Effects of implementation of EU-TIRADS risk stratification in a thyroid cancer programme in Western Sweden- a retrospective cohort study.

INTRODUCTION: The EU-Thyroid Imaging Report and Data System (EU-TIRADS) allows for selective fine needle aspiration cytology (FNAC). In 2017, EU-TIRADS was implemented as part of a nation-wide 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 FNAC in referred patients with thyroid nodules. MATERIAL AND 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 PET positive finding for examination with thyroid ultrasound and selective cytology between 2018 and 2022. Medical records on EU-TIRADS classification, corresponding FNAC results and histopathological diagnosis were retrospectively collected. Adherence to EU-TIRADS guidelines, use of selective FNAC and rate of malignancy (ROM) in patients undergoing surgery were assessed. RESULTS: In total, 1246 thyroid nodules in 990 patients were evaluated. The distribution of EU-TIRADS 2-5 n(%) was: 63(5); 462(37); 443(36); 278(22). FNAC was omitted in 7% of the investigated patients. FNAC was performed in 124 nodules (10%) despite not fulfilling EU-TIRADS criteria or absence of PET positive findings. ROM was 33% and 1/50 in patients undergoing "unnecessary" FNAC. DISCUSSION: Implementation of EU-TIRADS in routine management of thyroid nodules led to selective use of FNAC, but 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.

Postinjury Sepsis-Associations With Risk Factors, Impact on Clinical Course, and Mortality: A Retrospective Observational Study.

OBJECTIVES: Overall outcomes for trauma patients have improved over time. However, mortality for postinjury sepsis has been reported to be unchanged. Estimate incidence of and risk factors for sepsis in ICU patients after major trauma and the association between sepsis, mortality, and clinical course. DESIGN SETTING AND PATIENTS: ICU in a large urban trauma center in Sweden with a well-developed trauma system. Retrospective cohort study of trauma patients admitted to the ICU for more than 24 hours were included. MEASUREMENTS AND MAIN RESULTS: Primary outcome measure was 30-day mortality. Secondary outcomes were 1-year mortality and impact on clinical course. In total, 722 patients with a median Injury Severity Score of 26 (interquartile range, 18-38) were included. Incidence of sepsis was 22%. Septic patients had a four-fold increase in length of stay and need for organ supportive therapy. The overall 30-day mortality rate was 9.3%. After exclusion of early trauma-related deaths in the first 48 hours, the 30-day mortality rate was 6.7%. There was an association between sepsis and this adjusted 30-day mortality (day 3 odds ratio, 2.1 [95% CI, 1.1-3.9]; day 4 odds ratio, 3.1 [95% CI, 1.5-6.1]; day 5 odds ratio, 3.0 [95% CI, 1.4-6.2]). Septic patients had a 1-year mortality of 17.7% (nonseptic 11.0%). Development of sepsis was independently associated with age, spine and chest injury, shock, red cell transfusion, and positive blood alcohol concentration at admission. The risk of sepsis increased, in a dose-dependent manner, with the number of transfusions. CONCLUSIONS: Postinjury sepsis was associated with a complicated clinical course and with mortality after exclusion of early, trauma-related deaths.

Nationwide case-control study of risk factors and outcomes for community-acquired sepsis.

Sepsis is the main cause of death in the intensive care units (ICU) and increasing incidences of ICU admissions for sepsis are reported. Identification of patients at risk for sepsis and poor outcome is therefore of outmost importance. We performed a nation-wide case-control study aiming at identifying and quantifying the association between co-morbidity and socio-economic factors with intensive care admission for community-acquired sepsis. We also explored 30-day mortality. All adult patients (n = 10,072) with sepsis admitted from an emergency department to an intensive care unit in Sweden between 2008 and 2017 and a control population (n = 50,322), matched on age, sex and county were included. In the sepsis group, 69% had a co-morbid condition at ICU admission, compared to 31% in the control group. Multivariable conditional logistic regression analysis was performed and there was a large variation in the influence of different risk factors associated with ICU-admission, renal disease, liver disease, metastatic malignancy, substance abuse, and congestive heart failure showed the strongest associations. Low income and low education level were more common in sepsis patients compared to controls. The adjusted OR for 30-day mortality for sepsis patients was 132 (95% CI 110-159) compared to controls.

Inflammatory bowel disease and risk of severe COVID-19: A nationwide population-based cohort study in Sweden.

BACKGROUND: There are concerns that individuals with chronic immune-mediated diseases are at increased risk of COVID-19 and related severe adverse outcome, including intensive care admission or death. We aimed to explore the absolute and relative risk of severe COVID-19 in inflammatory bowel disease (IBD). METHODS: This population-based cohort study used nationwide registers in Sweden, with 67,292 individuals with a diagnosis of IBD 1969-2017 (Crohn's disease, n = 21,599; ulcerative colitis: n = 43,622; IBD-unclassified: n = 2071) and alive on 1 February 2020. Patients with IBD were matched to up to five controls from the general population (n = 297,910). Cox regression estimated hazard ratios (HRs) for (i) hospital admission with laboratory-confirmed COVID-19 as the primary diagnosis, and (ii) severe COVID-19 (composite outcome consisting of (a) COVID-19 intensive care admission, or (b) death from COVID-19 or (c) death within 30 days of COVID-19 hospital admission), were calculated. Analyses were conditioned on age, sex, calendar period, and county and adjusted for other comorbidities. RESULTS: Between 1 February and 31 July 2020, 179 (0.27%) IBD patients and 500 (0.17%) general population controls were admitted to hospital with COVID-19 (adjusted HR [aHR] = 1.43; 95% CI = 1.19-1.72). The corresponding numbers for severe COVID-19 was 65 (0.10%) and 183 (0.06%; aHR = 1.11; 95% CI = 0.81-1.52). Adjusted HRs were similar in Crohn's disease and ulcerative colitis. In a propensity score-matched model taking comorbidity into account until 2016, the increased risk for COVID-19 hospital admission remained (aHR = 1.32; 1.12-1.56), but there was no increased risk of severe COVID-19 (aHR = 1.12; 0.85-1.47). CONCLUSIONS: While individuals with IBD were more likely to be admitted to hospital for COVID-19 than the general population, the risk of severe COVID-19 was not higher.

Risk of Severe Covid-19 in Patients with Celiac Disease: A Population-Based Cohort Study.

BACKGROUND: Patients with celiac disease (CeD) are at increased risk of certain viral infections and of pneumococcal pneumonia, raising concerns that they may be susceptible to severe coronavirus disease 2019 (Covid-19). We aimed to quantify the association between CeD and severe outcomes related to Covid-19. METHODS: We performed a population-based cohort study, identifying individuals with CeD in Sweden, as defined by small intestinal villus atrophy diagnosed at all (n=28) Swedish pathology departments during the years spanning 1969-2017, and alive on February 1, 2020. We compared these patients to controls matched by sex, age, county, and calendar period. We performed Cox proportional hazards with follow-up through July 31, 2020, assessing risk of 1) hospital admission with a primary diagnosis of laboratory-confirmed Covid-19 (co-primary outcome); and 2) severe disease as defined by admission to intensive care unit and/or death attributed to Covid-19 (co-primary outcome). RESULTS: Among patients with CeD (n=40,963) and controls (n=183,892), the risk of hospital admission for Covid-19 was 2.9 and 2.2 per 1000 person-years respectively. After adjusting for comorbidities, the risk of hospitalization for Covid-19 was not significantly increased in patients with CeD (HR 1.10; 95% CI 0.80-1.50), nor was the risk of severe Covid-19 increased (HR 0.97; 95% CI 0.59-1.59). Results were similarly null when we compared CeD patients to their non-CeD siblings with regard to these outcomes. Among all patients with CeD and controls hospitalized with a diagnosis of Covid-19 (n=58 and n=202, respectively), there was no significant difference in mortality (HR for CeD compared to controls 0.96; 95% CI 0.46-2.02). CONCLUSION: In this population-based study, CeD was not associated with an increased risk of hospitalization for Covid-19 or intensive care unit and/or death attributed to Covid-19.