Isotopes prove advanced, integral crop production, and stockbreeding strategies nourished Trypillia mega-populations.

After 500 y of colonizing the forest-steppe area northwest of the Black Sea, on the territories of what is today Moldova and Ukraine, Trypillia societies founded large, aggregated settlements from ca. 4150 BCE and mega-sites (>100 ha) from ca. 3950 BCE. Covering up to 320 ha and housing up to 15,000 inhabitants, the latter were the world's largest settlements to date. Some 480 δ13C and δ15N measurements on bones of humans, animals, and charred crops allow the detection of spatio-temporal patterns and the calculation of complete agricultural Bayesian food webs for Trypillia societies. The isotope data come from settlements of the entire Trypillia area between the Prut and the Dnieper rivers. The datasets cover the development of the Trypillia societies from the early phase (4800-4200/4100 BCE), over the agglomeration of mega-sites (4200/4100-3650 BCE), to the dispersal phase (3650-3000 BCE). High δ15N values mostly come from the mega-sites. Our analyses show that the subsistence of Trypillia mega-sites depended on pulses cultivated on strongly manured (dung-)soils and on cattle that were kept fenced on intensive pastures to easy collect the manure for pulse cultivation. The food web models indicate a low proportion of meat in human diet (approximately 10%). The largely crop-based diet, consisting of cereals plus up to 46% pulses, was balanced in calories and indispensable amino acids. The flourishing of Europe's first mega-populations depended on an advanced, integral mega-economy that included sophisticated dung management. Their demise was therefore not economically, but socially, conditioned [Hofmann et al., PLoS One. 14, e0222243 (2019)].

Oral ivermectin versus malathion lotion for difficult-to-treat head lice.

BACKGROUND: Head-lice infestation is prevalent worldwide, especially in children 3 to 11 years old. Topical insecticides (i.e., pyrethroids and malathion) used as a lotion, applied twice at an interval of 7 to 11 days, are typically used for treatment. Resistance of lice to insecticides, particularly pyrethroids, results in treatment failure. The efficacy of alternative agents is controversial. METHODS: We conducted a multicenter, cluster-randomized, double-blind, double-dummy, controlled trial comparing oral ivermectin (at a dose of 400 microg per kilogram of body weight) with 0.5% malathion lotion, each given on days 1 and 8, for patients with live lice not eradicated by topical insecticide used 2 to 6 weeks before enrollment. The cluster was defined as the household. Infestation was confirmed and monitored by means of fine-toothed combing. Patients were at least 2 years of age and weighed at least 15 kg; all were treated at the study sites. The primary end point was the absence of head lice on day 15. RESULTS: A total of 812 patients from 376 households were randomly assigned to receive either ivermectin or malathion. In the intention-to-treat population, 95.2% of patients receiving ivermectin were lice-free on day 15, as compared with 85.0% of those receiving malathion (absolute difference, 10.2 percentage points; 95% confidence interval [CI], 4.6 to 15.7; P<0.001). In the per-protocol population, 97.1% of patients in the ivermectin group were lice-free on day 15, as compared with 89.8% of those in the malathion group (absolute difference, 7.3 percentage points; 95% CI, 2.8 to 11.8; P=0.002). There were no significant differences in the frequencies of adverse events between the two treatment groups. CONCLUSIONS: For difficult-to-treat head-lice infestation, oral ivermectin, given twice at a 7-day interval, had superior efficacy as compared with topical 0.5% malathion lotion, a finding that suggests that it could be an alternative treatment. (ClinicalTrials.gov number, NCT00819520.)

Two-photon laser-generated microtracks in 3D collagen lattices: principles of MMP-dependent and -independent collective cancer cell invasion.

Cancer invasion into an extracellular matrix (ECM) results from a biophysical reciprocal interplay between the expanding cancer lesion and tissue barriers imposed by the adjacent microenvironment. In vivo, connective tissue provides both densely packed ECM barriers adjacent to channel/track-like spaces and loosely organized zones, both of which may impact cancer invasion mode and efficiency; however little is known about how three-dimensional (3D) spaces and aligned tracks present in interstitial tissue guide cell invasion. We here describe a two-photon laser ablation procedure to generate 3D microtracks in dense 3D collagen matrices that support and guide collective cancer cell invasion. Whereas collective invasion of mammary tumor (MMT) breast cancer cells into randomly organized collagen networks required matrix metalloproteinase (MMP) activity for cell-derived collagen breakdown, re-alignment and track generation, preformed tracks supported MMP-independent collective invasion down to a track caliber of 3 µm. Besides contact guidance along the track of least resistance and initial cell deformation (squeezing), MMP-independent collective cell strands led to secondary track expansion by a pushing mechanism. Thus, two-photon laser ablation is useful to generate barrier-free microtracks in a 3D ECM which guide collective invasion independently of pericellular proteolysis.

Do electrical parameters of the cardiac cycle reflect the corresponding mechanical intervals as the heart rate changes?

AIMS: The evoked QT interval can be detected beat by beat through an implanted pacing system. The correlation between the right ventricular paced QT interval and the left ventricular systolic interval is not known. The aim of our study was to collect data on the correlation between QT and systolic and diastolic indexes at different heart rates in patients with dual-chamber rate-responsive pacemakers. METHOD AND RESULTS: The study involved 13 patients [67 +/- 9 years; ejection fraction (EF) 52 +/- 10%] with standard indication for dual-chamber pacing. Patients were evaluated at rest in the supine position. The AV delay was set at 130 ms, and the pacing rate was increased from 90 to 130 bpm (10 bpm steps for 3 min). At the end of each 3 min step, QT intervals were automatically evaluated in real time by means of pacemaker telemetry. We also evaluated heart performance by means of echo-2D (end-diastolic/end-systolic volumes, EF) and echo-Doppler measurements [left ventricular ejection time (LVET) and diastolic filling time (LVDFT), aortic velocity time integral, and systolic volume] and systemic arterial pressure. The QT interval progressively decreased from 330 +/- 20 to 280 +/- 10 ms as the pacing rate was increased from 90 to 130 bpm. The correlation between the QT interval and LVET as a function of the pacing rate was R(2) = 0.966, indicating a good and relatively parallel trend in these two parameters. The correlation between RR-QT (reflecting electrical diastole) and LVDFT (reflecting mechanical diastole) was R(2) = 0.975. The index LVET/QT (ratio between mechanical and electrical systole) was constant in the range 90-120 bpm, but significantly decreased at 130 bpm: the mechanical LVET shortens more than the electrical QT does at the highest heart rates. CONCLUSION: In paced patients at rest and during artificially increased heart rates, QT interval dynamics is closely correlated with changes in ejection time, thus constituting an electrical parameter of systolic time. A similar correlation exists between RR-QT, as a diastolic electrical interval, and the DFT.

Gene-flow from steppe individuals into Cucuteni-Trypillia associated populations indicates long-standing contacts and gradual admixture.

The Cucuteni-Trypillia complex (CTC) flourished in eastern Europe for over two millennia (5100-2800 BCE) from the end of the Neolithic to the Early Bronze Age. Its vast distribution area encompassed modern-day eastern Romania, Moldova and western/central Ukraine. Due to a lack of existing burials throughout most of this time, only little is known about the people associated with this complex and their genetic composition. Here, we present genome-wide data generated from the skeletal remains of four females that were excavated from two Late CTC sites in Moldova (3500-3100 BCE). All individuals carried a large Neolithic-derived ancestry component and were genetically more closely related to Linear Pottery than to Anatolian farmers. Three of the specimens also showed considerable amounts of steppe-related ancestry, suggesting influx into the CTC gene-pool from people affiliated with, for instance, the Ukraine Mesolithic. The latter scenario is supported by archaeological evidence. Taken together, our results confirm that the steppe component arrived in eastern Europe farming communities maybe as early as 3500 BCE. In addition, they are in agreement with the hypothesis of ongoing contacts and gradual admixture between incoming steppe and local western populations.

64-Detector CT angiography in renal artery stent evaluation: prospective comparison with selective catheter angiography.

PURPOSE: To prospectively assess the diagnostic accuracy of 64-detector computed tomographic (CT) renal artery (RA) angiography for the evaluation of RA in-stent restenosis (ISR) by using selective catheter RA angiography as the reference standard. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Eighty-six patients (46 men, 40 women; mean age +/- standard deviation, 71 years +/- 9) with 95 RA stents were examined with 64-detector CT RA angiography by experienced radiologists 1 day before selective catheter RA angiography was performed by experienced cardiologists. Each group was blinded to the results of the other imaging method. For image reconstruction, a standard (B25f) and an edge-enhancing (B46f) kernel were chosen. An ISR of more than 50% was considered as hemodynamically significant. Sensitivity, specificity, and positive and negative predictive values for the detection of ISR by using CT RA angiography were calculated. RESULTS: At CT RA angiography, 93 (98%) of 95 stents were assessable for diagnosis. Two stents could not be evaluated owing to hardening artifacts affected by vessel calcifications. All nine cases of significant ISR seen at selective catheter RA angiography were correctly diagnosed by using CT RA angiography, giving a sensitivity of 100% and a negative predictive value of 100%. One case of nonsignificant ISR seen at selective catheter RA angiography was interpreted as significant by using CT RA angiography, giving a specificity of 99% and a positive predictive value of 90%. In four of 78 patients without ISR seen at selective catheter RA angiography, CT RA angiography showed nonsignificant ISR, giving a specificity of 95% and a positive predictive value of 56%. CONCLUSION: Sixty-four-detector CT RA angiography can provide an excellent noninvasive technique to help detect and evaluate ISR within the RA stents used in our study.

Acute results of pulmonary vein isolation in patients with paroxysmal atrial fibrillation using a single mesh catheter.

INTRODUCTION: Catheter-based pulmonary vein isolation (PVI) is an established therapy to treat patients with paroxysmal atrial fibrillation. We evaluated the efficacy of a simplified interventional procedure for PVI by using a single mesh catheter for mapping as well as ablation and with guidance of fluoroscopic imaging only. METHODS AND RESULTS: Forty-eight patients with paroxysmal atrial fibrillation were screened by cardiac computed tomography for their anatomical suitability to undergo PVI with the high-density mesh ablator catheter as the only left atrial device. The procedure was performed in 26 patients (12 males, mean age 61 years) who met the criteria of four clearly separated pulmonary veins (PVs) with an ostial diameter of 15-25 mm. No three-dimensional mapping systems or additional ablation devices were used. In all 26 patients, all four PVs could be accessed and mapped with the high-density mesh ablator catheter. Electrical isolation was achieved in 99 of 102 (97%) of the pulmonary veins that revealed PV potentials. Mean total procedure time and fluoroscopy time were 187 +/- 36 minutes and 34.6 +/- 10.0 minutes, respectively. CONCLUSION: The single-catheter approach using the high-density mesh ablator catheter for mapping as well as ablation reveals a high acute success rate of PVI while, at the same time, reducing the complexity of the procedure, and the procedure time. Long-term data on clinical success are needed to justify this simplified approach.

Entropion-ectropion: the influence of axial globe projection on lower eyelid malposition.

PURPOSE: To evaluate the effect of axial globe projection on lower eyelid malposition with aging. METHODS: Consecutive patients presenting to 2 oculoplastic surgeons with lower eyelid and tarsal involutional ectropion or entropion underwent axial globe projection measurements with a Hertel exophthalmometer. RESULTS: Data on 36 eyelids of 31 white patients were collected. Axial globe projection in the ectropion group, mu = 19.9, was significantly greater than in the entropion group, mu = 16.1 (p = 0.000021). This held true even when the analysis was confined to the subgroup of male patients. CONCLUSION: Tarsal ectropion directly correlates with more prominent axial globe position, and patients with relatively enophthalmic eyes tend to develop entropion.

Governing Tripolye: Integrative architecture in Tripolye settlements.

Recently, high-resolution magnetometry surveys have led to the discovery of a special category of buildings-so-called 'mega-structures'-situated in highly visible positions in the public space of Tripolye giant-settlements of the late 5th and first half of the 4th millennium BCE. In this paper we explore what these buildings actually are and how they can contribute to the understanding of the development of social space in Tripolye giant-settlements. For this investigation, we linked newly obtained excavation data from the giant-settlement Maidanetske, Ukraine, with a much larger sample of such buildings from magnetic plans obtained in the region between the Carpathian foothills and the Dnieper River. Accordingly, Tripolye mega-structures represent a particular kind of integrative building documented in many non-ranked ethnographic contexts. Based on our results we are interpreting that these buildings were used for various ritual and non-ritual activities, joint decision-making, and the storage and consumption of surplus. In Tripolye giant-settlements at least three different categories of mega-structures could be identified which most likely represent different levels of socio-political integration and decision-making. The emergence of this hierarchical system of high-level integrative buildings for the whole community and different low-level integrative architectures for certain segments of local communities was related to the rise of Tripolye mega-sites. The presence of different integrative levels most likely reflects the fusion of different previously independent communities in the giant-settlements. Later in the mega-site development, we observe how low-level integrative buildings increasingly lose their importance indicated by shrinking size and, finally, their disappearance. This observation might indicate that the power which was previously distributed across the community was transferred to a central institution. It is argued that the non-acceptance of this concentration of power and the decline of lower decision-making levels might be a crucial factor for the disintegration of Tripolye giant-settlements around 3600 BCE.

Long-term outcomes in patients with atrioventricular block undergoing septal ventricular lead implantation compared with standard apical pacing.

AIMS: Left ventricular function may be altered by right ventricular apical pacing. The aims of the study were to compare the long-term course of different parameters of left ventricular dysfunction in patients undergoing implantation of a dual-chamber pacemaker with the ventricular lead in a septal position vs. in a standard apical position. METHODS: We randomized 98 patients with atrioventricular block (AV-block) undergoing pacemaker implantation to positioning the ventricular lead in the high or mid septum (n = 53) or in the apex (n = 45) of the right ventricle. N-terminal pro-brain natriuetic peptide (BNP) levels, left ventricular ejection fraction (LVEF), and exercise capacity were analysed 3 days, 3 months, and 18 months after the implantation. The primary endpoints were the changes of these parameters from baseline to 18 months. RESULTS: Changes of BNP levels, LVEF, and exercise capacity from baseline to 18 months were statistically not different between septal and apical stimulation. The clinical occurrence or deterioration of overt heart failure was similar in both treatment arms. CONCLUSION: With regard to different parameters of congestive heart failure, a septal stimulation site is not superior to conventional apical pacing in unselected patients undergoing pacemaker implantation for AV-block.

In-stent restenosis in bare metal stents versus sirolimus-eluting stents after primary coronary intervention for acute myocardial infarction and subsequent transcoronary transplantation of autologous stem cells.

BACKGROUND: Following stenting for acute myocardial infarction, transcoronary transplantation of granulocyte-colony stimulating factor (G-CSF) mobilized autologous stem cells (ASC) has been shown to result in an increased in-stent restenosis rate of bare metal stents (BMS). HYPOTHESIS: This study sought to compare the extent of neointimal growth in BMS and sirolimus-eluting stents (SES) after primary implantation, and subsequent transcoronary transplantation of G-CSF mobilized stem cells. METHODS: Patients with stenting of the left anterior descending coronary artery for acute anterior myocardial infarction were randomly assigned to receive a BMS or SES. Intracoronary stem cell injection was performed after G-CSF application for at least 4 d and cell apheresis. The angiograms obtained after cell transplantation and after 6 mo were analyzed by quantitative coronary angiography. RESULTS: We performed primary stenting and stem cell transplantion in 16 patients who received a BMS (n = 8) or an SES (n = 8). In 2 patients with a BMS, late stent thrombosis occurred after 58 d and 177 d, respectively. In the remaining patients, control angiography after 6 mo revealed in-stent restenosis of >50% in no patients with SES but in 4 patients with BMS (67%). Late lumen loss and in-stent plaque volume were significantly higher in patients with BMS compared with patients with SES. CONCLUSIONS: Compared with BMS, SES impair in-stent intima hyperplasia after stenting for acute myocardial infarction and transcoronary transplantation of G-CSF mobilized ASC.

Risk score for peri-interventional complications of carotid artery stenting.

BACKGROUND AND PURPOSE: Routinely available independent risk factors for the peri-interventional outcome of patients undergoing elective carotid artery stenting (CAS) are lacking. The rationale of the study was to create a risk score identifying high-risk patients. METHODS: We prospectively enrolled 606 consecutive patients assigned to CAS at a secondary care hospital. Various biochemical, clinical, and lesion-related risk factors were prospectively defined. The primary end point reflecting periprocedural complications encompassed minor and major stroke, nonfatal myocardial infarction and all-cause mortality within 30 days. RESULTS: Three percent of patients (n=18) experienced a nonfatal minor (n=13) or major (n=5) stroke. 1.3% of patients (n=8) died from fatal stroke (n=4) or other causes (n=4). No myocardial infarction was observed within 30 days after stenting. Multivariable analysis revealed diabetes mellitus with inadequate glycemic control (HbA1c > 7%), age > or = 80 years, ulceration of the carotid artery stenosis, and a contralateral stenosis > or = 50% as independent risk factors. A risk score formed with these variables showed a superior predictive value (C-statistic = 0.73) compared with single risk factors. The presence of 2 or more of these risk factors identified patients with a risk of 11% for a periprocedural complication compared with 2% in patients with a score of 0 or 1. CONCLUSIONS: In patients undergoing elective CAS, a risk score based on routinely accessible variables was able to identify patients at high-risk for atherothrombotic events and all-cause death within 30 days after the intervention.

Effects of peripheral blood stem cell mobilization with granulocyte-colony stimulating factor and their transcoronary transplantation after primary stent implantation for acute myocardial infarction.

BACKGROUND: There is increasing evidence that transplantation of autologous stem cells improves cardiac function after acute myocardial infarction (AMI). For propagation of peripheral blood stem cells (PBSCs), application of granulocyte-colony stimulating factor (G-CSF) has been shown to be feasible, effective, and safe. We sought to evaluate a clinical and angiographic long-term safety profile of G-CSF application combined with transcoronary PBSC transplantation after recent stent implantation for AMI. METHODS: In patients with AMI and successful primary stenting of the infarct-related coronary artery, pharmacological bone marrow stimulation with G-CSF was initiated on the second postinterventional day. At least after 4 days of G-CSF therapy, apheresis as well as transcoronary transplantation of PBSCs was performed. The PBSCs were infused via a balloon catheter which was inflated inside the stent. Ventriculography and quantitative coronary angiography were performed at baseline and after 6 months. RESULTS: In the 20 patients who received PBSCs, mean left ventricular ejection fraction improved from 46.4% +/- 8.1% at baseline to 54.3% +/- 11% after 6 months (P < .001) because of an increase in systolic function in the infarct region. Control coronary angiography revealed a significant in-stent restenosis of the infarct-related coronary artery, defined as >50% stenosis, in 8 patients (40%), which was complicated by reinfarction in 2 patients (10%). CONCLUSIONS: Transcoronary transplantation of G-CSF-mobilized PBSCs favorably influences cardiac function and can be performed without adverse periprocedural events. However, significant in-stent restenosis and reinfarction seem to occur frequently during the following 6 months.

3-[5-(4,5-dihydro-1H-imidazol-2-yl)-furan-2-yl]phenylamine (Amifuraline), a promising reversible and selective peripheral MAO-A inhibitor.

On the basis of the observation that the central side effects of MAO inhibitors may represent a major limit for their use in pathological processes involving peripheral MAOs, we investigated the possibility of generating novel inhibitors able to target specifically peripheral MAOs. To address this issue, we designed compounds 7-28. From biological results, the 2-(5-phenyl-furan-2-yl)-4,5-dihydro-1H-imidazole (Furaline, 17) proved to be a suitable lead. In fact, in enzyme assays on homogenate preparation from rat liver and HEK cells expressing MAO-A or MAO-B, compounds possessing the frame of 17 behaved as selective and reversible MAO-A inhibitors. Interestingly, in in vivo studies the amino derivative 21 (Amifuraline), endowed with good hydrophilic character, was able to significantly inhibit liver but not brain MAO-A.

Long-term follow-up in patients with lost coronary stents during interventional procedures.

The aim of this retrospective study was to determine the incidence of stent loss during interventional procedures and to identify the associated immediate and long-term consequences of such loss. We evaluated 36 cases in which the stents were prematurely displaced from the stent delivery device. Five stents were completely removed from the vascular system successfully. Five stents could not be retrieved from the coronary circulation and led to significant adverse events in 3 patients, in whom the lost stents were not excluded by the placement of another stent. In 26 patients, peripheral embolism below the renal arteries occurred after successful stent retrieval from the coronary arteries. Of these 26 patients, 1 patient died during hospital stay, unrelated to the peripheral stent loss. Additional follow-up examinations were performed for 20 of the remaining 25 patients. Clinical patient status and the ankle-brachial index were evaluated 59 +/- 30 months after stent loss. All patients were free of any stent-related peripheral ischemic symptoms. We also attempted to determine the exact physical locations of the lost stents using computed tomography during follow-up. In 15 patients, we were able to detect the stent in the peripheral arteries using computed tomography. In conclusion, if stents cannot be retrieved from the coronary system, severe problems may occur. Stent loss with peripheral embolization is asymptomatic in long-term follow-up.

Effects of a high dose intravenous bolus amiodarone in patients with atrial fibrillation and a rapid ventricular rate.

BACKGROUND: Amiodarone, given as intravenous bolus has not yet been studied in patients with atrial fibrillation and a high ventricular rate. METHODS: One hundred consecutive patients with atrial fibrillation and a ventricular rate above 135 bpm were randomized to receive either 450 mg amiodarone or 0.6 mg digoxin given as a single bolus through a peripheral venous access. If the ventricular rate exceeded 100 bpm after 30 min, another 300 mg amiodarone or 0.4 mg digoxin were added. Primary endpoints of the study were the ventricular rate and the occurrence of sinus rhythm after 30 and 60 min. Secondary endpoints were blood pressure during the first hour after drug administration, and safety regarding drug induced hypotension, and phlebitis at the infusion site. RESULTS: Baseline heart rate was 144+/-19 in the amiodarone group and 145+/-15 in the digoxin group (p=0.72). Following amiodarone, heart rate was 104+/-25 after 30 min compared to 116+/-23 in the digoxin group (p=0.02) and 94+/-22 versus 105+/-22 after 60 min (p=0.03). After 30 min, sinus rhythm was documented in 14 (28%) patients following amiodarone compared to 3 (6%) patients in the digoxin group (p=0.003), and after 60 min in 21 (42%) versus 9 (18%) patients (p=0.012). Asymptomatic hypotension was observed in 4 amiodarone treated patients, and superficial phlebitis in 1 patient. CONCLUSIONS: Amiodarone, given as an intravenous bolus is relatively safe and more effective than digoxin for heart rate control and conversion to sinus rhythm in patients with atrial fibrillation and a rapid ventricular rate.

Recurrent symptomatic bradycardia due to secret ingestion of beta-blockers--a rare manifestation of cardiac Münchhausen syndrome.

The term Münchhausen syndrome was established in 1951 by Asher to describe a severe psychiatric illness in which patients simulate false symptoms and signs. We report on a female general practitioner who repeatedly ingested high doses of beta-blockers in order to simulate symptomatic sick-sinus syndrome. She had been admitted to intermediate care units in several hospitals before the correct diagnosis was made by finding the tablets in her toilet bag. Following psychiatric exploration and psychotherapy, she has been working in her community again for about a year. This is the first report on the clinical presentation and course of disease in a patient with cardiac Münchhausen syndrome who secretly ingested beta-blockers to provoke a menacing bradycardia. The follow-up indicates that frequent and intense symptomatic episodes of this remarkable psychiatric disease can be interrupted by long normal intervals.

Comparison of Two Forms of Loperamide-Simeticone and a Probiotic Yeast (Saccharomyces boulardii) in the Treatment of Acute Diarrhoea in Adults: A Randomised Non-Inferiority Clinical Trial.

BACKGROUND: Acute diarrhoea is a frequent health problem in both travellers and residents that has a social and economic impact. This study compared the efficacy and tolerability of two loperamide-simeticone formulations and a Saccharomyces boulardii capsule as symptomatic treatment. METHODS: This was a prospective, randomised, single (investigator)-blind, three-arm, parallel group, non-inferiority clinical trial in adult subjects with acute diarrhoea at clinics in Mexico and India, with allocation to a loperamide-simeticone 2/125 mg caplet or chewable tablet (maximum eight in 48 h) or S. boulardii (250 mg twice daily for 5 days). OUTCOME MEASURES: The primary outcome measure was the number of unformed stools between 0 and 24 h following the initial dose of study medication (NUS 0-24). The secondary outcome measures were time to last unformed stool (TLUS), time to complete relief of diarrhoea (TCRD), time to complete relief of abdominal discomfort (TCRAD) and the subject's evaluation of treatment effectiveness. Follow-up endpoints at 7 days were feeling of complete wellness; stool passed since final study visit; and continued or recurrent diarrhoea. SUBJECTS: In this study, 415 subjects were randomised to either a loperamide-simeticone caplet (n = 139), loperamide-simeticone chewable tablet (n = 139) or S. boulardii capsule (n = 137) and were included in the intention-to-treat analysis. RESULTS: With regards to mean NUS 0-24, the loperamide-simeticone caplet was non-inferior to loperamide-simeticone tablets (3.4 vs. 3.3; one-sided 97.5 % confidence interval ≤0.5), with both significantly lower than S. boulardii (4.3; p < 0.001). The loperamide-simeticone groups had a shorter median TLUS [14.9 and 14.0 vs. 28.5 h (loperamide-simeticone caplet and chewable tablet groups, respectively, vs. S. boulardii); p < 0.001], TCRD (26.0 and 26.0 vs. 45.8 h; p < 0.001) and TCRAD (12.2 and 12.0 vs. 23.9 h; p < 0.005) than S. boulardii. Treatment effectiveness for overall illness, diarrhoea and abdominal discomfort relief was greater (p < 0.001) in the loperamide-simeticone groups than with S. boulardii. At 7-day follow-up most subjects reported passing stool at least once since the final study visit (loperamide-simeticone caplet 94.1 %, loperamide-simeticone chewable tablet 94.8 %, S. boulardii 97.0 %), did not experience continued or recurrent diarrhoea [loperamide-simeticone caplet 3.7 % (p < 0.03 vs. S. boulardii), loperamide-simeticone chewable tablet 3.7 %, S. boulardii 5.7 %] and felt completely well [loperamide-simeticone caplet 96.3 % (p < 0.02 vs. S. boulardii), loperamide-simeticone chewable tablet 96.3 % (p < 0.02 vs. S. boulardii), S. boulardii 88.6 %]. All treatments were well-tolerated with few adverse events. CONCLUSIONS: The loperamide-simeticone caplet was non-inferior to the original loperamide-simeticone chewable tablet formulation; both formulations can be expected to demonstrate similar clinical efficacy in the relief of symptoms of acute diarrhoea. Both loperamide-simeticone formulations were superior to the S. boulardii capsule in the primary and secondary endpoints. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00807326.