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Intrauterine preeclampsia exposure affects the lifelong cardiometabolic health of the child. Our study aimed to compare the growth (from birth to 6 months) of infants exposed to either a normotensive pregnancy or preeclampsia and explore the influence of being born small for gestational age (SGA). Participants were children of women participating in the Post-partum, Physiology, Psychology and Paediatric follow-up cohort study. Birth and 6-month weight and length z-scores were calculated for term and preterm (<37 weeks) babies, and change in weight z-score, rapid weight gain (≥0.67 increase in weight z-score) and conditional weight gain z-score were calculated. Compared with normotensive exposed infants (n = 298), preeclampsia exposed infants (n = 84) were more likely to be born SGA (7% versus 23%; P < 0.001), but weight gain from birth to 6 months, by any measure, did not differ between groups. Infants born SGA, irrespective of pregnancy exposure, were more likely to have rapid weight gain and had greater increases in weight z-score compared with those not born SGA. Preeclampsia exposed infants born SGA may benefit from interventions designed to prevent future cardiometabolic disease.
Approved treatments for bipolar depression are limited and associated with a spectrum of undesirable side effects. Lumateperone (lumateperone tosylate, ITI−007), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA-approved for the treatment of schizophrenia. Lumateperone is currently being investigated for the treatment of bipolar depression (major depressive episodes [MDE] associated with bipolar I and bipolar II disorder). This Phase 3 randomized, double-blind, parallel-group, placebo-controlled multinational study (NCT03249376) investigated the efficacy and safety of lumateperone in patients with bipolar I or bipolar II disorder experiencing a MDE.
Patients (18 75 years) with a clinical diagnosis of bipolar I or bipolar II disorder who were experiencing a MDE (Montgomery-Åsberg Depression Rating Scale [MADRS] Total score =20 and a Clinical Global Impression Scale-Bipolar Version-Severity [CGI-BP-S] score =4 at screening and baseline) were randomized to lumateperone 42mg or placebo for 6 weeks. The primary and key secondary efficacy endpoints were change from baseline to Day 43 in MADRS total score and CGI-BP-S scores, respectively. Secondary efficacy outcomes included response (MADRS improvement = 50%) and remission (MADRS total score =12) at Day 43. Safety assessments included treatment emergent adverse events, laboratory parameters, vital signs, extrapyramidal symptoms (EPS), and suicidality.
In this study, 377 patients received treatment (placebo, n=189; lumateperone 42mg, n=188) and 333 completed treatment. Patients in the lumateperone 42-mg group had significantly greater mean improvement on MADRS total score change from baseline to Day 43 compared with placebo (least squares mean difference [LSMD]=-4.6; 95% confidence interval [CI]=-6.34, −2.83; effect size vs placebo [ES]=-0.56; P<.0001). Lumateperone treatment was associated with significant MADRS improvement in both patients with bipolar I (LSMD=-4.0; 95% CI=-5.92, −1.99; ES=-0.49; P<.0001) and bipolar II (LSMD=-7.0; 95% CI=-10.92, −3.16; ES=-0.81; P=.0004). The lumateperone 42-mg group also had significantly greater mean improvement in CGI-BP-S total score compared with placebo (LSMD=-0.9; 95% CI=-1.37, −0.51; ES=-0.46; P<.001). Lumateperone compared with placebo had significantly greater MADRS response rate (51.1% vs 36.7%; odds ratio=2.98; P<.001) and remission rates (P=.02) at Day 43. Lumateperone treatment was well tolerated, with minimal risk of EPS, metabolic, and prolactin side effects.
Lumateperone 42 mg significantly improved depression symptoms in both patients with bipolar I and bipolar II depression. Lumateperone was generally well tolerated. These results suggest that lumateperone 42 mg may be a promising new treatment for bipolar depression associated with bipolar I or bipolar II disorder.
Current treatments for schizophrenia are often associated with increased rates of metabolic syndrome (MetSy). MetSy is defined as meeting 3 of the following 5 criteria: waist circumference >40in (men) or >35in (women), triglycerides =150mg/dL, high density lipoprotein cholesterol (HDL) <40mg/dL (men) or <50mg/dL (women), systolic blood pressure (BP) =130mmHg or diastolic BP =85mmHg, fasting glucose =100mg/dL. Patients with MetSy have an elevated risk of developing type II diabetes and increased mortality due to cardiovascular disease. Lumateperone (lumateperone tosylate, ITI−007), a mechanistically novel antipsychotic that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, is FDA approved for the treatment of schizophrenia. This distinct pharmacological profile has been associated with favorable tolerability and a low risk of adverse metabolic effects in clinical trials. This post hoc analysis of 2 randomized, double-blind, placebo-controlled studies of patients with an acute exacerbation of schizophrenia compared rates of MetSy with lumateperone and risperidone. Data from an open-label long-term trial of lumateperone were also evaluated.
The incidence and shift in MetSy were analyzed in data pooled from 2 short-term (4 or 6 week) placebo- and active-controlled (risperidone 4mg) studies of lumateperone 42mg (Studies 005 and 302). The pooled lumateperone data were compared with data for risperidone. Data from an open-label 1-year trial (Study 303) evaluated MetSy in patients with stable schizophrenia switched from prior antipsychotic (PA) treatment to lumateperone 42mg.
In the acute studies (n=256 lumateperone 42mg, n=255 risperidone 4mg), rates of MetSy were similar between groups at baseline (16% lumateperone, 19% risperidone). At the end of treatment (EOT), MetSy was less common with lumateperone than with risperidone (13% vs 25%). More lumateperone patients (46%) compared with risperidone (25%) patients improved from having MetSy at baseline to no longer meeting MetSy criteria at EOT. Conversely, more patients on risperidone than on lumateperone developed MetSy during treatment (13% vs 5%). Differences in MetSy conversion rates were driven by changes in triglycerides and glucose. In the long-term study (n=602 lumateperone 42mg), 33% of patients had MetSy at PA baseline. Thirty-six percent of patients (36%) with MetSy at PA baseline improved to no longer meeting criteria at EOT. Fewer than half that percentage shifted from not meeting MetSy criteria to having MetSy (15%).
In this post hoc analysis, lumateperone 42mg patients had reduced rates of MetSy compared with risperidone patients. In the long-term study, patients with MetSy on PA switched to lumateperone 42mg had a reduction in the risk of MetSy. These results suggest that lumateperone 42mg is a promising new treatment for schizophrenia with a favorable metabolic profile.
Froth flotation by small air bubbles has been traditionally used in industry to capture fine minerals and other hydrophobic particles. This method, however, is not efficient for capturing very small particles. The present work is motivated by a new agglomeration process that overcomes this lack of efficiency. It consists of mixing a particle suspension and saltwater-filled droplets covered with semi-permeable oil layers. This paper investigates the two-particle dynamics of a solid particle and a semi-permeable spherical drop that expands due to osmosis in an external, pure extensional flow field. A dimensionless engulfment parameter measures the relative effects of droplet growth and convective flow. The computational results from numerical integration determine a transient collision efficiency, which describes the influence of hydrodynamic interactions and osmotic flow on particle capture. The results show that drop expansion, which decays slowly with time, greatly increases particle capture rates, especially for small particles. Moreover, as the engulfment parameter increases, there is a transition from flow-dominated capture to expansion-dominated capture. For the case of a non-expanding droplet, we provide a numerical solution for the transient pair distribution function, which enables us to explain the transient particle-capture rate in terms of the microstructure of the suspension. Furthermore, we derive an analytical expression for the initial collision efficiency at zero times, which agrees with our numerical data. The numerical results for non-expanding droplets at long times show increasing collision efficiency as the permeability increases and when the size ratio is near unity, in agreement with previous steady-state calculations.
The importance of data science in society today is undeniable, and now is the time to prepare data science talent (National Academies of Sciences, Engineering, and Medicine 2018). Data science demands collaboration, but collaboration within political science departments has been weak in teaching data science. Bridging substantive and methods courses can critically aid in teaching data science because it facilitates this collaboration. Our innovation is to integrate data science into both substantive and methods courses through a dedicated data science course and modules on data science topics taught in substantive courses. This approach allows not only for more opportunities for teaching and practice of data science methods but also helps students to understand how social, economic, and political biases and incentives can affect their data.
A fully three-dimensional boundary-integral method (BIM) is developed for the interaction of drops, suspended in a uniform far-field flow at small Reynolds number, with arbitrary Lyapunov surfaces. The close approach of fluid interfaces to solid surfaces poses significant challenges for numerical BIM implementations, due to the highly singular behaviour of single- and double-layer boundary integrals. Two new methods are described that generalize the accurate calculation of the highly singular surface integrals used by high-order desingularization techniques. The first method is semi-analytical, and applies to axisymmetric solid obstacles (in an arbitrary three-dimensional configuration). An axisymmetric particle can be divided into a series of characteristic disks along its axis, for which closed-form expressions for single and double layers are derived in terms of elliptic integrals. To accommodate arbitrary smooth surfaces, a multimesh desingularization method is introduced that calculates surface integrals utilizing a hierarchy of embedded mesh resolutions, together with distance-activated mesh interactions. Several particle shapes, including spherocylinders (capsules) and flat plates, are used to represent major classes characteristic of porous media. A droplet approaching a capsule will break up after forming two lobes, connected by a thin filament, on either side of the capsule. The cross-sectional shape of the filament affects lubrication behaviour. A constriction made of two parallel capsules, even of low aspect ratio, significantly retards drop passage compared to two spheres. Trends in drop squeezing between two capsules are summarized over a range of capillary number, viscosity ratio, drop size and capsule length. A constriction of two coplanar plates results in notably different lubrication and squeezing behaviour. Flow rectification is demonstrated for constrictions that are non-symmetrical with respect to flow reversal, for several non-axisymmetric particles.
In this article, we present the results of an analysis of variation, whose main objectives are to ascertain the ethnocultural identities speakers declare and to measure the impact of internal, external and identity factors on the use of the connectors of consequence (ça) fait que vs donc vs alors vs so. Our research emphasizes that while there is no consensus as to the terminology chosen to express these identities, it is important to consider ethnocultural identities as a complementary factor conditioning linguistic variation. It also demonstrates that for communities whose linguistic practices and norms straddle those of minority- and majority-French language communities, the minority/majority dichotomy needs to be nuanced, according to the social and ethnocultural identity dynamics that may characterize specific communities.
Engagement of frontline staff, along with senior leadership, in competition-style healthcare-associated infection reduction efforts, combined with electronic clinical decision support tools, appeared to reduce antibiotic regimen initiations for urinary tract infections (P = .01). Mean monthly standardized infection and device utilization ratios also decreased (P < .003 and P < .0001, respectively).
Archaeologists have struggled to combine remotely sensed datasets with preexisting information for landscape-level analyses. In the American Southeast, for example, analyses of lidar data using automated feature extraction algorithms have led to the identification of over 40 potential new pre-European-contact Native American shell ring deposits in Beaufort County, South Carolina. Such datasets are vital for understanding settlement distributions, yet a comprehensive assessment requires remotely sensed and previously surveyed archaeological data. Here, we use legacy data and airborne lidar-derived information to conduct a series of point pattern analyses using spatial models that we designed to assess the factors that best explain the location of shell rings. The results reveal that ring deposit locations are highly clustered and best explained through a combination of environmental conditions such as distance to water and elevation as well as social factors.
Invasive predators have decimated island biodiversity worldwide. Rats (Rattus spp.) are perhaps the greatest conservation threat to island fauna. The ground nesting Palau Micronesian Scrubfowl Megapodius laperouse senex (Megapodiidae) inhabits many of the islands of Palau’s Rock Island Southern Lagoon Conservation Area (RISL) in the western Pacific. These islands are also heavily visited by tourists and support populations of introduced rats, both of which may act as added stressors for the scrubfowl. Using passive chew-tag and call playback surveys on five tourist-visited and five tourist-free islands, we investigated if rats and tourists negatively affect scrubfowl, and if higher rat activity is associated with tourist presence. Rat detection probability and site occupancy were significantly higher on tourist visited (89% and 99%, respectively) compared to tourist-free islands (52% and 73%). Scrubfowl were detected at significantly more stations on tourist-free (93%) than tourist visited (47%) islands and their relative abundance was higher (2.66 and 1.58 birds per station, respectively), although not statistically significantly. While rat occupancy probability likewise had a non-significant negative effect on scrubfowl numbers across islands, our results show a negative relationship between tourist presence and scrubfowl in the RISL. Our findings also suggest that rat populations may be augmented by tourist visitation in the RISL. Although this situation may not seriously affect the scrubfowl, it may be highly detrimental to populations of other threatened island landbirds.
This study investigated metabolic, endocrine, appetite and mood responses to a maximal eating occasion in fourteen men (mean: age 28 (sd 5) years, body mass 77·2 (sd 6·6) kg and BMI 24·2 (sd 2·2) kg/m2) who completed two trials in a randomised crossover design. On each occasion, participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until ‘comfortably full’ (ad libitum) and on the other, until they ‘could not eat another bite’ (maximal). Mean energy intake was double in the maximal (13 024 (95 % CI 10 964, 15 084) kJ; 3113 (95 % CI 2620, 3605) kcal) compared with the ad libitum trial (6627 (95 % CI 5708, 7547) kJ; 1584 (95 % CI 1364, 1804) kcal). Serum insulin incremental AUC (iAUC) increased approximately 1·5-fold in the maximal compared with ad libitum trial (mean: ad libitum 43·8 (95 % CI 28·3, 59·3) nmol/l × 240 min and maximal 67·7 (95 % CI 47·0, 88·5) nmol/l × 240 min, P < 0·01), but glucose iAUC did not differ between trials (ad libitum 94·3 (95 % CI 30·3, 158·2) mmol/l × 240 min and maximal 126·5 (95 % CI 76·9, 176·0) mmol/l × 240 min, P = 0·19). TAG iAUC was approximately 1·5-fold greater in the maximal v. ad libitum trial (ad libitum 98·6 (95 % CI 69·9, 127·2) mmol/l × 240 min and maximal 146·4 (95 % CI 88·6, 204·1) mmol/l × 240 min, P < 0·01). Total glucagon-like peptide-1, glucose-dependent insulinotropic peptide and peptide tyrosine–tyrosine iAUC were greater in the maximal compared with ad libitum trial (P < 0·05). Total ghrelin concentrations decreased to a similar extent, but AUC was slightly lower in the maximal v. ad libitum trial (P = 0·02). There were marked differences on appetite and mood between trials, most notably maximal eating caused a prolonged increase in lethargy. Healthy men have the capacity to eat twice the energy content required to achieve comfortable fullness at a single meal. Postprandial glycaemia is well regulated following initial overeating, with elevated postprandial insulinaemia probably contributing.
Lumateperone (lumateperone tosylate, ITI-007) is an investigational drug for the treatment of schizophrenia, bipolar depression, and other disorders. Lumateperone has a unique mechanism of action that simultaneously modulates serotonin, dopamine, and glutamate neurotransmission. This may provide advantages in the treatment of the broad symptoms associated with schizophrenia, including negative and depression symptoms. In 2 previous placebo-controlled trials in patients with acute schizophrenia, lumateperone 42mg (ITI-007 60mg) demonstrated statistically significant improvement in the Positive and Negative Syndrome Scale (PANSS) Total score compared with placebo. In these studies, lumateperone was well tolerated with a safety profile similar to placebo. This open-label long-term study evaluated the safety and effectiveness of lumateperone 42mg in patients with schizophrenia and stable symptoms.
Patients with stable schizophrenia were treated for up to 1 year with lumateperone 42mg. Safety assessments included adverse events (AEs), body weight, laboratory parameters, and extrapyramidal symptoms (EPS)/motor symptom assessments. Efficacy analyses included evaluation of changes in PANSS Total score and in depression symptoms, as measured by the Calgary Depression Scale for Schizophrenia (CDSS).
In the 1-year open-label study, 602 patients received at least 1 dose of lumateperone 42mg; at the time of this interim analysis, 107 patients had completed 1 year of treatment. Only 4 TEAEs occurred in ≥5% of patients (weight decrease, dry mouth, headache and diarrhea); the majority of AEs were mild or moderate in intensity. Most metabolic parameters and mean prolactin levels decreased from SOC baseline, as did mean body weight and BMI. Based on AE reporting and EPS/motor symptom scales, lumateperone treatment was associated with minimal EPS risk. Lumateperone 42mg treatment was associated with significant reductions in PANSS Total score from baseline, with continuing PANSS improvement throughout the study. In patients with moderate-to-severe depression symptoms at baseline (CDSS>5), mean CDSS scores decreased from 7.4 (baseline) to 3.1 (Day 300); 60% of patients met CDSS response criteria (50% improvement from baseline) by Day 75 and this response rate was maintained through day 300. Similar magnitude of CDSS improvement was seen regardless of concurrent antidepressant therapy.
In long-term treatment, lumateperone was associated with minimal metabolic, EPS, and cardiovascular safety issues relative to current SOC antipsychotic therapy. Lumateperone improved schizophrenia symptoms with continued long-term treatment. In patients with moderate-to-severe depression symptoms at baseline, lumateperone treatment was associated with marked improvement in CDSS scores. These data are consistent with and extend data previously reported in placebo-controlled studies in patients with acute schizophrenia treated with lumateperone.
Supported by funding from Intra-Cellular Therapies, Inc.
Lumateperone (ITI-007) is in late-phase clinical development for schizophrenia. Lumateperone has a unique mechanism of action that modulates serotonin, dopamine, and glutamate neurotransmission. This pooled analysis of lumateperone in 3 randomized, double-blind, placebo-controlled studies was conducted to evaluate the safety and tolerability of lumateperone 42mg (ITI-007 60mg).
Data were pooled from the 3 controlled late-phase studies of lumateperone 42mg in patients with acute exacerbation of schizophrenia. Safety assessments of all patients who received at least one dose of any treatment included treatment-emergent adverse events (TEAEs), changes in laboratory parameters, extrapyramidal symptoms (EPS), and vital signs.
The safety population comprised 1,073 patients (placebo [n=412], lumateperone 42mg [n=406], risperidone [n=255]). TEAEs that occurred in the lumateperone 42mg group at a rate of ≥5% and twice placebo were somnolence/sedation (24.1% vs 10.0%) and dry mouth (5.9% vs 2.2%). Rates of discontinuation due to TEAEs with lumateperone 42mg (0.5%) were similar to placebo (0.5%) and lower than risperidone (4.7%). Mean change in weight and rates of EPS-related TEAEs were less for lumateperone 42mg and placebo patients than risperidone patients. Mean change from baseline in metabolic parameters were similar or smaller for lumateperone 42mg vs placebo. Mean changes were notably higher in risperidone patients vs lumateperone 42mg and placebo for glucose, cholesterol, triglycerides, and prolactin.
In this pooled analysis, lumateperone 42mg showed good tolerability with potential benefits over risperidone for metabolic, prolactin, and EPS risks. The only TEAE that occurred in >10% of lumateperone patients was somnolence/sedation, which was impacted by morning administration; in subsequent studies that administered lumateperone in the evening, somnolence/sedation rates were markedly reduced. These results suggest that lumateperone 42mg may be a promising new treatment for schizophrenia.
Supported by funding from Intra-Cellular Therapies, Inc.
Home care for older people in England is commissioned through local authorities working predominantly with independent providers of care. Commissioners operate in a market model, planning and procuring home care services for local populations. Their role involves ‘managing’ and ‘shaping’ the market to ensure an adequate supply of care providers. Another imperative, emerging from the principles of personalisation, is the drive to achieve user outcomes rather than ‘time and task’ objectives. Little formal research has investigated the way commissioners reconcile these different requirements and organise commissioning. This study investigated commissioning approaches using qualitative telephone interviews with ten commissioners from different local authorities in England. The characteristics of commissioning were analysed thematically. Findings indicated (a) commissioning involved complex systems and processes, uniquely shaped for the local context, but frequently changed, suggesting a constant need for reframing commissioning arrangements; (b) partnerships with providers were mainly transactional, with occasional examples of collaborative models, that were considered to facilitate flexible services more appropriate for commissioning for personalised outcomes; and (c) only a small number of commissioners had attempted to reconcile the competing and incompatible goals of tightly prescribed contracting and working collaboratively with providers. A better understanding of flexible contracting arrangements and the hallmarks of a trusting collaboration is required to move beyond the procedural elements of contracting and commissioning.
UK Biobank is a well-characterised cohort of over 500 000 participants including genetics, environmental data and imaging. An online mental health questionnaire was designed for UK Biobank participants to expand its potential.
Describe the development, implementation and results of this questionnaire.
An expert working group designed the questionnaire, using established measures where possible, and consulting a patient group. Operational criteria were agreed for defining likely disorder and risk states, including lifetime depression, mania/hypomania, generalised anxiety disorder, unusual experiences and self-harm, and current post-traumatic stress and hazardous/harmful alcohol use.
A total of 157 366 completed online questionnaires were available by August 2017. Participants were aged 45–82 (53% were ≥65 years) and 57% women. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status. Lifetime depression was a common finding, with 24% (37 434) of participants meeting criteria and current hazardous/harmful alcohol use criteria were met by 21% (32 602), whereas other criteria were met by less than 8% of the participants. There was extensive comorbidity among the syndromes. Mental disorders were associated with a high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation.
The UK Biobank questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed because of selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health.
As life expectancy increases, more people have chronic psychiatric and medical health disorders. Comorbidity may increase the risk of premature mortality, an important challenge for health service delivery.
Population-based cohort study in Ontario, Canada of all 11 246 910 residents aged ⩾16 and <105 on 1 April 2012 and alive on 31 March 2014. Secondary analyses included subjects having common medical disorders in 10 separate cohorts. Exposures were psychiatric morbidity categories identified using aggregated diagnosis groups (ADGs) from Johns Hopkins Adjusted Clinical Groups software® (v10.0); ADG 25: Persistent/Recurrent unstable conditions; e.g. acute schizophrenic episode, major depressive disorder (recurrent episode), ADG 24: Persistent/Recurrent stable conditions; e.g. depressive disorder, paranoid personality disorder, ADG 23: Time-limited/minor conditions; e.g. adjustment reaction with brief depressive reaction. The outcome was all-cause mortality (April 2014–March 2016).
Over 2 years' follow-up, there were 188 014 deaths (1.7%). ADG 25 conferred an almost threefold excess mortality after adjustment compared to having no psychiatric morbidity [adjusted hazard ratio 2.94 (95% CI 2.91–2.98, p < 0.0001)]. Adjusted hazard ratios for ADG 24 and ADG 23 were 1.12 (95% CI 1.11–1.14, p < 0.0001) and 1.31 (95% CI 1.26–1.36, p < 0.0001). In all 10 medical disorder cohorts, ADG 25 carried significantly greater mortality risk compared to no psychiatric comorbidity.
Psychiatric disorders, particularly those graded persistent/recurrent and unstable, were associated with excess mortality in the whole population, and in the medical disorder cohorts examined. Future research should examine whether service design accounting for psychiatric disorder comorbidity improves outcomes across the spectrum of medical disorders.
Rectilinear collisions of three wetted spheres are considered under conditions of high capillary numbers, for which viscous lubrication forces dominate over capillary forces. The viscous forces resist the relative motion, as characterized by the Stokes number (a dimensionless ratio of particle inertia and viscous forces). At high Stokes numbers, the particles penetrate the fluid layers between them with sufficient inertia that they collide and rebound. Both simultaneous and sequential collisions are simulated, and various outcomes are demonstrated: full agglomeration of the three spheres at low Stokes numbers, full separation or Newton’s cradle at large Stokes numbers and even reverse Newton’s cradle at intermediate Stokes numbers when there is a thicker combined fluid layer between the two target spheres than between the striker sphere and the first target sphere. When there is an initial air gap between the two target spheres, even more exotic outcomes are predicted, such as full separation after the initial collisions followed by full agglomeration or reverse Newton’s cradle (intermediate Stokes numbers) or Newton’s cradle (large Stokes numbers) after the subsequent collisions when the striker sphere catches back up to the target spheres. The approach and findings of this work are expected to provide input and guidance to future work on discrete-element modelling of collisions of many wet particles.
The interfacial behaviour of surfactant-laden drops squeezing through tight constrictions in a uniform far-field flow is modelled with respect to capillary number, drop-to-medium viscosity ratio and surfactant contamination. The surfactant is treated as insoluble and non-diffusive, and drop surface tension is related to surfactant concentration by a linear equation of state. The constriction is formed by three solid spheres held rigidly in space. A characteristic aspect of this confined and contaminated multiphase system is the rapid development of steep surfactant-concentration gradients during the onset of drop squeezing. The interplay between two physical effects of surfactant, namely the greater interface deformability due to decreased surface tension and interface immobilization due to Marangoni stresses, results in particularly rich drop-squeezing dynamics. A three-dimensional boundary-integral algorithm is used to describe drop hydrodynamics, and accurate treatment of close squeezing and trapped states is enabled by advanced singularity subtraction techniques. Surfactant transport and hydrodynamics are coupled via the surface convection equation (or convection–diffusion equation, if artificial diffusion is included), the interfacial stress balance and a solid-particle contribution based on the Hebeker representation. For extreme conditions, such as drop-to-medium viscosity ratios significantly less than unity, it is found that upwind-biased methods are the only stable approaches for modelling surfactant transport. Two distinct schemes, upwind finite volume and flow-biased least squares, are found to provide results in close agreement, indicating negligible numerical diffusion. Surfactant transport is enhanced by low drop-to-medium viscosity ratios, at which extremely sharp concentration gradients form during various stages of the squeezing process. The presence of surfactant, even at low degrees of contamination, significantly decreases the critical capillary number for droplet trapping, due to the accumulation of surfactant at the downwind pole of the drop and its subsequent elongation. Increasing the degree of contamination significantly affects surface mobility and further decreases the critical capillary number as well as drop squeezing times, up to a threshold above which the addition of surfactant negligibly affects squeezing dynamics.