Recovery Trajectories in Children Requiring 3 or More Days of Invasive Ventilation.

OBJECTIVES: To characterize health-related quality of life (HRQL) and functional recovery trajectories and risk factors for prolonged impairments among critically ill children receiving greater than or equal to 3 days of invasive ventilation. DESIGN: Prospective cohort study. SETTING: Quaternary children's hospital PICU. PATIENTS: Children without a preexisting tracheostomy who received greater than or equal to 3 days of invasive ventilation, survived hospitalization, and completed greater than or equal to 1 postdischarge data collection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated 144 children measuring HRQL using proxy-report Pediatric Quality of Life Inventory and functional status using the Functional Status Scale (FSS) reflecting preillness baseline, PICU and hospital discharge, and 1, 3, 6, and 12 months after hospital discharge. They had a median age of 5.3 years (interquartile range, 1.1-13.0 yr), 58 (40%) were female, 45 (31%) had a complex chronic condition, and 110 (76%) had normal preillness FSS scores. Respiratory failure etiologies included lung disease ( n = 49; 34%), neurologic failure ( n = 23; 16%), and septic shock ( n = 22; 15%). At 1-month postdischarge, 68 of 122 (56%) reported worsened HRQL and 35 (29%) had a new functional impairment compared with preillness baseline. This improved at 3 months to 54 (46%) and 24 (20%), respectively, and remained stable through the remaining 9 months of follow-up. We used interaction forests to evaluate relative variable importance including pairwise interactions and found that therapy consultation within 3 days of intubation was associated with better HRQL recovery in older patients and those with better preillness physical HRQL. During the postdischarge year, 76 patients (53%) had an emergency department visit or hospitalization, and 62 (43%) newly received physical, occupational, or speech therapy. CONCLUSIONS: Impairments in HRQL and functional status as well as health resource use were common among children with acute respiratory failure. Early therapy consultation was a modifiable characteristic associated with shorter duration of worsened HRQL in older patients.

A Core Outcome Measurement Set for Pediatric Critical Care.

OBJECTIVES: To identify a PICU Core Outcome Measurement Set (PICU COMS), a set of measures that can be used to evaluate the PICU Core Outcome Set (PICU COS) domains in PICU patients and their families. DESIGN: A modified Delphi consensus process. SETTING: Four webinars attended by PICU physicians and nurses, pediatric surgeons, rehabilitation physicians, and scientists with expertise in PICU clinical care or research ( n = 35). Attendees were from eight countries and convened from the Pediatric Acute Lung Injury and Sepsis Investigators Pediatric Outcomes STudies after PICU Investigators and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network PICU COS Investigators. SUBJECTS: Measures to assess outcome domains of the PICU COS are as follows: cognitive, emotional, overall (including health-related quality of life), physical, and family health. Measures evaluating social health were also considered. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measures were classified as general or additional based on generalizability across PICU populations, feasibility, and relevance to specific COS domains. Measures with high consensus, defined as 80% agreement for inclusion, were selected for the PICU COMS. Among 140 candidate measures, 24 were delineated as general (broadly applicable) and, of these, 10 achieved consensus for inclusion in the COMS (7 patient-oriented and 3 family-oriented). Six of the seven patient measures were applicable to the broadest range of patients, diagnoses, and developmental abilities. All were validated in pediatric populations and have normative pediatric data. Twenty additional measures focusing on specific populations or in-depth evaluation of a COS subdomain also met consensus for inclusion as COMS additional measures. CONCLUSIONS: The PICU COMS delineates measures to evaluate domains in the PICU COS and facilitates comparability across future research studies to characterize PICU survivorship and enable interventional studies to target long-term outcomes after critical illness.

Identifying Long-Term Morbidities and Health Trajectories After Prolonged Mechanical Ventilation in Children Using State All Payer Claims Data.

OBJECTIVES: To identify postdischarge outcome phenotypes and risk factors for poor outcomes using insurance claims data. DESIGN: Retrospective cohort study. SETTING: Single quaternary center. PATIENTS: Children without preexisting tracheostomy who required greater than or equal to 3 days of invasive mechanical ventilation, survived the hospitalization, and had postdischarge insurance eligibility in Colorado's All Payer Claims Database. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used unsupervised machine learning to identify functional outcome phenotypes based on claims data representative of postdischarge morbidities. We assessed health trajectory by comparing change in the number of insurance claims between quarters 1 and 4 of the postdischarge year. Regression analyses identified variables associated with unfavorable outcomes. The 381 subjects had median age 3.3 years (interquartile range, 0.9-12 yr), and 147 (39%) had a complex chronic condition. Primary diagnoses were respiratory (41%), injury (23%), and neurologic (11%). We identified three phenotypes: lower morbidity (n = 300), higher morbidity (n = 62), and 1-year nonsurvivors (n = 19). Complex chronic conditions most strongly predicted the nonsurvivor phenotype. Longer PICU stays and tracheostomy placement most strongly predicted the higher morbidity phenotype. Patients with high but improving postdischarge resource use were differentiated by high illness severity and long PICU stays. Patients with persistently high or increasing resource use were differentiated by complex chronic conditions and tracheostomy placement. CONCLUSIONS: New morbidities are common after prolonged mechanical ventilation. Identifying phenotypes at high risk of postdischarge morbidity may facilitate prognostic enrichment in clinical trials.

Association of Socioeconomic Status With Postdischarge Pediatric Resource Use and Quality of Life.

OBJECTIVES: Socioeconomic factors may impact healthcare resource use and health-related quality of life, but their association with postcritical illness outcomes is unknown. This study examines the associations between socioeconomic status, resource use, and health-related quality of life in a cohort of children recovering from acute respiratory failure. DESIGN: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial. SETTING: Thirty-one PICUs. PATIENTS: Children with acute respiratory failure enrolled whose parent/guardians consented for follow-up. MEASUREMENTS AND MAIN RESULTS: Resource use included in-home care, number of healthcare providers, prescribed medications, home medical equipment, emergency department visits, and hospital readmission. Socioeconomic status was estimated by matching residential address to census tract-based median income. Health-related quality of life was measured using age-based parent-report instruments. Resource use interviews with matched census tract data (n = 958) and health-related quality of life questionnaires (n = 750/958) were assessed. Compared with high-income children, low-income children received care from fewer types of healthcare providers (ß = -0.4; p = 0.004), used less newly prescribed medical equipment (odds ratio = 0.4; p < 0.001), and had more emergency department visits (43% vs 33%; p = 0.04). In the youngest cohort (< 2 yr old), low-income children had lower quality of life scores from physical ability (-8.6 points; p = 0.01) and bodily pain/discomfort (+8.2 points; p < 0.05). In addition, health-related quality of life was lower in those who had more healthcare providers and prescribed medications. In older children, health-related quality of life was lower if they had prescribed medications, emergency department visits, or hospital readmission. CONCLUSIONS: Children recovering from acute respiratory failure have ongoing healthcare resource use. Yet, lower income children use less in-home and outpatient services and use more hospital resources. Continued follow-up care, especially in lower income children, may help identify those in need of ongoing healthcare resources and those at-risk for decreased health-related quality of life.

A Core Outcome Set for Pediatric Critical Care.

OBJECTIVES: More children are surviving critical illness but are at risk of residual or new health conditions. An evidence-informed and stakeholder-recommended core outcome set is lacking for pediatric critical care outcomes. Our objective was to create a multinational, multistakeholder-recommended pediatric critical care core outcome set for inclusion in clinical and research programs. DESIGN: A two-round modified Delphi electronic survey was conducted with 333 invited research, clinical, and family/advocate stakeholders. Stakeholders completing the first round were invited to participate in the second. Outcomes scoring greater than 69% "critical" and less than 15% "not important" advanced to round 2 with write-in outcomes considered. The Steering Committee held a virtual consensus conference to determine the final components. SETTING: Multinational survey. PATIENTS: Stakeholder participants from six continents representing clinicians, researchers, and family/advocates. MEASUREMENTS AND MAIN RESULTS: Overall response rates were 75% and 82% for each round. Participants voted on seven Global Domains and 45 Specific Outcomes in round 1, and six Global Domains and 30 Specific Outcomes in round 2. Using overall (three stakeholder groups combined) results, consensus was defined as outcomes scoring greater than 90% "critical" and less than 15% "not important" and were included in the final PICU core outcome set: four Global Domains (Cognitive, Emotional, Physical, and Overall Health) and four Specific Outcomes (Child Health-Related Quality of Life, Pain, Survival, and Communication). Families (n = 21) suggested additional critically important outcomes that did not meet consensus, which were included in the PICU core outcome set-extended. CONCLUSIONS: The PICU core outcome set and PICU core outcome set-extended are multistakeholder-recommended resources for clinical and research programs that seek to improve outcomes for children with critical illness and their families.

Postdischarge Outcome Domains in Pediatric Critical Care and the Instruments Used to Evaluate Them: A Scoping Review.

OBJECTIVES: Assessing outcomes after pediatric critical illness is imperative to evaluate practice and improve recovery of patients and their families. We conducted a scoping review of the literature to identify domains and instruments previously used to evaluate these outcomes. DESIGN: Scoping review. SETTING: We queried PubMed, EMBASE, PsycINFO, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Central Register of Controlled Trials Registry for studies evaluating pediatric critical care survivors or their families published between 1970 and 2017. We identified articles using key words related to pediatric critical illness and outcome domains. We excluded articles if the majority of patients were greater than 18 years old or less than 1 month old, mortality was the sole outcome, or only instrument psychometrics or procedural outcomes were reported. We used dual review for article selection and data extraction and categorized outcomes by domain (overall health, emotional, physical, cognitive, health-related quality of life, social, family). SUBJECTS: Manuscripts evaluating outcomes after pediatric critical illness. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 60,349 citations, 407 articles met inclusion criteria; 87% were published after 2000. Study designs included observational (85%), interventional (7%), qualitative (5%), and mixed methods (3%). Populations most frequently evaluated were traumatic brain injury (n = 96), general pediatric critical illness (n = 87), and congenital heart disease (n = 72). Family members were evaluated in 74 studies (18%). Studies used a median of 2 instruments (interquartile range 1-4 instruments) and evaluated a median of 2 domains (interquartile range 2-3 domains). Social (n = 223), cognitive (n = 183), and overall health (n = 161) domains were most frequently studied. Across studies, 366 unique instruments were used, most frequently the Wechsler and Glasgow Outcome Scales. Individual domains were evaluated using a median of 77 instruments (interquartile range 39-87 instruments). CONCLUSIONS: A comprehensive, generalizable understanding of outcomes after pediatric critical illness is limited by heterogeneity in methodology, populations, domains, and instruments. Developing assessment standards may improve understanding of postdischarge outcomes and support development of interventions after pediatric critical illness.

PICU-Based Rehabilitation and Outcomes Assessment: A Survey of Pediatric Critical Care Physicians.

OBJECTIVES: Characterize current practices for PICU-based rehabilitation, and physician perceptions and attitudes, barriers, resources, and outcome assessment in contemporary PICU settings. DESIGN: International, self-administered, quantitative, cross-sectional survey. SETTING: Online survey distributed from March 2017 to April 2017. PATIENTS OR SUBJECTS: Pediatric critical care physicians who subscribed to email distribution lists of the Pediatric Acute Lung Injury and Sepsis Investigators, the Pediatric Neurocritical Care Research Group, or the Prevalence of Acute Critical Neurological Disease in Children: A Global Epidemiological Assessment study group, and visitors to the World Federation of Pediatric Intensive and Critical Care Societies website. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 170 subjects who began the survey, 148 completed it. Of those who completed the optional respondent information, most reported working in an academic medical setting and were located in the United States. The main findings were 1) a large majority of PICU physicians reported working in institutions with no guidelines for PICU-based rehabilitation, but expressed interest in developing and implementing such guidelines; 2) despite this lack of guidelines, an overwhelming majority of respondents reported that their current practices would involve consultation of multiple rehabilitation services for each case example provided; 3) PICU physicians believed that additional research evidence is needed to determine efficacy and optimal implementation of PICU-based rehabilitation; 4) PICU physicians reported significant barriers to implementation of PICU-based rehabilitation across centers; and 5) low routine assessment of long-term functional outcomes of PICU patients, although some centers have developed multidisciplinary follow-up programs. CONCLUSIONS: Physicians lack PICU-based rehabilitation guidelines despite great interest and current practices involving a high degree of PICU-based rehabilitation consultation. Data are needed to identify best practices and necessary resources in the delivery of ICU-based multidisciplinary rehabilitation and long-term functional outcomes assessment to optimize recovery of children and families affected by critical illness.

New Morbidity and Discharge Disposition of Pediatric Acute Respiratory Distress Syndrome Survivors.

OBJECTIVES: Much of the research related to pediatric acute respiratory distress syndrome has focused on inhospital mortality and interventions affecting this outcome. Limited data exist on survivors' morbidity, hospital disposition, and 1-year survival. The aim of this study was to determine new morbidity rate, discharge disposition, and 1-year mortality for survivors of pediatric acute respiratory distress syndrome. DESIGN: Secondary analysis of prospective cohort study. SETTING: Quaternary children's hospital. PATIENTS: Three-hundred sixteen mechanically ventilated children with pediatric acute respiratory distress syndrome (Berlin and Pediatric Acute Lung Injury Consensus Conference criteria) between July 2011 and December 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We performed secondary analysis of a prospectively recruited cohort of 316 mechanically ventilated children with pediatric acute respiratory distress syndrome between July 2011, and December 2014. Preillness and hospital discharge Functional Status Scale score were determined via chart review, and factors associated with new morbidity, defined as an increase of Functional Status Scale score of 3 or more, were analyzed. Demographic variables, pediatric acute respiratory distress syndrome characteristics, and ventilator management were tested for association with development of new morbidity, discharge disposition, and 1-year mortality. Inhospital mortality of pediatric acute respiratory distress syndrome was 13.3% (42/316). Of 274 survivors to hospital discharge, new morbidity was seen in 63 patients (23%). Discharge to rehabilitation rate was 24.5% (67/274) and associated with development of new morbidity. One- and 3-year mortality of survivors was 5.5% (15 deaths) and 8% (22 deaths) and was associated with baseline Functional Status Scale, immunocompromised status, Pediatric Risk of Mortality III, and organ failures at pediatric acute respiratory distress syndrome onset, but not with pediatric acute respiratory distress syndrome severity. CONCLUSIONS: New morbidity was common after pediatric acute respiratory distress syndrome and appears to be intermediate phenotype between survival without morbidity and death, making it a useful metric in future interventional and outcome studies in pediatric acute respiratory distress syndrome.

Intensive care unit readmission during childhood after preterm birth with respiratory failure.

OBJECTIVE: To determine the incidence and risk factors for readmission to the intensive care unit (ICU) among preterm infants who required mechanical ventilation at birth. STUDY DESIGN: We studied preterm newborns (birth weight 500-1250 g) who required mechanical ventilation at birth and were enrolled in a multicenter trial of inhaled nitric oxide therapy. Patients were assessed up to 4.5 years of age via annual in-person evaluations and structured telephone interviews. Univariate and multivariable analyses of baseline and birth hospitalization predictors of ICU readmission were performed. RESULTS: Of 512 subjects providing follow-up data, 58% were readmitted to the hospital (51% of these had multiple readmissions, averaging 3.9 readmissions per subject), 19% were readmitted to an ICU, and 12% required additional mechanical ventilation support. In univariate analyses, ICU readmission was more common among male subjects (OR 2.01; 95% CI 1.27-3.18), infants with grade 3-4 intracranial hemorrhage (OR 2.13; 95% CI 1.23-3.69), increasing duration of birth hospitalization (OR 1.01 per day; 95% CI 1.00-1.02), and prolonged oxygen therapy (OR 1.01 per day; 95% CI 1.00-1.01). In the first year after birth hospitalization, children readmitted to an ICU incurred greater health care costs (median $69,700 vs $30,200 for subjects admitted to the ward and $9600 for subjects never admitted). CONCLUSIONS: Small preterm infants who were mechanically ventilated at birth have substantial risk for readmission to an ICU and late mechanical ventilation, require extensive health care resources, and incur high treatment costs.

Trends in the epidemiology of pediatric severe sepsis*.

OBJECTIVES: In the past decade, guidelines have been developed for the early detection and management of severe sepsis in children and neonates. However, severe sepsis continues to be a significant U.S. healthcare problem, accounting for over 720,000 annual hospitalizations. Large-scale epidemiologic studies of severe sepsis continue to be limited, particularly in children. We present data from 1995, 2000, and 2005 in seven U.S. states, examining how case mix, outcome, and resource use for pediatric severe sepsis have changed over time. DESIGN: We constructed a database including all acute-care hospitalizations for children in the seven states. For each case, we extracted data on demographic characteristics; the principal diagnosis, up to six secondary diagnoses, and six procedures as classified by the International Classification of Diseases, 9th Revision, Clinical Modification codes; and in-hospital fatality. We identified patients with severe sepsis using International Classification of Diseases, 9th Revision, Clinical Modification codes for both infection and acute organ failure. SETTING: Retrospective observational cohort dataset from seven U.S. states from 1995, 2000, and 2005. SUBJECTS: Children in the U.S. 0-19 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In 2005, 17,542 children were hospitalized with severe sepsis in the seven states; there was an 81% increase in pediatric severe sepsis cases since 1995 and a 45% increase since 2000. This corresponded to an increase in prevalence from 0.56 to 0.89 cases per 1,000 pediatric population. Between 1995 and 2005, the prevalence of severe sepsis in newborns more than doubled, from 4.5 to 9.7 cases per 1,000 births. The most common infecting organisms in all 3 years were Staphylococcus species. From 1995 to 2005, the case-fatality rate decreased from 10.3% to 8.9%. Case fatality associated with Staphylococcus aureus increased, whereas fatality associated with Streptococcus pneumoniae decreased by 75%. Nationally, there were 75,255 pediatric hospitalizations in 2005 involving severe sepsis, with an associated cost of $4.8 billion. CONCLUSIONS: Between 1995 and 2005, the prevalence of severe sepsis in U.S. children steadily rose, due to a significant increase in the prevalence of severe sepsis in newborns.

Role of sensory nervous system vasoactive peptides in hypertension.

The goal of the present research was to elucidate the roles and mechanisms by which the sensory nervous system, through the actions of potent vasodilator neuropeptides, regulates cardiovascular function in both the normal state and in the pathophysiology of hypertension. The animal models of acquired hypertension studied were deoxycorticosterone-salt (DOC-salt), subtotal nephrectomy-salt (SN-salt), and Nomega-nitro-L-arginine methyl ester (L-NAME)-induced hypertension during pregnancy in rats. The genetic model was the spontaneously hypertensive rat (SHR). Calcitonin gene-related peptide (CGRP) and substance P (SP) are potent vasodilating neuropeptides. In the acquired models of hypertension, CGRP and SP play compensatory roles to buffer the blood pressure (BP) increase. Their synthesis and release are increased in the DOC-salt model but not in the SN-salt model. This suggests that the mechanism by which both models lower BP in SN-salt rats is by increased vascular sensitivity. CGRP functions in a similar manner in the L-NAME model. In the SHR, synthesis of CGRP and SP is decreased. This could contribute to the BP elevation in this model. The CGRP gene knockout mouse has increased baseline mean arterial pressure. The long-term synthesis and release of CGRP is increased by nerve growth factor, bradykinin, and prostaglandins and is decreased by alpha2-adrenoreceptor agonists and glucocorticoids. In several animal models, sensory nervous system vasoactive peptides play a role in chronic BP elevation. In the acquired models, they play a compensatory role. In the genetic model, their decreased levels may contribute to the elevated BP. The roles of CGRP and SP in human hypertension are yet to be clarified.

Role of sensory nervous system vasoactive peptides in hypertension

The goal of the present research was to elucidate the roles and mechanisms by which the sensory nervous system, through the actions of potent vasodilator neuropeptides, regulates cardiovascular function in both the normal state and in the pathophysiology of hypertension. The animal models of acquired hypertension studied were deoxycorticosterone-salt (DOC-salt), subtotal nephrectomy-salt (SN-salt), and Nomega-nitro-L-arginine methyl ester (L-NAME)-induced hypertension during pregnancy in rats. The genetic model was the spontaneously hypertensive rat (SHR). Calcitonin gene-related peptide (CGRP) and substance P (SP) are potent vasodilating neuropeptides. In the acquired models of hypertension, CGRP and SP play compensatory roles to buffer the blood pressure (BP) increase. Their synthesis and release are increased in the DOC-salt model but not in the SN-salt model. This suggests that the mechanism by which both models lower BP in SN-salt rats is by increased vascular sensitivity. CGRP functions in a similar manner in the L-NAME model. In the SHR, synthesis of CGRP and SP is decreased. This could contribute to the BP elevation in this model. The CGRP gene knockout mouse has increased baseline mean arterial pressure. The long-term synthesis and release of CGRP is increased by nerve growth factor, bradykinin, and prostaglandins and is decreased by alpha2-adrenoreceptor agonists and glucocorticoids. In several animal models, sensory nervous system vasoactive peptides play a role in chronic BP elevation. In the acquired models, they play a compensatory role. In the genetic model, their decreased levels may contribute to the elevated BP. The roles of CGRP and SP in human hypertension are yet to be clarified

Intractable nausea, vomiting and diarrhea in a Mexican woman with No recent travel history.

A 45-year-old Mexican woman with a history of noninsulin dependent diabetes mellitus (NIDDM), hypertension, and coronary artery disease presented to the hospital after 2 months of intractable nausea, vomiting and diarrhea-all made worse by eating and drinking. She reported fever, chills, anorexia and a documented 50-pound weight loss during this period. She denied the signs and symptoms of melena, hematochezia, steatorrhea or constipation. She also reported left leg pain and decreased sensation and strength of her left leg compared to the right leg. She had been hospitalized 2 weeks prior to admission with the same symptoms and a diagnosis of viral gastroenteritis. She was also treated for H. pylori, but subsequent biopsy results were negative by Steiner stain.

Clustering of dyslipidemia, hyperuricemia, diabetes, and hypertension and its association with fasting insulin and central and overall obesity in a general population. Atherosclerosis Risk in Communities Study Investigators.

Clustering of elevated triglycerides, decreased high-density lipoprotein cholesterol (HDL-C), hyperuricemia, diabetes, and hypertension has been related to insulin resistance/high insulin levels and central and/or overall obesity. The extent to which these abnormalities cluster and whether hyperinsulinemia, central adiposity, and overall obesity each independently associate with this clustering were evaluated in 14,481 US whites and African-Americans 45 to 64 years of age. With the exception of hypertension, abnormalities rarely existed in isolated form. Clustering greatly exceeded chance association (P < .001). Although this clustering was greater in relative terms (ratio of observed to expected cluster frequency) in the lean and less centrally obese, it was greater in absolute terms (observed minus expected cluster frequency as a percent of total population) in the more centrally and more generally obese. The greatest excesses were found for clusters that included both hypertriglyceridemia and low HDL-C. Multiple logistic regression models showed strong and independent graded relationships of clusters with quintiles of fasting insulin (fifth quintile odds ratio, 10 to 54, P < .001) and to a lesser degree with quintiles of the waist to hip ratio (2.2 to 5.4, P < .001 for most) and of body mass index (1.6 to 4.5, P < .05 for most). In conclusion, all abnormalities cluster in excess of that predicted by chance, with clusters showing remarkable and graded independent associations with fasting hyperinsulinemia and to a lesser extent with central and overall obesity. Thus, a metabolic syndrome occurs in both lean and obese middle-aged US adults.

A metabolic syndrome in whites and African-Americans. The Atherosclerosis Risk in Communities baseline study.

OBJECTIVE: To describe clustering of hypertriglyceridemia, low HDL cholesterol, hypertension, diabetes, and hyperuricemia and its association with fasting insulin, waist-to-hip ratio (WHR), and BMI for African-American and white men and women. RESEARCH DESIGN AND METHODS: Observed frequencies of clusters were compared with those expected in 14,481 participants, 45-64 years of age, of the Atherosclerosis Risk in Communities (ARIC) baseline survey, 1987-1989. Associations of clusters with insulin, central adiposity, and overall obesity, as well as with abnormalities, were analyzed through multiple logistic regression. RESULTS: Clustering beyond chance was observed in all four sex/ethnic groups (P < 0.001), with 7% of the sample presenting 30% of the abnormalities in large clusters (> or = 3 abnormalities per individual). The odds ratio (OR) for the association of each abnormality with clustering of the remaining four ranged from 1.6 to 8.8 (P < 0.01). These odds of clustering were notably large in white women. Of the abnormalities, hypertriglyceridemia demonstrated the highest OR (5.0-8.8) and diabetes had the lower OR in African-American subjects than in white subjects (P < 0.001). Insulin, WHR, and BMI were statistically associated with clustering in all groups (P < 0.001, except for BMI in African-Americans.

Influence of racial origin on admission rates of patients with suspected myocardial infarction in Birmingham.

All patients with suspected myocardial infarction admitted to hospital in four Birmingham health districts were studied to test the hypothesis that Asian patients would be overrepresented and Caribbean patients underrepresented compared with the indigenous population. One thousand four hundred and ninety six patients had a final diagnosis of myocardial infarction or severe angina pectoris. The relative risk of admission for Asian men compared with white men aged 45-64 years was 2.65 (95% confidence interval 2.20 to 3.19) and the risk for Asian men was high for both myocardial infarction and ischaemia when analysed separately. The relative risk of admission for Caribbean men compared with white men was 0.53 (95% CI 0.33 to 1.20). The relative risk for Asian women compared with white women in the same age group was 2.58 (95% CI 1.68 to 3.96), but this was due to an excess of admissions diagnosed as ischaemia rather than infarction in the Asian women. For Caribbean and white women the risk of admission was the same, although significantly fewer Caribbean women were admitted with myocardial infarction. The study was undertaken in 1986-87 and population data had to be derived from the 1981 census. The resident population changed in those five years and so the results were recalculated making allowances for these changes in the health districts involved. Based on these data the admission rate for Asian men with suspected myocardial infarction aged 45-64 was nearly twice that for white men (1.8): the relative risk of admission for Asian men compared with white men was 2.04 (95% CI 1.53 to 2.18). For Caribbean men the relative risk compared with white men was 0.45 (95% CI 0.29 to 0.71). For Asian women the relative risk of admission calculated from the adjusted census data resemble that in white women aged 45-64 years. The relative risk for admission with coronary heart disease in Asians is higher than expected work; one possible explanation for this is that the Asian population resident in the area under study was larger than estimated. The single major difference in risk factors was the high prevalence of diabetes mellitus in Asians (19.5% compared with 8.3% for white residents) but this did not wholly account for the excess of admissions from the Asian community.

Immunohistochemical localization of cholecystokinin in the medial preoptic area and anterior hypothalamus of the Brazilian gray short-tailed opossum: a sex difference.

We have studied the anatomical localization of cholecystokinin-like immunoreactivity (CCK IR) in somata and fibers in the medial preoptic area (MPA) and anterior hypothalamus (AH) of the Brazilian gray short-tailed opossum, (Monodelphis domestica). With the aid of an avidin-biotin, nickel-enhanced, immunohistochemical technique, CCK IR neuronal elements were found within the MPA and AH. A large number of CCK IR cell bodies were located in the MPA of colchicine-treated opossums. The MPA also contained a CCK IR fiber plexus. Quantitative image analysis revealed that the periventricular preoptic area of noncolchicine-treated male opossums had a significantly higher percent of blocked light measurements than that of the noncolchicine-treated females, indicating a higher density of CCK IR neuronal elements in the males. Neuronal fibers and somata containing CCK IR were also found within the periventricular hypothalamic nucleus (Pe), and the suprachiasmatic nucleus (SCh). These results show that CCK IR neuronal elements are found within the MPA and AH of the Brazilian short-tailed opossum. Furthermore, there is a sexually dimorphic distribution of CCK IR elements within the MPA of this small marsupial.