A review of analytical parameters in 'rapid' liquid chromatographic methods for bioanalysis: Can we do better?

Rapid bioanalysis is beneficial to many applications. However, how 'rapid' a method is, or could be, is often an unanswered question. In this statistical review, the authors have assessed multiple pre-analytical (i.e. sample preparation), and analytical method parameters specifically for liquid chromatography to assist researchers in developing and validating 'rapid' bioanalytical methods. We restricted the search to urine and plasma matrices only. Data were extracted from over 2,000 recent studies and evaluated to assess how these parameters affected the 'on-instrument' analysis time. In addition to methods using ultra-violet (UV) detection, there were a large number of mass spectrometric (MS) methods, allowing additional review of the differences between high- and low-resolution MS on analysis time. We observed that most (N = 922, 70 %) methods used 5 or 10 cm columns, and that whilst uptake of ultra-high performance (U)HPLC columns was good, the use of sub-5 cm columns and/or flow rates in excess of 1 mL/min was incredibly rare (N = 25, 3 %). The detector of choice for quantitative (U)HPLC-MS remains the triple quadrupole, although a number of groups report the use of high-resolution MS for such methods.

Autopsy of a failed trial part 2: Outcomes, challenges, and lessons learnt from the DAISIES trial.

OBJECTIVE: The relative merits of inpatient or day-treatment for adults with anorexia nervosa (AN) are unknown. The DAISIES trial aimed to establish the non-inferiority of a stepped-care day patient treatment (DPT) approach versus inpatient treatment as usual (IP-TAU) for improving body mass index (BMI) at 12 months in adults with AN. The trial was terminated due to poor recruitment. This paper presents outcomes and investigates the reasons behind the trial's failure. METHOD: Fifteen patients with AN (of 53 approached) participated and were followed-up to 6 or 12 months. Summary statistics were calculated due to low sample size, and qualitative data concerning treatment experiences were analysed using thematic analysis. RESULTS: At baseline, participants in both trial arms rated stepped-care DPT as more acceptable. At 12 months, participants' BMIs had increased in both trial arms. Qualitative analysis highlighted valued and challenging aspects of care across settings. Only 6/12 sites opened for recruitment. Among patients approached, the most common reason for declining participation was their treatment preference (n = 12/38). CONCLUSIONS: No conclusions can be drawn concerning the effectiveness of IP-TAU and stepped-care DPT, but the latter was perceived more positively. Patient-related, service-related and systemic factors (COVID-19) contributed to the trial's failure. Lessons learnt can inform future studies.

A Qualitative Study Exploring Parental Perceptions of Telehealth in Early Intervention.

Using telehealth as a mode of service delivery has the potential to address some long-standing challenges in early intervention (EI) services such as waiting lists to access services. Yet, little is known about parent perceptions of telehealth in EI based on their lived experiences partnering with EI practitioners. The purpose of this study was to explore parent perceptions on using telehealth, especially on family-professional partnerships and coaching. Interviews were conducted with 15 parents of children receiving EI services via telehealth from June to August of 2021. Almost half of the participants reflected under-represented racial and ethnic backgrounds. Constant comparative analysis and emergent coding were used for data analysis. The findings showed that the advantages outnumbered the disadvantages regarding telehealth. Participants reported that telehealth provided a safe and flexible option and eliminated the wait to access EI services. However, participants identified some disadvantages to telehealth including telehealth precluded substantive interactions with therapists and limited access to technology. The findings also indicated that telehealth enhanced family-professional partnerships. Nearly all participants valued coaching during telehealth. Participants suggested initial supports to facilitate EI via telehealth, including stable internet access, telehealth training, and an initial in-person visit. Implications for research and practice are discussed. Supplementary Information: The online version contains supplementary material available at 10.1007/s10882-022-09853-w.

Multi-perspective region-based CNNs for vertebrae labeling in intraoperative long-length images.

PURPOSE: Effective aggregation of intraoperative x-ray images that capture the patient anatomy from multiple view-angles has the potential to enable and improve automated image analysis that can be readily performed during surgery. We present multi-perspective region-based neural networks that leverage knowledge of the imaging geometry for automatic vertebrae labeling in Long-Film images - a novel tomographic imaging modality with an extended field-of-view for spine imaging. METHOD: A multi-perspective network architecture was designed to exploit small view-angle disparities produced by a multi-slot collimator and consolidate information from overlapping image regions. A second network incorporates large view-angle disparities to jointly perform labeling on images from multiple views (viz., AP and lateral). A recurrent module incorporates contextual information and enforce anatomical order for the detected vertebrae. The three modules are combined to form the multi-view multi-slot (MVMS) network for labeling vertebrae using images from all available perspectives. The network was trained on images synthesized from 297 CT images and tested on 50 AP and 50 lateral Long-Film images acquired from 13 cadaveric specimens. Labeling performance of the multi-perspective networks was evaluated with respect to the number of vertebrae appearances and presence of surgical instrumentation. RESULTS: The MVMS network achieved an F1 score of >96% and an average vertebral localization error of 3.3 mm, with 88.3% labeling accuracy on both AP and lateral images - (15.5% and 35.0% higher than conventional Faster R-CNN on AP and lateral views, respectively). Aggregation of multiple appearances of the same vertebra using the multi-slot network significantly improved the labeling accuracy (p < 0.05). Using the multi-view network, labeling accuracy on the more challenging lateral views was improved to the same level as that of the AP views. The approach demonstrated robustness to the presence of surgical instrumentation, commonly encountered in intraoperative images, and achieved comparable performance in images with and without instrumentation (88.9% vs. 91.2% labeling accuracy). CONCLUSION: The MVMS network demonstrated effective multi-perspective aggregation, providing means for accurate, automated vertebrae labeling during spine surgery. The algorithms may be generalized to other imaging tasks and modalities that involve multiple views with view-angle disparities (e.g., bi-plane radiography). Predicted labels can help avoid adverse events during surgery (e.g., wrong-level surgery), establish correspondence with labels in preoperative modalities to facilitate image registration, and enable automated measurement of spinal alignment metrics for intraoperative assessment of spinal curvature.

Experimental Search for Neutron to Mirror Neutron Oscillations as an Explanation of the Neutron Lifetime Anomaly.

An unexplained >4σ discrepancy persists between "beam" and "bottle" measurements of the neutron lifetime. A new model proposed that conversions of neutrons n into mirror neutrons n^{'}, part of a dark mirror sector, can increase the apparent neutron lifetime by 1% via a small mass splitting Δm between n and n^{'} inside the 4.6 T magnetic field of the National Institute of Standards and Technology Beam Lifetime experiment. A search for neutron conversions in a 6.6 T magnetic field was performed at the Spallation Neutron Source which excludes this explanation for the neutron lifetime discrepancy.

The clinical effectiveness and cost-effectiveness of a 'stepping into day treatment' approach versus inpatient treatment as usual for anorexia nervosa in adult specialist eating disorder services (DAISIES trial): a study protocol of a randomised controlled multi-centre open-label parallel group non-inferiority trial.

BACKGROUND: Anorexia nervosa (AN) is a serious and disabling mental disorder with a high disease burden. In a proportion of cases, intensive hospital-based treatments, i.e. inpatient or day patient treatment, are required, with day patient treatment often being used as a 'step-down' treatment after a period of inpatient treatment. Demand for such treatment approaches has seen a sharp rise. Despite this, the relative merits of these approaches for patients, their families, and the NHS and wider society are relatively unknown. This paper describes the rationale for, and protocol of, a two-arm multi-centre open-label parallel group non-inferiority randomised controlled trial, evaluating the effectiveness and cost-effectiveness of these two intensive treatments for adults with severe AN: inpatient treatment as usual and a stepped care day patient approach (the combination of day patient treatment with the option of initial inpatient treatment for medical stabilisation). The main aim of this trial is to establish whether, in adults with severe AN, a stepped care day patient approach is non-inferior to inpatient treatment as usual in relation to improving body mass index (BMI) at 12 months post-randomisation. METHODS: 386 patients with a Diagnostic and Statistical Manual 5th edition diagnosis of severe AN or related disorder, with a BMI of ≤16 kg/m2 and in need of intensive treatment will be randomly allocated to either inpatient treatment as usual or a stepped care day patient approach. Patients in both groups will receive treatment until they reach a healthy weight or get as close to this point as possible. Assessments will be conducted at baseline (prior to randomisation), and at 6 and 12 months post-randomisation, with additional monthly symptom monitoring. The primary outcome will be BMI at the 12-month post-randomisation assessment. Other outcomes will include psychosocial adjustment; treatment motivation, expectations and experiences; cost-effectiveness; and carer burden. DISCUSSION: The results of this study will provide a rigorous evaluation of two intensive treatment approaches which will inform future national and international treatment guidelines and service provision. TRIAL REGISTRATION: ISRCTN ISRCTN10166784 . Registered 28 February 2020. ISRCTN is a primary registry of the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) network and includes all items from the WHO Trial Registration Data Set.

Clinicians' perspectives on supporting individuals with severe anorexia nervosa in specialist eating disorder intensive treatment settings during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has significantly affected intensive treatment settings (i.e., inpatient [IP] and day patient [DP]) in specialist eating disorder services. However, the impact on clinicians working in these services is largely unknown. We therefore explored the perspectives of those supporting individuals with severe anorexia nervosa (AN) in intensive treatment settings during the pandemic. METHODS: Between May 2020 and June 2021, we interviewed clinicians (n = 21) who delivered IP and/or DP treatment to patients with severe AN in four specialist eating disorder services in the United Kingdom. Data relating to experiences during COVID-19 were analysed using reflexive thematic analysis. RESULTS: We identified six themes: Disruptions to Routine Treatment; Introduction of Virtual Treatment; Separation from Treatment, Others and the World; Impact on Recovery; Impact on Staff; and Pressure on Referral Pathways. COVID-19 posed significant challenges to IP and DP services: forcing closures, operating with restrictions and virtual treatment, and impacting delivery of essential treatment components, referral pathways, clinician wellbeing, risk management, and patient isolation and recovery trajectories. Opportunities arose, in particular in DP services offering virtual support. CONCLUSIONS: COVID-19 challenged the continuation of multidisciplinary treatment. The findings underline the necessity for medical, psychological, practical, and nutritional support, as well as carer involvement and fostering social connections to remain at the forefront of intensive treatment for severe AN. They also emphasise the uncertainty surrounding which intensive treatment may be best suited to which patient when, particularly within the context of virtual DP support.

The COVID-19 pandemic has significantly affected eating disorder inpatient and day patient treatment. However, the impact of the pandemic on clinicians working in these settings is largely unknown. We interviewed twenty-one clinicians working in specialist inpatient and day patient eating disorder services to explore their views on supporting people with severe anorexia nervosa during the pandemic. We analysed the transcripts using thematic analysis. We identified that COVID-19 posed significant challenges for intensive treatment settings, forcing the closure or merging of eating disorder services, the delivery of treatment under restrictions, and the introduction of virtual treatment. These changes challenged the delivery of multidisciplinary treatment for people with severe anorexia nervosa and impacted referral pathways, clinicians' wellbeing, risk management, and patients' isolation and recovery trajectories. We also identified some opportunities as a result of the pandemic, in particular in day patient services offering virtual support. These opportunities included more accessible treatment for patients and their families, more individualised treatment, and the chance for treatment innovation and creativity.

Clinicians' perspectives on supporting individuals with severe anorexia nervosa in specialist eating disorder intensive treatment settings.

BACKGROUND: Admissions to intensive treatment (i.e., inpatient [IP] and/or day patient [DP]) for individuals with severe anorexia nervosa (AN) are common. Growing literature indicates potential risks and benefits of each intensive treatment approach; however, existing research has focused on patient and carer perspectives of these treatments. Also, there is scant empirical evidence available for guiding the parameters of intensive treatments for AN. We therefore explored clinicians' perspectives and experience of supporting adults with severe AN in intensive settings. METHODS: We conducted twenty one semi-structured interviews with clinicians who deliver intensive treatments (i.e., IP and/or DP) for individuals with severe AN across four specialist Eating Disorder Services in the United Kingdom between May 2020 and June 2021. We asked clinicians about their views and experiences of supporting individuals with severe AN in intensive treatment settings and the challenges and opportunities associated with IP and DP treatment. Data were analysed using reflexive thematic analysis supported by NVivo software. RESULTS: Five broad and interrelated themes were identified: (1) Intensive Support; (2) The Severity of Patients' Illnesses; (3) Hope and Recovery; (4) Which Treatment When; (5) Limited Resources; and (6) Carer Burden. We identified various similarities between the two intensive treatment approaches, including the value of intensive and multidisciplinary support and carer involvement, and the challenge of managing complex and unique needs in resource-limited intensive settings. We also found differences in the relationship of treatment to patients' home environments, the necessity of patient motivation, and the management of risk. CONCLUSIONS: Both intensive treatment settings are valued by clinicians; however, there are unique challenges and opportunities for supporting individuals with severe AN within each. Our findings suggest DP treatment may be used as an alternative to IP treatment for individuals with severe AN. However, clear questions remain over which intensive treatment setting is best suited to which patient when and should be the focus of future research.

Some people with anorexia nervosa will need intensive treatment (e.g., inpatient and day patient treatment) during the course of their illness. We interviewed twenty-one clinicians working in Specialist Eating Disorder Services to explore their views on supporting people with severe anorexia nervosa in inpatient and day patient services and about the perceived advantages and disadvantages of these. We analysed the transcripts of these interviews using thematic analysis. We identified similarities between the two intensive treatment approaches. These included the value of intensive and multidisciplinary support, the importance of carer involvement, and the challenge of managing patient's complex and unique needs in services with limited resources. We also found differences between inpatient and day patient treatment. These included how treatment relates to patients' home environments, the importance of patient motivation, and managing risk. Day patient treatment may be an alternative to inpatient treatment for people with severe anorexia nervosa. Future research should investigate which intensive treatment setting is best suited to which patient and when.

Current management of adults receiving oral anti-cancer medications: A scoping review.

PURPOSE: Oral anti-cancer medication (OAM) has revolutionised oncology care. Due to their potential toxicities and associated safety challenges ongoing assessment and monitoring is essential; currently generally performed in acute care settings. Internationally there exists a transformative vision to shift patient care from acute to primary care. A nurse-led integrated model of care could be developed for OAM patient management in primary care. The aim of this study was to examine international literature regarding current clinical management practices for assessment and monitoring of patients receiving OAM. METHODS: Following PRISMA-ScR guidelines, databases MEDLINE, CINAHL and Web of Science were searched for English studies published between 2010 and 2020 using keywords: assessment, cancer, care, management, oral anticancer medications. Articles were screened and assessed for eligibility. From eligible studies, data were extracted to summarize, collate and make a narrative account of the findings. RESULTS: 2261 papers were reviewed, 14 met inclusion criteria. Three phases of management are reported: 1. Patient treatment plan development; 2. Patient education; 3. Patient monitoring. Within these phases seven specific stages of care were identified broadly representing the patient's journey: (1) treatment decision, (2) prescribing of OAM, (3) OAM dispensing and administration, (4) maximising patient safety (5) ongoing patient assessment (6) patient support (7) communication with other health-care professionals. CONCLUSIONS: Despite a paucity of international literature, a dedicated OAM clinic was endorsed as a means to achieve improved care. Nurses and pharmacists were identified as being of particular importance especially in education and ongoing management of patients receiving OAMs.

Investigation of the association between gall bladder wall thickness and hypoalbuminaemia in dogs.

OBJECTIVES: To assess the correlation between gallbladder wall thickness and serum/plasma albumin concentrations in dogs. MATERIALS AND METHODS: Retrospective searches of digital medical record databases were conducted to identify dogs that had either severely low serum/plasma albumin concentration (<1.5 g/dL) or ultrasonographic evidence of gallbladder wall thickening (>2 mm). Analysis of covariance models were used to analyze gallbladder wall thickness with sample type (serum vs plasma), age, etiology, albumin, and albumin ' etiology as the covariates. RESULTS: A total of 216 dogs met inclusion criteria. One-hundred and forty-six dogs had a thickened gallbladder wall (Group 1). Median serum/plasma albumin concentration for dogs in this group was 2.2 g/dL (1 to 5 g/dL), and 84 dogs (57.5%) had hypoalbuminemia (<2.5 g/dL). The search for dogs with severe hypoalbuminemia (< 1.5 g/dL) identified 70 dogs (Group 2). In this group, median gallbladder wall thickness was 1.3 mm (0.2 to 6.1 mm) and 17 dogs (24.3%) had a thickened gallbladder wall. Serum/plasma albumin concentration and gallbladder wall thickness were not significantly correlated for Group 1 (r = 0.0044, p = 0.9580) or Group 2 (r = -0.1137, p = 0.3487). A moderate negative correlation (-0.64) was identified between gallbladder wall thickness and albumin concentration in dogs with immune-mediated diseases (p = 0.03). CLINICAL SIGNIFICANCE: Gallbladder wall thickness and serum/plasma albumin concentration are independent variables in dogs.

Does early surgery improve outcomes for periprosthetic fractures of the hip and knee? A systematic review and meta-analysis.

INTRODUCTION: Previous evidence has established that early surgery is beneficial to improve outcomes for individuals with native hip fractures in the elderly population. Patients who sustain a periprosthetic fracture have been demonstrated to have similar demographics and outcomes as those with native fractures around the hip and knee. We therefore set out to determine if there is a similar difference in perioperative outcomes between early and delayed surgery for periprosthetic fractures of the hip and knee through a systematic review and meta-analysis. METHODS: Literature search outputs were screened for studies meeting the inclusion criteria. The groups of early surgery and delayed surgery were defined by study authors. The primary outcome measure was 30 day mortality. Where there was sufficient study homogeneity, a random-effects meta-analysis was performed. Individual study risk of bias was assessed using the ROBINS-I criteria, with the GRADE criteria used for independent outcome evaluation. The review protocol was registered on PROSPERO prior to commencement (Registration number CRD42019149360). RESULTS: The inclusion criteria was met in 11 studies (n = 3006). Mean time to surgery from admission for reporting studies was 64 h. 59.6% patients underwent early surgery as defined by the study authors. We identified a significantly lower risk of 30 day mortality for those with early surgery versus delayed surgery (RR 0.21; 95% CI 0.05, 0.90; p = 0.04, n = 2022). There were also significantly better outcomes for early versus delayed surgery regarding: medical complications, length of stay, transfusion risk, and reoperation. The quality of evidence for all the individual outcomes was low or very low. CONCLUSIONS: There is evidence that delaying surgery in those with periprosthetic fractures of the hip and knee has a deleterious impact on mortality and other important patient outcomes. There are, however, notable limitations to the existing available literature, with further appropriately designed large-scale studies required to confirm these findings.

Prothrombin complex concentrate vs. fresh frozen plasma in adult patients undergoing heart surgery - a pilot randomised controlled trial (PROPHESY trial).

There is equipoise regarding the use of prothrombin complex concentrate vs. fresh frozen plasma in bleeding patients undergoing cardiac surgery. We performed a pilot randomised controlled trial to determine the recruitment rate for a large trial, comparing the impact of prothrombin complex concentrate vs. fresh frozen plasma on haemostasis (1 h and 24 h post-intervention), and assessing safety. Adult patients who developed bleeding within 24 h of cardiac surgery that required coagulation factor replacement were randomly allocated to receive prothrombin complex concentrate (15 IU.kg-1 based on factor IX) or fresh frozen plasma (15 ml.kg-1 ). If bleeding continued after the first administration of prothrombin complex concentrate or fresh frozen plasma administration, standard care was administered. From February 2019 to October 2019, 180 patients were screened, of which 134 (74.4% (95%CI 67-81%)) consented, 59 bled excessively and 50 were randomly allocated; 25 in each arm, recruitment rate 35% (95%CI 27-44%). There were 23 trial protocol deviations, 137 adverse events (75 prothrombin complex concentrate vs. 62 fresh frozen plasma) and 18 serious adverse events (5 prothrombin complex concentrate vs. 13 fresh frozen plasma). There was no increase in thromboembolic events with prothrombin complex concentrate. No patient withdrew from the study, four were lost to follow-up and two died. At 1 h after administration of the intervention there was a significant increase in fibrinogen, Factor V, Factor XII, Factor XIII, α2 -antiplasmin and antithrombin levels in the fresh frozen plasma arm, while Factor II and Factor X were significantly higher in the prothrombin complex concentrate group. At 24 h, there were no significant differences in clotting factor levels. We conclude that recruitment to a larger study is feasible. Haemostatic tests have provided useful insight into the haemostatic changes following prothrombin complex concentrate or fresh frozen plasma administration. A definitive trial is needed to ascertain the benefits and safety for each.

Correction to: Heparin resistance in COVID­19 patients in the intensive care unit.

In the original publication of this article, one of the co-author name "D. de Monteverde-Robb" was inadvertently mentioned as "R. de Monteverde-Robb". The correct author name is "D. de Monteverde-Robb". This error has been corrected with this erratum.

Meta-analysis of the impact of postoperative infective complications on oncological outcomes in colorectal cancer surgery.

BACKGROUND: Cancer outcomes are complex, involving prevention, early detection and optimal multidisciplinary care. Postoperative infection and surgical site-infection (SSI) are not only uncomfortable for patients and costly, but may also be associated with poor oncological outcomes. A meta-analysis was undertaken to assess the oncological effects of SSI in patients with colorectal cancer. METHODS: An ethically approved PROSPERO-registered meta-analysis was conducted following PRISMA guidelines. PubMed and Scopus databases were searched for studies published between 2007 and 2017 reporting the effects of postoperative infective complications on oncological survival in colorectal cancer. Results were separated into those for SSI and those concerning anastomotic leakage. Articles with a Methodological Index for Non-Randomized Studies score of at least 18 were included. Hazard ratios (HRs) with 95 per cent confidence intervals were computed for risk factors using an observed to expected and variance fixed-effect model. RESULTS: Of 5027 articles were reviewed, 43 met the inclusion criteria, with a total of 154 981 patients. Infective complications had significant negative effects on overall survival (HR 1·37, 95 per cent c.i. 1·28 to 1·46) and cancer-specific survival (HR 2·58, 2·15 to 3·10). Anastomotic leakage occurred in 7·4 per cent and had a significant negative impact on disease-free survival (HR 1·14, 1·09 to 1·20), overall survival (HR 1·34, 1·28 to 1·39), cancer-specific survival (HR 1·43, 1·31 to 1·55), local recurrence (HR 1·18, 1·06 to 1·32) and overall recurrence (HR 1·46, 1·27 to 1·68). CONCLUSION: This meta-analysis identified a significant negative impact of postoperative infective complications on overall and cancer-specific survival in patients undergoing colorectal surgery.

ANTECEDENTES: Los resultados del cáncer son complejos, implican prevención, detección precoz y atención multidisciplinaria óptima. La infección postoperatoria y la infección del sitio quirúrgico (surgical site infection, SSI) no solo son inconvenientes para los pacientes y costosas, sino que también pueden estar asociadas con malos resultados oncológicos. Este estudio realizó un metaanálisis para evaluar los efectos oncológicos de la SSI en pacientes con cáncer colorrectal. MÉTODOS: Se realizó un metaanálisis registrado en PROSPERO, aprobado por el comité ético, siguiendo las pautas de PRISMA y utilizando las bases de datos PubMed y Scopus para estudios entre 2007-2017 que describían los efectos de las complicaciones infecciosas postoperatorias en la supervivencia oncológica en el cáncer colorrectal. Los resultados se separaron para el grupo de infección del sitio quirúrgico (SSI) y de fuga anastomótica. Se incluyeron los artículos con una puntuación ≥ 18 según el índice MINORS. Para los factores de riesgo se calcularon los cocientes de riesgos instantáneos (hazard ratios, HR) mediante un modelo de efectos aleatorios y el método de Mantel-Haenszel con los i.c. del 95% utilizando el programe RevMan5. RESULTADOS: Se revisaron 5.027 artículos de los cuales 43 cumplieron con los criterios de inclusión. En total fueron 154.981 pacientes en los cuales las complicaciones infecciosas tuvieron efectos negativos significativos en la supervivencia global (HR: 1,37 i.c. del 95%: 1,28-1,46) y la supervivencia específica relacionada con el cáncer (HR: 2,58 i.c. del 95%: 2,15-3,10). La fuga anastomótica ocurrió en un 7,4% de los casos e impactó negativa y significativamente en la supervivencia libre de enfermedad (HR: 1,14 i.c. del 95%: 1,09-1,20), en la supervivencia global (HR: 1,34 i.c. del 95%: 1,28-1,39), en la supervivencia específica relacionada con el cáncer (HR: 1,43 i.c. del 95% 1.31-1.55), en la recidiva local (HR: 1,18 i.c. del 95%: 1,06-1,32) y en la recidiva global (HR: 1,46 i.c. del 95%: 1,27-1,68). CONCLUSIÓN: Este metaanálisis identificó un impacto negativo significativo en la supervivencia global y en la supervivencia específica relacionada con el cáncer en pacientes con complicaciones postoperatorias infecciosas sometidos a cirugía colorrectal.

Heparin resistance in COVID-19 patients in the intensive care unit.

Patients with COVID-19 have a coagulopathy and high thrombotic risk. In a cohort of 69 intensive care unit (ICU) patients we investigated for evidence of heparin resistance in those that have received therapeutic anticoagulation. 15 of the patients have received therapeutic anticoagulation with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH), of which full information was available on 14 patients. Heparin resistance to UFH was documented in 8/10 (80%) patients and sub-optimal peak anti-Xa following therapeutic LMWH in 5/5 (100%) patients where this was measured (some patients received both anticoagulants sequentially). Spiking plasma from 12 COVID-19 ICU patient samples demonstrated decreased in-vitro recovery of anti-Xa compared to normal pooled plasma. In conclusion, we have found evidence of heparin resistance in critically unwell COVID-19 patients. Further studies investigating this are required to determine the optimal thromboprophylaxis in COVID-19 and management of thrombotic episodes.

Applying a mechanistic model to predict interacting effects of chemical exposure and food availability on fish populations.

The potential environmental impacts of chemical exposures on wildlife are of growing concern. Freshwater ecosystems are vulnerable to chemical effects and wildlife populations, including fish, can be exposed to concentrations known to cause adverse effects at the individual level. Wild fish populations are also often subjected to numerous other stressors simultaneously which in temperate climates often include sustained periods of food limitation. The potential interactive effects of chemical exposures and food limitation on fish populations are however difficult to establish in the field. Mechanistic modelling approaches can be employed to help predict how the physiological effects of chemicals and food limitation on individuals may translate to population-level effects. Here an energy budget-individual-based model was developed and the control (no chemical) model was validated for the three-spined stickleback. Findings from two endocrine active chemical (EAC) case studies, (ethinyloestradiol and trenbolone) were then used to investigate how effects on individual fecundity translated into predicted population-level effects for environmentally relevant exposures. The cumulative effects of chemical exposure and food limitation were included in these analyses. Results show that effects of each EAC on the population were dependent on energy availability, and effects on population abundance were exacerbated by food limitation. Findings suggest that chemical effects and density dependent food competition interact to determine population responses to chemical exposures. Our study illustrates how mechanistic modelling approaches might usefully be applied to account for specific chemical effects, energy budgets and density-dependent competition, to provide a more integrated evaluation of population outcomes in chemical risk assessments.

Development of an artificial intelligence-based assessment model for prediction of embryo viability using static images captured by optical light microscopy during IVF.

STUDY QUESTION: Can an artificial intelligence (AI)-based model predict human embryo viability using images captured by optical light microscopy? SUMMARY ANSWER: We have combined computer vision image processing methods and deep learning techniques to create the non-invasive Life Whisperer AI model for robust prediction of embryo viability, as measured by clinical pregnancy outcome, using single static images of Day 5 blastocysts obtained from standard optical light microscope systems. WHAT IS KNOWN ALREADY: Embryo selection following IVF is a critical factor in determining the success of ensuing pregnancy. Traditional morphokinetic grading by trained embryologists can be subjective and variable, and other complementary techniques, such as time-lapse imaging, require costly equipment and have not reliably demonstrated predictive ability for the endpoint of clinical pregnancy. AI methods are being investigated as a promising means for improving embryo selection and predicting implantation and pregnancy outcomes. STUDY DESIGN, SIZE, DURATION: These studies involved analysis of retrospectively collected data including standard optical light microscope images and clinical outcomes of 8886 embryos from 11 different IVF clinics, across three different countries, between 2011 and 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: The AI-based model was trained using static two-dimensional optical light microscope images with known clinical pregnancy outcome as measured by fetal heartbeat to provide a confidence score for prediction of pregnancy. Predictive accuracy was determined by evaluating sensitivity, specificity and overall weighted accuracy, and was visualized using histograms of the distributions of predictions. Comparison to embryologists' predictive accuracy was performed using a binary classification approach and a 5-band ranking comparison. MAIN RESULTS AND THE ROLE OF CHANCE: The Life Whisperer AI model showed a sensitivity of 70.1% for viable embryos while maintaining a specificity of 60.5% for non-viable embryos across three independent blind test sets from different clinics. The weighted overall accuracy in each blind test set was >63%, with a combined accuracy of 64.3% across both viable and non-viable embryos, demonstrating model robustness and generalizability beyond the result expected from chance. Distributions of predictions showed clear separation of correctly and incorrectly classified embryos. Binary comparison of viable/non-viable embryo classification demonstrated an improvement of 24.7% over embryologists' accuracy (P = 0.047, n = 2, Student's t test), and 5-band ranking comparison demonstrated an improvement of 42.0% over embryologists (P = 0.028, n = 2, Student's t test). LIMITATIONS, REASONS FOR CAUTION: The AI model developed here is limited to analysis of Day 5 embryos; therefore, further evaluation or modification of the model is needed to incorporate information from different time points. The endpoint described is clinical pregnancy as measured by fetal heartbeat, and this does not indicate the probability of live birth. The current investigation was performed with retrospectively collected data, and hence it will be of importance to collect data prospectively to assess real-world use of the AI model. WIDER IMPLICATIONS OF THE FINDINGS: These studies demonstrated an improved predictive ability for evaluation of embryo viability when compared with embryologists' traditional morphokinetic grading methods. The superior accuracy of the Life Whisperer AI model could lead to improved pregnancy success rates in IVF when used in a clinical setting. It could also potentially assist in standardization of embryo selection methods across multiple clinical environments, while eliminating the need for complex time-lapse imaging equipment. Finally, the cloud-based software application used to apply the Life Whisperer AI model in clinical practice makes it broadly applicable and globally scalable to IVF clinics worldwide. STUDY FUNDING/COMPETING INTEREST(S): Life Whisperer Diagnostics, Pty Ltd is a wholly owned subsidiary of the parent company, Presagen Pty Ltd. Funding for the study was provided by Presagen with grant funding received from the South Australian Government: Research, Commercialisation and Startup Fund (RCSF). 'In kind' support and embryology expertise to guide algorithm development were provided by Ovation Fertility. J.M.M.H., D.P. and M.P. are co-owners of Life Whisperer and Presagen. Presagen has filed a provisional patent for the technology described in this manuscript (52985P pending). A.P.M. owns stock in Life Whisperer, and S.M.D., A.J., T.N. and A.P.M. are employees of Life Whisperer.