Effects of everolimus plus minimized tacrolimus on kidney function in liver transplantation: REDUCE, a prospective, randomized controlled study.

BACKGROUND AND AIM: reduction in calcineurin inhibitor levels is considered crucial to decrease the incidence of kidney dysfunction in liver transplant (LT) recipients. The aim of this study was to evaluate the safety and impact of everolimus plus reduced tacrolimus (EVR + rTAC) vs. mycophenolate mofetil plus tacrolimus (MMF + TAC) on kidney function in LT recipients from Spain. METHODS: the REDUCE study was a 52-week, multicenter, randomized, controlled, open-label, phase 3b study in de novo LT recipients. Eligible patients were randomized (1:1) 28 days post-transplantation to receive EVR + rTAC (TAC levels ≤ 5 ng/mL) or to continue with MMF + TAC (TAC levels = 6-10 ng/mL). Mean estimated glomerular filtration rate (eGFR), clinical benefit in renal function, and safety were evaluated. RESULTS: in the EVR + rTAC group (n = 105), eGFR increased from randomization to week 52 (82.2 [28.5] mL/min/1.73 m2 to 86.1 [27.9] mL/min/1.73 m2) whereas it decreased in the MMF + TAC (n = 106) group (88.4 [34.3] mL/min/1.73 m2 to 83.2 [25.2] mL/min/1.73 m2), with significant (p < 0.05) differences in eGFR throughout the study. However, both groups had a similar clinical benefit regarding renal function (improvement in 18.6 % vs. 19.1 %, and stabilization in 81.4 % vs. 80.9 % of patients in the EVR + rTAC vs. MMF + TAC groups, respectively). There were no significant differences in the incidence of acute rejection (5.7 % vs. 3.8 %), deaths (5.7 % vs. 2.8 %), and serious adverse events (51.9 % vs. 44.0 %) between the 2 groups. CONCLUSION: EVR + rTAC allows a safe reduction in tacrolimus exposure in de novo liver transplant recipients, with a significant improvement in eGFR but without significant differences in renal clinical benefit 1 year after liver transplantation.

Renal function improvement in liver transplant recipients after early everolimus conversion: A clinical practice cohort study in Spain.

A national, multicenter, retrospective study was conducted to assess the results obtained for liver transplant recipients with conversion to everolimus in daily practice. The study included 477 recipients (481 transplantations). Indications for conversion to everolimus were renal dysfunction (32.6% of cases), hepatocellular carcinoma (HCC; 30.2%; prophylactic treatment for 68.9%), and de novo malignancy (29.7%). The median time from transplantation to conversion to everolimus was 68.7 months for de novo malignancy, 23.8 months for renal dysfunction, and 7.1 months for HCC and other indications. During the first year of treatment, mean everolimus trough levels were 5.4 (standard deviation [SD], 2.7) ng/mL and doses remained stable (1.5 mg/day) from the first month after conversion. An everolimus monotherapy regimen was followed by 28.5% of patients at 12 months. Patients with renal dysfunction showed a glomerular filtration rate (4-variable Modification of Diet in Renal Disease) increase of 10.9 mL (baseline mean, 45.8 [SD, 25.3] versus 57.6 [SD, 27.6] mL/minute/1.73 m(2) ) at 3 months after everolimus initiation (P < 0.001), and 6.8 mL at 12 months. Improvement in renal function was higher in patients with early conversion (<1 year). Adverse events were the primary reason for discontinuation in 11.2% of cases. The probability of survival at 3 years after conversion to everolimus was 83.0%, 71.1%, and 59.5% for the renal dysfunction, de novo malignancy, and HCC groups, respectively. Everolimus is a viable option for the treatment of renal dysfunction, and earlier conversion is associated with better recovery of renal function. Prospective studies are needed to confirm advantages in patients with malignancy.

Underestimation of chronic renal dysfunction after liver transplantation: ICEBERG study.

AIM: To compare prevalence of chronic renal dysfunction (CRD) according to serum creatinine (sCr) vs estimated glomerular filtration rate (eGFR) among maintenance liver transplant patients. METHODS: The ICEBERG study was an observational, retrospective, cross-sectional, and multicenter study. Consecutive adult patients (aged 18 years or older) with liver transplantation (LT) performed at least two years previously were recruited. Multi-organ transplant recipients were excluded. Chronic renal dysfunction was defined according to sCr based criteria in routine clinical practice (≥ 2 mg/dL) and eGFR using MDRD-4 equation (< 60 mL/min per 1.73 m(2)). Agreement between sCr definition and eGFR assessment was evaluated using the Kappa index. Cox regression analysis was applied to identify predictive factors for developing CRD after LT. RESULTS: A total of 402 patients were analyzed (71.6% males). Mean ± SD age at transplant was 52.4 ± 9.8 years. Alcoholic cirrhosis without hepatocellular carcinoma was the most common reason for LT (32.8%). Mean time since LT was 6.9 ± 3.9 years. Based on sCr assessment, 35.3% of patients (95%CI: 30.6-40.0) had CRD; 50.2% (95%CI: 45.3-55.1) according to eGFR. In 32.2% of cases, sCr assessment had underestimated CRD. Multivariate analysis showed the following factors associated with developing CRD: eGFR < 60 mL/min per 1.73 m(2) at three months post-transplant [hazard ratio (HR) = 4.76; 95%CI: 2.78-8.33; P < 0.0001]; calcineurin inhibitor use (HR = 2.31; 95%CI: 1.05-5.07; P = 0.0371); male gender (HR = 1.98; 95%CI: 1.09-3.60; P = 0.0260); and ≥ 10 years post-transplantation (HR = 1.95; 95%CI: 1.08-3.54; P = 0.0279). CONCLUSION: Seven years after LT, CRD affected half our patients, which was underestimated by sCr. An eGFR < 60 mL/min per 1.73 m(2) three months post-LT was predictive of subsequent CRD.

Validity of the Spanish 8-item short-form generic health-related quality-of-life questionnaire in surgical patients: a population-based study.

BACKGROUND: Health-related quality of life is usually reported for specific rather than heterogeneous populations such as those treated in routine anesthesia practice. The 8-item short-form generic health-related quality-of-life questionnaire (SF-8) is a candidate instrument for this setting. The authors evaluated the feasibility, reliability, validity, and responsiveness to change of the Spanish version of SF-8 in a population-based surgical cohort. METHODS: Recruiting patients from a large population-based study of risk factors for pulmonary complications, before surgery, the authors administered the 1-week recall SF-8 to 2,991 patients undergoing nonobstetric elective or emergency surgery in 59 hospitals, each of which collected data on seven randomly assigned days in 2006. The SF-8 was administered again 3 months later. Reliability was evaluated using the Cronbach alpha coefficient and validity by comparing physical and mental component summary SF-8 scores with clinical variables. Responsiveness after surgery was evaluated using the standardized response mean. RESULTS: Cronbach alpha for the overall test was 0.92. Physical and mental component summary scores and all individual scores were lower (worse quality of life) in women (P < 0. 01) and decreased with age (P < 0.01). Preoperative scores were lower for those in worse clinical condition (higher body mass index, American Society of Anesthesiologists physical status class, or surgical risk scores), with preoperative respiratory symptoms, and in emergency situations (P < 0.01). The standardized response mean ranged from 0.1 to 0.5. CONCLUSIONS: The SF-8 is a feasible, reliable, valid, and responsive instrument for assessing health-related quality of life in a broad-spectrum surgical population.

Rates of asthma attacks in patients with previously inadequately controlled mild asthma treated in clinical practice with combination drug therapy: an exploratory post-hoc analysis.

BACKGROUND: Differences could exist in the likelihood of asthma attacks in patients treated with inhaled corticosteroid (ICS), long-acting beta-agonist (LABA), and montelukast (MON) (ICS/LABA/MON) and patients treated with an inhaled corticosteroid (ICS) and montelukast (MON) (ICS/MON). METHODS: This was a post-hoc analysis of a pretest-posttest retrospective cohort study. Patients with mild persistent asthma and allergic rhinitis, who were taking an ICS either alone or in combination with a LABA, started concomitant MON treatment as part of their routine care. Rates of asthma- and allergic rhinitis-related medical resource use in the 12-months after the initial (index) MON prescription were compared in the ICS/MON and ICS/LABA/MON groups. An asthma attack was defined as an asthma-related hospitalization, ER visit, or use of an oral corticosteroid. RESULTS: Of the total of 344 patients, 181 (53%) received ICS/MON and 163 (47%) received ICS/LABA/MON in the post-index period for means of 10.5 and 11.4 months, respectively, (P < 0.05). Short-acting beta-agonists were used by 74.6% in the ICS/MON and 71.8% in the ICS/LABA/MON groups (P > 0.05). An asthma attack occurred in 4.4% of the ICS/MON group and 6.8% of the ICS/LABA/MON group (P > 0.05). The adjusted odds of an asthma attack in the post-index period in the ICS/LABA/MON group relative to the ICS/MON group was 1.24, 95% confidence interval 0.35-4.44. CONCLUSION: In this observational study of combination drug treatment of mild persistent asthma and allergic rhinitis, no difference was observed between LABA/ICS/MON combination therapy and the ICS/MON combination without LABA use, for the rate of asthma attacks over one year.

[Quality of life specific questionnaire for constipated patients: development and validation of CVE-20]. / Cuestionario específico de calidad de vida para pacientes con estreñimiento: desarrollo y validación del CVE-20.

BACKGROUND AND OBJECTIVE: Although constipation affects quality of life, questionnaires hardly exist for its evaluation. We aimed to develop and validate a questionnaire able to measure the quality of life in patients with constipation. PATIENTS AND METHOD: A Spanish multicenter study was performed in 2 stages: a) questionnaire development (open interview to patients with constipation, pilot questionnaire, quantitative and factorial analysis, Rasch analysis, and specific questionnaire design), and b) questionnaire validation in 136 patients. These patients were divided in 2 groups: a) reliability group (n = 55; no need to begin or change treatment; re-tested after 15 days), and b) sensibility to change group (n = 81; need to begin or change treatment; re-tested after 3 months). We collected clinical and socio-demographic data and we evaluated the quality of life through the general questionnaire EuroQoL-5D (EQ-5D) and the specific one, design in the previous stage (25 items). After that, we analysed feasibility, reliability and validity (of content, convergent and longitudinal). RESULTS: The trial questionnaire was obtained during the development stage and the results were 51 items that were later reduced to 25 in the validation stage. A total of 126 patients (93% women; mean age [standard deviation]: 43.4 [1] years) completed the study properly. The answer average time was 12 min. The content validity process reduced the questionnaire to 20 items (CVE-20) within 4 domains: emotional, general physical, rectal physical and social. The reliability was good in relation to the general punctuation (Cronbach alpha coefficient = 0.87), being in the different domains of 0.79, 0.73, 0.75 and 0.60, respectively. The construct validity showed a good correlation between the CVE-20 results and constipation severity. The CVE-20 score positively correlated with EQ -5D changes. The test and re-test reliability were good: interclass correlation coefficient = 0.89 (ranging from 0.80 to 0.88 in the different domains). The clinically relevant and minimal difference was 17 points (95% confidence interval, 11-23). The content validity showed a strong correlation between CVE-20 and constipation severity. CONCLUSIONS: The CVE-20 is the first specific questionnaire in Spanish language for constipated patients; it is valid, reliable, sensitive to changes and it meets the psychometric requirements to be applied in daily practice and clinical trials.

[Sociosanitary impact on patients with rare diseases (ERES study)]. / Impacto sociosanitario en pacientes con enfermedades raras (estudio ERES).

BACKGROUND AND OBJECTIVE: The impact and burden of disease of the rare diseases (RD) is not known, also the type of disability that entail. The objective of the work is to analyze the socio-sanitary impact of the RD in Spain. PATIENTS AND METHOD: This is a nationwide study. The dimensions used were mobility, personal care and daily activities of the EUROQoL-5D questionnaire to analyze the degree of dependency of the patient with RD. RESULTS: 714 surveys were analyzed. 51.2% were men; 21.1% were children and 78.9% adults. The more frequent laboral status were: retired/pensioner, active and student (35.3%; 29.2%, and 17.1% respectively). In the last quarterly 8.4% of the patients were in situation of transitory labor incapacity: 5.7% men and 11.9% women (p < 0.005). The patients referred disability (slight or moderate degree) in the areas: physical (87.7%), emotional (83.6%), social (75.6%) and sensorial (53%). They presented severe mixed disability (sensorial and physic) in 6.4%. Patient organisations, physicians and Internet (80.1%; 48.2% and 47.3% respectively) were the used sources of information. The patients were more satisfied with doctor's care than social worker's (47% and 2.4% respectively), considering doctors more accessible than social workers (32.4% and 13.1% respectively). CONCLUSIONS: RD present a high percentage of disability and dependency, being both more severe in children. The patient organisations are the main source of information. Patients are more satisfied and consider the doctor more accessible than the social worker. This work might serve to make decisions in the socio-sanitary assistance for RD.

Impacto sociosanitario en pacientes con enfermedades raras (estudio ERES) / Sociosanitary impact on patients with rare diseases (ERES study)

Fundamento y objetivo: Se desconoce el impacto y la carga de enfermedad en las enfermedades raras (ER), así como el tipo de discapacidades que conllevan. El objetivo de este trabajo ha sido analizar el impacto sociosanitario de las ER en España. Pacientes y método: Se trata de un estudio de ámbito nacional. Se utilizaron las dimensiones movilidad, cuidado personal y actividades cotidianas del cuestionario EUROQoL-5D para analizar el grado de dependencia del paciente con ER. Resultados: Se analizaron 714 encuestas. Un 51,2% de los encuestados eran varones; el 21,1%, niños, y el 78,9%, adultos. Los grupos laborales más frecuentes fueron: jubilado/pensionista, activo y estudiante (un 35,3, un 29,2 y un 17,1%, respectivamente). En el último trimestre el 8,4% de los pacientes estaba en situación de incapacidad laboral transitoria; de ellos, un 5,7% eran varones y el 11,9%, mujeres (p < 0,005). Los pacientes refirieron discapacidad (grado leve o moderado) en las áreas física (87,7%), emocional (83,6%), social (75,6%) y sensorial (53%). Presentaba discapacidad mixta (sensorial más física) de carácter grave el 6,4%. Las asociaciones de afectados, el médico e internet (un 80,1, un 48,2 y un 47,3%, respectivamente) eran las fuentes de información utilizadas por los pacientes. Éstos estaban más satisfechos con la atención del médico que con la del trabajador social (el 47 y el 2,4%, respectivamente) y consideraban más accesible al primero que al segundo (el 32,4 y el 13,1%, respectivamente). Conclusiones: Las ER se acompañan de un elevado porcentaje de discapacidad y dependencia, y ambas son más graves en niños. Las asociaciones de afectados constituyen la principal fuente de información. Los pacientes están más satisfechos y consideran más accesible al médico que al trabajador social. Este trabajo puede servir para tomar decisiones en la asistencia sociosanitaria de las ER

Background and objective: The impact and burden of disease of the rare diseases (RD) is not known, also the type of disability that entail. The objective of the work is to analyze the socio-sanitary impact of the RD in Spain. Patients and method: This is a nationwide study. The dimensions used were mobility, personal care and daily activities of the EUROQoL-5D questionnaire to analyze the degree of dependency of the patient with RD. Results: 714 surveys were analyzed. 51.2% were men; 21.1% were children and 78.9% adults. The more frequent laboral status were: retired/pensioner, active and student (35.3%; 29.2%, and 17.1% respectively). In the last quarterly 8.4% of the patients were in situation of transitory labor incapacity: 5.7% men and 11.9% women (p < 0.005). The patients referred disability (slight or moderate degree) in the areas: physical (87.7%), emotional (83.6%), social (75.6%) and sensorial (53%). They presented severe mixed disability (sensorial and physic) in 6.4%. Patient organisations, physicians and Internet (80.1%; 48.2% and 47.3% respectively) were the used sources of information. The patients were more satisfied with doctor's care than social worker's (47% and 2.4% respectively), considering doctors more accessible than social workers (32.4% and 13.1% respectively). Conclusions: RD present a high percentage of disability and dependency, being both more severe in children. The patient organisations are the main source of information. Patients are more satisfied and consider the doctor more accessible than the social worker. This work might serve to make decisions in the socio-sanitary assistance for RD

Respiratory infection in congenital cardiac disease. Hospitalizations in young children in Spain during 2004 and 2005: the CIVIC Epidemiologic Study.

OBJECTIVES: To evaluate the rate of hospitalization for acute respiratory tract infection in children less than 24 months with haemodynamically significant congenital cardiac disease, and to describe associated risk factors, preventive measures, aetiology, and clinical course. MATERIALS AND METHODS: We followed 760 subjects from October 2004 through April 2005 in an epidemiological, multicentric, observational, follow-up, prospective study involving 53 Spanish hospitals. RESULTS: Of our cohort, 79 patients (10.4%, 95% CI: 8.2%-12.6%) required a total of 105 admissions to hospital related to respiratory infections. The incidence rate was 21.4 new admissions per 1000 patients-months. Significant associated risk factors for hospitalization included, with odds ratios and 95% confidence intervals shown in parentheses: 22q11 deletion (8.2, 2.5-26.3), weight below the 10th centile (5.2, 1.6-17.4), previous respiratory disease (4.5, 2.3-8.6), incomplete immunoprophylaxis against respiratory syncytial virus (2.2, 1.2-3.9), trisomy 21 (2.1, 1.1-4.2), cardiopulmonary bypass (2.0, 1.1-3.4), and siblings aged less than 11 years old (1.7, 1.1-2.9). Bronchiolitis (51.4%), upper respiratory tract infections (25.7%), and pneumonia (20%) were the main diagnoses. An infectious agent was found in 37 cases (35.2%): respiratory syncytial virus in 25, Streptococcus pneumoniae in 5, and Haemophilus influenzae in 4. The odds ratio for hospitalization due to infection by the respiratory syncytial virus increases by 3.05 (95% CI: 2.14 to 4.35) in patients with incomplete prophylaxis. The median length of hospitalization was 7 days. In 18 patients (17.1%), the clinical course of respiratory infection was complicated and 2 died. CONCLUSIONS: Hospital admissions for respiratory infection in young children with haemodynamically significant congenital cardiac disease are mainly associated with non-cardiac conditions, which may be genetic, malnutrition, or respiratory, and to cardiopulmonary bypass. Respiratory syncytial virus was the most commonly identified infectious agent. Incomplete immunoprophylaxis against the virus increased the risk of hospitalization.

Healthcare utilisation and costs associated with adding montelukast to current therapy in patients with mild to moderate asthma and co-morbid allergic rhinitis: PRAACTICAL study.

OBJECTIVE: To evaluate the healthcare resource use and costs associated with adding montelukast to therapy in patients with mild to moderate persistent asthma and co-morbid seasonal allergic rhinitis whose asthma is inadequately controlled by their current asthma therapy. METHODS: A multicentre, pre-post retrospective cohort study was conducted in three European countries (Italy, Poland and Spain). Consecutive patients who were receiving inhaled corticosteroid therapy (monotherapy or combination therapy with long-acting beta(2)-adrenoceptor agonists) and who started concomitant treatment with montelukast between January 1999 and December 2002 were identified from clinical charts. Asthma/seasonal allergic rhinitis-related concomitant medications and asthma-related outpatient care, ED visits and hospitalisations for the periods 12 months before and 12 months after montelukast initiation were recorded from patient charts and combined with country-specific published unit costs (adjusted to 2004 values). The analysis was performed from a third-party-payer perspective and thus direct healthcare resource utilisation due to asthma/seasonal allergic rhinitis and associated costs for each country were estimated. RESULTS: A total of 98 physicians provided data for 696 asthmatic patients with seasonal allergic rhinitis (Italy: n = 158; Poland: n = 334; and Spain: n = 204). The mean age of patients was 32.7 years, 57.5% were female and patients had asthma that was considered either mild-persistent (54.5%) or moderate-persistent (45.5%) according to the Global Initiative for Asthma classifications. The introduction of montelukast (10 mg/day daily cost range euro0.8-1.68) was associated with increases in the total annual mean healthcare cost per patient of 11.9%, 60.4% and 5.5% for Italy, Poland and Spain, respectively. However, mean annual costs for asthma-related outpatient care, ED visits and hospitalisations dropped significantly in all three countries (Italy: from euro805.00 to euro281.60 [p < 0.01]; Poland: from euro127.10 to euro99.00 [p < 0.01]; and Spain: from euro463.40 to euro119.70 [p < 0.01]). CONCLUSIONS: The addition of montelukast to therapy in patients with mild to moderate asthma and concomitant seasonal allergic rhinitis whose asthma was inadequately controlled by current asthma therapy significantly reduced the use of concomitant asthma-allergy medications, ED visits, outpatient care visits and hospitalisation. The total direct healthcare cost obtained after the addition of montelukast increased only as a result of the montelukast treatment cost.

Asthma control in patients with asthma and allergic rhinitis receiving add-on montelukast therapy for 12 months: a retrospective observational study.

BACKGROUND: Montelukast, a potent leukotriene receptor antagonist, is approved for treatment of both asthma and allergic rhinitis (AR). No studies to date have examined whether montelukast can improve asthma control over a long period of time in patients with seasonal AR and asthma. OBJECTIVE: To evaluate asthma control and use of asthma-related medical resources by patients with inadequately controlled mild to moderate persistent asthma and seasonal AR who required addition of montelukast as part of routine care. METHODS: This multicenter, 24-month, pre-post retrospective observational study included patients receiving current inhaled corticosteroid (ICS) therapy (alone or in combination with long-acting beta-agonist [LABA]), who received add-on treatment with montelukast for 12 consecutive months. The incidence of asthma attacks, defined as emergency department visit, hospitalization, or oral corticosteroid use for asthma, was compared for the year before and the year after addition of montelukast to therapy. RESULTS: For the 696 patients from Italy, Poland, and Spain who were included in the analyses, the proportion of patients experiencing an asthma attack declined from 31.5% in the year before to 10.1% (p < 0.001) the year after addition of montelukast to therapy. Proportions of patients with an asthma-related emergency room visit, hospitalization, and oral corticosteroid use declined from 18.7% to 3.9%, from 5.2% to 1.4%, and from 17.5% to 5.9% (all p < 0.01), respectively. The incidence of these outcomes declined in all three countries, regardless of baseline asthma severity or asthma therapy (ICS alone or ICS + LABA). Important study limitations include the possibility of selection bias or missing medical chart data in this retrospective study design. Also noteworthy is the inclusion of only those patients who remained persistent with montelukast therapy. Therefore, the results of the study are relevant for patients who remain persistent with montelukast therapy. CONCLUSIONS: Addition of montelukast to current ICS therapy improved long-term asthma control and resulted in substantial reductions in asthma-related resource use by patients with mild or moderate persistent asthma and concomitant seasonal AR who were persistent with montelukast therapy in this retrospective observational study.

Does physical activity modify the association between body mass index and colorectal adenomas?

Although both physical inactivity and obesity have been associated with an increased risk of colorectal adenomas, it is unclear whether physical activity modifies the relationship between obesity and colorectal adenomas or through what mechanism this might occur. The aim of this study is to evaluate whether physical activity modifies the relationship between body mass index (BMI) and colorectal adenomas and whether apoptosis is a plausible mechanism responsible for this effect modification. Study subjects were part of a large, cross-sectional study, the Diet and Health Study III. Consecutive patients underwent colonoscopy between August 1998 and March 2000. Apoptosis was measured by morphological evaluation of hematoxylin and eosin-stained sections obtained from rectal pinch biopsy samples. There were 226 patients with adenomas and 494 adenoma-free controls. When comparing overweight subjects with the referent group (high physical activity/normal BMI), the relative odds of having an adenoma decreased as physical activity increased: low (odds ratio, OR=1.6; 95% confidence interval, CI=0.7-3.4); moderate (OR=1.1; 95% CI=0.6-2.0); and high (OR=0.8; 95% CI=0.4-1.6). When comparing obese subjects with the referent group, relative odds of having an adenoma were increased regardless of physical activity level. Apoptosis was not associated with obesity or physical activity. Our results suggest that physical activity may modify the association between obesity and colorectal adenoma until a high level of obesity is achieved. Apoptosis does not appear to be associated with obesity or physical activity.

Bowel habit subtypes and temporal patterns in irritable bowel syndrome: systematic review.

UNLABELLED: Irritable bowel syndrome (IBS) is a heterogeneous condition characterized by the presence of abdominal discomfort or pain and bowel habit alterations: constipation (C-IBS), diarrhea (D-IBS), or alternating C and D (A-IBS). Its clinical course is poorly known. OBJECTIVES: (i) To compare bowel habit subtypes distribution in IBS according to sample origin and diagnosis criteria; (ii) To evaluate IBS temporal patterns based on follow-up studies. METHODS: A literature search (1966-2003) was conducted in the MEDLINE and EMBASE databases. A total of 72 studies were found and 22 were finally selected. RESULTS: Population-based studies from the United States (Manning) found similar distribution among C-IBS, D-IBS, and A-IBS, while European studies (Rome I, Rome II, or self-reporting) showed either C-IBS or A-IBS as the most prevalent subtypes. Primary care office-based studies (Rome I or Rome II) showed A-IBS as the most prevalent group. Gastroenterology specialized office-based studies found either C-IBS or D-IBS as the most frequently reported subtype. Prospective follow-up investigations showed that the most frequent IBS temporal pattern profile consists of mild to moderate symptoms appearing in cluster in an intermittent way, about once a week, and lasting 2-5 days on average. CONCLUSION: IBS clinical subtypes distribution differs depending on the population evaluated, the geographical location, and the criteria employed to define IBS and bowel habit subtypes. In most cases, clinical course is characterized by the presence of mild-to-moderate symptoms appearing sequentially. Prospective studies, using clear and stable diagnostic criteria and subtype definitions, and based on daily data collection should further characterize IBS clinical course.