Diagnosis and Treatment of Delirium

Delirium is not a clinical entity but a symptom-complex of manifold etiology. Its presence signifies acute cerebral insufficiency and often represents a medical and/or psychiatric emergency.Though some forms of delirium have distinctive features, the fundamental phenomena are common to all, with clouding of consciousness the sine qua non. The condition has two major components: (1) the basic “acute brain syndrome” and (2) associated release phenomena.Clinicians must first make the vital differentiation between delirium and “functional” mental disorder, then proceed with the elucidation of the underlying diagnosis and the concurrent organization of symptomatic and etiologic treatment.Proper treatment combines management of the acute brain syndrome with general and specific procedures for control of the underlying condition. Dealing with the symptom-complex itself involves the principles and practice of sedation, hydration, and nutrition, nursing care and supportive measures. Provided the basic organic condition is treatable, the prognosis today is usually good.     

Interstitial deletion 13q syndromes: A report on two unrelated patients

Summary A partial monosomy 13 by interstitial deletion was found in the complement of two patients with mental retardation and mild dysmorphic features. Neither of the patients had a retinoblastoma, even though the second patient had a 13q14 deletion. The karyotype-phenotype correlation in the two patients suggests the need to reconsider the clinical profile of these rare chromosomal syndromes in a large series of subjects.     

Candidate gene polymorphisms and the 9p21 locus in acute coronary syndromes

It is now widely accepted that the classic environmental risk factors for atherosclerosis only partly explain the incidence of coronary artery disease and the development of acute coronary syndromes. Therefore, genetic factors that vary among human populations seem to be involved in the clinical manifestations of such patients. Substantial data suggest that a significant proportion of genetic polymorphisms involved in endothelial function, inflammation, lipid metabolism, thrombosis and fibrinolysis are often present in patients with acute coronary syndromes. In particular, a common variant on chromosome 9p21 was recently identified to affect the risk of myocardial infarction. Here, we review the progress of candidate gene studies and genome-wide association studies in identifying the genetic bases of complex cardiovascular diseases such as acute coronary syndromes.     

Prognosis of delirium in elderly hospital patients.

OBJECTIVE: To determine the prognosis of delirium in elderly patients. DATA SOURCES: MEDLINE was searched for relevant articles published from January 1980 to March 1992. The bibliographies of identified articles were searched for additional references. STUDY SELECTION: Eight reports (involving 573 patients with delirium) met the following inclusion criteria: original research, published in English or French, prospective study design, diagnosis based on acute deterioration in mental state, sample of at least 20 patients, patients aged 60 years or over and follow-up of at least 1 week. The validity of the studies was independently assessed according to the criteria for prognostic studies established by McMaster University, Hamilton, Ont. No study met all the criteria. DATA EXTRACTION: Information about the patient sample, length of follow-up and results was systematically abstracted from each report and tabulated. DATA SYNTHESIS: A meta-analysis of the outcomes indicated that elderly patients with delirium had a mean length of stay of 20.7 days. One month after admission 46.5% were in institutions, and 14.2% had died; only 54.9% had improved mentally. Six months after admission 43.2% were in institutions. Compared with unmatched control subjects they had longer hospital stays, higher mortality rates at 1 month and higher rates of institutional care at 1 and 6 months. The presence of severe physical illness or dementia may have been related to some outcomes. CONCLUSIONS: Delirium in the elderly appears to have a poor prognosis. However, this finding may have been confounded by the presence of concomitant dementia or severe physical illness. Future studies must pay attention to methods and design, particularly the composition of study populations and the control of extraneous prognostic factors.     

Late Brain Recovery Processes after Drug Overdose

Though recovery of consciousness after drug overdose may occur within a day or two, the drug itself may not finally leave the brain for another one to three weeks, and at this late time a withdrawal syndrome can occur, with insomnia, restlessness, raised paradoxical (R.E.M.) sleep, epileptic phenomena, and even delirium. It is proposed that a high degree of drug-tolerance and dependence can be rapidly acquired after overdose.Abnormal sleep features of 10 patients resolved only slowly over a period of up to two months after overdose. The data support the view that R.E.M. sleep is concerned with processes of brain repair.     

Low Hemoglobin Level Is Associated with the Development of Delirium after Hepatectomy for Hepatocellular Carcinoma Patients

Background

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and liver resection is the only potential curative treatment option for those patients. Postoperative complications specific to elderly surgical patients such as delirium will be increasingly relevant in the coming decades. Herein, we aimed to investigate the risk factors for postoperative delirium in patients who have received hepatectomy for HCC.

Methods

This is a single medical center observational study and the study subjects comprised 401 individuals who underwent liver resection for hepatocellular carcinoma during January 2009 to October 2013. Multivariate analysis was used to examine whether preoperative, intra-operative, or postoperative variables were associated with the development of delirium.

Results

Of the 401 patients who underwent hepatectomy, 34 developed postoperative delirium (8.4%). In the majority of those patients, symptoms and signs of the syndrome occurred on postoperative day 2 and the mean duration of symptoms was 3.61 ± 3.71 days. Multivariate analysis revealed that advanced age (>71 years) [odds ratio (OR) = 1.133, 95% confidence interval (CI): 1.071–1.200, p<0.001], prolonged operative time (>190 minutes) (OR = 1.009, 95% CI: 1.000–1.017, p = 0.038), a decreased postoperative hemoglobin level (< 10.16 g/dL) (OR = 0.777, 95% CI: 0.613–0.983, p = 0.036), and history of hypnotic drug use (OR = 3.074, 95% CI: 1.045–9.039, p = 0.041) were independent risk factors for the development of postoperative delirium after hepatectomy.

Conclusions

Although the mechanism of postoperative delirium is not well understood, numbers of studies have shown that patients with postoperative delirium tend to have prolonged hospital stay, worse postoperative outcome and an increased risk of short- and long-term mortality. In this study, we found that advanced age, prolonged operative time, postoperative low hemoglobin level and history of hypnotic drug use are independent risk factors for postoperative delirium.     

Validation of a Consensus Method for Identifying Delirium from Hospital Records

Background

Delirium is increasingly considered to be an important determinant of trajectories of cognitive decline. Therefore, analyses of existing cohort studies measuring cognitive outcomes could benefit from methods to ascertain a retrospective delirium diagnosis. This study aimed to develop and validate such a method for delirium detection using routine medical records in UK and Ireland.

Methods

A point prevalence study of delirium provided the reference-standard ratings for delirium diagnosis. Blinded to study results, clinical vignettes were compiled from participants'' medical records in a standardised manner, describing any relevant delirium symptoms recorded in the whole case record for the period leading up to case-ascertainment. An expert panel rated each vignette as unlikely, possible, or probable delirium and disagreements were resolved by consensus.

Results

From 95 case records, 424 vignettes were abstracted by 5 trained clinicians. There were 29 delirium cases according to the reference standard. Median age of subjects was 76.6 years (interquartile range 54.6 to 82.5). Against the original study DSM-IV diagnosis, the chart abstraction method gave a positive likelihood ratio (LR) of 7.8 (95% CI 5.7–12.0) and the negative LR of 0.45 (95% CI 0.40–0.47) for probable delirium (sensitivity 0.58 (95% CI 0.53–0.62); specificity 0.93 (95% CI 0.90–0.95); AUC 0.86 (95% CI 0.82–0.89)). The method diagnosed possible delirium with positive LR 3.5 (95% CI 2.9–4.3) and negative LR 0.15 (95% CI 0.11–0.21) (sensitivity 0.89 (95% CI 0.85–0.91); specificity 0.75 (95% CI 0.71–0.79); AUC 0.86 (95% CI 0.80–0.89)).

Conclusions

This chart abstraction method can retrospectively diagnose delirium in hospitalised patients with good accuracy. This has potential for retrospectively identifying delirium in cohort studies where routine medical records are available. This example of record linkage between hospitalisations and epidemiological data may lead to further insights into the inter-relationship between acute illness, as an exposure, for a range of chronic health outcomes.     

Acetazolamide and Dexamethasone in the Prevention of Acute Mountain Sickness

We randomly assigned 32 healthy backpackers to receive placebo, acetazolamide (250 mg twice a day), dexamethasone acetate (4 mg four times a day), or both drugs in combination to determine the drug efficacy in preventing acute mountain sickness (AMS) at altitudes of 3,650 to 4,050m (12,000 to 13,300 ft). The incidence of AMS was high but symptoms were generally mild. Combined drug therapy was superior to both placebo and single drug therapy in risk reduction. Using acetazolamide alone was moderately beneficial in preventing the occurrence of AMS, although minor side effects were frequent. The use of dexamethasone alone did not significantly reduce the AMS incidence, and discontinuing its use resulted in symptoms suggestive of adrenal insufficiency. For recreational backpackers, routine drug prophylaxis is not recommended, in view of the mild nature of this illness and the adverse effects of medications. The efficacy of combined acetazolamide-dexamethasone therapy warrants further investigation at higher altitudes, where AMS is more severe, and the dexamethasone should be withdrawn gradually to avoid a possible adrenal crisis.     

The frequency of Toxocara infection in mental retarded children

Human toxocariasis is commonly seen in places where stray and Toxocara canis-infected dog population is high. There is a strong correlation between frequency of Toxocara infection, life style, and infection risk. Institutionalization of mental retarded patients increases to risk of toxocariasis. In this study, we aimed at investigating the frequency of Toxocara infection among children with mental retardation not requiring institutionalization. The study included 96 cases, who had educatable mental retardation and 85 healthy subjects who comprised the control group. Anti-Toxocara IgG or IgM antibodies were investigated in all serum samples, using ELISA method. The frequency of Toxocara infection was found significantly higher in mental retarded cases than in those in the control group (18.8% and 7.1% respectively) (p < 0.05). There was no significant difference between mental retarded children and the control group in terms of mean age, age groups, gender, owning dogs and cats and duration of their ownership, socio-economic level and behavioural factors, and personal hygiene (p > 0.05). We did not find any significant difference between Toxocara seropositive and seronegative mental retarded children in terms of demographic factors and epidemiological factors that could increase the risk of Toxocara infection (p > 0.05). The present study is the first seroprevalence study carried out with a mental retarded group not requiring institutionalization. Determination of high frequency of Toxocara infection suggests that these subjects constitute a risk factor for Toxocara infection, which may be attributed to their behavioural patterns.     

Ectrodactyly, ectodermal dysplasia, macular degeneration syndrome: a further contribution

EEM syndrome is a rare condition characterised by ectodermal dysplasia, ectrodactyly and macular dystrophy. Additional abnormalities such as alopecia, cataract, absent eyebrows, and oligodontia may occur. We report two brothers and a sister born to consanguineous parents with EEM syndrome. EEM syndrome differs from other ectrodactly syndromes by the characteristic findings in the ocular fundus showing extensive retinochoroidal atrophy with diffuse retinal pigmentation and mild arteriolar attenuation at the posterior pole. In contrast to other ectrodactyly syndromes autosomal recessive inheritance is most likely.     

Multi-system disorder syndromes associated with cystinuria type I

Cystinuria type I is an autosomal recessive disorder with an exclusively renal phenotype caused by inactivating mutations in SLC3A1. Recently 3 similar but distinct syndromes associated with cystinuria type I have been described: 2p21 deletion syndrome, Hypotonia-Cystinuria Syndrome (HCS) and atypical HCS. Genetic analysis indicated that these are recessive contiguous gene deletion syndromes which differ in the number of genes affected. Patients with HCS are missing both alleles of SLC3A1 and PREPL. In atypical HCS an additional gene (C2orf34) is deleted, and finally, in the 2p21 deletion syndrome the open reading frame of PPM1B is also disrupted. With the exception of SLC3A1, the gene products have not been fully characterized. The severity of the different syndromes reflects the number of genes which are deleted. HCS, a relatively mild syndrome, is characterised by cystinuria type I, generalised hypotonia at birth, growth retardation and minor facial dysmorphic features. On the other end of the spectrum is the 2p21 deletion syndrome, a severe syndrome with a number of additional features including a moderate to severe psychomotor retardation and a decrease in activity of the respiratory chain complexes I, III, IV and V. Finally, atypical HCS displays an intermediate phenotype comparable with classical HCS but associated with mild to moderate mental retardation and a decrease in activity of only the respiratory chain complex IV. This review will focus on the phenotypic similarities and differences observed in these syndromes. Furthermore, we speculate on the function of the gene products, based on the available data.     

Improving quality of care: focus on liaison old age psychiatry

Introduction Elderly patients occupy up to 65% of acute hospital beds and a significant proportion of them present with a comorbid psychiatric condition such as depression, delirium or dementia. Liaison old age psychiatry (LOAP) services have been developed to provide psychiatric consultation in medical and surgical settings, improving at the same time the knowledge and expertise of general ward staff.Objective The aim of this study is to evaluate clinical characteristics across different psychiatric disorders among elderly patients in medical wards.Method A prospective observational study was developed between October 2011 and January 2013, which involved 107 subjects aged 65 years or older that were hospitalised in the Department of Internal Medicine and referred to the LOAP service. Psychiatric diagnostic was assessed using the Confusion Assessment Method, the Geriatric Depression Scale, the Mini-Mental State Examination and the Clinical Global Impression Scale.Results Delirium (40.6%), depression (22.4%) and dementia (20.4%) were the most common psychiatric diagnoses. Patients with delirium were significantly older, had more severe psychiatric symptomatology (mean CGI = 5.35) and presented infectious processes as acute medical conditions more frequently than the other patients.Conclusion Psychiatric disturbances occurring in elderly inpatients in medical wards are highly prevalent and complex. A LOAP service may play an important role in effectively reducing the overutilisation and consumption of health resources through early recognition of these conditions, effective management and prevention of adverse outcomes, and effective communication with out-patient clinics, community mental health teams and day-care centres.     

Efficacy of Non-Pharmacological Interventions to Prevent and Treat Delirium in Older Patients: A Systematic Overview. The SENATOR project ONTOP Series

Background

Non-pharmacological intervention (e.g. multidisciplinary interventions, music therapy, bright light therapy, educational interventions etc.) are alternative interventions that can be used in older subjects. There are plenty reviews of non-pharmacological interventions for the prevention and treatment of delirium in older patients and clinicians need a synthesized, methodologically sound document for their decision making.

Methods and Findings

We performed a systematic overview of systematic reviews (SRs) of comparative studies concerning non-pharmacological intervention to treat or prevent delirium in older patients. The PubMed, Cochrane Database of Systematic Reviews, EMBASE, CINHAL, and PsychINFO (April 28th, 2014) were searched for relevant articles. AMSTAR was used to assess the quality of the SRs. The GRADE approach was used to assess the quality of primary studies. The elements of the multicomponent interventions were identified and compared among different studies to explore the possibility of performing a meta-analysis. Risk ratios were estimated using a random-effects model. Twenty-four SRs with 31 primary studies satisfied the inclusion criteria. Based on the AMSTAR criteria twelve reviews resulted of moderate quality and three resulted of high quality. Overall, multicomponent non-pharmacological interventions significantly reduced the incidence of delirium in surgical wards [2 randomized trials (RCTs): relative risk (RR) 0.71, 95% Confidence Interval (CI) 0.59 to 0.86, I²=0%; (GRADE evidence: moderate)] and in medical wards [2 CCTs: RR 0.65, 95%CI 0.49 to 0.86, I²=0%; (GRADE evidence: moderate)]. There is no evidence supporting the efficacy of non-pharmacological interventions to prevent delirium in low risk populations (i.e. low rate of delirium in the control group)[1 RCT: RR 1.75, 95%CI 0.50 to 6.10 (GRADE evidence: very low)]. For patients who have developed delirium, the available evidence does not support the efficacy of multicomponent non-pharmacological interventions to treat delirium. Among single component interventions only staff education, reorientation protocol (GRADE evidence: very low)] and Geriatric Risk Assessment MedGuide software [hazard ratio 0.42, 95%CI 0.35 to 0.52, (GRADE evidence: moderate)] resulted effective in preventing delirium.

Conclusions

In older patients multi-component non-pharmacological interventions as well as some single-components intervention were effective in preventing delirium but not to treat delirium.     

Early antiplatelet therapy in coronary artery bypass grafting: a calculated benefit

Studies have demonstrated that antagonists of platelet activity, including aspirin and clopidogrel, reduce the risk of major adverse events in patients with acute coronary syndromes. Although antiplatelet agents also convey an increased risk of bleeding, particularly in patients proceeding to coronary artery bypass graft surgery, in most cases, the benefits of early initiation of antiplatelet therapy outweigh the risks. The purpose of this review is to distinguish perceived and actual risk versus the benefit associated with early antiplatelet therapy to help clinicians make informed decisions on using these agents in an acute setting where patients may require coronary artery bypass grafting.     

Using support vector machines with multiple indices of diffusion for automated classification of mild cognitive impairment

Few studies have looked at the potential of using diffusion tensor imaging (DTI) in conjunction with machine learning algorithms in order to automate the classification of healthy older subjects and subjects with mild cognitive impairment (MCI). Here we apply DTI to 40 healthy older subjects and 33 MCI subjects in order to derive values for multiple indices of diffusion within the white matter voxels of each subject. DTI measures were then used together with support vector machines (SVMs) to classify control and MCI subjects. Greater than 90% sensitivity and specificity was achieved using this method, demonstrating the potential of a joint DTI and SVM pipeline for fast, objective classification of healthy older and MCI subjects. Such tools may be useful for large scale drug trials in Alzheimer's disease where the early identification of subjects with MCI is critical.     

Genetische Prädisposition für Wilms-Tumor

Wilms tumor (WT) is an embryonal tumor of the kidney and is due to aberrant proliferation of early precursor cells. WT1 mutations are found in 10–15% of WT. The WT1 gene has a function during normal kidney and genital development. Germline mutations in this gene are found in patients with urogenital abnormalities, isolated nephrotic syndrome, Denys Drash syndrome, Frasier syndrome, WAGR syndrome (Wilms tumor, aniridia, genital malformation, and mental retardation), and some rare cases of familial WT. These patients are at high risk of unilateral WT, and also of synchronous or metachronous bilateral WT, which may occur later in life. An elevated risk of WT is also observed in some overgrowth syndromes, various tumor predisposition syndromes, and specific constitutional aneuploidies. Embryonal tumors develop during early phases of development when cells still have a high doubling rate. Aberrations that delay or inhibit the switch from proliferation to differentiation lead to an expanded cell pool, in which further mutations can occur in various genes that regulate this process. This may explain the heterogeneous diseases/genetic aberrations that are associated with an elevated risk of WT.     

Estimation of survival rate and extinction probability for stage-structured populations with overlapping life stages

The development of methods providing reliable estimates of demographic parameters (e.g., survival rates, fecundity) for wild populations is essential to better understand the ecology and conservation requirements of individual species. A number of methods exist for estimating the demographics of stage-structured populations, but inherent mathematical complexity often limits their uptake by conservation practitioners. Estimating survival rates for pond-breeding amphibians is further complicated by their complex migratory and reproductive behaviours, often resulting in nonobservable states and successive cohorts of eggs and tadpoles. Here we used comprehensive data on 11 distinct breeding toad populations (Bufo calamita) to clarify and assess the suitability of a relatively simple method [the Kiritani–Nakasuji–Manly (KNM) method] to estimate the survival rates of stage-structured populations with overlapping life stages. The study shows that the KNM method is robust and provides realistic estimates of amphibian egg and larval survival rates for species in which breeding can occur as a single pulse or over a period of several weeks. The study also provides estimates of fecundity for seven distinct toad populations and indicates that it is essential to use reliable estimates of fecundity to limit the risk of under- or overestimating the survival rates when using the KNM method. Survival and fecundity rates for B. calamita populations were then used to define population matrices and make a limited exploration of their growth and viability. The findings of the study recently led to the implementation of practical conservation measures at the sites where populations were most vulnerable to extinction.     

Personality traits and behavioral syndromes in differently urbanized populations of house sparrows (Passer domesticus)

Urbanization creates novel environments for wild animals where selection pressures may differ drastically from those in natural habitats. Adaptation to urban life involves changes in various traits, including behavior. Behavioral traits often vary consistently among individuals, and these so-called personality traits can be correlated with each other, forming behavioral syndromes. Despite their adaptive significance and potential to act as constraints, little is known about the role of animal personality and behavioral syndromes in animals' adaptation to urban habitats. In this study we tested whether differently urbanized habitats select for different personalities and behavioral syndromes by altering the population mean, inter-individual variability, and correlations of personality traits. We captured house sparrows (Passer domesticus) from four different populations along the gradient of urbanization and assessed their behavior in standardized test situations. We found individual consistency in neophobia, risk taking, and activity, constituting three personality axes. On the one hand, urbanization did not consistently affect the mean and variance of these traits, although there were significant differences between some of the populations in food neophobia and risk taking (both in means and variances). On the other hand, both urban and rural birds exhibited a behavioral syndrome including object neophobia, risk taking and activity, whereas food neophobia was part of the syndrome only in rural birds. These results indicate that there are population differences in certain aspects of personality in house sparrows, some of which may be related to habitat urbanization. Our findings suggest that urbanization and/or other population-level habitat differences may not only influence the expression of personality traits but also alter their inter-individual variability and the relationships among them, changing the structure of behavioral syndromes.     

Delirium en centros residenciales para personas mayores. Estudio de la prevalencia y los factores asociados

Objectives

To study the prevalence of delirium in the residential environment and to analyse the associated clinical, functional and mental factors.

Material and methods

A cross-sectional epidemic study was conducted on a population of elderly persons institutionalised in 2011 in 6 nursing homes in Asturias. Socio-demographic, clinical, functional (Barthel Index [BI]) and mental (Mini-Mental State Examination [MMSE]) variables were collected. Delirium was defined by the Confusion Assessment Method.

Results

A total of 505 elderly were included in the study (age 83.30 ± 7.33 years, with 67.70% women), and scores on the MMSE of 17.19 ± 10.35 and a BI score of 55.11 ± 35.82. The prevalence of delirium was 11.70%. On examining the risk of delirium among the studied variables, there was statistical significance when considering: BI, MMSE, dementia, pressure ulcers, or urinary catheter, and the prescribing of clomethiazole, ACTH-I or trazodone. In the analysis of the variables in the logistic regression with BI, diagnosis of dementia, the prescribing of clomethiazole or trazodone, in the equation, there was a statistical significance associated with delirium.

Conclusions

The prevalence of delirium in a residential environment in our study population was 11.7%. The results show that BI, diagnosis of dementia, and prescribing of clomethiazole or trazodone were associated with risk of delirium in institutionalised patients.     

The effect of azithromycin on ivermectin pharmacokinetics--a population pharmacokinetic model analysis

Background

A recent drug interaction study reported that when azithromycin was administered with the combination of ivermectin and albendazole, there were modest increases in ivermectin pharmacokinetic parameters. Data from this study were reanalyzed to further explore this observation. A compartmental model was developed and 1,000 interaction studies were simulated to explore extreme high ivermectin values that might occur.

Methods and Findings

A two-compartment pharmacokinetic model with first-order elimination and absorption was developed. The chosen final model had 7 fixed-effect parameters and 8 random-effect parameters. Because some of the modeling parameters and their variances were not distributed normally, a second mixture model was developed to further explore these data. The mixture model had two additional fixed parameters and identified two populations, A (55% of subjects), where there was no change in bioavailability, and B (45% of subjects), where ivermectin bioavailability was increased 37%. Simulations of the data using both models were similar, and showed that the highest ivermectin concentrations fell in the range of 115–201 ng/mL.

Conclusions

This is the first pharmacokinetic model of ivermectin. It demonstrates the utility of two modeling approaches to explore drug interactions, especially where there may be population heterogeneity. The mechanism for the interaction was identified (an increase in bioavailability in one subpopulation). Simulations show that the maximum ivermectin exposures that might be observed during co-administration with azithromycin are below those previously shown to be safe and well tolerated. These analyses support further study of co-administration of azithromycin with the widely used agents ivermectin and albendazole, under field conditions in disease control programs.