J. Carel Goslings

Cortisol, interleukins and S100B in delirium in the elderly.

In independent studies delirium was associated with higher levels of cortisol, interleukin(IL)s, and S100B. The aim of this study was to simultaneously compare cortisol, IL-6, IL-8, and S100B levels in patients aged 65years and older admitted for hip fracture surgery with and without delirium. Cortisol, IL-6, IL-8, and S100B were assayed in repeated blood samples. 120 patients (mean age 84years, 62 patients with delirium) were included. Highest levels of IL-8 (27.1, 95% Confidence Interval (CI): 13.6-53.1pg/ml) and cortisol (666, 95% CI: 475-859nmol/L) were before delirium, but of IL-6 (84.3, 95% CI: 46.5-151.4pg/mL) and S100B (0.18, 95% CI: 0.12-0.24 microg/L) during delirium. In multivariable analysis cortisol, LogIL-6, and LogS100B were significantly associated with delirium, but adjusted for pre-existing cognitive impairment, only LogS100B remained significantly associated. Cortisol, IL-6 and S100B may have a role in the pathogenesis of delirium, but S100B is the strongest independent marker.

Reappraising the concept of massive transfusion in trauma

IntroductionThe massive-transfusion concept was introduced to recognize the dilutional complications resulting from large volumes of packed red blood cells (PRBCs). Definitions of massive transfusion vary and lack supporting clinical evidence. Damage-control resuscitation regimens of modern trauma care are targeted to the early correction of acute traumatic coagulopathy. The aim of this study was to identify a clinically relevant definition of trauma massive transfusion based on clinical outcomes. We also examined whether the concept was useful in that early prediction of massive transfusion requirements could allow early activation of blood bank protocols.MethodsDatasets on trauma admissions over a 1 or 2-year period were obtained from the trauma registries of five large trauma research networks. A fractional polynomial was used to model the transfusion-associated probability of death. A logistic regression model for the prediction of massive transfusion, defined as 10 or more units of red cell transfusions, was developed.ResultsIn total, 5,693 patient records were available for analysis. Mortality increased as transfusion requirements increased, but the model indicated no threshold effect. Mortality was 9% in patients who received none to five PRBC units, 22% in patients receiving six to nine PRBC units, and 42% in patients receiving 10 or more units. A logistic model for prediction of massive transfusion was developed and validated at multiple sites but achieved only moderate performance. The area under the receiver operating characteristic curve was 0.81, with specificity of only 50% at a sensitivity of 90% for the prediction of 10 or more PRBC units. Performance varied widely at different trauma centers, with specificity varying from 48% to 91%.ConclusionsNo threshold for definition exists at which a massive transfusion specifically results in worse outcomes. Even with a large sample size across multiple trauma datasets, it was not possible to develop a transportable and clinically useful prediction model based on available admission parameters. Massive transfusion as a concept in trauma has limited utility, and emphasis should be placed on identifying patients with massive hemorrhage and acute traumatic coagulopathy.

Accidental hypothermia: Rewarming treatments, complications and outcomes from one university medical centre

AIM OF THE STUDY Accidental hypothermia (AH) is a complex and life threatening condition. Knowledge about epidemiology, rewarming treatments, complications and outcome is limited. This study was initiated to obtain data on causes, rewarming treatments and complications. METHODS A retrospective cohort study of all patients with a body temperature ≤ 35°C admitted to the Emergency Department (ED) of the VU university medical centre, Amsterdam, The Netherlands, between January 1, 2000 and August 31, 2008. A predefined set of epidemiological and clinical data was retrieved. RESULTS Eighty-four patients were included (median age: 47 years). Categories of hypothermia included immersion (18), submersion (29) and exposure to cold (37); concomitant factors were intoxication (26), trauma (40) and homelessness (7). Temperature at admission in the ED was 31.6 ± 2.6°C (mean ± SD), lowest temperature 24.2°C. Fourteen different rewarming treatments were used resulting in a wide range of rewarming speeds. Seventy-nine complications occurred: pulmonary, renal and neurological complications in 20, 17 and 10 patients respectively. Seventeen patients had 2 or more late complications. Twenty-four patients (28.6%) died: 10 during rewarming and 14 after rewarming was completed. Prognosis was poor in older and colder patients and after indoor exposure and submersion. CONCLUSION AH is a rare diagnosis in an inhomogeneous population, treated with a large variety of rewarming techniques. Most complications and death occurred late, after rewarming was completed. Because individual teams gain little clinical experiences, we suggest multiple centre data collection as a first step towards an evidence-based standard of care.

Effect of melatonin on incidence of delirium among patients with hip fracture: a multicentre, double-blind randomized controlled trial

Background: Disturbance of the sleep–wake cycle is a characteristic of delirium. In addition, changes in melatonin rhythm influence the circadian rhythm and are associated with delirium. We compared the effect of melatonin and placebo on the incidence and duration of delirium. Methods: We performed this multicentre, double-blind, randomized controlled trial between November 2008 and May 2012 in 1 academic and 2 nonacademic hospitals. Patients aged 65 years or older who were scheduled for acute hip surgery were eligible for inclusion. Patients received melatonin 3 mg or placebo in the evening for 5 consecutive days, starting within 24 hours after admission. The primary outcome was incidence of delirium within 8 days of admission. We also monitored the duration of delirium. Results: A total of 452 patients were randomly assigned to the 2 study groups. We subsequently excluded 74 patients for whom the primary end point could not be measured or who had delirium before the second day of the study. After these postrandomization exclusions, data for 378 patients were included in the main analysis. The overall mean age was 84 years, 238 (63.0%) of the patients lived at home before admission, and 210 (55.6%) had cognitive impairment. We observed no effect of melatonin on the incidence of delirium: 55/186 (29.6%) in the melatonin group v. 49/192 (25.5%) in the placebo group; difference 4.1 (95% confidence interval −0.05 to 13.1) percentage points. There were no between-group differences in mortality or in cognitive or functional outcomes at 3-month follow-up. Interpretation: In this older population with hip fracture, treatment with melatonin did not reduce the incidence of delirium. Trial registration: Netherlands Trial Registry, NTR1576: MAPLE (Melatonin Against PLacebo in Elderly patients) study; www.trialregister.nl/trialreg/admin/rctview.asp?TC=1576

The effects of melatonin versus placebo on delirium in hip fracture patients: study protocol of a randomised, placebo-controlled, double blind trial

BackgroundWith an ageing population, older persons become a larger part of the hospital population. The incidence of delirium is high in this group, and experiencing delirium has major short- and long-term sequelae, which makes prevention crucial. During delirium, a disruption of the sleep-wake cycle is frequently observed. Melatonin plays an important role in the regulation of the sleep-wake cycle, so this raised the hypothesis that alterations in the metabolism of melatonin might play an important role in the development of delirium. The aim of this article is to describe the design of a randomised, placebo controlled double-blind trial that is currently in progress and that investigates the effects of melatonin versus placebo on delirium in older, postoperative hip fracture patients.Methods/DesignAcutely hospitalised patients aged 65 years or older admitted for surgical repair of hip fracture are randomised (n = 452) into a treatment or placebo group. Prophylactic treatment consists of orally administered melatonin (3 mg) at 21:00 h on five consecutive days. The primary outcome is the occurrence of delirium, to be diagnosed according to the Confusion Assessment Method, within eight days after start of the study medication. Secondary outcomes are delirium severity, measured by the Delirium Rating Scale; duration of delirium; differences in subtypes of delirium; differences in total length of hospital stay; total dose of antipsychotics and/or benzodiazepine use during delirium; and in-hospital complications. In the twelve-month follow up visit, cognitive function is measured by a Mini-Mental state examination and the Informant Questionnaire on Cognitive Decline in the Elderly. Functional status is assessed with the Katz ADL index score (patient and family version) and grip strength measurement. The outcomes of these assessments are compared to the outcomes that were obtained during admission.DiscussionThe proposed study will contribute to our knowledge because studies on the prophylactic treatment of delirium with long term follow up remain scarce. The results may lead to a prophylactic treatment for frail older persons at high risk for delirium that is safe, effective, and easily implementable in daily practice.Trial registrationDutch Clinical Trial Registry: NTR1576

Clinical Relevance of Routinely Measured Vital Signs in Hospitalized Patients: A Systematic Review

BACKGROUND Conflicting evidence exists on the effectiveness of routinely measured vital signs on the early detection of increased probability of adverse events. PURPOSE To assess the clinical relevance of routinely measured vital signs in medically and surgically hospitalized patients through a systematic review. DATA SOURCES MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature, and Meta-analysen van diagnostisch onderzoek (in Dutch; MEDION) were searched to January 2013. STUDY SELECTION Prospective studies evaluating routine vital sign measurements of hospitalized patients, in relation to mortality, septic or circulatory shock, intensive care unit admission, bleeding, reoperation, or infection. DATA EXTRACTION Two reviewers independently assessed potential bias and extracted data to calculate likelihood ratios (LRs) and predictive values. DATA SYNTHESIS Fifteen studies were performed in medical (n = 7), surgical (n = 4), or combined patient populations (n = 4; totaling 42,565 participants). Only three studies were relatively free from potential bias. For temperature, the positive LR (LR+) ranged from 0 to 9.88 (median 1.78; n = 9 studies); heart rate 0.82 to 6.79 (median 1.51; n = 5 studies); blood pressure 0.72 to 4.7 (median 2.97; n = 4 studies); oxygen saturation 0.65 to 6.35 (median 1.74; n = 2 studies); and respiratory rate 1.27 to 1.89 (n = 3 studies). Overall, three studies reported area under the Receiver Operator Characteristic (ROC) curve (AUC) data, ranging from 0.59 to 0.76. Two studies reported on combined vital signs, in which one study found an LR+ of 47.0, but in the other the AUC was not influenced. CONCLUSIONS Some discriminative LR+ were found, suggesting the clinical relevance of routine vital sign measurements. However, the subject is poorly studied, and many studies have methodological flaws. Further rigorous research is needed specifically intended to investigate the clinical relevance of routinely measured vital signs. CLINICAL RELEVANCE The results of this research are important for clinical nurses to underpin daily routine practices and clinical decision making.

Long-term outcomes of corrective osteotomy for the treatment of distal radius malunion.

Corrective osteotomy is an established but challenging treatment for distal radius malunion. Short- and intermediate-term results have been previously published while long-term results have not. The long-term results of 22 patients treated with corrective osteotomy for symptomatic distal radius malunion are presented (range 6—24 years, mean 13 years). All patients completed the DASH questionnaire and the modified Gartland and Werley, and Green and O’Brien scores postoperatively. Wrist alignment was assessed through standard wrist radiographs. Average wrist flexion—extension was 72.5% of the contralateral limb. Grip strength averaged 71%. The DASH score averaged 16 points corresponding to mild perceived disability. Results were categorized as fair on both the Gartland and Werley score (average 9 points) and the modified Green and O’Brien score (average 67 points). Wrist alignment was maintained over time but 13 patients presented mild to moderate symptomatic wrist arthritis. The outcome presented may be a reflection of the use of stricter evaluation instruments or reflect the development of post-traumatic arthritis.

The Minimum Clinically Important Difference of the Patient-rated Wrist Evaluation Score for Patients With Distal Radius Fractures

BackgroundThe Patient-rated Wrist Evaluation (PRWE) is a commonly used instrument in upper extremity surgery and in research. However, to recognize a treatment effect expressed as a change in PRWE, it is important to be aware of the minimum clinically important difference (MCID) and the minimum detectable change (MDC). The MCID of an outcome tool like the PRWE is defined as the smallest change in a score that is likely to be appreciated by a patient as an important change, while the MDC is defined as the smallest amount of change that can be detected by an outcome measure. A numerical change in score that is less than the MCID, even when statistically significant, does not represent a true clinically relevant change. To our knowledge, the MCID and MDC of the PRWE have not been determined in patients with distal radius fractures.Questions/PurposesWe asked: (1) What is the MCID of the PRWE score for patients with distal radius fractures? (2) What is the MDC of the PRWE?MethodsOur prospective cohort study included 102 patients with a distal radius fracture and a median age of 59 years (interquartile range [IQR], 48–66 years). All patients completed the PRWE questionnaire during each of two separate visits. At the second visit, patients were asked to indicate the degree of clinical change they appreciated since the previous visit. Accordingly, patients were categorized in two groups: (1) minimally improved or (2) no change. The groups were used to anchor the changes observed in the PRWE score to patients’ perspectives of what was clinically important. We determined the MCID using an anchor-based receiver operator characteristic method. In this context, the change in the PRWE score was considered a diagnostic test, and the anchor (minimally improved or no change as noted by the patients from visit to visit) was the gold standard. The optimal receiver operator characteristic cutoff point calculated with the Youden index reflected the value of the MCID.ResultsIn our study, the MCID of the PRWE was 11.5 points. The area under the curve was 0.54 (95% CI, 0.37–0.70) for the pain subscale and 0.71 (95% CI, 0.57−0.85) for the function subscale. We determined the MDC to be 11.0 points.ConclusionsWe determined the MCID of the PRWE score for patients with distal radius fractures using the anchor-based approach and verified that the MDC of the PRWE was sufficiently small to detect our MCID.Clinical RelevanceWe recommend using an improvement on the PRWE of more than 11.5 points as the smallest clinically relevant difference when evaluating the effects of treatments and when performing sample-size calculations on studies of distal radius fractures.

Predictors of surgical complications: A systematic review

BACKGROUND Operative complications occur more frequently, often are more preventable, and their consequences can be more severe than other types of complications. Controversy exists regarding how best to identify and predict operative complications. Several studies on predictive factors for operative complications focused on a specific predictor for a specific outcome. To develop a reliable tool to identify patients with operative complications, insight in predictive factors for operative complications is required. PATIENTS AND METHODS We searched all publications addressing predictive factors for the development of operative complications in adult patients admitted to the gastrointestinal, vascular, or general surgery departments. Data were extracted regarding study design, patient characteristics, operative specialty, types of operative procedures, types of complications, possible predictors, and associated complication risk increase (expressed as an odds ratio; OR). RESULTS The final set of 30 articles yielded a total of 53 predictive factors studied in various settings, operative specialties, and disorders. To focus our analysis we selected the 25 most robust and clinically applicable factors (ie, appearing in 3 or more studies). These factors were then categorized into 4 different groups: Patient-related factors, Co-morbidities, Laboratory values, and Surgery-related factors. The most predictive factors for morbidity in these groups were body mass index (ORs from 1.80 to 6.30), age (1.02-4.62 years), American Society of Anesthesiologists classification (1.77-7.10), dyspnea (1.23-1.30), serum creatinine (1.39-2.14), emergency surgery (1.50-2.54), and functional status (1.36-4.07). CONCLUSION This review presents a set of factors predictive of operative complications for general surgery departments. These easily retrievable factors can and should be validated in the specific patient populations of each hospital.

Prevalence of Intimate Partner Violence Across Medical and Surgical Health Care Settings A Systematic Review

Intimate partner violence (IPV) is a serious health problem and a leading cause of nonfatal injury in North American females. Prevalence of IPV has ranged from less than 20% to more than 50% across primary care, emergency medicine, and family medicine. We conducted a systematic review and meta-analysis of the literature to examine best estimates of IPV prevalence as opportunities for targeted interventions in health care specialties. We included 37 articles in this study. Based on our pooled data, best estimates of the lifetime prevalence of any type of IPV were 38% in family medicine and 40% in emergency medicine.