CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom.

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.

Shift work characteristics and burnout among nurses: cross-sectional survey.

BACKGROUND: Nurses working long shifts (≥12 h) experience higher levels of burnout. Yet other shift characteristics, including fixed versus rotating night work, weekly hours and breaks have not been considered. Choice over shift length may moderate the relationship; however, this has not been tested. AIMS: To examine the association between shift work characteristics and burnout and exhaustion, and whether choice over shift length influences burnout and exhaustion. METHODS: Cross-sectional online survey of nursing staff working in the UK and Ireland. We recruited two large National Health Service Trusts, through trade union membership, online/print nursing magazines and social media. We assessed associations using both univariable and multivariable generalized linear models. RESULTS: We had 873 valid responses. Reports of inadequate staffing levels (odds ratio [OR] = 2.84; 95% confidence interval [CI] 2.08-3.90) and less choice over shift length (OR = 0.20; 95% CI 0.06-0.54) were associated with higher burnout in multivariable models. Similar associations were found for exhaustion, where rarely or never taking breaks was also a predictor (OR = 1.61; 95% CI 1.05-2.52). Nurses who worked long shifts had less choice than those working shifts of 8 h or less (66% of 12-h shift nurses versus 44% 8-h shift nurses reporting having no choice), but choice did not moderate the relationship between shift length and burnout and exhaustion. CONCLUSIONS: The relationship between long shifts and increased burnout reported previously might have arisen from a lack of choice for those staff working long shifts. Whether limited choice for staff is intrinsically linked to long shifts is unclear.

Mixed-methods process evaluation of a residence-based SARS-CoV-2 testing participation pilot on a UK university campus during the COVID-19 pandemic.

BACKGROUND: Regular testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is an important strategy for controlling virus outbreaks on university campuses during the COVID-19 pandemic but testing participation rates can be low. The Residence-Based Testing Participation Pilot (RB-TPP) was a novel intervention implemented at two student residences on a large UK university campus over 4 weeks. The aim of the pilot was to increase the frequency of asymptomatic SARS-CoV-2 saliva testing onsite. This process evaluation aimed to determine whether RB-TPP was implemented as planned and identify implementation barriers and facilitators. METHODS: A mixed-methods process evaluation was conducted alongside the RB-TPP. Evaluation participants were students (opting in, or out of RB-TPP) and staff with a role in service provision or student support. Monitoring data were collected from the intervention delivery team and meeting records. Data were collected from students via online survey (n = 152) and seven focus groups (n = 30), and from staff via individual interviews (n = 13). Quantitative data were analysed descriptively and qualitative data thematically. Barriers and facilitators to implementation were mapped to the 'Capability, Opportunity, Motivation-Behaviour' (COM-B) behaviour change framework. RESULTS: Four hundred sixty-four students opted to participate in RB-TPP (98% of students living onsite). RB-TPP was implemented broadly as planned but relaxed social distancing was terminated early due to concerns relating to national escalation of the COVID-19 Delta variant, albeit testing continued. Most students (97.9%) perceived the period of relaxed social distancing within residences positively. The majority engaged in asymptomatic testing (88%); 46% (52% of testers) were fully compliant with pre-determined testing frequency. Implementation was facilitated by convenience and efficiency of testing, and reduction in the negative impacts of isolation through opportunities for students to socialise. Main barriers to implementation were perceived mixed-messages about the rules, ambivalent attitudes, and lack of adherence to COVID-19 protective measures in the minority. CONCLUSIONS: This process evaluation identifies factors that help or hinder the success of university residence-based outbreak prevention and management strategies. RB-TPP led to increased rates of SARS-CoV-2 testing participation among students in university residences. Perceived normalisation of university life significantly enhanced student mental wellbeing. The complexity and challenge generated by multiple lines of communication and rapid adaptions to a changing pandemic context was evident. TRIAL REGISTRATION NUMBER: UKAS 307727-02-01; Pre-results. CLINICALTRIALS: gov Identifier: NCT05045989 ; post-results (first posted, 16/09/21). ETHICAL APPROVAL: Faculty of Medicine & Health Sciences Research Ethics Committee, University of Nottingham (Ref: FMHS 96-0920).

Axisymmetry of critical points for the Onsager functional.

A simple proof is given of the classical result (Fatkullin I, Slastikov V. 2005 Critical points of the Onsager functional on a sphere. Nonlinearity 18, 2565-2580 (doi:10.1088/0951-7715/18/6/008); Liu H et al. 2005 Axial symmetry and classification of stationary solutions of Doi-Onsager equation on the sphere with Maier-Saupe potential. Commun. Math. Sci. 3, 201-218 (doi:10.4310/CMS.2005.v3.n2.a7)) that critical points for the Onsager functional with the Maier-Saupe molecular interaction are axisymmetric, including the case of stable critical points with an additional dipole-dipole interaction (Zhou H et al. 2007 Characterization of stable kinetic equilibria of rigid, dipolar rod ensembles for coupled dipole-dipole and Maier-Saupe potentials. Nonlinearity 20, 277-297 (doi:10.1088/0951-7715/20/2/003)). The proof avoids spherical polar coordinates, instead using an integral identity on the sphere S2. For general interactions with absolutely continuous kernels the smoothness of all critical points is established, generalizing a result in (Vollmer MAC. 2017 Critical points and bifurcations of the three-dimensional Onsager model for liquid crystals. Archive for Rational Mechanics and Analysis 226, 851-922 (doi:10.1007/s00205-017-1146-8)) for the Onsager interaction. It is also shown that non-axisymmetric critical points exist for a wide variety of interactions including that of Onsager. This article is part of the theme issue 'Topics in mathematical design of complex materials'.

In Silico Finite Element Analysis of the Foot Ankle Complex Biomechanics: A Literature Review.

Computational approaches, especially finite element analysis (FEA), have been rapidly growing in both academia and industry during the last few decades. FEA serves as a powerful and efficient approach for simulating real-life experiments, including industrial product development, machine design, and biomedical research, particularly in biomechanics and biomaterials. Accordingly, FEA has been a "go-to" high biofidelic software tool to simulate and quantify the biomechanics of the foot-ankle complex, as well as to predict the risk of foot and ankle injuries, which are one of the most common musculoskeletal injuries among physically active individuals. This paper provides a review of the in silico FEA of the foot-ankle complex. First, a brief history of computational modeling methods and finite element (FE) simulations for foot-ankle models is introduced. Second, a general approach to build an FE foot and ankle model is presented, including a detailed procedure to accurately construct, calibrate, verify, and validate an FE model in its appropriate simulation environment. Third, current applications, as well as future improvements of the foot and ankle FE models, especially in the biomedical field, are discussed. Finally, a conclusion is made on the efficiency and development of FEA as a computational approach in investigating the biomechanics of the foot-ankle complex. Overall, this review integrates insightful information for biomedical engineers, medical professionals, and researchers to conduct more accurate research on the foot-ankle FE models in the future.

Understanding and addressing vaccine hesitancy in the context of COVID-19: development of a digital intervention.

OBJECTIVES: Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) was identified in late 2019, spreading to over 200 countries and resulting in almost two million deaths worldwide. The emergence of safe and effective vaccines provides a route out of the pandemic, with vaccination uptake of 75-90% needed to achieve population protection. Vaccine hesitancy is problematic for vaccine rollout; global reports suggest only 73% of the population may agree to being vaccinated. As a result, there is an urgent need to develop equitable and accessible interventions to address vaccine hesitancy at the population level. STUDY DESIGN: & Method: We report the development of a scalable digital intervention seeking to address COVID-19 vaccine hesitancy and enhance uptake of COVID-19 vaccines in the United Kingdom. Guided by motivational interviewing (MI) principles, the intervention includes a series of therapeutic dialogues addressing 10 key concerns of vaccine-hesitant individuals. Development of the intervention occurred linearly across four stages. During stage 1, we identified common reasons for COVID-19 vaccine hesitancy through analysis of existing survey data, a rapid systematic literature review, and public engagement workshops. Stage 2 comprised qualitative interviews with medical, immunological, and public health experts. Rapid content and thematic analysis of the data provided evidence-based responses to common vaccine concerns. Stage 3 involved the development of therapeutic dialogues through workshops with psychological and digital behaviour change experts. Dialogues were developed to address concerns using MI principles, including embracing resistance and supporting self-efficacy. Finally, stage 4 involved digitisation of the dialogues and pilot testing with members of the public. DISCUSSION: The digital intervention provides an evidence-based approach to addressing vaccine hesitancy through MI principles. The dialogues are user-selected, allowing exploration of relevant issues associated with hesitancy in a non-judgmental context. The text-based content and digital format allow for rapid modification to changing information and scalability for wider dissemination.

Associations between antibiotic prescriptions and recurrent urinary tract infections in female college students.

Urinary tract infections (UTIs) are common among college-aged women and often recur. Some antibiotics recommended to treat UTIs trigger dysbiosis of intestinal and vaginal microbiomes - where uropathogens originate, though few studies have investigated associations between these therapies with recurrent infections. We retrospectively analysed the electronic medical records of 6651 college-aged women diagnosed with a UTI at a US university student health centre between 2006 and 2014. Women were followed for 6 months for incidence of a recurrent infection. In a secondary analysis, associations in women whose experienced UTI recurrence within 2 weeks were also considered for potential infection relapse. Logistic regression was used to assess associations between infection recurrence or relapse and antibiotics prescribed, in addition to baseline patient characteristics including age, race/ethnicity, region of origin, year of encounter, presence of symptomology, pyelonephritis, vaginal coinfection and birth control consultation. There were 1051 instances of infection recurrence among the 6620 patients, indicating a prevalence of 16%. In the analysis of patient characteristics, Asian women were statistically more likely to experience infection recurrence whereas African American were less likely. No significant associations were identified between the antibiotic administered at the initial infection and the risk of infection recurrence after multivariable adjustment. Treatment with trimethoprim-sulphamethoxazole and being born outside of the USA were significantly associated with increased odds of infection relapse in the multivariate analysis. The results of the analyses suggest that treatment with trimethoprim-sulphamethoxazole may lead to an increased risk of UTI relapse, warranting further study.

Closing the Wearable Gap-Part V: Development of a Pressure-Sensitive Sock Utilizing Soft Sensors.

The purpose of this study was to evaluate the use of compressible soft robotic sensors (C-SRS) in determining plantar pressure to infer vertical and shear forces in wearable technology: A ground reaction pressure sock (GRPS). To assess pressure relationships between C-SRS, pressure cells on a BodiTrakTM Vector Plate, and KistlerTM Force Plates, thirteen volunteers performed three repetitions of three different movements: squats, shifting center-of-pressure right to left foot, and shifting toes to heels with C-SRS in both anterior-posterior (A/P) and medial-lateral (M/L) sensor orientations. Pearson correlation coefficient of C-SRS to BodiTrakTM Vector Plate resulted in an average R-value greater than 0.70 in 618/780 (79%) of sensor to cell comparisons. An average R-value greater than 0.90 was seen in C-SRS comparison to KistlerTM Force Plates during shifting right to left. An autoregressive integrated moving average (ARIMA) was conducted to identify and estimate future C-SRS data. No significant differences were seen in sensor orientation. Sensors in the A/P orientation reported a mean R2 value of 0.952 and 0.945 in the M/L sensor orientation, reducing the effectiveness to infer shear forces. Given the high R values, the use of C-SRSs to infer normal pressures appears to make the development of the GRPS feasible.

Center of Mass Motion of Short-Range Correlated Nucleon Pairs studied via the A(e,e

Short-range correlated (SRC) nucleon pairs are a vital part of the nucleus, accounting for almost all nucleons with momentum greater than the Fermi momentum (k_{F}). A fundamental characteristic of SRC pairs is having large relative momenta as compared to k_{F}, and smaller center of mass (c.m.) which indicates a small separation distance between the nucleons in the pair. Determining the c.m. momentum distribution of SRC pairs is essential for understanding their formation process. We report here on the extraction of the c.m. motion of proton-proton (pp) SRC pairs in carbon and, for the first time in heavier and ansymetric nuclei: aluminum, iron, and lead, from measurements of the A(e,e^{'}pp) reaction. We find that the pair c.m. motion for these nuclei can be described by a three-dimensional Gaussian with a narrow width ranging from 140 to 170 MeV/c, approximately consistent with the sum of two mean-field nucleon momenta. Comparison with calculations appears to show that the SRC pairs are formed from mean-field nucleons in specific quantum states.

Measurement of the Q

We measured the g_{1} spin structure function of the deuteron at low Q^{2}, where QCD can be approximated with chiral perturbation theory (χPT). The data cover the resonance region, up to an invariant mass of W≈1.9 GeV. The generalized Gerasimov-Drell-Hearn sum, the moment Γ_{1}^{d} and the spin polarizability γ_{0}^{d} are precisely determined down to a minimum Q^{2} of 0.02 GeV^{2} for the first time, about 2.5 times lower than that of previous data. We compare them to several χPT calculations and models. These results are the first in a program of benchmark measurements of polarization observables in the χPT domain.

Standard vs. intensified management of heart failure to reduce healthcare costs: results of a multicentre, randomized controlled trial.

AIMS: To determine if an intensified form of heart failure management programme (INT-HF-MP) based on individual profiling is superior to standard management (SM) in reducing health care costs during 12-month follow-up (primary endpoint). METHODS AND RESULTS: A multicentre randomized trial involving 787 patients (full analysis set) discharged from four tertiary hospitals with chronic HF who were randomized to SM (n = 391) or INT-HF-MP (n = 396). Mean age was 74 ± 12 years, 65% had HF with a reduced ejection fraction (31.4 ± 8.9%) and 14% were remote-dwelling. Study groups were well matched. According to Green, Amber, Red Delineation of rIsk And Need in HF (GARDIAN-HF) profiling, regardless of location, patients in the INT-HF-MP received a combination of face-to-face (home visits) and structured telephone support (STS); only 9% (`low risk') were designated to receive the same level of management as the SM group. The median cost in 2017 Australian dollars (A$1 equivalent to ∼EUR €0.7) of applying INT-HF-MP was significantly greater than SM ($152 vs. $121 per patient per month; P < 0.001), However, at 12 months, there was no difference in total health care costs for the INT-HF-MP vs. SM group (median $1579, IQR $644 to $3717 vs. $1450, IQR $564 to $3615 per patient per month, respectively). This reflected minimal differences in all-cause mortality (17.7% vs. 18.4%; P = 0.848) and recurrent hospital stay (18.6 ± 26.5 vs. 16.6 ± 24.8 days; P = 0.199) between the INT-HF-MP and SM groups, respectively. CONCLUSION: During 12-months follow-up, an INT-HF-MP did not reduce healthcare costs or improve health outcomes relative to SM.

First Exclusive Measurement of Deeply Virtual Compton Scattering off

We report on the first measurement of the beam-spin asymmetry in the exclusive process of coherent deeply virtual Compton scattering off a nucleus. The experiment uses the 6 GeV electron beam from the Continuous Electron Beam Accelerator Facility (CEBAF) accelerator at Jefferson Lab incident on a pressurized ^{4}He gaseous target placed in front of the CEBAF Large Acceptance Spectrometer (CLAS). The scattered electron is detected by CLAS and the photon by a dedicated electromagnetic calorimeter at forward angles. To ensure the exclusivity of the process, a specially designed radial time projection chamber is used to detect the recoiling ^{4}He nuclei. We measure beam-spin asymmetries larger than those observed on the free proton in the same kinematic domain. From these, we are able to extract, in a model-independent way, the real and imaginary parts of the only ^{4}He Compton form factor, H_{A}. This first measurement of coherent deeply virtual Compton scattering on the ^{4}He nucleus, with a fully exclusive final state via nuclear recoil tagging, leads the way toward 3D imaging of the partonic structure of nuclei.

Beam-Target Helicity Asymmetry for γ[over →]n[over →]→π

We report the first beam-target double-polarization asymmetries in the γ+n(p)→π^{-}+p(p) reaction spanning the nucleon resonance region from invariant mass W=1500 to 2300 MeV. Circularly polarized photons and longitudinally polarized deuterons in solid hydrogen deuteride (HD) have been used with the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. The exclusive final state has been extracted using three very different analyses that show excellent agreement, and these have been used to deduce the E polarization observable for an effective neutron target. These results have been incorporated into new partial wave analyses and have led to significant revisions for several γnN^{*} resonance photocouplings.

Increased fronto-striatal reward prediction errors moderate decision making in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) has been linked to functional abnormalities in fronto-striatal networks as well as impairments in decision making and learning. Little is known about the neurocognitive mechanisms causing these decision-making and learning deficits in OCD, and how they relate to dysfunction in fronto-striatal networks. METHOD: We investigated neural mechanisms of decision making in OCD patients, including early and late onset of disorder, in terms of reward prediction errors (RPEs) using functional magnetic resonance imaging. RPEs index a mismatch between expected and received outcomes, encoded by the dopaminergic system, and are known to drive learning and decision making in humans and animals. We used reinforcement learning models and RPE signals to infer the learning mechanisms and to compare behavioural parameters and neural RPE responses of the OCD patients with those of healthy matched controls. RESULTS: Patients with OCD showed significantly increased RPE responses in the anterior cingulate cortex (ACC) and the putamen compared with controls. OCD patients also had a significantly lower perseveration parameter than controls. CONCLUSIONS: Enhanced RPE signals in the ACC and putamen extend previous findings of fronto-striatal deficits in OCD. These abnormally strong RPEs suggest a hyper-responsive learning network in patients with OCD, which might explain their indecisiveness and intolerance of uncertainty.

Atrial fibrillation is associated with cognitive decline in stroke-free subjects: the Tromsø Study.

BACKGROUND AND PURPOSE: Previous studies have shown associations between atrial fibrillation (AF) and cognitive decline. We investigated this association in a prospective population study, focusing on whether stroke risk factors modulated this association in stroke-free women and men. METHODS: We included 4983 participants (57% women) from the fifth survey of the Tromsø Study (Tromsø 5, 2001), of whom 2491 also participated in the sixth survey (Tromsø 6, 2007-2008). Information about age, education, blood pressure, body mass index, lipids, smoking, coffee consumption, physical activity, depression, coronary and valvular heart disease, heart failure and diabetes was obtained at baseline. AF status was based on hospital records. The outcome was change in cognitive score from Tromsø 5 to Tromsø 6, measured by the verbal memory test, the digit-symbol coding test and the tapping test. RESULTS: Mean age at baseline was 65.4 years. The mean reduction in the tapping test scores was significantly larger in participants with AF (5.3 taps/10 s; 95% CI: 3.9, 6.7) compared with those without AF (3.8 taps/10 s; 95% CI: 3.5, 4.1). These estimates were unchanged when adjusted for other risk factors and were similar for both sexes. AF was not associated with change in the digit-symbol coding or the verbal memory tests. CONCLUSION: Atrial fibrillation in stroke-free participants was independently associated with cognitive decline as measured with the tapping test.

Arsenic in Groundwater: The Deep Late Pleistocene Aquifers of the Western Bengal Basin.

in groundwaters from 145 wells across central West Bengal, India, those from Pleistocene aquifers at depths >70 m beneath paleo-interfluves contain <10 µg/L As. Pleistocene aquifers beneath deep paleo-channels typically host groundwaters containing 10-100 µg/L As at depths between 120 and 180 m. The depth profiles of As and SO4 and the conservative tracers Cl/Br, δ(18)O, and δ(2)H show that the As in Pleistocene groundwater beneath deep paleo-channels is relict and does not arise from migration downward of As-polluted groundwater in overlying aquifers. We postulate that the As was liberated in situ by reduction of minimal iron oxyhydroxides in the gray Pleistocene sands by organic matter infiltrating from riverbeds during late Pleistocene or earliest Holocene times. Mitigation of the widespread As-pollution in shallow aquifers through exploitation of deep Pleistocene aquifers would improve if guided by an understanding of the distribution of buried paleo-channels and paleo-interfluves and the knowledge that As may be present naturally in groundwater at depths >150 m beneath deep paleo-channels.

Cross Sections for the Exclusive Photon Electroproduction on the Proton and Generalized Parton Distributions.

Unpolarized and beam-polarized fourfold cross sections (d^{4}σ/dQ^{2}dx_{B}dtdϕ) for the ep→e^{'}p^{'}γ reaction were measured using the CLAS detector and the 5.75-GeV polarized electron beam of the Jefferson Lab accelerator, for 110 (Q^{2},x_{B},t) bins over the widest phase space ever explored in the valence-quark region. Several models of generalized parton distributions (GPDs) describe the data well at most of our kinematics. This increases our confidence that we understand the GPD H, expected to be the dominant contributor to these observables. Through a leading-twist extraction of Compton form factors, these results support the model predictions of a larger nucleon size at lower quark-momentum fraction x_{B}.

Towards a resolution of the proton form factor problem: new electron and positron scattering data.

There is a significant discrepancy between the values of the proton electric form factor, G(E)(p), extracted using unpolarized and polarized electron scattering. Calculations predict that small two-photon exchange (TPE) contributions can significantly affect the extraction of G(E)(p) from the unpolarized electron-proton cross sections. We determined the TPE contribution by measuring the ratio of positron-proton to electron-proton elastic scattering cross sections using a simultaneous, tertiary electron-positron beam incident on a liquid hydrogen target and detecting the scattered particles in the Jefferson Lab CLAS detector. This novel technique allowed us to cover a wide range in virtual photon polarization (ϵ) and momentum transfer (Q(2)) simultaneously, as well as to cancel luminosity-related systematic errors. The cross section ratio increases with decreasing ϵ at Q(2)=1.45 GeV(2). This measurement is consistent with the size of the form factor discrepancy at Q(2)≈1.75 GeV(2) and with hadronic calculations including nucleon and Δ intermediate states, which have been shown to resolve the discrepancy up to 2-3 GeV(2).

Strangeness suppression of qq creation observed in exclusive reactions.

We measured the ratios of electroproduction cross sections from a proton target for three exclusive meson-baryon final states: ΛK(+), pπ(0), and nπ(+), with the CLAS detector at Jefferson Lab. Using a simple model of quark hadronization, we extract qq creation probabilities for the first time in exclusive two-body production, in which only a single qq pair is created. We observe a sizable suppression of strange quark-antiquark pairs compared to nonstrange pairs, similar to that seen in high-energy production.

Cardiac complications associated with goal-directed therapy in high-risk surgical patients: a meta-analysis.

Patients with limited cardiopulmonary reserve are at risk of mortality and morbidity after major surgery. Augmentation of oxygen delivery index (DO2I) with i.v. fluids and inotropes (goal-directed therapy, GDT) has been shown to reduce postoperative mortality and morbidity in high-risk patients. Concerns regarding cardiac complications associated with fluid challenges and inotropes may prevent clinicians from performing GDT in patients who need it most. We hypothesized that GDT is not associated with an increased risk of cardiac complications in high-risk, non-cardiac surgical patients. We performed a systematic search of Medline, Embase, and CENTRAL databases for randomized controlled trials (RCTs) of GDT in high-risk surgical patients. Studies including cardiac surgery, trauma, and paediatric surgery were excluded. We reviewed the rates of all cardiac complications, arrhythmias, myocardial ischaemia, and acute pulmonary oedema. Meta-analyses were performed using RevMan software. Data are presented as odds ratios (ORs), [95% confidence intervals (CIs)], and P-values. Twenty-two RCTs including 2129 patients reported cardiac complications. GDT was associated with a reduction in total cardiovascular (CVS) complications [OR=0.54, (0.38-0.76), P=0.0005] and arrhythmias [OR=0.54, (0.35-0.85), P=0.007]. GDT was not associated with an increase in acute pulmonary oedema [OR=0.69, (0.43-1.10), P=0.12] or myocardial ischaemia [OR=0.70, (0.38-1.28), P=0.25]. Subgroup analysis revealed the benefit is most pronounced in patients receiving fluid and inotrope therapy to achieve a supranormal DO2I, with the use of minimally invasive cardiac output monitors. Treatment of high-risk surgical patients GDT is not associated with an increased risk of cardiac complications; GDT with fluids and inotropes to optimize DO2I during early GDT reduces postoperative CVS complications.