Differential effect sizes of growth hormone replacement on quality of life, well-being and health status in growth hormone deficient patients: a meta-analysis

BACKGROUND: Patients with growth hormone deficiency (GHD) frequently report to suffer from an impaired Quality of Life (QoL) and growth hormone (GH) substitution is found to improve this. However, the same test may be used for measuring QoL, well-being or health status in different studies. QoL has been defined as the subjective appraisal of one's current life based primarily on psychological function. The most important in the appraisal of well-being is mental function and concerning health status patients evaluate physical function as most important. To differentiate the effects of GH replacement on psychological variables in patients with GHD we carried out a number of meta-analyses, classifying questionnaires into instruments measuring QoL, psychological well-being and health status. METHODS: We searched the electronic databases PUBMED and PiCarta from 1985 to 2004. Studies were included that evaluated the effect of GH on patient-reported outcomes in adults with GHD (aged 18 years and above). According to generally accepted definitions we classified the questionnaires as instruments measuring QoL, well-being and health status. By means of meta-analyses the average effect size (d) for QoL, well-being and health status was calculated. RESULTS AND DISCUSSION: Based on open studies GH replacement is found to improve QoL with a small effect size (d = 0.18), well-being with a medium effect size (d = 0.47) and health status with a small effect size (d = 0.26). As the effect size of well-being is most pronounced the generally reported effects of GH replacement on QoL may be overestimated and actually reflect the effect on well-being. CONCLUSION: To get more insight in the specific psychological effects of GH treatment it is recommended that instruments selected for these studies should be more consistently classified as instruments measuring QoL, well-being or health status

Preoperative cerebrospinal fluid cytokine levels and the risk of postoperative delirium in elderly hip fracture patients

Aging and neurodegenerative disease predispose to delirium and are both associated with increased activity of the innate immune system resulting in an imbalance between pro- and anti-inflammatory mediators in the brain. We examined whether hip fracture patients who develop postoperative delirium have altered levels of inflammatory mediators in cerebrospinal fluid (CSF) prior to surgery. Patients were 75 years and older and admitted for surgical repair of an acute hip fracture. CSF samples were collected preoperatively. In an exploratory study, we measured 42 cytokines and chemokines by multiplex analysis. We compared CSF levels between patients with and without postoperative delirium and examined the association between CSF cytokine levels and delirium severity. Delirium was diagnosed with the Confusion Assessment Method; severity of delirium was measured with the Delirium Rating Scale Revised-98. Mann-Whitney U tests or Student t-tests were used for between-group comparisons and the Spearman correlation coefficient was used for correlation analyses. Sixty-one patients were included, of whom 23 patients (37.7%) developed postsurgical delirium. Concentrations of Fms-like tyrosine kinase-3 (P=0.021), Interleukin-1 receptor antagonist (P=0.032) and Interleukin-6 (P=0.005) were significantly lower in patients who developed delirium postoperatively. Our findings fit the hypothesis that delirium after surgery results from a dysfunctional neuroinflammatory response: stressing the role of reduced levels of anti-inflammatory mediators in this process. The Effect of Taurine on Morbidity and Mortality in the Elderly Hip Fracture Patient.Registration number: NCT00497978. Local ethical protocol number: NL16222.094.0

Differential effect sizes of growth hormone replacement on quality of life, well-being and health status in growth hormone deficient patients: a meta-analysis

Abstract Background Patients with growth hormone deficiency (GHD) frequently report to suffer from an impaired Quality of Life (QoL) and growth hormone (GH) substitution is found to improve this. However, the same test may be used for measuring QoL, well-being or health status in different studies. QoL has been defined as the subjective appraisal of one's current life based primarily on psychological function. The most important in the appraisal of well-being is mental function and concerning health status patients evaluate physical function as most important. To differentiate the effects of GH replacement on psychological variables in patients with GHD we carried out a number of meta-analyses, classifying questionnaires into instruments measuring QoL, psychological well-being and health status. Methods We searched the electronic databases PUBMED and PiCarta from 1985 to 2004. Studies were included that evaluated the effect of GH on patient-reported outcomes in adults with GHD (aged 18 years and above). According to generally accepted definitions we classified the questionnaires as instruments measuring QoL, well-being and health status. By means of meta-analyses the average effect size (d) for QoL, well-being and health status was calculated. Results and Discussion Based on open studies GH replacement is found to improve QoL with a small effect size (d = 0.18), well-being with a medium effect size (d = 0.47) and health status with a small effect size (d = 0.26). As the effect size of well-being is most pronounced the generally reported effects of GH replacement on QoL may be overestimated and actually reflect the effect on well-being. Conclusion To get more insight in the specific psychological effects of GH treatment it is recommended that instruments selected for these studies should be more consistently classified as instruments measuring QoL, well-being or health status.</p

Feasibility and potential of a bedside mini-EEG for diagnosing delirium superimposed on dementia

Objective: Delirium superimposed on dementia (DSD) is difficult to diagnose because symptoms of delirium might be interpreted as symptoms of dementia. To improve diagnostic accuracy, we investigated the potential of a brief point-of-care EEG measurement. Methods: Thirty older patients were included, all with Major Neurocognitive Disorder (i.e. dementia) according to DSM-5 criteria. EEG was registered at right prefrontal and right temporal site, with eyes either open or closed for three minutes, simultaneously with the Discomfort Scale for Dementia of Alzheimer Type. The Confusion Assessment Method for the Intensive Care Unit was administered to determine the presence of symptoms of a delirium at the time of EEG administration. Video registrations were reviewed independently by two delirium experts. Results: Higher activities of delta and theta1, and lower activities of theta2, alpha, and beta activity, were found in DSD when compared to dementia only. The ratio of delta and theta power during eyes-open conditions had the highest accuracy (AUC = 0.80 [0.63–0.94]; p <.001) to distinguish DSD from dementia alone. All subjects were on benzodiazepines and half on clozapine, thus the effects of psychotropics on EEG cannot be fully excluded. Conclusions: A brief point-of-care EEG at two sites of the head has the potential to aid in the detection of DSD. Significance: The diagnostic accuracy of EEG in recognizing or excluding delirium in patients who already have dementia is of large potential given the lack of proper diagnostic tools

Delirium in Elderly Patients and the Risk of Postdischarge Mortality, Institutionalization, and Dementia A Meta-analysis

Context Delirium is a common and serious complication in elderly patients. Evidence suggests that delirium is associated with long-term poor outcome but delirium often occurs in individuals with more severe underlying disease. Objective To assess the association between delirium in elderly patients and long-term poor outcome, defined as mortality, institutionalization, or dementia, while controlling for important confounders. Data Sources Asystematic search of studies published between January 1981 and April 2010 was conducted using the databases of MEDLINE, EMBASE, PsycINFO, and CINAHL. Study Selection Observational studies of elderly patients with delirium as a study variable and data on mortality, institutionalization, or dementia after a minimum follow-up of 3 months, and published in the English or Dutch language. Titles, abstracts, and articles were reviewed independently by 2 of the authors. Of 2939 references in the original search, 51 relevant articles were identified. Data Extraction Information on study design, characteristics of the study population, and outcome were extracted. Quality of studies was assessed based on elements of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cohort studies. Data Synthesis The primary analyses included only high-quality studies with statistical control for age, sex, comorbid illness or illness severity, and baseline dementia. Pooled-effect estimates were calculated with random-effects models. The primary analysis with adjusted hazard ratios (HRs) showed that delirium is associated with an increased risk of death compared with controls after an average follow-up of 22.7 months (7 studies; 271/714 patients [38.0%] with delirium, 616/2243 controls [27.5%]; HR, 1.95 [95% confidence interval {CI}, 1.51-2.52]; I-2, 44.0%). Moreover, patients who had experienced delirium were also at increased risk of institutionalization (7 studies; average follow-up, 14.6 months; 176/527 patients [33.4%] with delirium and 219/2052 controls [10.7%]; odds ratio [OR], 2.41 [95% CI, 1.77-3.29]; I-2, 0%) and dementia (2 studies; average follow-up, 4.1 years; 35/56 patients [62.5%] with delirium and 15/185 controls [8.1%]; OR, 12.52 [95% CI, 1.86-84.21]; I-2, 52.4%). The sensitivity, trim-and-fill, and secondary analyses with unadjusted high-quality risk estimates stratified according to the study characteristics confirmed the robustness of these results. Conclusion This meta-analysis provides evidence that delirium in elderly patients is associated with poor outcome independent of important confounders, such as age, sex, comorbid illness or illness severity, and baseline dementia. JAMA. 2010; 304(4): 443-45

Preoperative Cerebrospinal Fluid Cortisol and the Risk of Postoperative Delirium: A Prospective Study of Older Hip Fracture Patients

Background: Ageing, depression, and neurodegenerative disease are common risk factors for delirium in the elderly. These risk factors are associated with dysregulation of the hypothalamic-pituitary-adrenal axis, resulting in higher levels of cortisol under normal and stressed conditions and a slower return to baseline. Objectives: We investigated whether elevated preoperative cerebrospinal fluid (CSF) cortisol levels are associated with the onset of postoperative delirium. Methods: In a prospective cohort study CSF samples were collected after cannulation for the introduction of spinal anesthesia of 75 patients aged 75 years and older admitted for surgical repair of acute hip fracture. Delirium was assessed with the confusion assessment method (CAM) and the Delirium Rating Scale-Revised-98 (DRS-R98). Because the CAM and DRS-R98 were available for time of admission and 5 postoperative days, we used generalized estimating equations and linear mixed modeling to examine the association between preoperative CSF cortisol levels and the onset of postoperative delirium. Results: Mean age was 83.5 (SD 5.06) years, and prefracture cognitive decline was present in one-third of the patients (24 [33%]). Postoperative delirium developed in 27 (36%) patients. We found no association between preoperative CSF cortisol levels and onset or severity of postoperative delirium. Conclusions: These findings do not support the hypothesis that higher preoperative CSF cortisol levels are associated with the onset of postoperative delirium in elderly hip fracture patients

The trajectory of C-reactive protein serum levels in older hip fracture patients with postoperative delirium

Objectives: Important precipitating risk factors for delirium such as infections, vascular disorders, and surgery are accompanied by a systemic inflammatory response. Systemic inflammatory mediators can induce delirium in susceptible individuals. Little is known about the trajectory of systemic inflammatory markers and their role in the development and outcome of delirium. Methods: This is a prospective cohort study of older patients undergoing acute surgery for hip fracture. Baseline characteristics were assessed preoperatively. During hospital admission, presence of delirium was assessed daily according to the Confusion Assessment Method criteria. This study compared the trajectory of serum levels of the C-reactive protein (CRP) between people with and without postoperative delirium. Blood samples were taken at baseline and at postoperative day 1 through postoperative day 5. Results: Forty-one out of 121 patients developed postoperative delirium after hip fracture surgery. Longitudinal analysis of the trajectory of serum CRP levels using the Generalized Estimating Equations (GEE) method identified that higher CRP levels were associated with postoperative delirium. CRP levels were higher from postoperative day 2 through postoperative day 5. No significant differences in serum CRP levels were found when we compared patients with short (1-2 days) and more prolonged delirium (3 days or more). Conclusions: Delirium is associated with an increased systemic inflammatory response, and our results suggest that CRP plays a role in the underlying (inflammatory-vascular) pathological pathway of postoperative delirium

Preoperative Cerebrospinal Fluid Cortisol and the Risk of Postoperative Delirium: A Prospective Study of Older Hip Fracture Patients

Background: Ageing, depression, and neurodegenerative disease are common risk factors for delirium in the elderly. These risk factors are associated with dysregulation of the hypothalamic-pituitary-adrenal axis, resulting in higher levels of cortisol under normal and stressed conditions and a slower return to baseline. Objectives: We investigated whether elevated preoperative cerebrospinal fluid (CSF) cortisol levels are associated with the onset of postoperative delirium. Methods: In a prospective cohort study CSF samples were collected after cannulation for the introduction of spinal anesthesia of 75 patients aged 75 years and older admitted for surgical repair of acute hip fracture. Delirium was assessed with the confusion assessment method (CAM) and the Delirium Rating Scale-Revised-98 (DRS-R98). Because the CAM and DRS-R98 were available for time of admission and 5 postoperative days, we used generalized estimating equations and linear mixed modeling to examine the association between preoperative CSF cortisol levels and the onset of postoperative delirium. Results: Mean age was 83.5 (SD 5.06) years, and prefracture cognitive decline was present in one-third of the patients (24 [33%]). Postoperative delirium developed in 27 (36%) patients. We found no association between preoperative CSF cortisol levels and onset or severity of postoperative delirium. Conclusions: These findings do not support the hypothesis that higher preoperative CSF cortisol levels are associated with the onset of postoperative delirium in elderly hip fracture patients

Affective functioning after delirium in elderly hip fracture patients

Delirium in elderly patients is associated with various long-term sequelae that include cognitive impairment and affective disturbances, although the latter is understudied. For a prospective cohort study of elderly patients undergoing hip fracture surgery, baseline characteristics and affective and cognitive functioning were assessed preoperatively. During hospital admission, presence of delirium was assessed daily. Three months after hospital discharge, affective and global cognitive functioning was evaluated again in patients free from delirium at the time of this follow-up. This study compared baseline characteristics and affective functioning between patients with and without in-hospital delirium. We investigated whether in-hospital delirium is associated with increased anxiety and depressive levels, and post-traumatic stress disorder (PTSD) symptoms three months after discharge. Among 53 eligible patients, 23 (43.4%) patients experienced in-hospital delirium after hip fracture repair. Patients who had experienced in-hospital delirium showed more depressive symptoms at follow-up after three months compared to the 30 patients without in-hospital delirium. This association persisted in a multivariate model controlling for age, baseline cognition, baseline depressive symptoms, and living situation. The level of anxiety and symptoms of PTSD at follow-up did not differ between both groups. This study suggests that in-hospital delirium is associated with an increased burden of depressive symptoms three months after discharge in elderly patients who were admitted to the hospital for surgical repair of hip fracture. Symptoms of depression in patients with previous in-hospital delirium cannot be fully explained by persistent (sub)syndromal delirium or baseline cognitive impairmen