Childhood neurodevelopmental markers and risk of premature mortality: Follow-up to age 60-65 years in the Aberdeen Children of the 1950s study.

BACKGROUND: Individual neurodevelopmental disorders are associated with premature mortality. Little is known about the association between multiple neurodevelopmental markers and premature mortality at a population level. The ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations) approach considers multiple neurodevelopmental parameters, assessing several markers in parallel that cluster, rather than considering individual diagnostic categories in isolation. OBJECTIVES: To determine whether childhood neurodevelopmental markers, including reduced intellectual functioning, are associated with all-cause premature mortality. METHODS AND PROCEDURES: In a general population cohort study (n = 12,150) with longitudinal follow up from childhood to middle age, Cox proportional hazard models were used to study the associations between childhood neurodevelopmental markers (Rutter B scale and IQ) and premature all-cause mortality. OUTCOMES AND RESULTS: The cognitive measures and 21 of the 26 Rutter B items were significantly associated with premature mortality in bivariate analyses with hazard ratios from 1.24 (95% CI 1.05-1.47) to 2.25 (95% CI 1.78-2.90). In the final adjusted model, neurodevelopmental markers suggestive of several domains including hyperactivity, conduct problems and intellectual impairment were positively associated with premature mortality and improved prediction of premature mortality. CONCLUSIONS: A wide range of neurodevelopmental markers, including childhood IQ, were found to predict premature mortality in a large general population cohort with longitudinal follow up to 60-65 years of age. IMPLICATIONS: These findings highlight the importance of a holistic assessment of children with neurodevelopmental markers that addresses a range of neurodevelopmental conditions. Our findings could open the door to a shift in child public mental health focus, where multiple and/or cumulative markers of neurodevelopmental conditions alert clinicians to the need for early intervention. This could lead to a reduction in the risk of broad health outcomes at a population level.

Association of Delirium during Critical Illness With Mortality: Multicenter Prospective Cohort Study.

BACKGROUND: The temporal association of delirium during critical illness with mortality is unclear, along with the associations of hypoactive and hyperactive motoric subtypes of delirium with mortality. We aimed to evaluate the relationship of delirium during critical illness, including hypoactive and hyperactive motoric subtypes, with mortality in the hospital and after discharge up to 1 year. METHODS: We analyzed a prospective cohort study of adults with respiratory failure and/or shock admitted to university, community, and Veterans Affairs hospitals. We assessed patients using the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the intensive care unit (ICU) and defined the motoric subtype according to the corresponding Richmond Agitation-Sedation Scale if delirium was present. We used Cox proportional hazard models, adjusted for baseline characteristics, coma, and daily hospital events, to determine whether delirium on a given day predicted mortality the following day in patients in the hospital and also to determine whether delirium presence and duration predicted mortality after discharge up to 1 year in patients who survived to hospital discharge. We performed similar analyses for hypoactive and hyperactive subtypes of delirium. RESULTS: Among 1040 critically ill patients, 214 (21%) died in the hospital and 204 (20%) died out-of-hospital by 1 year. Delirium was common, occurring in 740 (71%) patients for a median (interquartile range [IQR]) of 4 (2-7) days. Hypoactive delirium occurred in 733 (70%) patients, and hyperactive occurred in 185 (18%) patients, with a median (IQR) of 3 (2-7) days and 1 (1-2) days, respectively. Delirium on a given day (hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.32-6.21; P = .008), in particular the hypoactive subtype (HR, 3.35; 95% CI, 1.51-7.46; P = .003), was independently associated with an increased risk of death the following day in the hospital. Hyperactive delirium was not associated with an increased risk of death in the hospital (HR, 4.00; 95% CI, 0.49-32.51; P = .19). Among hospital survivors, neither delirium presence (HR, 1.01; 95% CI, 0.82-1.24; P = .95) nor duration (HR, 0.99; 95% CI, 0.97-1.01; P = .56), regardless of motoric subtype, was associated with mortality after hospital discharge up to 1 year. CONCLUSIONS: Delirium during critical illness is associated with nearly a 3-fold increased risk of death the following day for patients in the hospital but is not associated with mortality after hospital discharge. This finding appears primarily driven by the hypoactive motoric subtype. The independent relationship between delirium and mortality occurs early during critical illness but does not persist after hospital discharge.

The role of restraint in fatal excited delirium: a research synthesis and pooled analysis.

The purpose of the present study was to perform a comprehensive scientific literature review and pooled data risk factor analysis of excited delirium syndrome (ExDS) and agitated delirium (AgDS). All cases of ExDS or AgDS described individually in the literature published before April 23, 2020 were used to create a database of cases, including demographics, use of force, drug intoxication, mental illness, and survival outcome. Odds ratios were used to quantify the association between death and diagnosis (ExDS vs. AgDS) across the covariates. There were 61 articles describing 168 cases of ExDS or AgDS, of which 104 (62%) were fatal. ExDS was diagnosed in 120 (71%) cases, and AgDS in 48 (29%). Fatalities were more likely to be diagnosed as ExDS (OR: 9.9, p < 0.0001). Aggressive restraint (i.e. manhandling, handcuffs, and hobble ties) was more common in ExDS (ORs: 4.7, 14, 29.2, respectively, p < 0.0001) and fatal cases (ORs: 7.4, 10.7, 50, respectively, p < 0.0001). Sedation was more common in AgDS and survived cases (OR:11, 25, respectively, p < 0.0001). The results of the study indicate that a diagnosis of ExDS is far more likely to be associated with both aggressive restraint and death, in comparison with AgDS. There is no evidence to support ExDS as a cause of death in the absence of restraint. These findings are at odds with previously published theories indicating that ExDS-related death is due to an occult pathophysiologic process. When death has occurred in an aggressively restrained individual who fits the profile of either ExDS or AgDS, restraint-related asphyxia must be considered a likely cause of the death.

Differences in 90-day mortality of delirium subtypes in the intensive care unit: A retrospective cohort study.

INTRODUCTION: Many intensive care unit (ICU) patients suffer from delirium which is associated with deleterious short-term and long-term effects, including mortality. We determined the association between different delirium subtypes and 90-day mortality. MATERIALS AND METHODS: Retrospective cohort study in ICU patients admitted in 2015-2017. Delirium, including its subtypes, was determined using the confusion assessment method-ICU (CAM-ICU) and Richmond agitation sedation scale (RASS). Exclusion criteria were insufficient assessments and persistent coma. Cox-regression analysis was used to determine associations of delirium subtypes with 90-day mortality, including relevant covariates (APACHE-IV, length of ICU stay and mechanical ventilation). RESULTS: 7362 ICU patients were eligible of whom 6323 (86%) were included. Delirium occurred in 1600 (25%) patients (stratified for delirium subtype: N = 571-36% mixed, N = 485-30% rapidly reversible, N = 433-27% hypoactive, N = 111-7% hyperactive). The crude hazard ratio (HR) for overall prevalent delirium with 90-day mortality was 2.84 (95%CI: 2.32-3.49), and the adjusted HR 1.29 (95%CI: 1.01-1.65). The adjusted HR for 90-day mortality was 1.57 (95%CI: 1.51-2.14) for the mixed subtype, 1.40 (95%CI: 0.71-2.73) for hyperactive, 1.31 (95%CI: 0.93-1.84) for hypoactive and 0.95 (95%CI: 0.64-1.42) for rapidly reversible delirium. CONCLUSION: After adjusting for covariates, including competing risk factors, only the mixed delirium subtype was significantly associated with 90-day mortality.

Clinical and cost-effectiveness of the Managing Agitation and Raising Quality of Life (MARQUE) intervention for agitation in people with dementia in care homes: a single-blind, cluster-randomised controlled trial.

BACKGROUND: Many people with dementia living in care homes have distressing and costly agitation symptoms. Interventions should be efficacious, scalable, and feasible. METHODS: We did a parallel-group, cluster-randomised controlled trial in 20 care homes across England. Care homes were eligible if they had 17 residents or more with dementia, agreed to mandatory training for all eligible staff and the implementation of plans, and more than 60% of eligible staff agreed to participate. Staff were eligible if they worked during the day providing face-to-face care for residents with dementia. Residents were eligible if they had a known dementia diagnosis or scored positive on screening with the Noticeable Problems Checklist. A statistician independent of the study randomised care homes (1:1) to the Managing Agitation and Raising Quality of Life (MARQUE) intervention or treatment as usual (TAU) using computer-generated randomisation in blocks of two, stratified by type of home (residential or nursing). Care home staff were not masked to the intervention but were asked not to inform assessors. Residents with dementia, family carers, outcome assessors, statisticians, and health economists were masked to allocation until the data were analysed. MARQUE is an evidence-based manualised intervention, delivered by supervised graduate psychologists to staff in six interactive sessions. The primary outcome was agitation score at 8 months, measured using the Cohen-Mansfield Agitation Inventory (CMAI). Analysis of the primary outcome was done in the modified intention-to-treat population, which included all randomly assigned residents for whom CMAI data was available at 8 months. Mortality was assessed in all randomly assigned residents. This study is registered with the ISRCTN registry, number ISRCTN96745365. FINDINGS: Between June 14, 2016, and July 4, 2017, we randomised ten care homes (189 residents) to the MARQUE intervention and ten care homes (215 residents) to TAU. At 8 months, primary outcome data were available for 155 residents in the MARQUE group and 163 residents in the TAU group. At 8 months, no significant differences in mean CMAI scores were identified between the MARQUE and TAU groups (adjusted difference -0·40 [95% CI -3·89 to 3·09; p=0·8226]). In the intervention care homes, 84% of all eligible staff completed all sessions. The mean difference in cost between the MARQUE and TAU groups was £204 (-215 to 623; p=0·320) and mean difference in quality-adjusted life-years was 0·015 (95% CI -0·004 to 0·034; p=0·127). At 8 months, 27 (14%) of 189 residents in the MARQUE group and 41 (19%) of 215 residents in the TAU group had died. The prescription of antipsychotic drugs was not significantly different between the MARQUE group and the TAU group (odds ratio 0·66; 95% CI 0·26 to 1·69, p=0·3880). INTERPRETATION: The MARQUE intervention was not efficacious for agitation although feasible and cost-effective in terms of quality of life. Addressing agitation in care homes might require resourcing for delivery by professional staff of a more intensive intervention, implementing social and activity times, and a longer time to implement change. FUNDING: UK Economic and Social Research Council and the National Institute of Health Research.

[Frequency of symptoms and drug treatment among dying patients in the last 24 hours of life at Landspitali - The National University Hospital of Iceland and in nursing homes].

INTRODUCTION: The purpose of this study was to evaluate the frequency of 5 common symptoms and drug treatments prescribed and given in the last 24 hours of life in 11 medical units at Landspitali National University Hospital of Iceland (LUH) and in 7 nursing homes (NH). MATERIAL AND METHODS: Data was collected retrospectively from 232 charts of patients who died in 2012, using documentation in the Liverpool Care Pathway (LCP) and the medication management system. RESULTS: About half of the patients died at LUH with similar gender ratio but 70% of patients in NH were women. The LCP was used for 50% of all deaths at LUH and 58% in NH. In 45% of all deaths LCP was used for 24 hours or less. The most common symptoms were pain (51%), agitation (36%) and respiratory tract secretions (36%). Frequency of symptoms was similar between institutions and age groups. Cancer patients had significantly higher incidence of agitation and were prescribed and given higher doses of morphine compared to other groups. Regular medication for agitation was haloperidol (45%), diazepam (40%) and midazolam (5%). Close to 70% of the patients were treated with a scopolamin patch for death rattle. CONCLUSION: A large number of patients have symptoms in the last 24 hours of life both in hospital and in nursing homes. Symptom control can be improved by adjusting morphine doses to patients need, using regular doses of benzodiazepine for agitation and better use of anticholinergic medication for death rattle. Key words: symptoms, medication, dying patients, last 24 hours of life, hospital, nursing homes. Correspondence: Svandis Iris Halfdanardottir, svaniris@landspitali.is.

Estudio y análisis médico-legal de las muertes en privación de libertad en Málaga (2004-2012) / Study and forensic analysis of deaths in custody in Malaga, Spain (2004-2012)

Se presenta un estudio sobre todos los casos de muertes en privación de libertad ocurridos en la provincia de Málaga durante los años 2004-2012, que fueron 41. En cuanto al origen y la causa de la muerte, la mayoría fueron accidentales (46,3%, incluyendo reacción adversa a drogas), seguidas de suicidios (24,3%), muertes de origen natural (21,9%) y homicidios (7,3%). En el estudio se detalla también la edad, el sexo, la nacionalidad, el consumo de tóxicos y el lugar del suceso. Finalmente se exponen cuatro interesantes casos: dos accidentes, un suicidio y un homicidio (AU)

A study of all cases of deaths in custody occurred in the province of Malaga, Spain, during the years 2004 to 2012 is presented. These were 41. As for the origin and etiology of death, most were accidents 46.3% (including adverse drug reaction), followed by suicides (24.3%), natural deaths (21.9%) and homicides (7.3%). In the study; age, sex, national consumption of toxic and location of occurrence is detailed. Finally four interesting cases are discussed: twoaccidents, one suicide and a homicide (AU)

Motor subtypes of postoperative delirium in older adults.

HYPOTHESIS: Increased knowledge about motor subtypes of delirium may aid clinicians in the management of postoperative geriatric patients. DESIGN: Prospective cohort study defining preoperative risk factors, outcomes, and adverse events related to motor subtypes of postoperative delirium. SETTING: Referral medical center. PATIENTS: Persons 50 years and older with planned postoperative intensive care unit (ICU) admission following an elective operation were recruited. MAIN OUTCOME MEASURES: Before surgery, a standardized frailty assessment was performed. After surgery, delirium and its motor subtypes were measured using the validated tools of the Confusion Assessment Method-ICU and the Richmond Agitation-Sedation Scale. Statistical analysis included the univariate t and χ(2) tests and analysis of variance with post hoc analysis. RESULTS: Delirium occurred in 43.0% (74 of 172) of patients, representing 67.6% (50 of 74) hypoactive, 31.1% (23 of 74) mixed, and 1.4% (1 of 74) hyperactive motor subtypes. Compared with those having mixed delirium, patients having hypoactive delirium were older (mean [SD] age, 71 [9] vs 65 [9] years) and more anemic (mean [SD] hematocrit, 36% [8%] vs 41% [6%]) (P = .002 for both). Patients with hypoactive delirium had higher 6-month mortality (32.0% [16 of 50] vs 8.7% [2 of 23], P = .04). Delirium-related adverse events occurred in 24.3% (18 of 74) of patients with delirium; inadvertent tube or line removals occurred more frequently in the mixed group (P = .006), and sacral skin breakdown was more common in the hypoactive group (P = .002). CONCLUSIONS: Motor subtypes of delirium alert clinicians to differing prognosis and adverse event profiles in postoperative geriatric patients. Hypoactive delirium is the most common motor subtype and is associated with worse prognosis (6-month mortality, 1 in 3 patients). Knowledge of differing adverse event profiles can modify clinicians' management of older patients with postoperative delirium.

Relationship between neuroleptic extrapyramidal syndromes and patients' all-cause mortality.

INTRODUCTION: It is important to understand factors contributing to a neuroleptic-related increased mortality risk. The objective of this study was to test whether the occurrence of neuroleptic-induced extrapyramidal syndromes (EPS) including tardive dyskinesia (TD) is associated with an increased patients' all-cause mortality. METHODS: In 1995, a sample of 200 patients on neuroleptics was assessed with regard to the presence of Parkinson syndrome, akathisia, and TD. By 2003-2004, i.e., during the following 8-9 year period, 63 patients had died. Patients who had died were compared with 120 patients known to be still alive with regard to several socio-demographic variables and the presence of EPS at the first examination. RESULTS: At the basic assessment, there were no significant differences between patients later still alive and deceased patients with regard to TD. The deceased patients were more frequently women, older, suffered more frequently from an organic disorder, had higher average scores for Parkinson syndrome and less frequently akathisia. Multivariate analysis confirmed age as the only factor contributing to the group difference. Repeating the meta-analysis by Ballesteros et al. (2000) after inclusion of our data, TD remains a weak but a significant predictor of death (OR=1.4). DISCUSSION: Neuroleptic-induced EPS of parkinsonism, akathisia, and TD did not contribute to the patients' all-cause mortality in this study. The association between TD and mortality merits further attention.

Discontinuation of droperidol for the control of acutely agitated out-of-hospital patients.

OBJECTIVE: To identify the effects of the removal of droperidol as a treatment option for sedation of agitated out-of-hospital patients. METHODS: This was a retrospective review conducted January 1, 2001, through December 5, 2002, of patients with an out-of-hospital diagnosis of agitation who received either droperidol or midazolam prior to arrival in the emergency department (ED). The need for continuous cardiac or pulse oximetry monitoring, intubation, critical care ED management, intensive care unit admission, and mortality was reviewed. RESULTS: Seventy-one patients received droperidol or midazolam for acute agitation in the out-of-hospital setting. Forty-one patients received droperidol in 2001 (D2001); three patients received midazolam in 2001 (M2001). No patients received droperidol in 2002, and 27 patients received midazolam (M2002). Comparing the D2001 and M2002 groups, the need for continuous pulse oximetry monitoring in the ED [14/41 (34.1%) versus 18/27 (66.7%)], intubations [4/41 (9.8%) versus 10/27 (37.0%)], critical emergency medical services transports [5/41 (12.2%) versus 11/27 (40.7%)], critical ED care cases [6/41 (14.6%) versus 11/27 (40.7%)], and intensive care unit admissions [6/13 (46.2%) versus 14/15 (93.3%)] were increased in the M2002 group. No difference was found in the frequencies of ED cardiac monitoring, hospital admission, complications, or death. CONCLUSIONS: Since the removal of droperidol as a treatment option for out-of-hospital agitated patients, the authors have observed an increased frequency of continuous pulse oximetry monitoring, intubation, ED critical care management, and intensive care unit admission in patients requiring chemical sedation for control of agitation in the out-of-hospital setting.

Haloperidol use is associated with lower hospital mortality in mechanically ventilated patients.

OBJECTIVE: To determine whether haloperidol use is associated with lower mortality in mechanically ventilated patients. DESIGN: Retrospective cohort analysis. SETTING: A large tertiary care academic medical center. PATIENTS: A total of 989 patients mechanically ventilated for >48 hrs. MEASUREMENTS AND MAIN RESULTS: We compared differences in hospital mortality between patients who received haloperidol within 2 days of initiation of mechanical ventilation and those who never received haloperidol. Despite similar baseline characteristics, patients treated with haloperidol had significantly lower hospital mortality compared with those who never received haloperidol (20.5% vs. 36.1%; p = .004). The lower associated mortality persisted after adjusting for age, comorbidity, severity of illness, degree of organ dysfunction, admitting diagnosis, and other potential confounders. CONCLUSIONS: Haloperidol was associated with significantly lower hospital mortality. These findings could have enormous implications for critically ill patients. Because of their observational nature and the potential risks associated with haloperidol use, they require confirmation in a randomized, controlled trial before being applied to routine patient care.

The effect of a structured intervention on caregivers of patients with dementia and problem behaviors: a randomized controlled pilot study.

The objective was to assess the effect of a structured intervention on caregiver stress and the institutionalization rate of patients with dementia and problem behaviors. Caregivers contacting the Federazione Alzheimer Italia (AI) to receive help, advice, or information in relation to problem behaviors of outpatients were enrolled. Eligible caregiver-patient dyads were randomized to receive either a structured intervention or the counseling AI usually provides (control group). After basal assessment, families were reassessed at 6 and 12 months. Problem behavior (particularly agitation) was the only variable significantly correlated (P = 0.006) with the baseline caregivers' stress score. Thirty-nine families completed the 12-month follow-up; the mean problem behavior score was significantly lower in the intervention than the control group (p < 0.03); the time needed for care of the patient increased by 0.5 +/- 9.7 hours/day in the control group and decreased by 0.3 +/- 4.1 in the intervention group (p = 0.4, Wilcoxon test). The main determinant of institutionalization seemed to be the level of caregiver stress (p = 0.03). In patients of the intervention group, there was a significant reduction in the frequency of delusions. This pilot study suggests that caregiver stress is relieved by a structured intervention. The number of families lost to follow-up, the relatively short duration of the study, and the ceiling effect due to the severity of the clinical characteristics of patients probably all partly dilute the observed findings.

Life-threatening brain failure and agitation in the intensive care unit.

The modern intensive care unit (ICU) has evolved into an area where mortality and morbidity can be reduced by identification of unexpected hemodynamic and ventilatory decompensations before long-term problems result. Because intensive care physicians are caring for an increasingly heterogeneous population of patients, the indications for aggressive monitoring and close titration of care have expanded. Agitated patients are proving difficult to deal with in nonmonitored environments because of the unpredictable consequences of the agitated state on organ systems. The severe agitation state that is associated with ethanol withdrawal and delirium tremens (DT) is examined as a model for evaluating the efficacy of the ICU environment to ensure consistent stabilization of potentially life-threatening agitation and delirium.

The significance of patient appearance in predicting severity of injury.

The observations of pallor, sweating, agitation and restlessness, at the time of an injured patient's admission to the resuscitation room, were compared with other more complex indices of injury severity and the ability of each observation to predict mortality was observed. The number of positive observations was significantly related to the Revised Trauma Score and the Injury Severity Score, and pallor was significantly related to mortality. The observation that an injured patient is pale is an important index of severity.