King Edward VIII Hospital

. Here we investigated Omicron escape from neutralization by antibodies from South African individuals vaccinated with Pfizer BNT162b2. We used blood samples taken soon after vaccination from individuals who were vaccinated and previously infected with SARS-CoV-2 or vaccinated with no evidence of previous infection. We isolated and sequence-confirmed live Omicron virus from an infected person and observed that Omicron requires the angiotensin-converting enzyme 2 (ACE2) receptor to infect cells. We compared plasma neutralization of Omicron relative to an ancestral SARS-CoV-2 strain and found that neutralization of ancestral virus was much higher in infected and vaccinated individuals compared with the vaccinated-only participants. However, both groups showed a 22-fold reduction in vaccine-elicited neutralization by the Omicron variant. Participants who were vaccinated and had previously been infected exhibited residual neutralization of Omicron similar to the level of neutralization of the ancestral virus observed in the vaccination-only group. These data support the notion that reasonable protection against Omicron may be maintained using vaccination approaches.

The prevalence of urinary incontinence was investigated by determining the number of incontinent patients under the care of various health and social service agencies in two London boroughs and by a postal survey of the 22 430 people aged 5 years and over on the practice lists of 12 general practitioners in different parts of the country. The prevalence of incontinence known to the health and social service agencies was 0.2% in women and 0.1% in men aged 15-64 and 2.5% in women and 1.3% in men aged 65 and over. The postal survey, to which 89% of the people whose correct address was known replied, showed a prevalence of urinary incontinence of 8.5% in women and 1.6% in men aged 15-64 and 11.6% in women and 6.9% in men aged 65 and over. Nulliparous women had a lower prevalence than those who had had one, two, or three babies, but within the parity range of one to three there were no differences in prevalence. The prevalence was appreciably increased in women who had had four or more babies. Incontinence was moderate or severe in a fifth of those who reported it in the postal survey, of whom less than a third were receiving health or social services for the condition. Incontinence is a common symptom, and many unrecognised cases appear to exist. There may be considerable scope for improving its management.

BACKGROUND: Cohort studies in Bangladesh showed promising cure rates among patients with multidrug-resistant tuberculosis who received existing drugs in regimens shorter than that recommended by the World Health Organization (WHO) in 2011. METHODS: at 132 weeks and at a previous occasion, with no intervening positive culture or previous unfavorable outcome. An upper 95% confidence limit for the between-group difference in favorable status that was 10 percentage points or less was used to determine noninferiority. RESULTS: Of 424 participants who underwent randomization, 383 were included in the modified intention-to-treat population. Favorable status was reported in 79.8% of participants in the long-regimen group and in 78.8% of those in the short-regimen group - a difference, with adjustment for human immunodeficiency virus status, of 1.0 percentage point (95% confidence interval [CI], -7.5 to 9.5) (P = 0.02 for noninferiority). The results with respect to noninferiority were consistent among the 321 participants in the per-protocol population (adjusted difference, -0.7 percentage points; 95% CI, -10.5 to 9.1). An adverse event of grade 3 or higher occurred in 45.4% of participants in the long-regimen group and in 48.2% in the short-regimen group. Prolongation of either the QT interval or the corrected QT interval (calculated with Fridericia's formula) to 500 msec occurred in 11.0% of participants in the short-regimen group, as compared with 6.4% in the long-regimen group (P = 0.14); because of the greater incidence in the short-regimen group, participants were closely monitored and some received medication adjustments. Death occurred in 8.5% of participants in the short-regimen group and in 6.4% in the long-regimen group, and acquired resistance to fluoroquinolones or aminoglycosides occurred in 3.3% and 2.3%, respectively. CONCLUSIONS: In persons with rifampin-resistant tuberculosis that was susceptible to fluoroquinolones and aminoglycosides, a short regimen was noninferior to a long regimen with respect to the primary efficacy outcome and was similar to the long regimen in terms of safety. (Funded by the U.S. Agency for International Development and others; Current Controlled Trials number, ISRCTN78372190; ClinicalTrials.gov number, NCT02409290.).

BACKGROUND: Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis. METHODS: Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. RESULTS: There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P=0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P=0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P=0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P=0.03, respectively), owing mainly to an increase in HIV-associated cancer. CONCLUSIONS: In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. (Funded by the Canadian Institutes of Health Research and others; IMPI ClinicalTrials.gov number, NCT00810849.).

Anidulafungin is a novel antifungal agent of the echinocandin class. This randomized, double-blind, double-dummy study compared the efficacy and safety of intravenous anidulafungin to that of oral fluconazole in 601 patients with endoscopically and microbiologically documented esophageal candidiasis. Patients received intravenous anidulafungin (100 mg on day 1, followed by 50 mg per day) or oral fluconazole (200 mg on day 1, followed by 100 mg per day) for 7 days beyond resolution of symptoms (range, 14-21 days). At the end of therapy, the rate of endoscopic success for anidulafungin (242 [97.2%] of 249 treated patients) was found to be statistically noninferior to that for fluconazole (252 [98.8%] of 255 treated patients; treatment difference, -1.6%; 95% confidence interval, -4.1 to 0.8). The safety profile of anidulafungin was similar to that of fluconazole; treatment-related adverse events occurred in 9.3% and 12.0% of patients, respectively. Laboratory parameters were similar between treatment arms. Anidulafungin is as safe and effective as oral fluconazole for the treatment of esophageal candidiasis, when assessed at the completion of therapy.

A patient who presented with incomplete abortion developed severe persistent haemorrhage from the genital tract after evacuation of the uterus, as a result of erosion of a major vessel in a sacculus in a previous caesarean section scar. Detection and management of this condition are discussed.

This study analysed clinical features and laboratory investigations in 145 patients with tuberculous peritonitis diagnosed by peritoneoscopy at this hospital between 1984 and 1988. Tuberculous peritonitis was found in 2% of all patients with tuberculosis and in 59.8% of all those with abdominal tuberculosis admitted to the hospital during the study period. Tuberculous peritonitis was more common in women than men (1.4:1) and was most frequently encountered in the third and fourth decades of life. The commonest presenting symptoms were abdominal swelling (73.1%), fever and night sweats (53.8%), anorexia (46.9%), weight loss (44.1%), and abdominal pain (35.9%). The mean duration of symptoms was 1.5 months. Ascites was the commonest (95.2%) physical sign. Tuberculin skin testing was positive in 57.6% of patients (n = 118). The mean erythrocyte sedimentation rate was 75 mm/1st hour (n = 58). Chest radiography on 98 patients showed pleuropulmonary pathology in 40 patients (40.8%). Sputum examination confirmed active pulmonary tuberculosis in 26 patients. The ascitic fluid was an exudate in 96.4% and a transudate in 3.6% of patients, with 91.3% showing a straw coloured ascites. Cirrhosis, detected by biopsy specimen, was a finding in 6.2% of patients.

Six cases of ulnar nerve injury resulted from crossed K-wire fixation of displaced supracondylar humeral fractures in children. The age ranged between 4 and 10 years. Pain on extension of the little and ring fingers and early clawing were important post operative signs of ulnar nerve involvement. Early exploration of all six cases revealed medial pin placement in the cubital tunnel in five cases. In two of these, the nerve was directly penetrated, and in three, it was constricted by the cubital tunnel retinaculum. In the case 6, the nerve was hypermobile and found to be fixed anterior to its groove over the medial epicondyle. The nerve was decompressed in all cases, and the wire was repositioned. Follow-up ranged from 4 to 14 months. Full nerve recovery occurred in three cases, partial in two, and no recovery in one. Early exploration rather than simple pin removal is safer and diagnostic of the mechanism of injury.

Six cases of ulnar nerve injury resulted from crossed K-wire fixation of displaced supracondylar humeral fractures in children. The age ranged between 4 and 10 years. Pain on extension of the little and ring fingers and early clawing were important post operative signs of ulnar nerve involvement. Early exploration of all six cases revealed medial pin placement in the cubital tunnel in five cases. In two of these, the nerve was directly penetrated, and in three, it was constricted by the cubital tunnel retinaculum. In the case 6, the nerve was hypermobile and found to be fixed anterior to its groove over the medial epicondyle. The nerve was decompressed in all cases, and the wire was repositioned. Follow-up ranged from 4 to 14 months. Full nerve recovery occurred in three cases, partial in two, and no recovery in one. Early exploration rather than simple pin removal is safer and diagnostic of the mechanism of injury.

CONTEXT: South Africa has the most HIV infections of any country in the world, yet little is known about the adolescent continuum of care from HIV diagnosis through viral suppression. OBJECTIVE: To determine the adolescent HIV continuum of care in South Africa. DATA SOURCES: We searched PubMed, Google Scholar and online conference proceedings from International AIDS Society (IAS), International AIDS Conference (AIDS) and Conference on Retrovirology and Opportunistic Infections (CROI) from 1 January 2005 to 31 July 2015. DATA EXTRACTION: We selected published literature containing South African cohorts and epidemiological data reporting primary data for youth (15-24 years of age) at any stage of the HIV continuum of care (ie, diagnosis, treatment, retention, viral suppression). For the meta-analysis we used six sources for retention in care and nine for viral suppression. RESULTS: Among the estimated 867 283 HIV-infected youth from 15 to 24 years old in South Africa in 2013, 14% accessed antiretroviral therapy (ART). Of those on therapy, ∼83% were retained in care and 81% were virally suppressed. Overall, we estimate that 10% of HIV-infected youth in South Africa in 2013 were virally suppressed. LIMITATIONS: This analysis relies on published data from large mostly urban South Africa cohorts limiting the generalisability to all adolescents. CONCLUSIONS: Despite a large increase in ART programmes in South Africa that have relatively high retention rates and viral suppression rates among HIV-infected youth, only a small percentage are virally suppressed, largely due to low numbers of adolescents and young adults accessing ART.

In this article I present a tentative model for the study of politeness in Zulu against the background of politeness theory. I argue that such a model may not solely reflect verbal means of expressing politeness, but must further draw on non-verbal aspects and on discourse conventions more generally. This in its turn necessitates locating a study of politeness in the context of the cultural values of the speech community concerned. These considerations lead me finally to query the link between politeness and indirectness, which has been proposed as a linguistic universal.

Tinea capitis is a relatively common fungal infection of childhood. Griseofulvin has been the mainstay of management. However, newer oral antifungal agents are being used more frequently. A multicenter, prospective, randomized, single-blinded, non-industry-sponsored study was conducted in centers in Canada and South Africa to determine the relative efficacy and safety of griseofulvin, terbinafine, itraconazole, and fluconazole in the treatment of tinea capitis caused by Trichophyton species. The regimens for treating tinea capitis were griseofulvin microsize 20 mg/kg/day x 6 weeks, terbinafine [> 40 kg, one 250 mg tablet; 20-40 kg, 125 mg (half of a 250 mg tablet); < 20 kg, 62.5 mg (one-quarter of a 250 mg tablet)] x 2-3 weeks, itraconazole 5 mg/kg/day x 2-3 weeks, and fluconazole 6 mg/kg/day x 2-3 weeks. Patients were asked to return at weeks 4, 8, and 12 from the start of the study. Griseofulvin was administered for 6 weeks and the final evaluation was at week 12. Terbinafine, itraconazole, and fluconazole were administered for 2 weeks and the patient evaluated 4 weeks from the start of therapy. At this time, if clinically indicated, one extra week of therapy was given. There were 200 patients randomized to four treatment groups (50 in each group). At the final evaluation at week 12, the number of evaluable patients were griseofulvin, 46; terbinafine, 48; itraconazole, 46; and fluconazole, 46. Patients who discontinued therapy or were lost to follow-up were griseofulvin, 1/3; itraconazole, 0/4; terbinafine, 0/4; and fluconazole, 0/4. The causative organisms were Trichophyton tonsurans and T. violaceum species. Patients were regarded as effectively treated at week 12 if there was mycologic cure and either clinical cure or only a few residual symptoms. Effective treatment was recorded in, intention to treat, griseofulvin (46 of 50, 92.0%), terbinafine (47 of 50, 94.0%), itraconazole (43 of 50, 86.0%), and fluconazole (42 of 50, 84.0%) (p=0.33). Adverse effects were reported only in the griseofulvin group (gastrointestinal effects in six patients). Discontinuation from therapy due to adverse effects occurred only in the griseofulvin group (nausea in one patient). For the treatment of tinea capitis caused by the Trichophyton species, in this study, griseofulvin given for 6 weeks is similar in efficacy to terbinafine, itraconazole, and fluconazole given for 2-3 weeks. Each of the agents has a favorable adverse-effects profile.

BACKGROUND: The incidence of tuberculous pericarditis has increased in Africa as a result of the human immunodeficiency virus (HIV) epidemic. However, the effect of HIV co-infection on clinical features and prognosis in tuberculous pericarditis is not well characterised. We have used baseline data of the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry to assess the impact of HIV co-infection on clinical presentation, diagnostic evaluation, and treatment of patients with suspected tuberculous pericarditis in sub-Saharan Africa. METHODS: Consecutive adult patients in 15 hospitals in three countries in sub-Saharan Africa were recruited on commencement of treatment for tuberculous pericarditis, following informed consent. We recorded demographic, clinical, diagnostic and therapeutic information at baseline, and have used the chi-square test and analysis of variance to assess probabilities of significant differences (in these variables) between groups defined by HIV status. RESULTS: A total of 185 patients were enrolled from 01 March 2004 to 31 October 2004, 147 (79.5%) of whom had effusive, 28 (15.1%) effusive-constrictive, and 10 (5.4%) constrictive or acute dry pericarditis. Seventy-four (40%) had clinical features of HIV infection. Patients with clinical HIV disease were more likely to present with dyspnoea (odds ratio [OR] 3.2, 95% confidence interval [CI] 1.4 to 7.4, P = 0.005) and electrocardiographic features of myopericarditis (OR 2.8, 95% CI 1.1 to 6.9, P = 0.03). In addition to electrocardiographic features of myopericarditis, a positive HIV serological status was associated with greater cardiomegaly (OR 3.89, 95% CI 1.34 to 11.32, P = 0.01) and haemodynamic instability (OR 9.68, 95% CI 2.09 to 44.80, P = 0.0008). However, stage of pericardial disease at diagnosis and use of diagnostic tests were not related to clinical HIV status. Similar results were obtained for serological HIV status. Most patients were treated on clinical grounds, with microbiological evidence of tuberculosis obtained in only 13 (7.0%) patients. Adjunctive corticosteroids were used in 109 (58.9%) patients, with patients having clinical HIV disease less likely to be put on them (OR 0.37, 95% CI 0.20 to 0.68). Seven patients were on antiretroviral drugs. CONCLUSION: Patients with suspected tuberculous pericarditis and HIV infection in Africa have greater evidence of myopericarditis, dyspnoea, and haemodynamic instability. These findings, if confirmed in other studies, may suggest more intensive management of the cardiac disease is warranted in patients with HIV-associated pericardial disease.

OBJECTIVE: HIV-infected patients with treated cryptococcal meningitis are at risk for further neurological deterioration after commencing combination antiretroviral therapy (cART), mostly because of cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS). Identifying predictors of C-IRIS could enable risk stratification. DESIGN: Prospective, longitudinal cohort study for 24 weeks. SETTING: Durban, South Africa. PARTICIPANTS: One hundred and thirty HIV-infected patients with first cryptococcal meningitis episode INTERVENTION: : Antifungal therapy (amphotericin 1 mg/kg median 14 days, followed by consolidation and maintenance fluconazole) and cART (commenced median of 18 days from cryptococcal meningitis diagnosis). MAIN OUTCOME MEASURE: Clinical, blood, and cerebrospinal fluid (CSF) markers associated with C-IRIS before and during cART and clinical significance of CSF cryptococcal culture negativity pre-cART commencement. RESULTS: Of 106 patients commencing cART, 27 (25.5%) developed C-IRIS, 16 (15.1%) neurological deterioration-not C-IRIS, and 63 (59.4%) no neurological deterioration. On multivariable analysis, C-IRIS was associated with persistent CSF cryptococcal growth [hazard ratio (HR) 0.27, P=0.026] and lower CSF protein (HR 0.53, P=0.059) prior to cART and lower CD4 T-cell increases (HR 0.99, P=0.026) but not change in HIV viral load during cART. Using survival analysis, patients with a negative cryptococcal culture pre-cART commencement (n=51; 48.1%) experienced fewer episodes of neurological deterioration, C-IRIS, and cryptococcal relapse/persistence than patients with culture positivity (n=55; 51.9%, HR 0.33, 0.33, and 0.12 and P=0.0003, 0.0042, and 0.0004, respectively). CONCLUSION: Persistent CSF cryptococcal growth at cART initiation and poor CD4 T-cell increases on cART are strong predictors of C-IRIS. Approaches aimed at achieving CSF culture negativity prior to cART should be evaluated as a strategy to reduce rates of C-IRIS.

We retrospectively compared the clinical manifestations, laboratory features, and outcome of cryptococcal meningitis in 44 human immunodeficiency virus (HIV)-positive and 21 HIV-negative patients in Durban, South Africa, and contrasted our findings with those in the developed world. Cryptococcal meningitis was the initial AIDS-defining illness in 84% of patients. Headache, fever, convulsions, neck stiffness, and neurological signs were more common in HIV-positive patients. We detected neurological abnormalities in 50% of the HIV-positive group. Seventeen percent of HIV-positive patients had completely normal CSF indices. HIV-positive patients with cryptococcal meningitis frequently had oral candidiasis and tuberculosis as coexistent illnesses. Prognostic factors identified in the West do not appear to be applicable in Africa. Death during hospitalization was significantly higher in the HIV-positive group. HIV-associated cryptococcal meningitis in Africa is apparently associated with higher rates of neurological complications and death than is such disease in developed countries of the world.

It is estimated that almost 300,000 children in South Africa have human immunodeficiency virus (HIV) infection. The disease is responsible for reversing decreases in child mortality. Few data exist evaluating the outcomes of the prevention of mother-to-child transmission of HIV (PMTCT) program, although PMTCT coverage appears to be low. Hospitals are still witnessing large numbers of admissions of HIV-infected children. Postnatal transmission of HIV is high, reflecting poor education of and support for women in their infant feeding choices. Too few infants and children are entering care through early diagnosis, which should be widely available. Cotrimoxazole prophylaxis coverage is inadequate, contributing to high morbidity and mortality in infants. The number of children receiving antiretroviral therapy (ART) is increasing steadily. However, significant inequalities in access to ART exist between and within provinces. Challenges for pediatric ART include a lack of sufficiently trained health care personnel and inadequate facilities, as well as the complexity of drug regimens and formulations. The compartmentalization of the ART rollout program hinders PMTCT and makes it difficult for children to be identified and referred into appropriate services. This article delineates the challenges to pediatric HIV care in South Africa and provides some practical recommendations to improve it.

Twenty patients with gastrointestinal mucormycosis are reviewed. This often fatal opportunistic fungal infection was diagnosed histologically, and was categorized as colonization (five patients), infiltration (seven patients), or vascular invasion (eight patients). There were no fatalities from colonization. In 10 patients, mucormycosis complicated peptic ulcer disease. Seven of these patients had infiltrative or invasive disease. The presentation and operative findings mimicked malignancy in five of these seven patients, and six had successful surgical intervention. The other patient was cured by medical therapy alone. Ten patients had infection associated with other gastrointestinal diseases: post-traumatic peritonitis (four patients), transmural amoebiasis (two patients), tuberculosis (one patient), gastroenteritis (one patient), gastric carcinoma (one patient) and diabetes (one patient). Eight patients had significant infection and only one survived. In this series, mucormycosis had a less aggressive course when complicating peptic ulcer than when it occurred in association with other gut diseases.

The prevalence of diffuse idiopathic skeletal hyperostosis (DISH) was studied in a hospital based population of African Blacks over the age of 40 years. The study was based on an analysis of the lateral chest radiographs of 1000 patients in a retrospective study and 500 consecutive medical admissions in a prospective study. The overall prevalence of DISH was 3.9% (males 3.8% and females 4.2%). There was a rise in the prevalence of DISH with increasing age from 1% in the 40-49 year age group to 13.6% in those over 70 years. The prevalence of diabetes was 52.4% in the 21 patients with DISH who were seen in the prospective analysis. Ankylosing spondylitis, which is associated with HLA-B27, is rare in African Blacks. However, DISH is not uncommon but its prevalence is lower than in a similar hospital based study of Jews in Israel.

BACKGROUND: Children with human immunodeficiency virus type 1 (HIV-1) infection have limited options for effective antiretroviral treatment (ART). METHODS: We conducted an open-label, randomized, noninferiority trial comparing three-drug ART based on the HIV integrase inhibitor dolutegravir with standard care (non-dolutegravir-based ART) in children and adolescents starting first- or second-line ART. The primary end point was the proportion of participants with virologic or clinical treatment failure by 96 weeks, as estimated by the Kaplan-Meier method. Safety was assessed. RESULTS: From September 2016 through June 2018, a total of 707 children and adolescents who weighed at least 14 kg were randomly assigned to receive dolutegravir-based ART (350 participants) or standard care (357). The median age was 12.2 years (range, 2.9 to 18.0), the median weight was 30.7 kg (range, 14.0 to 85.0), and 49% of the participants were girls. By design, 311 participants (44%) started first-line ART (with 92% of those in the standard-care group receiving efavirenz-based ART), and 396 (56%) started second-line ART (with 98% of those in the standard-care group receiving boosted protease inhibitor-based ART). The median follow-up was 142 weeks. By 96 weeks, 47 participants in the dolutegravir group and 75 in the standard-care group had treatment failure (estimated probability, 0.14 vs. 0.22; difference, -0.08; 95% confidence interval, -0.14 to -0.03; P = 0.004). Treatment effects were similar with first- and second-line therapies (P = 0.16 for heterogeneity). A total of 35 participants in the dolutegravir group and 40 in the standard-care group had at least one serious adverse event (P = 0.53), and 73 and 86, respectively, had at least one adverse event of grade 3 or higher (P = 0.24). At least one ART-modifying adverse event occurred in 5 participants in the dolutegravir group and in 17 in the standard-care group (P = 0.01). CONCLUSIONS: In this trial involving children and adolescents with HIV-1 infection who were starting first- or second-line treatment, dolutegravir-based ART was superior to standard care. (Funded by ViiV Healthcare; ODYSSEY ClinicalTrials.gov number, NCT02259127; EUDRACT number, 2014-002632-14; and ISRCTN number, ISRCTN91737921.).

Twenty adult Indian patients suffering from the spastic form of irritable colon, i.e. abdominal pain and constipation, were given trimebutine (Mebutin), 2-phenyl, 2-dimethylamino-n-butyl 3, 4, 5-trimethoxybenzoate. Patients were given treatment with 200 mg trimebutine three times daily, or placebo for 4 weeks, and then crossed over. In addition, stool transit times were assessed by the single stool transit time (SST) method of Cummings. Results showed a statistical improvement in abdominal pain and constipation with both trimebutine and placebo after 4 weeks, but only with trimebutine after 8 weeks. Single stool transit time was significantly reduced after trimebutine.