Association of aggressive behaviours with psychiatric disorders, age, sex and degree of intellectual disability: a large-scale survey.

BACKGROUND: The link between aggression and mental disorders has been the focus of diverse studies in persons with and without intellectual disabilities (ID). Because of discrepancies in the finding of studies in persons with ID to date, and because of differences in research design, instruments used and the population studied, more research is needed. The purpose of this study was to delineate any significant association between certain psychiatric disorders and specific domains of aggressive behaviours in a large sample of persons with ID controlling for sex, age, autism and degree of ID. METHOD: Data from the present study were obtained from 47% of all persons with ID receiving services from New York State agencies, using the Institute for Basic Research - Modified Overt Aggression Scale (IBR-MOAS between 2006 and 2007). The IBR-MOAS was completed by the chief psychologists of 14 agencies based on information from the participants' files. Demographic information obtained included the psychiatric diagnosis made by the treating psychiatrist as well as information on age, sex and degree of ID. Data from 4069 participants were analysed. RESULTS: Impulse control disorder and bipolar disorder were strongly associated with all five domains of aggressive behaviour in the IBR-MOAS. Psychotic disorder was highly associated with four domains except for physical aggression against self (PASLF), which was of borderline significance. Anxiety was most associated with PASLF and verbal aggression against self (VASLF); depression with VASLF; obsessive compulsive disorder with physical aggression against objects (PAOBJ); personality disorders with verbal aggression against others (VAOTH), VASLF and PASLF; and autism with physical aggression against others (PAOTH), PAOBJ and PASLF. Mild to moderate ID was associated with VAOTH and VASLF and severe to profound ID with PAOBJ and PASLF. Female sex was most associated with VASLF. CONCLUSIONS: Impulse control, mood dysregulation and perceived threat appear to underlie most of the aggressive behaviours reported. Psychosis and depression appeared to have been over-diagnosed in persons with mild to moderate ID and under-diagnosed in persons with severe and profound ID. These findings replicate and extend findings from previous studies. The pattern of associations reported can be used as helpful indicators by professionals involved in the treatment of aggressive behaviours in persons with ID.

Autism severity is associated with child and maternal MAOA genotypes.

Autism severity is associated with child and maternal MAOA genotypes. We replicated and extended a previously reported association between autism severity and a functional polymorphism in the monoamine oxidase A (MAOA) promoter region, MAOA-uVNTR, in a sample of 119 males, aged 2-13 years, with autism spectrum disorder from simplex families. We demonstrated that (i) boys with the low activity 3-repeat MAOA allele had more severe sensory behaviors, arousal regulation problems, and aggression, and worse social communication skills than males with the high activity allele; and (ii) problems with aggression, as well as with fears and rituals, were modified by the mothers' genotype. Boys with the 4-repeat high activity allele who had homozygous 4-repeat mothers showed increased severity of these behaviors relative to those born to heterozygous mothers. These findings indicate the importance of considering maternal genotype in examining associations of MAOA and other genes with behavior in male offspring.

Association of autism severity with a monoamine oxidase A functional polymorphism.

A functional polymorphism (the upstream variable-number tandem repeat region, or uVNTR) in the monoamine oxidase A (MAOA) promoter region has been reported to be associated with behavioral abnormalities as well as increased serotonergic responsivity. We examined the relation between MAOA-uVNTR alleles and the phenotypic expression of autism in 41 males younger than 12.6 years of age. Children with the low-activity MAOA allele had both lower intelligence quotients (IQ) and more severe autistic behavior than children with the high-activity allele. In follow-up testing of 34 of the males at the 1-year time-point, those with the low-activity allele showed a worsening in IQ but no change in the severity of their autistic behavior. We conclude that functional MAOA-uVNTR alleles may act as a genetic modifier of the severity of autism in males.

Famotidine treatment of children with autistic spectrum disorders: pilot research using single subject research design.

Using single subject research design, we performed pilot research to evaluate the safety and efficacy of famotidine for the treatment of children with autistic spectrum disorders. We studied 9 Caucasian boys, 3.8-8.1 years old, with a DSM-IV diagnosis of a pervasive developmental disorder, living with their families, receiving no chronic medications, and without significant gastrointestinal symptoms. The dose of oral famotidine was 2 mg/kg/day (given in two divided doses); the maximum total daily dose was 100 mg. Using single-subject research analysis and medication given in a randomized, double-blind, placebo-controlled, cross-over design, 4 of 9 children randomized (44%) had evidence of behavioral improvement. Primary efficacy was based on data kept by primary caregivers, including a daily diary; daily visual analogue scales of affection, reciting, or aspects of social interaction; Aberrant Behavior Checklists (ABC, Aman); and Clinical Global Improvement scales. Children with marked stereotypy (meaningless, repetitive behaviors) did not respond. Our subjects did not have prominent gastrointestinal symptoms and endoscopy was not part of our protocol; thus, we cannot exclude the possibility that our subjects improved due to the effective treatment of asymptomatic esophagitis. The use of famotidine for the treatment of children with autistic spectrum disorders warrants further investigation.

Alpha2 macroglobulin elevation without an acute phase response in depressed adults with Down's syndrome: implications.

Studies of immune function during depression in persons without intellectual disability (ID) have revealed elevated levels of alpha2 macroglobulin (alpha2M) and an acute phase protein (APP) response. Clinical observation suggests that people with Down's syndrome (DS) may have associated genetic abnormalities in their immune systems. The APP response and alpha2M changes in depressed versus non-depressed adults with DS was the subject of the present study. The serum pan-proteinase inhibitor alpha2M, and the AP proteins c-reactive protein (CRP), alpha1 antitrypsin (alpha1AT), ceruloplasmin (Cp), beta2 Macroglobulin (beta2M), transthyretin (Trans), serum amyloid protein (SAP), and albumin (Alb) were measured in 38 adults with DS, 19 of whom were diagnosed with and 19 without depression using a sandwich enzyme-linked immunosorbent assay (ELISA). The DSM-IV criteria were used for diagnoses. Medical and neurological examinations excluded medical disorders associated with APP response. Only alpha2M and CRP were significantly different in the depressed versus non-depressed groups. The alpha2M was higher, a response similar to one observed in depressed people without ID, but the CRP was lower in the depressed group, especially in those subjects not on psychotropic medications, contrary to the expected APP response to depression. The results suggest that alpha2M elevation in depressed adults with DS is independent of the APP response. An alternative explanation for its elevation is proposed linking the core symptom of depression with the mammalian dormancy/hibernation process. Further studies are needed to confirm that alpha2M elevation is specific to depression and that it might provide a helpful marker for the diagnosis of depression in people with ID.

Patterns in costs and outcomes for patients with prolonged mechanical ventilation undergoing tracheostomy: an analysis of discharges under diagnosis-related group 483 in New York State from 1992 to 1996.

OBJECTIVE: To analyze the costs and discharge status for patients with prolonged mechanical ventilation undergoing tracheostomy. DESIGN: Retrospective analysis of a statewide database. PATIENTS: All patients (n = 37,573) >18 yrs of age who had prolonged mechanical ventilation (procedure code 96.72) and were discharged from the hospital between 1992 and 1996 with a final DRG code of 483. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Rates of change in discharges and hospital reimbursements and the cost per survivor were examined by case payment groups and discharge year. A direct relation between volume and reimbursement rate was seen over time, although the patient age distributions remained relatively stable. The greatest increase in volume was from 1995 to 1996. For most years, there was a consistent inverse relation between age and survival, with older survivors being more likely to be discharged to residential healthcare facilities and younger patients more likely to be discharged home. There was a consistent direct relation between age and cost per survivor, mainly the result of improved survival rather than decreased reimbursements in later years. CONCLUSIONS: More controlled reimbursements and improved overall survival rates for DRG 483 have contributed to the improved cost per survivor among all age groups over the period. Given the greater proportion of elderly that do not survive or who are placed into residential healthcare facilities, more scrutiny is needed concerning the use of DRG 483 resources so that care is better coordinated for these patients in the inpatient and postacute care settings.

Clinical and economic outcome of mechanically ventilated patients in New York State during 1993: analysis of 10,473 cases under DRG 475.

STUDY OBJECTIVES: To examine and describe the relationship between age and disposition in patients undergoing mechanical ventilation. DESIGN: Retrospective analysis of a statewide database. SETTING: All acute-care hospitals in New York State. PATIENTS: All patients (n=10,473) aged > or = 18 years discharged from hospital during 1993 with a final diagnosis related group (DRG) coding of 475. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The final disposition, according to six codes (other acute-care facility, residential health-care facility, other health-care facility, home, home health-care services, and death) were examined for the whole population. Cost per case was assumed to equal the average statewide Medicaid rate. An inverse relationship between survival rate and age was observed and this resulted in an age-related increased cost per survivor. Also, survivors in older age groups have an increasing rate of hospital discharge to residential health-care facilities. CONCLUSION: Patients who undergo mechanical ventilation are expensive to care for. The older they are, the less satisfactory is the outcome both from clinical and economic perspectives.

Guidelines on admission and discharge for adult intermediate care units. American College of Critical Care Medicine of the Society of Critical Care Medicine.

OBJECTIVE: To present guidelines for writing admission and discharge policies for adult intermediate care units. DATA SOURCES: Opinion of practitioners with experience and expertise in managing critical and intermediate care units. DATA SYNTHESIS: Consensus was reached regarding the characteristics of patients best suited for management in an intermediate care unit, as supported by a literature review. CONCLUSION: Criteria were developed that define patients who are optimal candidates for management in an intermediate care unit.

Reducing resource consumption through work redesign in a surgical intensive care unit: a multidisciplinary, protocol-based Progressive Care Area.

Patients with prolonged intensive care unit (ICU) length of stay, though few in number, consume as much as 50% of ICU resources. With increasing pressures for cost containment in health care, the availability of ICU beds may be jeopardized. To improve the efficiency of care for patients requiring a surgical intensive care unit (SICU) stay of 3 or more days, a multidisciplinary, highly "protocolized," Progressive Care Area was developed within the existing SICU environment. Entry into this area is limited to patients whose acuity level is not high by ICU standards, but too high for a general surgical floor. In designing the Progressive Care Area, we drew on a number of published management strategies-including total quality management concepts and our prior experience in establishing ventilator management teams. The Progressive Care Area has resulted in a reduction in both the frequency and variation of resources used. A Progressive Care Area within an existing ICU is a viable alternative for the care of the patients who have prolonged lengths of stay and are less acutely ill, and it significantly improves ICU efficiency.

Clinical and economic outcome of patients undergoing tracheostomy for prolonged mechanical ventilation in New York state during 1993: analysis of 6,353 cases under diagnosis-related group 483.

OBJECTIVE: To examine and describe the relation between age and disposition in patients undergoing tracheostomy. DESIGN: Retrospective analysis of a statewide database. SETTING: All acute care hospitals in New York state. PATIENTS: All patients (n = 6,353) > or = 18 yrs of age who were discharged from the hospital during 1993 with a final diagnosis-related groups code of 483. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The final disposition, according to six disposition codes (other acute care facility, residential healthcare facility, other healthcare facility, home, home healthcare services, and death) was examined for the entire population. Cost per case was assumed to equal the average statewide Medicaid rate. An inverse relation between survival rate and age was observed, which resulted in an age-related increased cost per survivor. Also, survivors in older age groups had an increased rate of discharge to residential healthcare facilities. There was a negative, albeit less marked, effect of older age on the rates of survivors discharged to home and to other healthcare facilities. CONCLUSIONS: Care of patients who undergo tracheostomy for prolonged mechanical ventilation is expensive. The older the patient, the less satisfactory the outcome from an economic, clinical, and possibly social perspective.

Mosaicism for the FMR1 gene influences adaptive skills development in fragile X-affected males.

Fragile X syndrome is one of the most common forms of inherited mental retardation, and the first of a new class of genetic disorders associated with expanded trinucleotide repeats. Previously, we found that about 41% of affected males are mosaic for this mutation in that some of their blood cells have an active fragile X gene and others do not. It has been hypothesized that these mosaic cases should show higher levels of functioning than those who have only the inactive full mutation gene, but previous studies have provided negative or equivocal results. In the present study, the cross-sectional development of communication, self-care, socialization, and motor skills was studied in 46 males with fragile X syndrome under age 20 years as a function of two variables: age and the presence or absence of mosaicism. The rate of adaptive skills development was 2-4 times as great in mosaic cases as in full mutation cases. There was also a trend for cases with autism to be more prevalent in the full-mutation group. These results have implications for prognosis, for the utility of gene or protein replacement therapies for this disorder, and for understanding the association between mental retardation, developmental disorders, and fragile X syndrome.

Critical care medicine: opportunities and strategies for improvement.

BACKGROUND: Like other areas of health care, critical care faces increasing pressure to improve the quality while reducing the cost of care. Strategies drawn from the literature and the authors' experiences are presented. STRATEGIES AND OPPORTUNITIES FOR IMPROVEMENTS: Ten process- or structure-related areas are targeted as strategically important focuses of improvement: (1) restructuring administrative lines to better suit key processes; (2) physician leadership in critical care units; (3) management training for critical care managers; (4) triage; (5) multidisciplinary critical care; (6) standardization of care; (7) developing alternatives to critical care units; (8) timeliness of care delivery; (9) appropriate use of critical care resources; and (10) tracking quality improvement. TIMELINESS OF CARE DELIVERY: Whatever the root cause(s) of unnecessary delays, the result is inefficient use of critical care resources-and ultimately either a need for more resources or longer wait times. Innovations designed to reduce wait times and waste, such as the establishment of a microchemistry stat laboratory, may prove valuable. APPROPRIATE USE OF CRITICAL CARE RESOURCES: Possible strategies for the appropriate use of critical care resources include better selection of well-informed patients who undergo procedures. Reduction in variation among physicians and organizations in providing therapies will also likely lead to a reduction in some high-risk procedures offering little or no benefit, and therefore a reduction in need for critical care services. Better preparation of patients and families should also make end-of-life decisions easier when questions of "futility" arise. Better information on outcomes and cost-effectiveness and consensus on withdrawal of critical care treatments represent two additional strategies.

Investigating the impact of age on outcome of mechanical ventilation using a population of 41,848 patients from a statewide database.

STUDY OBJECTIVE: To examine the impact of age on outcome from mechanical ventilation. DESIGN: Retrospective analysis of a statewide database. SETTING: All acute-care hospitals in New York State. PATIENTS: All patients, aged 18 years and over, requiring mechanical ventilation during 1990 who could be identified with a mechanical ventilation procedure code (93.92) were studied. Data were obtained in aggregate form (six or more cases) from the New York State Department of Health. This process required a detailed request letter to the Statewide Planning and Cooperative System (SPARCS). Transmission of confidential information was not desired or permitted. MEASUREMENTS AND RESULTS: Age and mortality rate (MR) fit a cuboidal regression model best (MR = -25.55 + 3.98Age - 0.072Age2 + 0.00043Age3, R2 = 0.85). Mortality rates vary significantly across various broad diagnostic groups (p < 0.01, analysis of variance [ANOVA]) and increase as a function of ICU duration (p < 0.01, ANOVA). CONCLUSIONS: Age has an important effect on outcome from mechanical ventilation. Other factors, such as ICU duration and diagnosis, also influence outcome, and age should not be used as a sole criterion in evaluating the potential benefit of mechanical ventilation to an individual patient. Large, existing databases, such as SPARCS, may be useful in studying the application of mechanical ventilation.

Effect of hemorrhagic shock and reperfusion on the respiratory quotient in swine.

OBJECTIVES: Respiratory quotient, the ratio of CO2 production to oxygen consumption (VO2), is principally affected by the fuel source used for aerobic metabolism. Since the respiratory quotient, VO2, and CO2 production cannot be directly measured easily, indirect calorimetry is commonly used to determine the value of these variables at the airway level (i.e., airway respiratory quotient, airway VO2, and airway CO2 production). However, under nonsteady-state conditions, a variety of phenomena can alter the relationship between true metabolic activity and measurements determined by indirect calorimetry. During exercise, for example, airway respiratory quotient increases as anaerobic threshold is reached because of the disproportionate increase in airway CO2 production that results from the CO2 liberated through the buffering of excess hydrogen ions by bicarbonate. We hypothesized that hemorrhage and reinfusion might change airway respiratory quotient in a consistent manner as shock is produced and reversed. DESIGN: Prospective laboratory study. SETTING: University animal laboratory. SUBJECTS: Eight pigs (25 +/- 2 [SD] kg), anesthetized with fentanyl and relaxed with pancuronium bromide, and mechanically ventilated on room air. INTERVENTIONS: The animals were sequentially hemorrhaged and then autotransfused while metabolic and hemodynamic measurements were obtained, using continuous indirect calorimetry and continuous applications of the Fick principle. Hemoglobin, arterial lactate concentration, and blood gases for calibration were measured serially. Analysis of variance was used to compare various periods in time. MEASUREMENTS AND MAIN RESULTS: Between baseline and peak hemorrhage, and between peak hemorrhage and postreinfusion, all of the following variables changed significantly (p < .05): airway VO2 (baseline 6.4 +/- 0.9 mL/min/kg, peak hemorrhage 3.9 +/- 0.6 mL/min/kg, postreinfusion 7.0 +/- 1.4 mL/min/kg); airway CO2 production (baseline 5.5 +/- 0.9 mL/min/kg, peak hemorrhage 4.5 +/- 0.9 mL/min/kg, postreinfusion 6.0 +/- 1.4 mL/min/kg); airway respiratory quotient (baseline 0.87 +/- 0.07, peak hemorrhage 1.16 +/- 0.07, postreinfusion 0.87 +/- 0.05); lactate concentration (baseline 2.4 +/- 1.2 mmol/L, peak hemorrhage 6.7 +/- 1.9 mmol/L, postreinfusion 5.1 +/- 2.0 mmol/L); and delta PCO2 (venous PCO2-PaCO2) (baseline 4.5 +/- 3.6 torr [0.6 +/- 0.5 kPa], peak hemorrhage 12.1 +/- 5.3 torr [1.6 +/- 0.7 kPa], postreinfusion 2.7 +/- 2.7 torr [0.4 +/- 0.4 kPa]). CONCLUSIONS: Airway respiratory quotient increases in hemorrhagic shock and decreases again as shock is reversed during reinfusion. This phenomenon appears related to the buffering of excess of hydrogen ion during hemorrhagic shock.

Cost containment and mechanical ventilation in the United States.

In many ICUs, admission and discharge hinge on the need for intubation and ventilatory support. As few as 5% to 10% of ICU patients require prolonged mechanical ventilation, and this patient group consumes > or = 50% of ICU patient days and ICU resources. Prolonged ventilatory support and chronic ventilator dependency, both in the ICU and non-ICU settings, have a significant and growing impact on healthcare economics. In the United States, the need for prolonged mechanical ventilation is increasingly recognized as separate and distinct from the initial diagnosis and/or procedure that leads to hospitalization. This distinction has led to improved reimbursement under the prospective diagnosis-related group (DRG) system, and demands more precise accounting from healthcare providers responsible for these patients. Using both published and theoretical examples, mechanical ventilation in the United States is discussed, with a focus on cost containment. Included in the discussion are ventilator teams, standards of care, management protocols, stepdown units, rehabilitation units, and home care. The expanding role of total quality management (TQM) is also presented.

An artificial neural network analogue of learning in autism.

An artificial neural network is simulated that shares formal qualitative similarities with the selective attention and generalization deficits seen in people with autism. The model is based on neuropathological studies which suggest that affected individuals have either too few or too many neuronal connections in various regions of the brain. In simulations where the model was taught to discriminate children with autism from children with mental retardation, having too few simulated neuronal connections led to relatively inferior discrimination of the two groups in a training set and, consequently, relatively inferior generalization of the discrimination to a novel test set. Too many connections produced excellent discrimination but inferior generalization because of overemphasis on details unique to the training set. It is concluded that, within the context of the current model, the neuropathological observations that have been described in the literature are sufficient to explain some of the unique pattern recognition and discrimination learning abilities seen in some people with autism as well as their problems with generalization and concept acquisition. The model generates testable hypotheses that have implications for understanding the pathogenesis, treatment, and phenomenology of autism.

Feasibility of continuous oxygen delivery and cardiac output measurement by application of the Fick principle.

Continuous mixed venous oxygen saturation (SVO2) measurements from fiberoptic pulmonary artery catheters, arterial oxygen saturation (SaO2) measurements from pulse oximetry, and minute-by-minute oxygen consumption (VO2) measurements from indirect calorimetry can be used for near-continuous estimation of cardiac output (Qt) and oxygen delivery (DO2) by application of the Fick Principle. Assumptions required for calculation of blood oxygen contents include constant hemoglobin concentration (Hgb) and constant or negligible physically dissolved oxygen. First, the influence of these assumptions on continuous Qt and DO2 determinations was tested. Unmeasured changes in Hgb resulted in substantial error in calculated Qt, whereas calculated DO2 was minimally affected. Both Qt and DO2 were little altered by errors in PaO2 or PVO2. Second, the effects of SVO2, SaO2, and VO2 measurement errors on Qt and DO2 calculations under normal and extreme conditions were quantified. Relative errors in SVO2 were increased by a factor of 4.2 in Qt estimations and by a factor of 3.2 in DO2 measurements under normal conditions. These factors increased with increasing SVO2, and thus, Qt and DO2 became increasingly unreliable as oxygen extraction fell. Third, we compared continuous measurements of Qt and DO2 with intermittent measurements made by thermodilution cardiac output and blood sampling, and found correlation coefficients of 0.85 for Qt and 0.89 for DO2. Fourth, common measurement errors in VO2 and DO2 calculated in this way were found to bias regressions between VO2 and DO2, and this bias could be minimized only if the DO2 range were high and SVO2 were low.(ABSTRACT TRUNCATED AT 250 WORDS)

A neural network approach to the classification of autism.

A nonlinear pattern recognition system, neural network technology, was explored for its utility in assisting in the classification of autism. It was compared with a more traditional approach, simultaneous and stepwise linear discriminant analyses, in terms of the ability of each methodology to both classify and predict persons as having autism or mental retardation based on information obtained from a new structured parent interview: the Autistic Behavior Interview. The neural network methodology was superior to discriminant function analysis both in its ability to classify groups (92 vs. 85%) and to generalize to new cases that were not part of the training sample (92 vs. 82%). Interrater and test-retest reliabilities and measures of internal consistency were satisfactory for most of the subscales in the Autistic Behavior Interview. The implications of neural network technology for diagnosis, in general, and for understanding of possible core deficits in autism are discussed.