Mortality following admission to the paediatric intensive care unit: A Swedish longitudinal cohort study.

AIM: This study aimed to compare outcomes post-admission to a Swedish paediatric intensive care unit (PICU) in children with complex chronic conditions (CCC) and without CCC. METHODS: In this observational registry-based study, consecutive admissions to the Astrid Lindgren Children's Hospital PICU from 1 January 2008 to 31 December 2016 were analysed. Data on demographics, predicted death rates (PDR), admission diagnoses and causes of death were collected. Mortality was recorded up to 15 years after admission and compared between groups. RESULTS: Patients with CCC constituted 64.6% (n = 3026) of PICU admissions and 83.5% (n = 111) of PICU deaths. The crude mortality rate in PICU was 2.84% overall. CCC-patients were 2.83 times more likely to die in PICU compared to non-CCC (OR 2.83; 95% CI: 1.78-4.49). Mortality increased in the CCC-cohort up to 5 years after PICU discharge, while non-CCC patients generally survived if they survived in PICU. Of the patients who died in PICU, the median PDR was 22.9% for CCC-patients and 66.5% in the non-CCC cohort. CONCLUSION: Children with CCC accounted for most admissions and deaths in PICU. Despite lower severity of illness scores upon admission, CCC patients were nearly three times more likely to die in PICU compared to non-CCC patients.

Antidepressant drug use after intensive care: a nationwide cohort study.

Modern intensive care has improved survival rates, but emerging evidence suggests a high prevalence of post-intensive care unit (ICU) health problems, including post-traumatic stress disorder, depression and anxiety. These symptoms may have a detrimental effect on quality of life and increase mortality. The primary objective of this study is to examine the extent of initiation of antidepressant medication among ICU survivors and identify the factors associated with its usage. The secondary objective is to investigate whether the use of these medications is linked to an increased mortality. The nationwide study cohort included 125,130 ICU survivors admitted between 2010 and 2017. Within the first 3 months after ICU discharge, 7% of patients initiated antidepressant medication, by 1 year 15.5% had started medication. We found no tendency to a decrease during the 2-year follow-up period. Factors associated with antidepressant use included middle age, female sex, psychiatric and somatic comorbid conditions, substance dependence, higher illness severity, and longer ICU stay. Antidepressant users had a higher mortality rate, and deaths due to external causes and suicide were more frequent in this group. This study emphasizes the importance of detecting and addressing depression in ICU survivors to improve their quality of life and reduce mortality rates.

Onset of Prolonged High-Potency Benzodiazepine Use Among ICU Survivors: A Nationwide Cohort Study.

OBJECTIVES: Exposure to critical illness and intensive care may lead to long-term psychologic and physical impairments. To what extent ICU survivors become prolonged users of benzodiazepines after exposure to critical care is not fully explored. This study aimed to describe the extent of onset of prolonged high-potency benzodiazepine use among ICU survivors not using these drugs before admission, identify factors associated with this use, and analyze whether such usage is associated with increased mortality. DESIGN: Retrospective cohort study. SETTING: Sweden, including all registered ICU admissions between 2010 and 2017. PATIENTS: ICU patients surviving for at least 3 months, not using high-potency benzodiazepine before admission, were eligible for inclusion. INTERVENTIONS: Admission to intensive care. MEASUREMENTS AND MAIN RESULTS: A total of 237,904 patients were screened and 137,647 were included. Of these 5338 (3.9%) became prolonged users of high-potency benzodiazepines after ICU discharge. A peak in high-potency benzodiazepine prescriptions was observed during the first 3 months, followed by sustained usage throughout the follow-up period of 18 months. Prolonged usage was associated with older age, female sex, and a history of both somatic and psychiatric comorbidities, including substance abuse. Additionally, a longer ICU stay, a high estimated mortality rate, and prior consumption of low-potency benzodiazepines were associated with prolonged use. The risk of death between 6 and 18 months post-ICU admission was significantly higher among high-potency benzodiazepine users, with an adjusted hazard ratio of 1.8 (95% CI, 1.7-2.0; p < 0.001). No differences were noted in causes of death between users and nonusers. Conclusions: Despite the lack of evidence supporting long-term treatment, prolonged usage of high-potency benzodiazepines 18 months following ICU care was notable and associated with an increased risk of death. Considering the substantial number of ICU admissions, prevention of benzodiazepine misuse may improve long-term outcomes following critical care.

Effects of Implementation of European Thyroid Imaging Reporting and Data System Risk Stratification in a Thyroid Cancer Program in Western Sweden: A Retrospective Cohort Study.

OBJECTIVE: The European Thyroid Imaging Reporting and Data System (EU-TIRADS) allows for selective fine needle aspiration cytology (FNAC). In 2017, EU-TIRADS was implemented as part of a nationwide standardized care bundle for thyroid cancer in Western Sweden with a population of approximately 1.7 million. The objective of this study was to investigate the clinical value of EU-TIRADS attempting to reduce the number of unnecessary FNACs in referred patients with thyroid nodules. METHODS: The study cohort consisted of all patients referred to Sahlgrenska University Hospital due to a palpable, newly detected or growing thyroid nodules or a positron emission tomography-positive finding for examination with thyroid ultrasound and selective cytology between 2018 and 2022. Medical records on EU-TIRADS classification, corresponding FNAC results, and histopathologic diagnosis were retrospectively collected. Adherence to the EU-TIRADS guidelines, use of selective FNAC, and rate of malignancy in patients who underwent surgery were assessed. RESULTS: In total, 1246 thyroid nodules in 990 patients were evaluated. The distributions of EU-TIRADS 2 to 5 (number [percentage]) for all examined nodules were 63 (5%), 462 (37%), 443 (36%), and 278 (22%), respectively. FNAC was omitted in 7% of the investigated patients. FNAC was performed in 124 nodules (10%) despite not fulfilling the EU-TIRADS criteria or absence of positron emission tomography-positive findings. The rate of malignancy was 33% and 1/50 in patients who underwent "unnecessary" FNAC. CONCLUSION: Implementation of EU-TIRADS in routine management of thyroid nodules led to the selective use of FNAC; however, the clinical impact was limited. This study provides real-world data on the value and magnitude of diagnostic improvement by implementing EU-TIRADS in clinical practice.

End-of-life decision-making in critically ill old patients with and without coronavirus disease 2019.

BACKGROUND: There are few studies on the differences in end-of-life decisions making in critically ill patients with and without coronavirus disease 2019 (COVID-19). This study aimed to investigate the independent factors that predicted the decision to withdraw or withhold life-sustaining treatments (LST) in critically ill patients and if these decisions were based on different variables for critically ill patients with COVID-19 compared to those for critically ill patients with other diagnoses in a Swedish intensive care unit. METHODS: This observational pilot study was performed at Sahlgrenska University Hospital, Gothenburg, Sweden. Patients ≥65 years were included from 1 March 2020 to 30 April 2021. The association between a decision to limit LST and a priori selected variables including sex, age, Simplified Acute Physiology Score 3 (SAPS 3), Clinical Frailty Scale ≥4, Charlson Comorbidity Index, Body Mass Index, living at home, invasive and non-invasive mechanical ventilation was assessed using a univariate and multivariable logistic regression model and presented as odds ratio with corresponding 95% confidence intervals. RESULTS: There were 394 patients included in this study, 131 in the non-COVID-19 group and 263 in the COVID-19 group. For the non-COVID-19 cohort, the univariate analysis demonstrated that age and SAPS 3 were significantly associated with the decision to withdraw or withhold life-sustaining treatments, and this association remained in the multivariable analysis, with odds ratios of 1.10 (1.03-1.19) p = .009 and 1.06 (1.03-1.10) p < .001, respectively. For the COVID-19 cohort, the univariate analysis indicated that age, SAPS 3, and Charlson comorbidity index were significantly associated with the decision to withdraw or withhold life-sustaining treatments. However, in multivariable analysis, only the Charlson comorbidity index remained independently associated with the decision to withdraw or withhold life-sustaining treatments, with an odds ratio of 1.26 (1.07-1.49), p = .006. CONCLUSION: Decisions to withdraw or withhold life-sustaining treatments were based on other variables for the critically ill COVID-19 cohort compared to those for the critically ill non-COVID-19 cohort. Further studies are warranted to forge a common path for ethical end-of-life decision-making in critically ill patients.

Investigating sources for variability in volunteer kinematics in a braking maneuver, a sensitivity analysis with an active human body model.

Occupant kinematics during evasive maneuvers, such as crash avoidance braking or steering, varies within the population. Studies have tried to correlate the response to occupant characteristics such as sex, stature, age, and BMI, but these characteristics explain no or very little of the variation. Therefore, hypothesis have been made that the difference in occupant response stems from voluntary behavior. The aim of this study was to investigate the effect from other sources of variability: in neural delay, in passive stiffness of fat, muscle tissues and skin, in muscle size and in spinal alignment, as a first step towards explaining the variability seen among occupants in evasive maneuvers. A sensitivity analysis with simulations of the SAFER Human Body Model in braking was performed, and the displacements from the simulations were compared to those of volunteers. The results suggest that the head and torso kinematics were most sensitive to spinal alignment, followed by muscle size. For head and torso vertical displacements, the range in model kinematics was comparable to the range in volunteer kinematics. However, for forward displacements, the included parameters only explain some of the variability seen in the volunteer experiment. To conclude, the results indicate that the variation in volunteer vertical kinematics could be partly attributed to the variability in human characteristics analyzed in this study, while these cannot alone explain the variability in forward kinematics. The results can be used in future tuning of HBMs, and in future volunteer studies, when further investigating the potential causes of the large variability seen in occupant kinematics in evasive maneuvers.

An easy-to-use high-throughput selection system for the discovery of recombinant protein binders from alternative scaffold libraries.

Selection by phage display is a popular and widely used technique for the discovery of recombinant protein binders from large protein libraries for therapeutic use. The protein library is displayed on the surface of bacteriophages which are amplified using bacteria, preferably Escherichia coli, to enrich binders in several selection rounds. Traditionally, the so-called panning procedure during which the phages are incubated with the target protein, washed and eluted is done manually, limiting the throughput. High-throughput systems with automated panning already in use often require high-priced equipment. Moreover, the bottleneck of the selection process is usually the screening and characterization. Therefore, having a high-throughput panning procedure without a scaled screening platform does not necessarily increase the discovery rate. Here, we present an easy-to-use high-throughput selection system with automated panning using cost-efficient equipment integrated into a workflow with high-throughput sequencing and a tailored screening step using biolayer-interferometry. The workflow has been developed for selections using two recombinant libraries, ADAPT (Albumin-binding domain-derived affinity proteins) and CaRA (Calcium-regulated affinity) and has been evaluated for three new targets. The newly established semi-automated system drastically reduced the hands-on time and increased robustness while the selection outcome, when compared to manual handling, was very similar in deep sequencing analysis and generated binders in the nanomolar affinity range. The developed selection system has shown to be highly versatile and has the potential to be applied to other binding domains for the discovery of new protein binders.

Long-term survival after intensive care for COVID-19: a nationwide cohort study of more than 8000 patients.

BACKGROUND: Was it worth it-what is the outcome after the extended ICU (intensive care unit) length of stay for COVID-19 patients? Surprisingly, data on long-term mortality in large cohorts are lacking. We investigate long-term mortality including differences between men and women, as previous studies show that men generally suffer a more severe course of COVID-19 in terms of severity of illness and short-term mortality. METHODS: Nationwide cohort including all adult COVID-19 patients admitted to Swedish ICUs until August 12, 2022. Primary outcome was 360-day mortality after ICU admission. Logistic regression was used to estimate associations between demographics, comorbidities, clinical characteristics and mortality. RESULTS: In total, 8392 patients were included. Median (IQR) age was 63 (52-72) years and the majority (70.1%) were men. Among the 7390 patients with complete 360-day mortality data, 1775 (24.4%) patients died within 30 days, 2125 (28.8%) within 90 days and 2206 (29.8%) within 360 days from ICU admission. 360-day mortality was 27.1% in women and 31.0% in men. Multivariable logistic regression analysis showed increased risk of 360-day mortality in men compared to women (OR: 1.33, 95% CI: 1.17-1.52). Other variables associated with poor 360-day mortality were age, cardiac disease, COPD/asthma, diabetes, immune deficiency, chronic kidney disease, neuromuscular disease, and malignancy. CONCLUSION: This study confirms the increased severity of disease in critically ill men with COVID-19, even in a long-term perspective. However, mortality beyond 90 days was strikingly low, indicating high probability of survival after the acute phase of illness.

New prolonged opioid consumption after major surgery in Sweden: a population-based retrospective cohort study.

OBJECTIVE: Given that long-term opioid usage is an important problem worldwide and postsurgical pain is a common indication for opioid prescription, our primary objective was to describe the frequency of new prolonged opioid consumption after major surgery in Sweden and, second, to evaluate potential associated risk factors. DESIGN: Cohort study including data from 1 January 2007 to 31 December 2014. Data regarding surgical procedures, baseline characteristics and outcomes was retrieved from the Orbit surgical planning system, the Swedish national patient register and the Swedish cause of death register. SETTING: Observational multicentre cohort study with data from 23 Swedish hospitals. PARTICIPANTS: We included 216 877 patients aged ≥18 years, undergoing non-cardiac surgery, not exposed to opioids 180 days before and alive 12 months after surgery. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was collection of at least three opioid prescriptions during the first postoperative year; within 90 days, day 91-180 and 181-365 after surgery in a previously opioid-naïve patient. Second, multivariable logistic regression analysis was conducted to explore potential risk factors associated with prolonged opioid use. RESULTS: Of the 216 877 patients identified to undergo analysis, 15 081 (7.0%) developed new prolonged opioid consumption. Several risk factors were identified. Having a history of psychiatric disease was identified as the strongest risk factor (adjusted odds ratio: 1.94; 95% CI: 1.87 to 2.00). CONCLUSION: In a large Swedish cohort of surgical patients, 7% developed new prolonged opioid consumption after major surgery. Our data on susceptible patients could help clinicians reduce the number of prolonged opioid users by adapting their analgesic and preventative strategies.

Calcium-dependent affinity ligands for the purification of antibody fragments at neutral pH.

The emerging formats of antibody fragments for biotherapeutics suffer from inadequate purification methods, delaying the advances of innovative therapies. One of the top therapeutic candidates, the single-chain variable fragment (scFv), requires the development of individual purification protocols dependent on the type of scFv. The available approaches that are based on selective affinity chromatography but do not involve the use of a purification tag, such as Protein L and Protein A chromatography, require acidic elution buffers. These elution conditions can cause the formation of aggregates and thereby greatly compromise the yield, which can be a major problem for scFvs that are generally unstable molecules. Due to the costly and time-consuming production of biological drugs, like antibody fragments, we have engineered novel purification ligands that elute the scFvs in a calcium-dependent manner. The developed ligands are equipped with new, selective binding surfaces and were shown to efficiently elute all captured scFv at neutral pH with the use of a calcium chelator. Further, two of three ligands were proven not to bind to the CDRs of the scFv, indicating potential for use as generic affinity ligands to a range of different scFvs. Multimerization and optimization of the most promising ligand led to a 3-fold increase in binding capacity for the hexamer compared to the monomer, in addition to highly selective and efficient purification of a scFv with >95% purity in a single purification step. This calcium-dependent ligand could revolutionize the scFv industry, greatly facilitating the purification procedure and improving the quality of the final product.

Predicting occupant head displacements in evasive maneuvers; tuning and comparison of a rotational based and a translational based neck muscle controller.

Objective: Real-life car crashes are often preceded by an evasive maneuver, which can alter the occupant posture and muscle state. To simulate the occupant response in such maneuvers, human body models (HBMs) with active muscles have been developed. The aim of this study was to implement an omni-directional rotational head-neck muscle controller in the SAFER HBM and compare the bio-fidelity of the HBM with a rotational controller to the HBM with a translational controller, in simulations of evasive maneuvers. Methods: The rotational controller was developed using an axis-angle representation of head rotations, with x, y, and z components in the axis. Muscle load sharing was based on rotational direction in the simulation and muscle activity recorded in three volunteer experiments in these directions. The gains of the rotational and translational controller were tuned to minimize differences between translational and rotational head displacements of the HBM and volunteers in braking and lane change maneuvers using multi-objective optimizations. Bio-fidelity of the model with tuned controllers was evaluated objectively using CORrelation and Analysis (CORA). Results: The results indicated comparable performance for both controllers after tuning, with somewhat higher bio-fidelity for rotational kinematics with the translational controller. After tuning, good or excellent bio-fidelity was indicated for both controllers in the loading direction (forward in braking, and lateral in lane change), with CORA scores of 0.86-0.99 and 0.93-0.98 for the rotational and translational controllers, respectively. For rotational displacements, and translational displacements in the other directions, bio-fidelity ranged from poor to excellent, with slightly higher average CORA scores for the HBM with the translational controller in both braking and lane changing. Time-averaged muscle activity was within one standard deviation of time-averaged muscle activity from volunteers. Conclusion: Overall, the results show that when tuned, both the translational and rotational controllers can be used to predict the occupant response to an evasive maneuver, allowing for the inclusion of evasive maneuvers prior to a crash in evaluation of vehicle safety. The rotational controller shows potential in controlling omni-directional head displacements, but the translational controller outperformed the rotational controller. Thus, for now, the recommendation is to use the translational controller with tuned gains.

CaRA - A multi-purpose phage display library for selection of calcium-regulated affinity proteins.

Protein activity regulated by interactions with metal ions can be utilized for many different purposes, including biological therapies and bioprocessing, among others. Calcium ions are known to interact with the frequently occurring EF-hand motif, which can alter protein activity upon binding through an induced conformational change. The calcium-binding loop of the EF-hand motif has previously been introduced into a small protein domain derived from staphylococcal Protein A in a successful effort to render antibody binding dependent on calcium. Presented here, is a combinatorial library for calcium-regulated affinity, CaRA, based on this domain. CaRA is the first alternative scaffold library designed to achieve novel target specificities with metal-dependent binding. From this library, several calcium-dependent binders could be isolated through phage display campaigns towards a set of unrelated target proteins (IgE Cε3-Cε4, TNFα, IL23, scFv, tPA, PCSK9 and HER3) useful for distinct applications. Overall, these monomeric CaRA variants showed high stability and target affinities within the nanomolar range. They displayed considerably higher melting temperatures in the presence of 1 mM calcium compared to without calcium. Further, all discovered binders proved to be calcium-dependent, with the great majority showing complete lack of target binding in the absence of calcium. As demonstrated, the CaRA library is highly capable of providing protein-binding domains with calcium-dependent behavior, independent of the type of target protein. These binding domains could subsequently be of great use in gentle protein purification or as novel therapeutic modalities.

Prevalence and impact of early prone position on 30-day mortality in mechanically ventilated patients with COVID-19: a nationwide cohort study.

BACKGROUND: COVID-19 ARDS shares features with non-COVID ARDS but also demonstrates distinct physiological differences. Despite a lack of strong evidence, prone positioning has been advocated as a key therapy for COVID-19 ARDS. The effects of prone position in critically ill patients with COVID-19 are not fully understood, nor is the optimal time of initiation defined. In this nationwide cohort study, we aimed to investigate the association between early initiation of prone position and mortality in mechanically ventilated COVID-19 patients with low oxygenation on ICU admission. METHODS: Using the Swedish Intensive Care Registry (SIR), all Swedish ICU patients ≥ 18 years of age with COVID-19 admitted between March 2020, and April 2021 were identified. A study-population of patients with PaO2/FiO2 ratio ≤ 20 kPa on ICU admission and receiving invasive mechanical ventilation within 24 h from ICU admission was generated. In this study-population, the association between early use of prone position (within 24 h from intubation) and 30-day mortality was estimated using univariate and multivariable logistic regression models. RESULTS: The total study cohort included 6350 ICU patients with COVID-19, of whom 46.4% were treated with prone position ventilation. Overall, 30-day mortality was 24.3%. In the study-population of 1714 patients with lower admission oxygenation (PaO2/FiO2 ratio ≤ 20 kPa), the utilization of early prone increased from 8.5% in March 2020 to 48.1% in April 2021. The crude 30-day mortality was 27.2% compared to 30.2% in patients not receiving early prone positioning. We found no significant association between early use of prone positioning and survival. CONCLUSIONS: During the first three waves of the COVID-19 pandemic, almost half of the patients in Sweden were treated with prone position ventilation. We found no association between early use of prone positioning and survival in patients on mechanical ventilation with severe hypoxemia on ICU admission. To fully elucidate the effect and timing of prone position ventilation in critically ill patients with COVID-19 further studies are desirable.

Critical Influenza and COVID-19-A Comparative Nationwide Case-Control Study.

Refined knowledge of risk factors for critical influenza and COVID-19 may lead to improved understanding of pathophysiology and better pandemic preparedness. OBJECTIVES: To compare risk-factor profiles of patients admitted to intensive care with critical influenza and COVID-19. DESIGN SETTING AND PATIENTS: A nationwide retrospective matched case-control study, including all adults admitted to an ICU in Sweden with influenza or COVID-19 between 2014 and September 2020 and a matched control population (ratio 1:5, patients:controls). MEASUREMENTS AND MAIN RESULTS: Admission to an ICU. The study included 1,873 influenza and 2,567 COVID-19 ICU patients, and 9,365 and 12,835 controls, respectively, matched on sex, age, and geographical region. Influenza patients were older and less likely male, and carried a larger burden of comorbidity and a higher Simplified Acute Physiology Score III score, whereas short-term mortalities were similar when compared to COVID-19 patients. The risk-factor profiles at ICU admission were largely comparable including socioeconomic, psychiatric, and several somatic variables. Hypertension was a strong risk factor in critical COVID-19 patients compared with influenza. Nonglucocorticoid immunosuppressive therapy was associated with critical influenza but not COVID-19. Premorbid medication with statins and renin-angiotensin-aldosterone system inhibitors reduced the risk for both conditions, the opposite was a seen for glucocorticoid medication. Notably, medication with betablockers, oral anticoagulation, and platelet inhibitors reduced the risk of critical COVID-19 but not influenza. CONCLUSIONS: The risk-factor profiles for critical influenza and COVID-19 were largely comparable; however, some important differences were noted. Hypertension was a stronger risk factor for developing critical COVID-19, whereas the use of betablockers, oral anticoagulants, and platelet inhibitors all reduced the risk of ICU admission for COVID-19 but not influenza. Findings possibly reflected differences in pathophysiological mechanisms between these conditions.

Chronic dysglycemia and risk of SARS-CoV-2 associated respiratory failure in hospitalized patients.

BACKGROUND: Diabetes is common among patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced respiratory failure. We aimed to investigate the relationship between different stages of chronic dysglycemia and development of respiratory failure in hospitalized SARS-CoV-2 positive patients. METHODS: In this retrospective observational study, we included 385 hospitalized SARS-CoV-2 positive patients at Karolinska University Hospital, Sweden with an HbA1c test obtained within 3 months before admission. Based on HbA1c level and previous diabetes history, we classified patients into the following dysglycemia categories: prediabetes, unknown diabetes, controlled diabetes, or uncontrolled diabetes. We used multivariable logistic regression analysis adjusted for age, sex, and body mass index, to assess the association between dysglycemia categories and development of SARS-CoV-2-induced respiratory failure. RESULTS: Of the 385 study patients, 88 (22.9%) had prediabetes, 68 (17.7%) had unknown diabetes, 36 (9.4%) had controlled diabetes, and 83 (21.6%) had uncontrolled diabetes. Overall, 299 (77.7%) patients were admitted with or developed SARS-CoV-2-induced respiratory failure during hospitalization. In multivariable logistic regression analysis compared with no chronic dysglycemia, prediabetes (OR 14.41, 95% CI 5.27-39.43), unknown diabetes (OR 15.86, 95% CI 4.55-55.36), and uncontrolled diabetes (OR 17.61, 95% CI 5.77-53.74) was independently associated with increased risk of SARS-CoV-2-induced respiratory failure. CONCLUSION: In our cohort of hospitalized SARS-CoV-2 positive patients with available HbA1c data, prediabetes, undiagnosed diabetes, and poorly controlled diabetes were associated with a markedly increased risk of SARS-CoV-2-associated respiratory failure.

Dynamic Spatial Tuning Patterns of Shoulder Muscles with Volunteers in a Driving Posture.

Computational human body models (HBMs) of drivers for pre-crash simulations need active shoulder muscle control, and volunteer data are lacking. The goal of this paper was to build shoulder muscle dynamic spatial tuning patterns, with a secondary focus to present shoulder kinematic evaluation data. 8M and 9F volunteers sat in a driver posture, with their torso restrained, and were exposed to upper arm dynamic perturbations in eight directions perpendicular to the humerus. A dropping 8-kg weight connected to the elbow through pulleys applied the loads; the exact timing and direction were unknown. Activity in 11 shoulder muscles was measured using surface electrodes, and upper arm kinematics were measured with three cameras. We found directionally specific muscle activity and presented dynamic spatial tuning patterns for each muscle separated by sex. The preferred directions, i.e. the vector mean of a spatial tuning pattern, were similar between males and females, with the largest difference of 31° in the pectoralis major muscle. Males and females had similar elbow displacements. The maxima of elbow displacements in the loading plane for males was 189 ± 36 mm during flexion loading, and for females, it was 196 ± 36 mm during adduction loading. The data presented here can be used to design shoulder muscle controllers for HBMs and evaluate the performance of shoulder models.

A cohort study investigating the occurrence of differences in care provided to men and women in an intensive care unit.

It has been reported that there are differences in the care given within the intensive care unit (ICU) between men and women. The aim of this study is to investigate if any differences still exist between men and women regarding the level of intensive care provided, using prespecified intensive care items. This is a retrospective cohort study of 9017 ICU patients admitted to a university hospital between 2006 and 2016. Differences in use of mechanical ventilation, invasive monitoring, vasoactive treatment, inotropic treatment, echocardiography, renal replacement therapy and central venous catheters based on the sex of the patient were analysed using univariate and multivariable logistic regressions. Subgroup analyses were performed on patients diagnosed with sepsis, cardiac arrest and respiratory disease. Approximately one third of the patients were women. Overall, men received more mechanical ventilation, more dialysis and more vasoactive treatment. Among patients admitted with a respiratory disease, men were more likely to receive mechanical ventilation. Furthermore, men were more likely to receive levosimendan if admitted with cardiac arrest. We conclude that differences in the level of intensive care provided to men and women still exist.

Risk of severe COVID-19 and mortality in patients with established chronic liver disease: a nationwide matched cohort study.

BACKGROUND AND AIMS: Some, but not all, prior studies have suggested that patients with chronic liver disease are at increased risk of contracting COVID-19 and developing more severe disease. However, nationwide data are lacking from well-phenotyped cohorts with liver histology and comparisons to matched general population controls. METHODS: We conducted a nationwide cohort study of all Swedish adults with chronic liver disease (CLD) confirmed by liver biopsy between 1966 and 2017 (n = 42,320), who were alive on February 1, 2020. CLD cases were matched to ≤ 5 population comparators by age, sex, calendar year and county (n = 182,147). Using Cox regression, we estimated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for COVID-19 hospitalization and severe COVID-19 (intensive care admission or death due to COVID-19). RESULTS: Between February 1 and July 31, 2020, 161 (0.38%) CLD patients and 435 (0.24%) general population controls were hospitalized with COVID-19 (aHR = 1.36, 95% CI = 1.11-1.66), while 65 (0.15%) CLD patients and 191 (0.10%) controls developed severe COVID-19 (aHR = 1.08, 95% CI = 0.79-1.48). Results were similar in patients with CLD due to alcohol use, nonalcoholic fatty liver disease, viral hepatitis, autoimmune hepatitis, and other etiologies. Among patients with cirrhosis (n = 2549), the aHRs for COVID-19 hospitalization and for severe COVID-19 were 1.08 (95% CI 0.48-2.40) and 1.23 (95% CI = 0.37-4.04), respectively, compared to controls. Moreover, among all patients diagnosed with COVID-19, the presence of underlying CLD was not associated with increased mortality (aHR = 0.85, 95% CI = 0.61-1.19). CONCLUSIONS: In this nationwide cohort, patients with CLD had a higher risk of hospitalization for COVID-19 compared to the general population, but they did not have an increased risk of developing severe COVID-19.

Identification and Evaluation of Methodologies to Assess the Quality of Mobile Health Apps in High-, Low-, and Middle-Income Countries: Rapid Review.

BACKGROUND: In recent years, there has been rapid growth in the availability and use of mobile health (mHealth) apps around the world. A consensus regarding an accepted standard to assess the quality of such apps has yet to be reached. A factor that exacerbates the challenge of mHealth app quality assessment is variations in the interpretation of quality and its subdimensions. Consequently, it has become increasingly difficult for health care professionals worldwide to distinguish apps of high quality from those of lower quality. This exposes both patients and health care professionals to unnecessary risks. Despite progress, limited understanding of the contributions of researchers in low- and middle-income countries (LMICs) exists on this topic. Furthermore, the applicability of quality assessment methodologies in LMIC settings remains relatively unexplored. OBJECTIVE: This rapid review aims to identify current methodologies in the literature to assess the quality of mHealth apps, understand what aspects of quality these methodologies address, determine what input has been made by authors from LMICs, and examine the applicability of such methodologies in LMICs. METHODS: This review was registered with PROSPERO (International Prospective Register of Systematic Reviews). A search of PubMed, EMBASE, Web of Science, and Scopus was performed for papers related to mHealth app quality assessment methodologies, which were published in English between 2005 and 2020. By taking a rapid review approach, a thematic and descriptive analysis of the papers was performed. RESULTS: Electronic database searches identified 841 papers. After the screening process, 52 papers remained for inclusion. Of the 52 papers, 5 (10%) proposed novel methodologies that could be used to evaluate mHealth apps of diverse medical areas of interest, 8 (15%) proposed methodologies that could be used to assess apps concerned with a specific medical focus, and 39 (75%) used methodologies developed by other published authors to evaluate the quality of various groups of mHealth apps. The authors in 6% (3/52) of papers were solely affiliated to institutes in LMICs. A further 15% (8/52) of papers had at least one coauthor affiliated to an institute in an LMIC. CONCLUSIONS: Quality assessment of mHealth apps is complex in nature and at times subjective. Despite growing research on this topic, to date, an all-encompassing appropriate means for evaluating the quality of mHealth apps does not exist. There has been engagement with authors affiliated to institutes across LMICs; however, limited consideration of current generic methodologies for application in LMIC settings has been identified. TRIAL REGISTRATION: PROSPERO CRD42020205149; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=205149.