selective serotonin reuptake inhibitors [SSRIs]); antispasmodics (including peppermint oil); cognitive behavioural therapy (CBT); hypnotherapy; soluble and insoluble fibre supplementation; and loperamide.
Key Points
The key features of irritable bowel syndrome (IBS) are chronic, recurrent abdominal pain or discomfort, associated with disturbed bowel habit, in the absence of any structural abnormality to account for these symptoms. The prevalence of IBS varies depending on the criteria used to diagnose it, but it ranges from about 5% to 20%.IBS is associated with abnormal GI motor function, enhanced visceral perception, abnormalities in central pain processing, and altered gut flora, as well as psychosocial and genetic factors.People with IBS often have other bodily and psychiatric symptoms, and have an increased likelihood of having unnecessary surgery compared with people without IBS.A positive symptom-based diagnosis and a graded general treatment approach are cornerstones in the management of people with IBS.
Antidepressants (tricyclic antidepressants and SSRIs) may reduce global symptoms of IBS and abdominal pain compared with placebo.
Antispasmodics (including peppermint oil) may reduce global symptoms of IBS and abdominal pain compared with placebo.
Soluble fibre supplementation may reduce global symptoms of IBS and abdominal pain compared with placebo.
Insoluble fibre supplementation does not reduce global symptoms of IBS or abdominal pain compared with placebo, but we found no evidence from RCTs that it exacerbates symptoms.
The 5HT4 receptor agonist tegaserod reduces global symptoms of IBS and abdominal pain compared with placebo in people with constipation-predominant IBS. CAUTION: Tegaserod may be associated with cerebrovascular and cardiovascular ischaemic events.
5HT3 receptor agonists (alosetron and ramosetron) reduce global symptoms of IBS and abdominal pain compared with placebo. Alosetron reduces global symptoms of IBS and abdominal pain in diarrhoea-predominant IBS compared with placebo in women, but we don’t know whether it is effective in men, or whether this effect applies to those with IBS with an alternating bowel habit.Alosetron may be more effective than mebeverine at reducing symptoms in women with diarrhoea-predominant IBS, but we don't know whether it is effective in men.CAUTION: Alosetron may be associated with severe constipation and ischaemic colitis.Ramosetron may reduce global symptoms of IBS and abdominal pain, and improve abnormal bowel habits, compared with placebo in people with diarrhoea-predominant IBS.
CBT may reduce IBS symptoms compared with control therapy or physician’s usual care in the short term. We don't know whether it is beneficial in the longer term.
Hypnotherapy may reduce IBS symptoms compared with control therapy or physician’s usual care in the short term.
Loperamide may reduce stool frequency in diarrhoea-predominant IBS, but it may not improve other symptoms compared with placebo.
PMCID: PMC2907616  PMID: 21718578
14.  Irritable bowel syndrome 
Clinical Evidence  2012;2012:0410.
Introduction
The prevalence of irritable bowel syndrome (IBS) varies depending on the criteria used to diagnose it, but it ranges from about 5% to 20%. IBS is associated with abnormal gastrointestinal motor function and enhanced visceral perception, as well as psychosocial and genetic factors. People with IBS often have other bodily and psychiatric symptoms, and have an increased likelihood of having unnecessary surgery compared with people without IBS.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments in people with IBS? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 27 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: 5HT3 receptor antagonists (alosetron and ramosetron), 5HT4 receptor agonists (tegaserod), antidepressants (tricyclic antidepressants and selective serotonin reuptake inhibitors [SSRIs]), antispasmodics (including peppermint oil), cognitive behavioural therapy (CBT), hypnotherapy, loperamide, and soluble and insoluble fibre supplementation.
Key Points
The key features of irritable bowel syndrome (IBS) are chronic, recurrent abdominal pain or discomfort, associated with disturbed bowel habit, in the absence of any structural abnormality to account for these symptoms. The prevalence of IBS varies depending on the criteria used to diagnose it, but it ranges from about 5% to 20%.IBS is associated with abnormal GI motor function, enhanced visceral perception, abnormalities in central pain processing, and altered gut flora, as well as psychosocial and genetic factors.People with IBS often have other bodily and psychiatric symptoms, and have an increased likelihood of having unnecessary surgery compared with people without IBS.A positive symptom-based diagnosis and a graded general treatment approach are cornerstones in the management of people with IBS.
Antidepressants (tricyclic antidepressants and SSRIs) may reduce global symptoms of IBS and abdominal pain compared with placebo.
Antispasmodics (including peppermint oil) may reduce global symptoms of IBS and abdominal pain compared with placebo.
We don't know whether soluble fibre supplementation (ispaghula) is more effective than placebo at improving global symptoms or abdominal pain in IBS as the data are contradictory.
Insoluble fibre supplementation does not reduce global symptoms of IBS or abdominal pain compared with placebo, but we found no evidence from RCTs to support the observation reported by some investigators that it in fact exacerbates symptoms.
The 5HT4 receptor agonist tegaserod reduces global symptoms of IBS and abdominal pain compared with placebo in people with constipation-predominant IBS. CAUTION: Tegaserod may be associated with cerebrovascular and cardiovascular ischaemic events.
5HT3 receptor agonists (alosetron and ramosetron) reduce global symptoms of IBS and abdominal pain compared with placebo. Alosetron reduces global symptoms of IBS and abdominal pain in diarrhoea-predominant IBS compared with placebo in women, but we don't know whether it is effective in men, or whether this effect applies to those with IBS with an alternating bowel habit.Alosetron may be more effective than mebeverine at reducing symptoms in women with diarrhoea-predominant IBS, but we don't know whether it is effective in men.CAUTION: Alosetron may be associated with severe constipation and ischaemic colitis.Ramosetron may reduce global symptoms of IBS and abdominal pain, and improve abnormal bowel habits, compared with placebo in people with diarrhoea-predominant IBS.
CBT may reduce IBS symptoms compared with control therapy or physician's usual care in the short term. We don't know whether it is beneficial in the longer term.
Hypnotherapy may reduce IBS symptoms compared with control therapy or physician's usual care in the short term.
Loperamide may reduce stool frequency in diarrhoea-predominant IBS, but it may not improve other symptoms compared with placebo.
PMCID: PMC4196731  PMID: 22296841
15.  Irritable Bowel Syndrome and Migraine: Bystanders or Partners? 
Irritable bowel syndrome (IBS) and migraine are distinct clinical disorders. Apart from the characteristics of chronic and recurrent pain in nature, these pain-related disorders apparently share many similarities. For example, IBS is female predominant with community prevalence about 5-10%, whereas that of migraine is 1-3% also showing female predominance. They are often associated with many somatic and psychiatric comorbidities in terms of fibromyaglia, chronic fatigue syndrome, interstitial cystitis, insomnia and depression etc., even the IBS subjects may have coexisted migraine with an estimated odds ratio of 2.66. They similarly reduce the quality of life of victims leading to the social, medical and economic burdens. Their pathogeneses have been somewhat addressed in relation to biopsychosocial dysfunction, heredity, genetic polymorphism, central/visceral hypersensitivity, somatic/cutaneous allodynia, neurolimbic pain network, gonadal hormones and abuses etc. Both disorders are diagnosed according to the symptomatically based criteria. Multidisciplinary managements such as receptor target new drugs, melantonin, antispasmodics, and psychological drugs and measures, complementary and alternatives etc. are recommended to treat them although the used agents may not be necessarily the same. Finally, the prognosis of IBS is pretty good, whereas that of migraine is less fair since suicide attempt and stroke are at risk. In conclusion, both distinct chronic pain disorders to share many similarities among various aspects probably suggest that they may locate within the same spectrum of a pain-centered disorder such as central sensitization syndromes. The true pathogenesis to involve these disorders remains to be clarified in the future.
doi:10.5056/jnm.2013.19.3.301
PMCID: PMC3714407  PMID: 23875096
Biopsychosocial model; Comorbidity; Irritable bowel syndrome; Migraine; Quality of life
16.  Lessons learned in developing family medicine residency training programs in Japan 
Background
While family medicine is not well established as a discipline in Japan, a growing number of Japanese medical schools and training hospitals have recently started sougoushinryoubu (general medicine departments). Some of these departments are incorporating a family medicine approach to residency training. We sought to learn from family medicine pioneers of these programs lessons for developing residency training.
Methods
This qualitative project utilized a long interview research design. Questions focused on four topics: 1) circumstances when becoming chair/faculty member; 2) approach to starting the program; 3) how Western ideas of family medicine were incorporated; and 4) future directions. We analyzed the data using immersion/crystallization to identify recurring themes. From the transcribed data, we selected representative quotations to illustrate them. We verified the findings by emailing the participants and obtaining feedback.
Results
Participants included: five chairpersons, two program directors, and three faculty members. We identified five lessons: 1) few people understand the basic concepts of family medicine; 2) developing a core curriculum is difficult; 3) start with undergraduates; 4) emphasize clinical skills; and 5) train in the community.
Conclusion
While organizational change is difficult, the identified lessons suggest issues that merit consideration when developing a family medicine training program. Lessons from complexity science could inform application of these insights in other countries and settings newly developing residency training.
doi:10.1186/1472-6920-5-33
PMCID: PMC1253513  PMID: 16162298
17.  Functional abdominal pain and irritable bowel syndrome in children and adolescents 
Therapy  2011;8(3):315-331.
Functional abdominal pain (FAP) and irritable bowel syndrome (IBS) are both associated with recurrent abdominal pain and are among the most commonly diagnosed medical problems in pediatrics. The majority of patients with mild complaints improve with reassurance and time. For a distinct subset of patients with more severe and disabling illness, finding effective treatment for these disorders remains a challenge. Based on the biopsychosocial model of functional disease, the Rome III criteria have helped frame FAP and IBS in terms of being a positive diagnosis and not a diagnosis of exclusion. However, the lack of a single, proven intervention highlights the complex interplay of pathologic mechanisms likely involved in the development of childhood FAP and IBS and the need for a multidisciplinary, integrated approach. This article discusses the epidemiology, proposed mechanisms, clinical approach and therapeutic options for the management of FAP and IBS in children and adolescents.
PMCID: PMC3127202  PMID: 21731470
biopsychosocial model; cognitive behavioral therapy; dietary interventions; functional abdominal pain; functional gastrointestinal disorders; irritable bowel syndrome; pharmacotherapy; psychosocial interventions; recurrent abdominal pain
18.  Giant anterior urethral diverticulum with a calculus masquerading as left inguinal hernia: A missed diagnosis, a lesson to learn 
Congenital anterior urethral diverticulum is an infrequent but important cause of infravesical obstructive uropathy in children. Clinical spectrum usually includes obstructive or irritative urinary symptoms or penile ballooning during the act of micturition. We share our experience in a case of giant anterior urethral diverticulum with a contained calculus presenting as a huge inguino-scrotal swelling and masquerading as left inguinal hernia. The fluctuation in the size of the swelling related to the act of micturition was mistaken for cough impulse. He was subjected to a left inguinal herniotomy, following which he developed urine leak from the surgery wound and was subsequently referred to our centre for further management. The importance of a detailed history, meticulous physical examination, and diagnostic imaging has been stressed. The surgical approach in such cases has also been highlighted.
doi:10.4103/0971-9261.116044
PMCID: PMC3760309  PMID: 24019642
Anterior urethral diverticulum; calculus; inguino-scrotal swelling; infra-vesical obstructive uropathy; left inguinal hernia
19.  Management of functional abdominal pain and irritable bowel syndrome in children and adolescents 
Functional abdominal pain (FAP) and irritable bowel syndrome (IBS) are among the most commonly diagnosed medical problems in pediatrics. Symptom-based Rome III criteria for FAP and IBS have been validated and help the clinician in making a positive diagnosis. The majority of patients with mild complaints improve with reassurance and time. For a distinct subset of patients with more severe and disabling illness, finding effective treatment for these disorders remains a challenge. Over the years, a wide range of therapies have been proposed and studied. The lack of a single, proven intervention highlights the complex interplay of biopsychosocial factors probably involved in the development of childhood FAP and IBS, and the need for a multidisciplinary, integrated approach. This article reviews the current literature on the efficacy of pharmacologic, dietary and psychosocial interventions for FAP and IBS in children and adolescents.
doi:10.1586/egh.10.28
PMCID: PMC2904303  PMID: 20528117
children; cognitive–behavioral therapy; dietary therapy; functional abdominal pain; irritable bowel syndrome; pharmacotherapy; psychosocial intervention; recurrent abdominal pain
20.  Methods for implementing a medicine outlet survey: lessons from the anti-malarial market 
Malaria Journal  2013;12:52.
Background
In recent years an increasing number of public investments and policy changes have been made to improve the availability, affordability and quality of medicines available to consumers in developing countries, including anti-malarials. It is important to monitor the extent to which these interventions are successful in achieving their aims using quantitative data on the supply side of the market. There are a number of challenges related to studying supply, including outlet sampling, gaining provider cooperation and collecting accurate data on medicines. This paper provides guidance on key steps to address these issues when conducting a medicine outlet survey in a developing country context. While the basic principles of good survey design and implementation are important for all surveys, there are a set of specific issues that should be considered when conducting a medicine outlet survey.
Methods
This paper draws on the authors’ experience of designing and implementing outlet surveys, including the lessons learnt from ACTwatch outlet surveys on anti-malarial retail supply, and other key studies in the field. Key lessons and points of debate are distilled around the following areas: selecting a sample of outlets; techniques for collecting and analysing data on medicine availability, price and sales volumes; and methods for ensuring high quality data in general.
Results and conclusions
The authors first consider the inclusion criteria for outlets, contrasting comprehensive versus more focused approaches. Methods for developing a reliable sampling frame of outlets are then presented, including use of existing lists, key informants and an outlet census. Specific issues in the collection of data on medicine prices and sales volumes are discussed; and approaches for generating comparable price and sales volume data across products using the adult equivalent treatment dose (AETD) are explored. The paper concludes with advice on practical considerations, including questionnaire design, field worker training, and data collection. Survey materials developed by ACTwatch for investigating anti-malarial markets in sub-Saharan Africa and Asia provide a helpful resource for future studies in this area.
doi:10.1186/1475-2875-12-52
PMCID: PMC3599752  PMID: 23383972
Medicine; Retail outlet survey methods; Price; availability; Market share; Health facility survey; Private sector
21.  More accurate diagnosis of irritable bowel syndrome by the use of 'non-colonic' symptomatology. 
Gut  1991;32(7):784-786.
The criteria now used in an attempt to distinguish irritable bowel syndrome from organic gastrointestinal disease rely almost entirely on symptoms of colonic origin. 'Non-colonic' symptoms, however, arising either from elsewhere in the gut or of a more general nature, are common in irritable bowel syndrome and may have even better diagnostic potential. The prevalence of these non-colonic features was assessed in 107 patients with the irritable bowel syndrome and 295 subjects with other gut disorders. Gastrointestinal type non-colonic symptoms are useful in differentiating irritable bowel syndrome from inflammatory bowel disease but, with the exception of early satiety, are not helpful when there is gastro-oesophageal or biliary disease. More general 'non-colonic' features, such as lethargy and backache, are much commoner in irritable bowel syndrome than in all the organic gastrointestinal diseases studied and have good discriminant function. Multiple logistic regression analysis identified certain features that had a particularly significant independent risk for irritable bowel syndrome. Those were lethargy (relative risk 6.7), incomplete evacuation (RR 5.2), age under 40 (RR 2.1), backache (RR 2.0), early satiety (RR 1.8), and frequency of micturition (RR 1.8). These relative risks can be multiplied together to give an overall risk when more than one of these features is present in a patient. Until a diagnostic test is available more confident diagnosis of irritable bowel syndrome can be achieved by identifying symptoms that have good discriminant function. The results of this study indicate that the non-colonic features of irritable bowel syndrome may be especially valuable in this respect.
PMCID: PMC1378996  PMID: 1855685
22.  The road to commercialization in Africa: lessons from developing the sickle-cell drug Niprisan 
Background
Developing novel drugs from traditional medicinal knowledge can serve as a means to improve public health. Yet countries in sub-Saharan Africa face barriers in translating traditional medicinal knowledge into commercially viable health products. Barriers in moving along the road towards making a new drug available include insufficient manufacturing capacity; knowledge sharing between scientists and medical healers; regulatory hurdles; quality control issues; pricing and distribution; and lack of financing. The case study method was used to illustrate efforts to overcome these barriers during the development in Nigeria of Niprisan – a novel drug for the treatment of sickle cell anemia, a chronic blood disorder with few effective therapies.
Discussion
Building on the knowledge of a traditional medicine practitioner, Nigeria’s National Institute for Pharmaceutical Research and Development (NIPRD) developed the traditional herbal medicine Niprisan. The commercialization of Niprisan reached a number of commercial milestones, including regulatory approval in Nigeria; securing US-based commercial partner XeChem; demonstrating clinical efficacy and safety; being awarded orphan drug status by the US Food and Drug Administration; and striking important relationships with domestic and international groups. Despite these successes, however, XeChem did not achieve mainstream success for Niprisan in Nigeria or in the United States. A number of reasons, including inconsistent funding and manufacturing and management challenges, have been put forth to explain Niprisan’s commercial demise. As of this writing, NIPRD is considering options for another commercial partner to take the drug forward.
Summary
Evidence from the Niprisan experience suggests that establishing benefit-sharing agreements, fostering partnerships with established research institutions, improving standardization and quality control, ensuring financial and managerial due diligence, and recruiting entrepreneurial leaders capable of holding dual scientific and business responsibilities should be incorporated into future drug development initiatives based on traditional medicines. Country-level supporting policies and conditions are also important. With more experience and support, and an improved environment for innovation, developing new drugs from traditional medicines may be an attractive approach to addressing diseases in sub-Saharan Africa and other regions.
doi:10.1186/1472-698X-10-S1-S11
PMCID: PMC3001608  PMID: 21144071
23.  Lessons for neurologists from the United Kingdom Third National Morbidity Survey. 
The Third National Morbidity Survey lists data about the primary care consultations for more than 300,000 person-years at risk. Data of interest to neurologists have been extracted from the complex tables of the Survey, many of which are on micro-fiche. Assuming that any one subject has only one neurological symptom, 9.5% of the population will consult their general practitioner about a neurological symptom each year. The five most common groups of disorders for which advice is sought are headache/migraine, dizziness, syndromes related to the cervical or lumbar spine, faints or fits, and symptoms due to cerebrovascular disease. About 7% of all patients seen with neurological symptoms are referred to hospital clinics for further advice.
PMCID: PMC1032280  PMID: 2786920
24.  Simple objective criteria for diagnosis of causes of acute diarrhoea on rectal biopsy. 
Journal of Clinical Pathology  1997;50(7):580-585.
AIM: To identify simple, objective, accurate histological criteria for distinguishing acute infective-type colitis, chronic idiopathic inflammatory bowel disease, and irritable bowel syndrome on rectal biopsy in patients with acute onset diarrhoea at first presentation, one to 10 weeks after onset. METHODS: Cell counts and measurements of mucosal architecture were made on initial rectal biopsies from 18 patients with acute infective-type colitis, 17 patients with first acute presentation of chronic idiopathic inflammatory bowel disease, and 23 patients with irritable bowel syndrome. The data were analysed by ANOVA and discriminant analysis. RESULTS: Lamina propria cells were mainly in the upper third in irritable bowel syndrome patients. Increased lamina propria cellularity, mainly in the middle third, and numbers of crypt intraepithelial neutrophils distinguished acute infective-type colitis from irritable bowel syndrome in 93% of cases. Chronic idiopathic inflammatory bowel disease differed from irritable bowel syndrome and acute infective-type colitis in a decreased number of crypts and altered crypt architecture. Chronic idiopathic inflammatory bowel disease showed higher lamina propria cellularity, especially in the basal third, with an increased number of lamina propria neutrophils. On discriminant analysis, crypt numbers distinguished 86% of the cases of chronic idiopathic inflammatory bowel disease from the other groups. CONCLUSION: At one week or more from onset, acute infective-type colitis is characterised by a superficial increase in lamina propria cellularity, with only a slight increase in the number of polymorphs. At this stage, chronic idiopathic inflammatory bowel disease is characterised by a transmucosal increase in cellularity together with crypt loss and architectural abnormality. Thus, measurement of mucosal architecture establishes simple, accurate, objective criteria for routine biopsy diagnosis of chronic idiopathic inflammatory bowel disease from acute infective-type colitis and irritable bowel syndrome at initial presentation, one to 10 weeks after onset.
Images
PMCID: PMC500059  PMID: 9306939
25.  Irritable bowel syndrome in the general population. 
BMJ : British Medical Journal  1992;304(6819):87-90.
OBJECTIVE--To determine the prevalence of symptoms compatible with a clinical diagnosis of irritable bowel syndrome in the general population. DESIGN--Validated postal questionnaire sent to 2280 subjects randomly selected in 10 year age bands from the lists of eight general practitioners. The Manning criteria were used to define irritable bowel syndrome. SETTING--Urban population in Southampton and mixed urban-rural population in Andover, Hampshire. RESULTS--A response of 71% yielded 1620 questionnaires for analysis, of which 412 (25%) reported more than six episodes of abdominal pain in the preceding year, with 350 (22%) reporting symptoms consistent with the diagnosis of irritable bowel syndrome. The male: female ratio was 1:1.38. More subjects with irritable bowel syndrome had constipation and diarrhoea and 35% with the syndrome reported rectal bleeding compared with an overall prevalence of 20%. Other symptoms and conditions including heartburn, dyspepsia, flushing, palpitations, migraine, and urinary symptoms were significantly more common in the group with irritable bowel syndrome. Abdominal pain in childhood was more common in the subjects with irritable bowel syndrome (12%) than without (3%). One third of the group with irritable bowel syndrome had sought medical advice during the study period (male:female ratio 1:1.21); consultation behaviour was influenced by age and the presence of associated symptoms, varied considerably among patients registered with different general practitioners, and was poorly correlated with symptom severity. CONCLUSION--Symptoms consistent with a diagnosis of irritable bowel syndrome are present in almost one quarter of the general population and tend to be associated with a number of other complaints and conditions, some of which may reflect smooth muscle dysfunction.
PMCID: PMC1880997  PMID: 1737146

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