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.

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.

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.

Opioid Use After Intensive Care: A Nationwide Cohort Study.

OBJECTIVE: To describe opioid use after ICU admission, identify factors associated with chronic opioid use after critical care, and determine if chronic opioid use is associated with an increased risk of death. DESIGN: Retrospective cohort study. SETTING: Sweden including all registered ICU admissions between 2010 and 2018. PATIENTS: Adults surviving the first two quarters after ICU admission were eligible for inclusion. A total of 265,496 patients were screened and 61,094 were ineligible. INTERVENTIONS: Admission to intensive care. MEASUREMENTS AND MAIN RESULTS: Among 204,402 individuals included in the cohort, 22,138 developed chronic opioid use following critical care. Mean opioid consumption peaked after admission followed by a continuous decline without returning to baseline during follow-up of 24 months. Factors associated with chronic opioid use included high age, female sex, presence of comorbidities, preadmission opioid use, and ICU length of stay greater than 2 days. Adjusted hazard ratio for death 6-18 months after admission for chronic opioid users was 1.7 (95% CI, 1.6-1.7; p < 0.001). In the subset of patients not using opioids prior to admission, similar findings were noted. CONCLUSIONS: Mean opioid consumption is increased 24 months after ICU admission despite the lack of evidence for long-term opioid treatment. Given the high number of ICU entries and risk of excess mortality for chronic users, preventing opioid misuse is important when improving long-term outcomes after critical care.

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.

Long-term outcome after intensive care for COVID-19: differences between men and women-a nationwide cohort study.

BACKGROUND: Questions remain about long-term outcome for COVID-19 patients in general, and differences between men and women in particular given the fact that men seem to suffer a more dramatic course of the disease. We therefore analysed outcome beyond 90 days in ICU patients with COVID-19, with special focus on differences between men and women. METHODS: We identified all patient ≥ 18 years with COVID-19 admitted between March 6 and June 30, 2020, in the Swedish Intensive Care Registry. Patients were followed until death or study end-point October 22, 2020. Association with patient sex and mortality, in addition to clinical variables, was estimated using Cox regression. We also performed a logistic regression model estimating factors associated with 90-day mortality. RESULTS: In total, 2354 patients with COVID-19 were included. Four patients were still in the ICU at study end-point. Median follow-up time was 183 days. Mortality at 90-days was 26.9%, 23.4% in women and 28.2% in men. After 90 days until end of follow-up, only 11 deaths occurred. On multivariable Cox regression analysis, male sex (HR 1.28, 95% CI 1.06-1.54) remained significantly associated with mortality even after adjustments. Additionally, age, COPD/asthma, immune deficiency, malignancy, SAPS3 and admission month were associated with mortality. The logistic regression model of 90-day mortality showed almost identical results. CONCLUSIONS: In this nationwide study of ICU patients with COVID-19, men were at higher risk of poor long-term outcome compared to their female counterparts. The underlying mechanisms for these differences are not fully understood and warrant further studies.

Characteristics and outcomes of patients with COVID-19 admitted to ICU in a tertiary hospital in Stockholm, Sweden.

BACKGROUND: Information on characteristics and outcomes of intensive care unit (ICU) patients with COVID-19 remains limited. We examined characteristics, clinical course and early outcomes of patients with COVID-19 admitted to ICU. METHODS: We included all 260 patients with COVID-19 admitted to nine ICUs at the Karolinska University Hospital (Stockholm, Sweden) between 9 March and 20 April 2020. Primary outcome was in-hospital mortality among patients with definite outcomes (discharged from ICU or death), as of 30 April 2020 (study end point). Secondary outcomes included ICU length of stay, the proportion of patients receiving mechanical ventilation and renal replacement therapy, and hospital discharge destination. RESULTS: Of 260 ICU patients with COVID-19, 208 (80.0%) were men, the median age was 59 (IQR 51-65) years, 154 (59.2%) had at least one comorbidity, and the median duration of symptoms preceding ICU admission was 11 (IQR 8-14) days. Sixty-two (23.8%) patients remained in ICU at study end point. Among the 198 patients with definite outcomes, ICU length of stay was 12 (IQR, 6-18) days, 163 (82.3%) received mechanical ventilation, 28 (14.1%) received renal replacement therapy, 60 (30.3%) died, 62 (31.3%) were discharged home, 47 (23.7%) were discharged to ward, and 29 (14.6%) were discharged to another health care facility. On multivariable logistic regression analysis, older age and admission from the emergency department was associated with higher mortality. CONCLUSION: This study presents detailed data on clinical characteristics and early outcomes of consecutive patients with COVID-19 admitted to ICU in a large tertiary hospital in Sweden.

Cytokinin-Auxin Crosstalk in the Gynoecial Primordium Ensures Correct Domain Patterning.

The Arabidopsis (Arabidopsis thaliana) gynoecium consists of two congenitally fused carpels made up of two lateral valve domains and two medial domains, which retain meristematic properties and later fuse to produce the female reproductive structures vital for fertilization. Polar auxin transport (PAT) is important for setting up distinct apical auxin signaling domains in the early floral meristem remnants allowing for lateral domain identity and outgrowth. Crosstalk between auxin and cytokinin plays an important role in the development of other meristematic tissues, but hormone interaction studies to date have focused on more accessible later-stage gynoecia and the spatiotemporal interactions pivotal for patterning of early gynoecium primordia remain unknown. Focusing on the earliest stages, we propose a cytokinin-auxin feedback model during early gynoecium patterning and hormone homeostasis. Our results suggest that cytokinin positively regulates auxin signaling in the incipient gynoecial primordium and strengthen the concept that cytokinin regulates auxin homeostasis during gynoecium development. Specifically, medial cytokinin promotes auxin biosynthesis components [YUCCA1/4 (YUC1/4)] in, and PINFORMED7 (PIN7)-mediated auxin efflux from, the medial domain. The resulting laterally focused auxin signaling triggers ARABIDOPSIS HISTIDINE PHOSPHOTRANSFER PROTEIN6 (AHP6), which then represses cytokinin signaling in a PAT-dependent feedback. Cytokinin also down-regulates PIN3, promoting auxin accumulation in the apex. The yuc1, yuc4, and ahp6 mutants are hypersensitive to exogenous cytokinin and 1-napthylphthalamic acid (NPA), highlighting their role in mediolateral gynoecium patterning. In summary, these mechanisms self-regulate cytokinin and auxin signaling domains, ensuring correct domain specification and gynoecium development.

How anorexia nervosa patients with high and low autistic traits respond to group Cognitive Remediation Therapy.

BACKGROUND: The current study aimed to evaluate group Cognitive remediation therapy (CRT) inpatients with Anorexia Nervosa (AN). We aimed to examine the treatment response of group CRT in AN patients with high or low levels of autistic traits. METHODS: Thirty-five in patients with an AN diagnosis received group CRT intervention for 6 sessions in a national eating disorder unit. All participants completed self-report questionnaires on thinking styles and motivation before and after the intervention. RESULTS: Patients with low autistic traits had statistically significant medium size effect improvements in self-reported thinking style scales as well as confidence (ability) to change. Patients with high autistic traits showed no statistically significant improvements in any outcome measure. CONCLUSIONS: The brief group format CRT intervention improves self-reported cognitive and motivational aspects in people with AN without autistic traits. For patients with higher autistic traits brief group CRT does not improve self-reported cognitive style or motivation. This finding suggests that brief group format CRT might not be the best suited format for individuals with elevated autistic traits and individual or more tailored CRT should be explored.

Polar auxin transport is essential for medial versus lateral tissue specification and vascular-mediated valve outgrowth in Arabidopsis gynoecia.

Although it is generally accepted that auxin is important for the patterning of the female reproductive organ, the gynoecium, the flow as well as the temporal and spatial actions of auxin have been difficult to show during early gynoecial development. The primordium of the Arabidopsis (Arabidopsis thaliana) gynoecium is composed of two congenitally fused, laterally positioned carpel primordia bisected by two medially positioned meristematic regions that give rise to apical and internal tissues, including the ovules. This organization makes the gynoecium one of the most complex plant structures, and as such, the regulation of its development has remained largely elusive. By determining the spatiotemporal expression of auxin response reporters and localization of PINFORMED (PIN) auxin efflux carriers, we have been able to create a map of the auxin flow during the earliest stages of gynoecial primordium initiation and outgrowth. We show that transient disruption of polar auxin transport (PAT) results in ectopic auxin responses, broadened expression domains of medial tissue markers, and disturbed lateral preprocambium initiation. Based on these results, we propose a new model of auxin-mediated gynoecial patterning, suggesting that valve outgrowth depends on PIN1-mediated lateral auxin maxima as well as subsequent internal auxin drainage and provascular formation, whereas the growth of the medial domains is less dependent on correct PAT. In addition, PAT is required to prevent the lateral domains, at least in the apical portion of the gynoecial primordium, from obtaining medial fates.

Quality of anaesthesia for Caesarean sections: a cross-sectional study of a university hospital in a low-income country.

OBJECTIVE: To evaluate the quality of anaesthesia for Caesarean sections at Muhimbili National Hospital, Dar es Salaam, Tanzania. METHOD: We developed an instrument consisting of 40 quality indicators using an expert group process based on the existing literature. Using the instrument, we observed 50 Caesarean sections. Twenty-eight of the indicators were structural indicators, such as essential drugs, oxygen supply and anaesthetic equipment. Twelve were process indicators such as evaluation of airway, blood pressure assessment or insertion of an intravenous line. RESULTS: The median patient age was 28.5 years. A total of 75% (range 61-82%) of the structural indicators were present in the operating theatres, and 55% (range 33-83%) of the process indicators were performed. The neonates' median Apgar score was 9 (range 3-10). Seven babies required ventilation, four babies were stillborn, and all others were alive at follow-up 2 days after partus. All mothers were alive 2 days post-surgery. CONCLUSION: The low process score suggests that quality improvement initiatives should focus on the processes of anaesthesia for Caesarean sections rather than new drugs and equipment.

Socio-economic status and co-morbidity as risk factors for trauma.

Clinical experience and previous studies indicate that low socioeconomic positions are overrepresented in trauma populations. The reason for this social variation in injury risk is likely to be multifactorial. Both individual and environmental sources of explanation are plausible to contribute. We investigated the impact of the influence of socioeconomic factors and co-morbidity on the risk of becoming a trauma victim in a case-control study including 7,382 trauma patients matched in a one to five ratio with controls matched by age-, gender- and municipality from a level 1 trauma centre. Data from the trauma cohort were linked to national registries. Associations between socioeconomic factors and co-morbidity were estimated by conditional logistic regression. The trauma patients had been treated for psychiatric, substance abuse and somatic diagnoses to a higher extent than the controls. In the conditional logistic regression analysis a low level of education and income as well as co-morbidity (divided into psychiatric, substance abuse and somatic diagnoses) were all independent risk factors for trauma. Analysing patients with an injury severity score >15 separately did not alter the results, except for somatic diagnoses not being a risk factor. Recent treatment for substance abuse significantly increased the risk for trauma. Low level of education and income as well as psychiatric, substance abuse and somatic co-morbidity were all independent risk factors for trauma. Active substance abuse strongly influenced the risk for trauma and had a time dependent pattern. These insights can facilitate future implementation of injury prevention strategies tailored to specific risk groups.

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.

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.

Auxin and the Arabidopsis thaliana gynoecium.

Recent research is beginning to reveal how intricate networks of hormones and transcription factors coordinate the complex patterning of the gynoecium, the female reproductive structure of flowering plants. This review summarizes recent advances in understanding of how auxin biosynthesis, transport, and responses together generate specific gynoecial domains. This review also highlights areas where future research endeavours are likely to provide additional insight into the homeostatic molecular mechanisms by which auxin regulates gynoecium development.

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.