Multimodal Prediction of 3- and 12-Month Outcomes in ICU Patients with Acute Disorders of Consciousness.

BACKGROUND: In intensive care unit (ICU) patients with coma and other disorders of consciousness (DoC), outcome prediction is key to decision-making regarding prognostication, neurorehabilitation, and management of family expectations. Current prediction algorithms are largely based on chronic DoC, whereas multimodal data from acute DoC are scarce. Therefore, the Consciousness in Neurocritical Care Cohort Study Using Electroencephalography and Functional Magnetic Resonance Imaging (i.e. CONNECT-ME; ClinicalTrials.gov identifier: NCT02644265) investigates ICU patients with acute DoC due to traumatic and nontraumatic brain injuries, using electroencephalography (EEG) (resting-state and passive paradigms), functional magnetic resonance imaging (fMRI) (resting-state) and systematic clinical examinations. METHODS: We previously presented results for a subset of patients (n = 87) concerning prediction of consciousness levels in the ICU. Now we report 3- and 12-month outcomes in an extended cohort (n = 123). Favorable outcome was defined as a modified Rankin Scale score ≤ 3, a cerebral performance category score ≤ 2, and a Glasgow Outcome Scale Extended score ≥ 4. EEG features included visual grading, automated spectral categorization, and support vector machine consciousness classifier. fMRI features included functional connectivity measures from six resting-state networks. Random forest and support vector machine were applied to EEG and fMRI features to predict outcomes. Here, random forest results are presented as areas under the curve (AUC) of receiver operating characteristic curves or accuracy. Cox proportional regression with in-hospital death as a competing risk was used to assess independent clinical predictors of time to favorable outcome. RESULTS: Between April 2016 and July 2021, we enrolled 123 patients (mean age 51 years, 42% women). Of 82 (66%) ICU survivors, 3- and 12-month outcomes were available for 79 (96%) and 77 (94%), respectively. EEG features predicted both 3-month (AUC 0.79 [95% confidence interval (CI) 0.77-0.82]) and 12-month (AUC 0.74 [95% CI 0.71-0.77]) outcomes. fMRI features appeared to predict 3-month outcome (accuracy 0.69-0.78) both alone and when combined with some EEG features (accuracies 0.73-0.84) but not 12-month outcome (larger sample sizes needed). Independent clinical predictors of time to favorable outcome were younger age (hazard ratio [HR] 1.04 [95% CI 1.02-1.06]), traumatic brain injury (HR 1.94 [95% CI 1.04-3.61]), command-following abilities at admission (HR 2.70 [95% CI 1.40-5.23]), initial brain imaging without severe pathological findings (HR 2.42 [95% CI 1.12-5.22]), improving consciousness in the ICU (HR 5.76 [95% CI 2.41-15.51]), and favorable visual-graded EEG (HR 2.47 [95% CI 1.46-4.19]). CONCLUSIONS: Our results indicate that EEG and fMRI features and readily available clinical data predict short-term outcome of patients with acute DoC and that EEG also predicts 12-month outcome after ICU discharge.

Glycaemic control for patients with severe acute brain injury: Protocol for a systematic review.

BACKGROUND: Hyperglycaemia is common in patients with acute brain injury admitted to an intensive care unit (ICU). Many studies have found associations between development of hyperglycaemia and increased mortality in hospitalised patients. However, the optimal target for blood glucose control is unknown. We want to conduct a systematic review with meta-analysis and trial sequential analysis to explore the beneficial and harmful effects of restrictive versus liberal glucose control on patient outcomes in adults with severe acute brain injury. METHODS: We will systematically search medical databases including CENTRAL, Embase, MEDLINE and trial registries. We will search the following websites for ongoing or unpublished trials: http://www.controlled-trials.com/, http://www. CLINICALTRIALS: gov/, www.eudraCT.com, http://centerwatch.com/, The Cochrane Library's CENTRAL, PubMed, EMBASE, Science Citation Index Expanded and CINAHL. Two authors will independently review and select trials and extract data. We will include randomised trials comparing levels of glucose control in our analyses and observational studies will be included to address potential harms. The primary outcomes are defined as all-cause mortality, functional outcome and health-related quality of life. Secondary outcomes include serious adverse events including hypoglycaemia, length of ICU stay and duration of mechanical ventilation, and explorative outcomes including intracranial pressure and infection. Trial Sequential Analysis will be used to investigate the risk of type I error due to repetitive testing and to further explore imprecision. Quality of trials will be evaluated using the Cochrane Risk of Bias tool, and quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. DISCUSSION: The results of the systematic review will be disseminated through peer-reviewed publication. With the review, we hope to inform future randomised clinical trials and improve clinical practice.

Hospitalisation in short-stay units for adults with internal medicine diseases and conditions.

BACKGROUND: Short-stay units are hospital units that provide short-term care for selected patients. Studies have indicated that short-stay units might reduce admission rates, time of hospital stays, hospital readmissions and expenditure without compromising the quality of care. Short-stay units are often defined by a target patient category, a target function, and a target time frame. Hypothetically, short-stay units could be established as part of any department, but this review focuses on short-stay units that provide care for participants with internal medicine diseases and conditions. OBJECTIVES: To assess beneficial and harmful effects of short-stay unit hospitalisation compared with usual care in people with internal medicine diseases and conditions. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three other databases and two trials registers up to 13 December 2017 together with reference checking, citation searching and contact with study authors to identify additional studies. We also searched several grey literature sources and performed a forward citation search for included studies. SELECTION CRITERIA: We included randomised trials and cluster-randomised trials, comparing hospitalisation in a short-stay unit with usual care (hospitalisation in a traditional hospital ward or other services). We defined a short-stay unit to be a hospital ward where the targeted length of stay in hospital for patients was five days or less. We included both multipurpose and specialised short-stay units. Participants were adults admitted to hospital with an internal medicine disease or condition. We excluded surgical, obstetric, psychiatric, gynaecological, and ambulatory participants. Trials were included irrespective of publication status, date, and language. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently extracted data and assessed the risk of bias of each included trial. We measured intervention effect sizes by meta-analyses for two primary outcomes, mortality and serious adverse events, and one secondary outcome, hospital readmission. We narratively reported the following important outcomes: quality of life, activities of daily living, non-serious adverse events, and costs. We used risk ratio differences of 15% for mortality and of 20% for serious adverse events for minimal relevant clinical consideration. We rated the certainty of the evidence and the strength of recommendations of the outcomes using the GRADE approach. MAIN RESULTS: We included 19 records reporting on 14 randomised trials with a total of 2872 participants. One trial was ongoing. Thirteen trials evaluated short-stay unit hospitalisation for six specific conditions (acute decompensated heart failure (one trial), asthma (one trial), atrial fibrillation (one trial), chest pain (seven trials), syncope (two trials), and transient ischaemic attack (one trial)) and one trial investigated participants presenting with miscellaneous internal medicine disease and conditions. The components of the intervention differed among the trials as dictated by the trial participants' condition. All included trials were at high risk of bias.The certainty of the evidence for all outcomes was very low. Consequently, it is uncertain whether hospitalisation in short-stay units compared with usual care reduces mortality (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.47 to 1.15) 5 trials (seven additional trials reporting on 1299 participants reported no deaths in either group)); serious adverse events (RR 0.95, 95% CI 0.59 to 1.54; 7 trials (one additional trial with 108 participants reported no serious adverse events in either group)), and hospital readmission (RR 0.80, 95% CI 0.54 to 1.19, 8 trials (one additional trial with 424 participants did not report results for participants)). There was not enough information to confirm or refute that short-stay unit hospitalisation had relevant effects on quality of life, activities of daily living, non-serious adverse events, and costs. AUTHORS' CONCLUSIONS: Overall, the quantity and the certainty of the evidence was very low. Consequently, it is uncertain whether there are any beneficial or harmful effects of short-stay unit hospitalisation for adults with internal medicine diseases and conditions - more trials comparing the effects of short-stay units with usual care are needed. Such trials ought to be conducted with low risk of bias and low risks of random errors to improve the overall confidence in the evidence.

Dose-related beneficial and harmful effects of gabapentin in postoperative pain management - post hoc analyses from a systematic review with meta-analyses and trial sequential analyses.

BACKGROUND: During the last 15 years, gabapentin has become an established component of postoperative pain treatment. Gabapentin has been employed in a wide range of doses, but little is known about the optimal dose, providing the best balance between benefit and harm. This systematic review with meta-analyses aimed to explore the beneficial and harmful effects of various doses of gabapentin administered to surgical patients. MATERIALS AND METHODS: Data in this paper were derived from an original review, and the subgroup analyses were predefined in an International Prospective Register of Systematic Reviews published protocol: PROSPERO (ID: CRD42013006538). The methods followed Cochrane guidelines. The Cochrane Library's CENTRAL, PubMed, EMBASE, Science Citation Index Expanded, Google Scholar, and FDA database were searched for relevant trials. Randomized clinical trials comparing gabapentin versus placebo were included. Four different dose intervals were investigated: 0-350, 351-700, 701-1050, and >1050 mg. Primary co-outcomes were 24-hour morphine consumption and serious adverse events (SAEs), with emphasis put on trials with low risk of bias. RESULTS: One hundred and twenty-two randomized clinical trials, with 8466 patients, were included. Sixteen were overall low risk of bias. No consistent increase in morphine-sparing effect was observed with increasing doses of gabapentin from the trials with low risk of bias. Analyzing all trials, the smallest and the highest dose subgroups demonstrated numerically the most prominent reduction in morphine consumption. Twenty-seven trials reported 72 SAEs, of which 83% were reported in the >1050 mg subgroup. No systematic increase in SAEs was observed with increasing doses of gabapentin. CONCLUSION: Data were sparse, and the small number of trials with low risk of bias is a major limitation for firm conclusions. Taking these limitations into account, we were not able to demonstrate a clear relationship between the dosage of gabapentin and opioid-sparing or harmful effects. These subgroup analyses are exploratory and hypothesis-generating for future trialists.

Gabapentin in procedure-specific postoperative pain management - preplanned subgroup analyses from a systematic review with meta-analyses and trial sequential analyses.

BACKGROUND: It has been argued that postoperative pain treatment should be "procedure-specific", since different analgesics may have specific effects dependent on the surgical procedure. The aim of the present subgroup analysis was to compare the beneficial and harmful effects of perioperative gabapentin treatment in different surgical procedures. METHODS: Relevant databases were searched for randomized clinical trials (RCTs) comparing gabapentin versus placebo. Two authors independently screened titles and abstracts, extracted data and assessed risk of bias. The primary outcomes were differences in 24-h morphine consumption, and serious adverse events (SAE) between surgical procedures. These subgroup analyses were predefined in a PRISMA compliant systematic review registered at PROSPERO (ID: CRD42013006538). It was predefined that conclusions should primarily be based on trials classified as overall low risk of bias. RESULTS: Seventy-four RCTs with 5645 patients were included, assessing benefit and harm in cholecystectomy, hysterectomy, mastectomy, and arthroplasty surgery, spinal surgery, and thoracic surgery. Only eight of 74 trials were classified as overall low risk of bias limiting our ability to conclude on the estimates in most meta-analyses. The differences between surgical procedures in these trials were not statistically significant when tested for subgroup differences. Fifteen trials with 1377 patients reported a total of 59 SAEs, most of which were observed in the thoracic surgery group. CONCLUSION: Both beneficial and harmful effects in these subgroup analyses were influenced by bias and insufficient data, limiting conclusions. With these limitations, we could not adequately test for differences in beneficial or harmful outcomes between six surgical subgroups undergoing perioperative gabapentin treatment.

Effect of Total Dose of Lidocaine on Duration of Adductor Canal Block, Assessed by Different Test Methods: A Report of Two Blinded, Randomized, Crossover Studies in Healthy Volunteers.

BACKGROUND: The binary aims of this study were to investigate the effect of total dose of lidocaine on duration of an adductor canal block (ACB) and to validate different methods used to assess nerve blocks. METHODS: We performed 2 blinded, randomized, controlled crossover trials, including healthy, young men. In study 1, 14 subjects received 4 ACBs with saline and 40, 80, and 160 mg lidocaine. In study 2, 14 new subjects received 2 ACBs with 100 and 300 mg lidocaine. We kept volume constant at 20 mL for all blocks, only altering concentration. ACB duration was assessed every hour postblock using mechanical (primary outcome) and temperature discrimination; warmth and heat pain detection thresholds; pain during heat stimulation; and tolerance to electrical current in the saphenous distribution. Finally, we measured quadriceps femoris muscle strength (clinical trial registration: NCT02172729). RESULTS: In study 1, block duration assessed by mechanical discrimination differed significantly when comparing the 40-mg dose with the 80-mg dose (mean difference, 1.15 hours; 99% confidence interval [CI], 0.38-2.09 hours) and with the 160-mg dose (mean difference, 0.92 ours; 99% CI, 0.17-1.62). However, there was no difference between the 80-mg and 160-mg doses (mean difference, -0.23 hour; 99% CI, -1.12 to 0.46 hours). Neither for the secondary outcomes were there any differences between the 80- and 160-mg doses (99% CI including 0). Because of 38% (5/13) failed blocks in the 40-mg group, we decided to perform study 2. In study 2, all but 1 test showed no difference in duration despite a 3-fold increase in dose. The temperature discrimination test showed 100% sensitivity and specificity for differentiating between the presence and absence of block and was the only test with scores >90% for both parameters. CONCLUSIONS: We did not find evidence that increasing the total dose of lidocaine may prolong duration of an ACB. The temperature discrimination test was the only test with scores >90% for both specificity and sensitivity.

Adductor Canal Block With 10 mL Versus 30 mL Local Anesthetics and Quadriceps Strength: A Paired, Blinded, Randomized Study in Healthy Volunteers.

BACKGROUND AND OBJECTIVES: Adductor canal block (ACB) is predominantly a sensory nerve block, but excess volume may spread to the femoral triangle and reduce quadriceps strength. We hypothesized that reducing the local anesthetic volume from 30 to 10 mL may lead to fewer subjects with quadriceps weakness. METHODS: We performed a paired, blinded, randomized trial including healthy men. All subjects received bilateral ACBs with ropivacaine 0.1%; 10 mL in 1 leg and 30 mL in the other leg. The primary outcome was the difference in number of subjects with quadriceps strength reduced by more than 25% from baseline in 2 consecutive assessments. Secondary outcomes were quadriceps strength as a percentage of baseline at predefined time points, functional outcome assessed by the 30-Second Chair Stand Test (1 leg at a time), and sensory block. Clinicaltrials.gov Identifier: NCT01981746. RESULTS: We included and analyzed 26 subjects. For either volume, 2 subjects had a reduction in quadriceps strength by more than 25% from baseline (difference, 0%; 95% confidence interval, -13 to 13; P > 0.999). Similarly, we found no significant differences between volumes in quadriceps strength at any of the predefined time points or in sensory block. The only statistically significant difference between volumes was found in the 30-Second Chair Stand Test at 2 hours (P = 0.02), but this difference had disappeared at 4 hours (P = 0.06). CONCLUSIONS: Varying the volume of ropivacaine 0.1% used for ACB between 10 and 30 mL did not have a statistically significant or clinically relevant impact on quadriceps strength.

Imperfect implementation of an early warning scoring system in a Danish teaching hospital: a cross-sectional study.

BACKGROUND: In 2007, the initiation of a patient safety campaign led to the introduction of Ward Observational Charts (WOC) and Medical Early Warning Score (MEWS) at Naestved Regional Hospital. This included systematic measuring of vital signs of all patients in order to prevent patient deterioration and assure timely and correct initiation of treatment. The aim of this study was to assess to what degree WOC guidelines being followed by ward staff. DESIGN AND SETTING: A 7-day prospective, observational, randomised, cross-sectional, point prevalence study of WOC guideline compliance in hospitalised patients on twelve wards at Naestved Hospital. RESULTS: The study included 132 patients. Of these, 58% had been observed and managed correctly according to WOC guidelines. 77% had all MEWS elements recorded by staff. One patient had no MEWS elements recorded. Only 38% of patients with abnormal MEWS were correctly escalated by nursing staff. Staff was aware of the abnormal MEWS observed by investigator in 60% of the patients. Each element of WOC was on average recorded by staff in 90% of the patients. CONCLUSION: At the time of our study, the long-term implementation of WOC guidelines has not been completed satisfactorily. The lacking component in the implementation of MEWS and WOC is the documentation of action taken upon finding an abnormal value. Unsuccessful implementation could result in incorrect results from evaluation of an early warning system. We suggest a redesign of the training programme to educate staff in recognising and caring for critically ill patients at Naestved Hospital.