In 2010, under the guidance of the DGAI (German Society of Anaesthesiology and Intensive Care Medicine) and DIVI (German Interdisciplinary Association for Intensive Care and Emergency Medicine), twelve German medical societies published the "Evidence- and Consensus-based Guidelines on the Management of Analgesia, Sedation and Delirium in Intensive Care". Since then, several new studies and publications have considerably increased the body of evidence, including the new recommendations from the American College of Critical Care Medicine (ACCM) in conjunction with Society of Critical Care Medicine (SCCM) and American Society of Health-System Pharmacists (ASHP) from 2013. For this update, a major restructuring and extension of the guidelines were needed in order to cover new aspects of treatment, such as sleep and anxiety management. The literature was systematically searched and evaluated using the criteria of the Oxford Center of Evidence Based Medicine. The body of evidence used to formulate these recommendations was reviewed and approved by representatives of 17 national societies. Three grades of recommendation were used as follows: Grade "A" (strong recommendation), Grade "B" (recommendation) and Grade "0" (open recommendation). The result is a comprehensive, interdisciplinary, evidence and consensus-based set of level 3 guidelines. This publication was designed for all ICU professionals, and takes into account all critically ill patient populations. It represents a guide to symptom-oriented prevention, diagnosis, and treatment of delirium, anxiety, stress, and protocol-based analgesia, sedation, and sleep-management in intensive care medicine.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides, particularly granulomatosis with polyangiitis and microscopic polyangiitis, are rare but severe systemic diseases frequently requiring intensive care unit (ICU) admission due to life-threatening renal and pulmonary involvement. Despite advances in immunosuppressive therapy, these patients remain at high risk of mortality and end-stage kidney disease, with prognosis driven by organ failure (notably diffuse alveolar haemorrhage [DAH]) and treatment-related complications such as infection. ICU management is complex and relies on rapid diagnosis, aggressive induction therapy, and tailored organ support. Current remission-induction strategies centre on high-dose glucocorticoids combined with cyclophosphamide or rituximab, with growing emphasis on minimizing steroid exposure. Plasma exchange (PLEX), once widely used for severe renal disease and DAH, remains debated, although selected high-risk subgroups may still derive benefit. Optimal management in the ICU requires a multidisciplinary approach, including careful selection of immunosuppressive regimens, individualized use of adjunctive therapies such as PLEX and the management of infectious complications. Advances in supportive care, including lung-protective ventilation, renal replacement therapy, and extracorporeal support, have improved short-term outcomes. However, significant uncertainty persists regarding optimal therapeutic strategies in the critically ill populations, highlighting the need for further research and phenotype-driven approaches.
Myasthenia gravis is an autoimmune disorder of the neuromuscular junction characterized by fatigable muscle weakness. Myasthenic crisis is a life-threatening condition characterized by acute respiratory failure resulting from severe weakness of the respiratory muscles. Currently, no established guidelines exist for physiological assessment at the time of mobilization, or for the content and intensity of exercise therapy, in patients with severe myasthenia gravis presenting with myasthenic crisis. We report a case of newly diagnosed myasthenia gravis with myasthenic crisis wherein exercise therapy was initiated in the intensive care unit, with careful monitoring of vital signs and muscle fatigability, ultimately leading to discharge. A 67-year-old woman presented with a dropped head, gait disturbance, and respiratory failure, and was diagnosed with myasthenia gravis at our hospital. On the same day, the patient developed hypoxemia, underwent endotracheal intubation, and was admitted to the intensive care unit for mechanical ventilation. Exercise therapy was initiated on hospital day 3, and the exercise workload progressively increased while vital signs and fatigability were monitored. Standing training began on day 12; and ambulation training while receiving mechanical ventilation was introduced on day 17 without adverse events. The patient was successfully weaned off mechanical ventilation on day 24, and exercise therapy was continued thereafter. Physical function improved after steroid pulse therapy and a thymectomy; she achieved independent ambulation with a cane on day 64 and was discharged on day 78. Early exercise therapy guided by monitoring and muscle fatigue assessments may facilitate functional recovery without clinical deterioration. However, larger studies are required to evaluate its safety and efficacy.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a major cause of hospital-acquired infections, particularly in intensive care units (ICUs). Chemical disinfectants are widely used for environmental decontamination in ICUs. However, their long-term application is associated with bacterial tolerance, material corrosion, and reduced lifespan of frequently touched surfaces. Environmentally friendly and effective alternative disinfection strategies are therefore urgently needed. CRKP remained viable on high-touch ICU surfaces for at least 72 h on stainless steel and up to two weeks on cotton fabrics. In liquid culture, high concentrations of phages XDRKpn-1, XDRKpn-2, and the phage cocktail reduced CRKP populations by approximately 4 log units within 12 h. In biofilm inhibition assays, phages XDRKpn-1 and XDRKpn-2 achieved inhibition rates of 78.66% and 64.22% at 109 PFU/mL, respectively (P < 0.05), while the phage cocktail resulted in a 77.64% reduction in biofilm biomass (P < 0.05).When applied to high-touch ICU surface materials, individual phages achieved maximum reduction rates of 99.94% on cotton, 99.75% on stainless steel, 99.74% on plywood, and 99.81% on plastic. The phage cocktail exhibited comparable or enhanced bactericidal activity, achieving reduction rates of 99.994%, 99.998%, 99.74%, and 99.93% on cotton, stainless steel, plywood, and plastic surfaces, respectively. Phages XDRKpn-1 and XDRKpn-2 effectively reduced CRKP contamination on ICU-relevant high-touch surfaces under laboratory conditions, highlighting their potential as a targeted and environmentally friendly alternative or complement to conventional chemical disinfectants. However, further studies are required to validate their efficacy and stability in the complex, real-world ICU environment.
Patients with acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) frequently suffer severe complications requiring intensive care unit (ICU) admission. While sepsis is a recognized driver of these poor outcomes, its precise impact on short-term mortality in this specific population requires further clarification. We conducted a retrospective cohort study of 65 adult AML patients admitted to the ICU within 100 days post-allo-HSCT at a single tertiary care center. Patients were stratified by the presence of sepsis. Clinical and microbiological data were collected, and univariable Cox proportional hazards regression was used to identify predictors of the primary outcome i.e. 90-day mortality. Sepsis was diagnosed in 70.8 % patients (n=46) and required significantly more organ support, including invasive mechanical ventilation (67.4 % vs 15.8 %; p<0.001) and renal replacement therapy (37.0% vs 5.3%; p=0.009). The presence of sepsis was associated with significantly lower 90-day survival (log-rank p=0.012). In univariable analysis, sepsis was the strongest predictor of 90-day mortality (Hazard Ratio [HR], 3.34; 95% CI, 1.47-7.57; p=0.004). Mechanical ventilation (HR, 3.14; p<0.001) and renal replacement therapy (HR, 2.35; p=0.010) were also 4 significant predictors. The most frequently identified pathogens were Klebsiella species (18.5%), Enterococcus species (13.8%). Vancomycin-resistant Enterococcus (VRE) found in 9.2% patients. Sepsis is a primary and statistically significant driver of 90-day mortality in AML patients admitted to the ICU following allo-HSCT. These findings underscore the urgent need for early sepsis recognition, aggressive management, and robust antimicrobial stewardship in this highly vulnerable population.
Traumatic brain injury (TBI) is a major cause of death and disability, with large variations in management strategies and outcomes across countries. Nordic countries are similar in demographics, but differences in treatment strategies likely exist and outcome differences have been reported. We aimed to assess temporal differences in treatments and outcomes in three large Nordic centers, with a hypothesis that outcomes, after adjustment for injury severity, are generally similar and have improved over time. We performed an international, multicenter, retrospective, observational registry study including consecutive intensive care unit (ICU) managed TBI patients from three of the largest university hospitals in the Nordics (Helsinki (HUS), Finland [2005-2020]; Stockholm (KUH), Sweden [2005-2022]; Oslo (OUH), Norway [2015-2022]). Our primary outcome was 6-12-month unfavorable Glasgow Outcome Scale (GOS, 1-3) and secondary outcome was 30-day mortality. We compared outcomes after adjusting for TBI outcome predictors: age, pupil responsiveness and admission Glasgow Coma Scale (GCS) over time. Other known outcome predictors like computerized tomography (CT) scores (Marshall CT classification and Rotterdam CT score) were collected if available, and intracranial pressure monitoring (ICP) for GCS 3-8 patients was specifically analyzed. In total, 5,970 patients were included (HUS = 2,769, KUH = 1,390, OUH = 1,811). Six-months crude unfavorable outcome was 43% and predicted unfavorable outcome was 44%. Crude 30-day mortality was 17% and predicted 30-day mortality was 18%. Of the included patients, 72% had a moderate-to-severe TBI (GCS 3-12) and 54% underwent some form of neurosurgical intervention. Model application diminished differences between centers, across both outcome measures. Minimal variation in outcomes between hospitals was observed, with a hospital-level variance after applying the model of 0.02 (SD 0.15) for unfavorable outcome and 0.06 (SD 0.24) for 30-day mortality. Overall, no significant temporal trend in predicted unfavorable outcome was observed (OR per year 0.95, 95% CI 0.88-1.03, p = 0.20). Variations in ICP monitoring, but also caseload, were observed. Differences in patient case-mix and caseload between hospitals were associated with variation in treatment strategies and crude outcomes. However, after adjusting for TBI outcome predictors, no meaningful between-hospital variation in outcomes was observed, and no temporal trends in outcome found over the study period.
Intensive care unit-acquired weakness (ICU-AW) is a consequence of critical illness and is associated with functional limitations. Objective assessment using handgrip strength (HGS) and surface electromyography (sEMG) may support monitoring of early rehabilitation in the ICU. This study aimed to evaluate associations between sEMG parameters, mobility level, and HGS in ICU patients. In this single-center observational study, ICU patients were assessed when they met criteria for early rehabilitation using bilateral sEMG and handgrip strength measurement, then classified into four functional mobility levels. Spearman's rank correlation was used to assess HGS-sEMG associations. The Mann-Whitney U test compared sEMG activity between patients who achieved marching in place and those who remained at lower functional mobility levels. A total of 57 ICU patients were assessed. In men, HGS correlated with biceps brachii, flexor digitorum superficialis, and rectus femoris activity during contraction. No significant HGS-sEMG associations were identified in women, which may be related to the smaller female subgroup and reduced statistical power. Men who achieved marching in place showed higher contraction-phase sEMG values for flexor digitorum superficialis and rectus femoris, possibly reflecting upper-limb-assisted standing and stabilization during verticalization. In women, a difference was observed for rectus femoris activity during contraction on the left side. Combined HGS and sEMG assessment may provide complementary exploratory information on neuromuscular function.
Herbaspirillum huttiense is a rare environmental Gram-negative bacillus increasingly recognized as an emerging opportunistic pathogen in humans. Due to its phenotypic similarities with other non-fermenting Gram-negative bacteria, it is frequently misidentified, and data on its clinical characteristics and management remain limited. This was a retrospective case series study conducted over one month (March 2023) in the Microbiology Department of Mohammed VI University Hospital, Marrakesh, Morocco. The study included neonates hospitalized in the Neonatal Intensive Care Unit (NICU) with at least one positive blood culture for Herbaspirillum spp. Patients with negative blood cultures or with bloodstream infections caused by pathogens other than Herbaspirillum spp. were excluded. Clinical and biological characteristics, including signs of sepsis, were collected retrospectively from medical records for descriptive analysis. Identification was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS, BD, Franklin Lakes, NJ). Antimicrobial susceptibility testing was performed using the automated Phoenix M50 system (BD Diagnostics, Sparks, MD) in accordance with EUCAST guidelines. Only descriptive statistics were used. Six neonates were included in the study, with an equal sex distribution (three males and three females). The majority were preterm infants (83.3%), with a mean gestational age of 34.2 weeks (range: 30.4-37.4 weeks) and a mean birth weight of 2.3 kg (range: 1.48-3.20 kg). Most deliveries were vaginal (83.3%). The main reasons for admission were neonatal respiratory distress (66.7%), followed by neonatal seizures and hypoglycemia (16.7% each). Comorbidities included severe perinatal asphyxia, persistent pulmonary hypertension of the newborn, and omphalocele. During hospitalization, the neonates developed clinical signs of sepsis after a mean delay of seven days (range: days four and nine), presenting with fever, tachycardia, and skin mottling. Biologically, patients developed leukopenia (mean leukocyte count: 9,500/mm³), elevated C-reactive protein (CRP) levels (mean: 89 mg/L), and thrombocytopenia (mean platelet count: 77,833/mm³). Blood cultures became positive after incubation, yielding Gram-negative, oxidase-positive bacilli identified as H. huttiense. The isolates were susceptible to carbapenems, cefepime, and amikacin, but resistant to colistin. All patients had a favorable outcome, with a 100% survival rate and a mean hospital stay of 16 days. H. huttiense is an emerging opportunistic pathogen in neonatal infections, often associated with diagnostic challenges due to misidentification. Advanced diagnostic tools such as MALDI-TOF significantly improve detection. Although no standardized treatment guidelines exist, most isolates appear susceptible to broad-spectrum antibiotics, with favorable clinical outcomes under appropriate therapy.
Postoperative neurosurgical patients often require pain management and agitation control while still being assessed for consciousness and focal neurological signs. General ICU trials suggest that minimizing the use of hypnotic sedatives may be feasible for selected mechanically ventilated patients; however, neurocritical care patients may have different safety requirements. This study aims to explore the feasibility and safety of an analgesia-first strategy, without the routine use of hypnotic sedatives, in adult patients admitted to the ICU after neurosurgical craniotomy. This is a single-center, single-arm, open-label, exploratory prospective study. A total of 65 adult patients after neurosurgical craniotomy with an anticipated ICU stay of more than 24 h and Richmond Agitation-Sedation Scale (RASS) score ≥ + 1 will be enrolled, provided that they do not require deep sedation. Eligible patients will receive protocolized nonpharmacological measures and remifentanil-based analgesia titrated from 0.1 to 0.2 μg/kg/min every 10-15 min to achieve a target RASS score of -2 to +1 and Critical-Care Pain Observation Tool (CPOT) score of 0-1. Rescue sedation with midazolam or propofol is permitted when clinically required for safety. The primary endpoint is successful protocol management during the first 24 h after initiation, defined as absence of protocol failure caused by rescue hypnotic sedative use, sustained RASS scores outside the target range, a serious safety event requiring protocol discontinuation, or clinical deterioration. Key safety endpoints include significant agitation, accidental extubation, accidental catheter or drain removal, respiratory depression, severe hypotension or bradycardia, delirium, opioid-induced rigidity, neurological deterioration, seizures, emergent neurosurgical intervention, and urgent unplanned computed tomography (CT) or magnetic resonance imaging (MRI) for suspected neurological worsening. Secondary endpoints include analgesic and sedative exposure, nursing workload, bispectral index (BIS) values, duration of intubation, ventilator-free days through day 28, ICU and hospital length of stay, ICU costs, pneumonia, and in-hospital mortality. ClinicalTrials.gov, identifier NCT06727435.
Obesity hypoventilation syndrome (OHS), wherein there is wake hypercapnia in the obese not attributable to other hypoventilation etiologies can lead to frequent ICU admissions for respiratory failure. Our study analyzed clinical characteristics and outcomes in OHS patients admitted in a safety-net community-based hospital ICU. A retrospective cohort of known or suspected OHS patients admitted to the ICU with respiratory failure was analyzed by BMI subgroups. mortality, ventilator length of stay (LOS), and ICU LOS. Secondary outcomes included predictors for heart failure, noninvasive ventilation (NIV) and high-flow nasal cannula use, right ventricular (RV) failure and other complications. Heart failure exacerbation and sepsis were commonly associated with respiratory failure in our cohort of 188 patients admitted over 5 years. Median ventilator and ICU LOS were 3 and 4 days respectively. Class 1 obesity (BMI 30-34.9 kg/m2) patients had worse outcomes when compared to patients with class 4 obesity (BMI > 50 kg/m2), with increased rates of NIV failure (69% vs 34%; P=0.007), RV failure (32% vs 20%, P=0.17) and readmissions (5 vs 2; P=0.002). Overall mortality rate in the cohort was 7%. In multivariable analysis, CKD demonstrated a trend towards increased mortality; however, this association did not remain statistically significant after adjustment for multiple comparisons. RV failure was significantly associated with increased ventilator duration. In our cohort of OHS patients in the ICU with respiratory failure, prevalence of heart failure and sepsis was high. NIV was frequently successful, particularly in class 4 obesity. Patients with milder obesity showed several unfavorable clinical characteristics and respiratory support outcomes, although these findings should be interpreted cautiously.
The journey to motherhood is complex for individuals with kidney disease. Fertility progressively declines as kidney function worsens, particularly in patients with advanced chronic kidney disease and kidney failure. When pregnancy does occur, it often carries a high risk of significant potential complications for both mother and fetus. These risks are not limited to chronic conditions; patients with relapsing-remitting diseases such as some glomerular disorders, or those who experience acute kidney injury, also face considerable challenges during pregnancy. Chronic kidney disease is estimated to be present in 3%-4% of pregnancies and is associated with higher risk of preeclampsia, prematurity, and intrauterine growth restriction. The causes of acute kidney injury vary by trimester, with hyperemesis gravidarum in the first trimester, and preeclampsia, and thrombotic microangiopathies in later phases contributing to maternal and fetal morbidity. Pregnancy in kidney failure is less frequent because of diminished fertility and requires intensive dialysis protocols to optimize outcomes. Disease-specific outcomes depend on factors such as stage, comorbidities, and response to treatment. Physiological adaptations during pregnancy-such as increased glomerular filtration rate and renal plasma flow-complicate diagnosis and necessitate careful interpretation of biomarkers. Additional challenges arise from diseases such as lupus nephritis, focal segmental glomerulosclerosis, and IgA nephropathy, where immunosuppressive therapy must be carefully balanced to minimize maternal and fetal risk. Successful management of kidney disease in pregnancy requires early risk stratification, multidisciplinary care involving nephrologists and maternal-fetal medicine specialists, and individualized therapeutic strategies tailored to the stage of pregnancy and kidney disease. This review highlights current evidence on kidney disease in pregnancy, emphasizing recommendations for improving maternal and fetal health.
Randomized clinical trials are a mainstay of medical research, but have drawbacks including time and cost. Bayesian adaptive trials can improve the speed and efficiency of clinical trials and are an increasingly common trial design in critical care. However, the complexity of Bayesian adaptive trials may prevent clinicians from easily interpreting their results. Do intensivist physicians perceive, understand, and accept results from Bayesian adaptive clinical trials differently than results from traditional frequentist trials when presented with otherwise identical data? We surveyed US intensivists from March through April 2022 about their perceptions of Bayesian adaptive trials. Within the survey, participants were randomized to read an abstract for a hypothetical new sepsis drug trial that used either Bayesian adaptive methods or traditional frequentist methods, with both abstracts based on the same simulated trial data. Participants then were asked about perceived understanding, validity, and general acceptance of the trial's methods and results. Survey responses were compared between experimental groups using Mann-Whitney U tests and ordinal logistic regressions. We received complete results from 273 of 592 eligible physicians (response rate, 46.1%). Participants in the Bayesian group reported lesser understanding of the methods (mean rating in frequentist vs Bayesian groups, 3.18 vs 2.85; P < .001) and the results of the trial (mean rating, 3.36 vs 3.00; P < .001) compared with the frequentist group. Participants in the Bayesian group also expressed greater concerns about trial validity (eg, mean rating about the risk of type 1 error, 2.70 vs 2.99; P = .001) compared with the frequentist group. Participants in both groups reported similar beliefs about acceptance of trial results (eg, mean rating in frequentist vs Bayesian group about the effectiveness of the study drug, 3.87 vs 3.86; P = .47). Our results show that despite lower perceived understanding of Bayesian trials and skepticism about elements of their validity, no substantive differences were found in intensivist physician acceptance of Bayesian trial results compared with frequentist trial results. CHEST Critical Care 2026; 4(2):100264.
Identifying subgroups of intensive care unit (ICU) patients with high mortality rates can provide directions in policy making about appropriate intensive care medicine. The objective of the study was to identify demographical and clinical characteristics of subgroups of ICU patients with high (≥80%) mortality rates at six months post-ICU admission. Data from all Dutch ICU patients admitted between 2013 and 2023 are used. Data are obtained from the Dutch National Intensive Care Evaluation (NICE) registry, including 807,727 ICU admissions from 84 hospitals. A machine learning model was trained on four samples, defined at different stages of the ICU admission with varying amounts of available data. Training was performed on 70% of the hospitals and validation on the other 30% for the years 2013-2022. A temporal validation was performed on data from 2023. Ten high-mortality subgroups were identified. Reduced urine output and a low combined score on the eye & motor components of the Glasgow Coma Scale (GCS) were the most common risk factors defining high-mortality subgroups. External validation showed small deviations in mortality (median absolute deviations -1% and -2%), with one subgroup falling below the 80% mortality threshold. Interpretable machine learning can identify ICU patient subgroups with ≥80% 6-month mortality using routinely collected data. These groups are predominantly marked by impaired consciousness and reduced urine output. Future work should integrate these insights into ethical, patient-centered frameworks that support appropriate care.
To identify latent profiles of change fatigue among nurses in Southwestern China and explore factors associated with distinct profiles. Healthcare resources in Southwestern China are unevenly distributed, and the region features considerable ethnic diversity. Against the backdrop of ongoing reforms in the healthcare system, nurses-as frontline implementers-are constantly exposed to intensive and frequent updates in policies, technologies, and workflows, making them susceptible to change fatigue. This sustained exposure precipitates "change fatigue," a syndrome that erodes psychological resilience and professional identity, and is prospectively linked to heightened turnover intention, measurable deterioration in nursing quality and an increased incidence of patient-safety events. From July to September 2025, we recruited nurses from various tiers and types of medical institutions across Southwestern China. Data were collected using a general information questionnaire, the Change-Related Stress Scale, the Grandey Emotional Labor Strategy Scale, the Connor-Davidson Resilience Scale (CD-RISC), and the Chinese Nurse Job Stressors Scale. Latent profile analysis (LPA) was employed to identify subgroups of change fatigue. Univariate analysis and multinomial logistic regression with Firth's penalized likelihood estimation were used to examine factors associated with profile membership. A total of 1383 valid questionnaires were included. LPA revealed three distinct profiles of change fatigue: low fatigue (17.5%, n = 242), moderate fatigue (61.6%, n = 852), and high fatigue (20.9%, n = 289). Multinomial logistic regression showed that nurses in the high fatigue group were significantly more likely to work in the intensive care unit (OR = 2.31, 95% CI: 1.40-3.85, p = 0.001) and internal medicine (OR = 2.12, 95% CI: 1.26-3.61, p = 0.005). Working 1-2 night shifts per week increased odds of high fatigue by 53% (OR = 1.53, 95% CI: 1.03-2.27, p = 0.034). Compared with minimal emotional labor (Level 1, 14-30 points), both moderate (Level 2, 31-50 points: OR = 0.14, p = 0.030) and high (Level 3, 51-70 points: OR = 0.09, p = 0.010) emotional labor levels were associated with significantly lower odds of high fatigue, suggesting that deficient emotional labor engagement may represent a risk configuration. Work stress Level 3 increased odds of high fatigue 33-fold (OR = 32.71, 95% CI: 13.27-103.37, p < 0.001). Psychological resilience showed no independent significant association with profile membership in multivariate models. Change fatigue exhibits a heterogeneous tripartite structure. Minimal emotional labor engagement (Level 1) was associated with higher odds of high fatigue compared with moderate and high levels, suggesting that deficient emotional labor may represent a distinct risk configuration. Both modifiable workplace factors (ICU/internal medicine placement, night shifts, and job stress) and emotional labor patterns were associated with profile membership, supporting the potential value of organizational interventions and targeted emotional labor training. These findings provide an evidence-based foundation for precision prevention. Nursing leaders should integrate the six-item Change Fatigue Measurement Scale into routine occupational health surveillance to enable profile-based risk stratification. High-fatigue nurses (20.9%) require immediate workload relief and mental health referral; moderate-fatigue nurses (61.6%) represent a critical prevention window for resilience training and peer support; low-fatigue nurses (17.5%) should serve as peer mentors and change champions. Priority interventions should target ICU and internal medicine units given the 2- to 2.3-fold increased high-fatigue risk. Leaders should limit consecutive night duties to ≤ 2 shifts, ensure ≥ 11 h rest between shifts, and enforce weekly overtime caps (≤ 8 h). Differentiated emotional labor training is essential: Nurses with minimal engagement need professional identity strengthening and authentic expression workshops, while those with excessive engagement require boundary-setting training and mindfulness-based stress reduction. Resilience-building interventions must be embedded within organizational support initiatives rather than implemented as standalone programs. In ethnically diverse, resource-constrained contexts, culturally tailored change communications and phased implementation timelines are critical to avoid "reform stacking."
Variability in glycemic (GV) and systolic blood pressure (SBPV) are independent risk factors for adverse outcomes in stroke. However, their combined impact on mortality in stroke patients requiring intensive care remains unclear. This study aimed to evaluate the individual and additive effects of short-term GV and SBPV on mortality in critically ill stroke patients. We retrospectively analyzed hemorrhagic and ischemic stroke patients from the Medical Information Mart for Intensive Care IV database. GV and SBPV were calculated as the coefficient of variation from all glucose and systolic blood pressure measurements within the first 72 hours of intensive care unit admission. High variability was defined as the highest tertile. The additive effect was assessed by the number of high-variability parameters and a composite variability score (0-4). The study included 2659 hemorrhagic and 3606 ischemic stroke patients. After full adjustment, the highest GV tertile was associated with significantly increased 28-day mortality (Hemorrhagic: hazard ratio [HR] = 1.84, 95% confidence interval [CI] 1.38-2.44; Ischemic: HR = 1.35, 95% CI 1.08-1.70). Similarly, the highest SBPV tertile was associated with higher mortality (Ischemic: HR = 1.67, 95% CI 1.35-2.06). Most importantly, patients with both high GV and high SBPV had the most significant risk, with adjusted HRs of 2.51 (95% CI 1.89-3.33) for 28-day mortality in hemorrhagic stroke and 2.01 (95% CI 1.57-2.58) in ischemic stroke. A graded, dose-response relationship was observed between increasing variability score and mortality risk (P for trend < .001). Short-term GV and SBPV during intensive care unit stay are independent and additive predictors of mortality in critically ill stroke patients. Stabilizing these parameters may be a potential therapeutic target to improve outcomes.
Previous studies suggest an increased risk of new-onset type 2 diabetes (T2D) following SARS-CoV-2 infection, which may be subject to detection bias from increased health care contacts among the infected. We aimed to assess the causal effect of SARS-CoV-2 infection on new-onset T2D using a test-negative design and negative control outcomes. We included all individuals aged ≥ 18 years registered in Sweden on 1 February 2020 without prior T2D who ordered a SARS-CoV-2 test through the Swedish healthcare service between 1 February 2020 and 28 February 2022 (N = 3,175,958). A test-negative design was applied, matching infected individuals with up to five controls based on birth year, sex, region, vaccination status, and test date. Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between infection and new-onset T2D. The influence of COVID-19 severity was assessed using stratified Cox regression. Negative control outcomes anaemia, chronic kidney disease, and thyroid disorder were used to evaluate detection bias. SARS-CoV-2 infection was associated with a 12% (HR 1.12, 95% CI 1.04-1.20) increase in T2D risk, driven by elevated incidence during weeks 1-4 post-infection. Increased risk was concentrated among individuals hospitalized (HR 3.60, 95% CI 2.71-4.78) or admitted to intensive care (HR 4.85, 95% CI 2.60-9.05). Negative control outcomes showed similar patterns. Our findings do not support a causal effect of SARS-CoV-2 infection on new-onset T2D. Instead, observed increases appear largely attributable to increased detection of early-phase, sub-clinical T2D cases during hospitalization or intensive care.
暂无摘要（点击查看详情）
The association between early magnesium sulfate administration and outcomes in sepsis remains incompletely understood, particularly in relation to differences in systemic immune-inflammatory status. In this retrospective cohort study using Medical Information Mart for Intensive Care IV (version 3.1), adult critically ill patients with sepsis were included. Systemic immune-inflammation index (SII) was calculated from platelet, neutrophil, and lymphocyte counts obtained within a peri-intensive care unit window (6 hours before to 24 hours after intensive care unit admission). Early magnesium administration was defined as intravenous magnesium sulfate initiated within the same window. The primary outcome was 30-day all-cause mortality. Propensity score matching was performed to balance baseline characteristics. Associations were examined overall and across SII quartiles using stratified multivariable Cox proportional hazards models, with nonlinear relationships explored using restricted cubic splines. Among 12,087 patients, 6039 received early intravenous magnesium. After propensity score matching, 3396 matched pairs were analyzed. Early magnesium administration was associated with lower 30-day mortality overall (15.8% vs 18.3%, P = .007). In stratified analyses, adjusted hazard ratios were 0.66 (95% confidence interval: 0.51-0.87), 0.65 (0.49-0.85), 0.75 (0.59-0.94), and 0.85 (0.70-1.04) across quartiles 1 to 4. Restricted cubic spline analyses showed descriptive attenuation at higher SII values (P for interaction = .208), without evidence of a statistically definitive interaction. Early magnesium administration was associated with lower 30-day mortality in critically ill patients with sepsis. Although formal interaction testing did not reach statistical significance, adjusted hazard ratios showed a descriptive gradient of attenuation across increasing SII quartiles, directionally consistent across sensitivity analyses. These findings are hypothesis-generating and require prospective validation.
Immersive virtual reality proved effective in pediatric procedural pain and anxiety management, yet the extent to which age modifies these effects remains uncertain. Notably, the two most recent and widely cited meta-analyses (Eijlers et al., 2019 and Tas et al., 2022) reported conflicting conclusions. We performed a Bayesian meta-reanalysis of the above mentioned meta-analyses. We extracted standardized mean differences (SMD) for pain (n = 21) and anxiety (n = 10), plus study-level age, sex distribution, quality score, and procedure type. Primary outcomes were pooled SMDs; the secondary outcome was the age effect estimated with a Bayesian random-effects meta-regression. We report pooled effects, age slope (ΔSMD/year), heterogeneity, 95% credible intervals (CrI), and posterior probabilities (P[β_age>0]). Virtual reality is strongly associated with reductions in both pain (SMD -0.69, CrI -0.93 to -0.47) and anxiety (SMD -0.75, CrI -1.05 to -0.49). Age was associated with variation in effect size for both pain: 0.10 ΔSMD/year (CrI 0.02-0.19; P[βage > 0] = 0.988), and anxiety: 0.13 ΔSMD/year (CrI 0.02-0.25; P[βage > 0] = 0.991), indicating attenuation of benefit with increasing age. Immersive virtual reality proves effective in pediatric procedural pain and anxiety management, with benefits diminishing with increasing age. Bayesian evidence synthesis should be increasingly applied to pediatric research, where studies are small and highly heterogeneous. Immersive virtual reality significantly reduces procedural pain and anxiety in children, but its effectiveness decreases with increasing age. This Bayesian meta-reanalysis reconciles conflicting findings from prior frequentist meta-analyses, showing that age is a key determinant of non-pharmacological pain management efficacy. Findings advocate for age-specific implementation of immersive virtual reality and encourage adoption of Bayesian evidence synthesis methods to better inform pediatric clinical guidelines where studies are small and heterogeneous.
Hypertensive disorders of pregnancy, particularly preeclampsia, are a leading cause of maternal and perinatal morbidity. While antihypertensive therapy is recommended, clinical uncertainty persists regarding the optimal agent to maximize maternal safety while minimizing adverse neonatal outcomes such as neonatal intensive care unit (NICU) admission. This review aimed to evaluate the comparative effectiveness and safety of pharmacological antihypertensive agents versus standard care or placebo in the management of hypertensive disorders of pregnancy through a network meta-analysis (NMA). A systematic review and frequentist random-effects NMA of randomized controlled trials (RCTs) was conducted. Major databases were searched for RCTs comparing antihypertensive agents (labetalol, nifedipine, methyldopa, hydralazine, prazosin) and controls. The primary neonatal outcome evaluated in this network was NICU admission. Risk of bias was assessed using the Cochrane RoB 2 tool, and the certainty of evidence was evaluated using the GRADE framework. Twenty-five RCTs were included in the qualitative and quantitative synthesis. The network geometry was anchored by labetalol and nifedipine. In the NMA, no individual antihypertensive agent demonstrated a statistically significant reduction in the risk of NICU admission compared to labetalol. However, probabilistic ranking (P-scores) identified methyldopa (P-score = 0.859) and hydralazine (0.791) as the most favourable interventions for minimizing NICU admissions. Nifedipine showed a slightly elevated, though non-significant, risk profile compared to labetalol (RR 1.09, 95% CI 0.80-1.49). The placebo and standard care ranked lowest. The overall certainty of evidence ranged from moderate to very low due to imprecision and indirectness. Active pharmacological management of hypertension in pregnancy is superior to placebo or standard care. While labetalol and nifedipine remain mainstays for acute blood pressure control, methyldopa and hydralazine probabilistically rank higher for minimizing NICU admissions. These findings support individualized antihypertensive selection based on clinical acuity and maternal-fetal hemodynamics.