Borderline personality disorder in transition age youth with bipolar disorder.

OBJECTIVE: To determine the longitudinal impact of borderline personality disorder (BPD) on the course and outcome of bipolar disorder (BP) in a pediatric BP sample. METHOD: Participants (N = 271) and parents from the Course and Outcome of Bipolar Youth (COBY) study were administered structured clinical interviews and self-reports on average every 8.7 months over a mean of 93 months starting at age 13.0 ± 3.1 years. The structured interview for DSM-IV personality disorders (SIDP-IV) was administered at the first follow-up after age 18 to assess for symptoms of BPD. BPD operationalized at the disorder, factor, and symptom level, was examined as a predictor of poor clinical course of BP using all years of follow-up data. RESULTS: The number of BPD symptoms was significantly associated with poor clinical course of BP, above and beyond BP characteristics. Affective dysregulation was most strongly associated with poor course at the factor level; the individual symptoms most strongly associated with poor course were dissociation/stress-related paranoid ideation, impulsivity, and affective instability. CONCLUSION: BPD severity adds significantly to the burden of BP illness and is significantly associated with a more chronic and severe course and outcome beyond what can be attributable to BP characteristics.

Parameter signature of a reel problem.

Clinics involved in follow-up of cardiac implantable electronic devices, especially implantable cardiac defibrillators (ICDs), increasing rely upon remote monitoring. This case describes the parameter signature characteristic of an uncommon but well-described syndrome. Analysis of the nature and timing of the sequence of abnormalities contained in the archived device data, all of which is available for review via remote monitoring, reveals the cause for failure of this primary prevention ICD system.

Use and impact of an automated telephone outreach system for asthma in a managed care setting.

OBJECTIVE: To test the ability of an automated telephone outreach intervention to reduce acute healthcare utilization and improve quality of life among adult asthma patients in a large managed care organization. STUDY DESIGN: Randomized clinical trial. METHODS: Patients with persistent asthma were randomly assigned to telephone outreach (automated = 3389, live caller = 192) or usual care (n = 3367). Intervention participants received 3 outreach calls over a 10-month period. The intervention provided brief, supportive information and flagged individuals with poor asthma control for follow-up by a provider. A survey was mailed to 792 intervention participants and 236 providers after the intervention. Additional feedback was obtained as part of the final intervention contact. RESULTS: The intent-to-treat analysis found no significant differences between the intervention and usual-care groups for medication use, healthcare utilization, asthma control, or quality of life. Post hoc analyses found that, compared with the control group, individuals who actually participated in the intervention were significantly more likely to use inhaled steroids and to have had a routine medical visit for asthma during the follow-up period and less likely to use short-acting beta-agonists. They also reported higher satisfaction with their asthma care and better asthma-specific quality of life. Of surveyed providers, 59% stated the program helped them to clinically manage their asthma patients and 70% thought the program should be continued. CONCLUSIONS: This study did not find improved health outcomes in the primary analyses. The intervention was well accepted by providers, however, and the individuals who participated in the calls appeared to have benefited from them. These findings suggest that further studies of automated telephone outreach interventions seem warranted.

Gender differences in asthma management and quality of life.

We mailed a survey to a sample of adults with persistent asthma to assess gender differences in asthma management and quality of life. Women were more likely to regularly use a peak flow meter, have a regular clinician for their asthma care, and to have a written asthma management plan. No gender differences in self-reported asthma severity were observed, and men and women ranked their knowledge and confidence in their self-management skills similarly. Women reported significantly worse health status than men, but the differences observed were small and were attenuated after adjusting for socioeconomic status, smoking, body mass index, and comorbid illness.

A randomized clinical trial of peak flow versus symptom monitoring in older adults with asthma.

OBJECTIVE: To determine whether peak flow monitoring has value above and beyond symptom monitoring when used as part of an asthma management plan. METHODS: From a large managed-care organization, 296 adults, aged 50-92 yr, were recruited and randomly assigned in equal numbers to either use of symptoms or peak flow rate (twice daily or "as needed") for asthma monitoring, and monitored every 6 mo for 2 yr. Interventions were delivered in four 90-min small-group classes and included a personalized action plan and coaching in proper use of asthma inhalers. RESULTS: We found no significant differences between peak flow rate and symptom monitoring, or between twice-daily and as-needed peak flow monitoring in the primary or secondary study outcomes: health care utilization (acute, nonacute, or total asthma visits), Asthma Quality-of-Life Questionnaire (AQLQ) scores, and lung function. AQLQ scores and prebronchodilator FEV1 increased significantly for both groups between baseline and 6 mo (AQLQ: mean, 0.4 units; 95% confidence interval, 0.3, 0.5; p < 0.0001; FEV1% predicted: mean, 4%). Inhaler technique improved substantially in both groups. CONCLUSIONS: Peak flow monitoring has no advantage over symptom monitoring as an asthma management strategy for older adults with moderate-severe asthma when used in a comprehensive asthma management program. Improved outcomes in both groups suggest that understanding proper medication use, regular monitoring of asthma status, and understanding how to respond to changes are of primary importance.

Incidence of work-related asthma in members of a health maintenance organization.

OBJECTIVE: The objective of this study was to evaluate work-related asthma among health maintenance organization (HMO) members. Recent reports suggest that the incidence of work-related asthma may be much higher than Sentinel Event Notification Systems for Occupational Risks (SENSOR) data estimate. METHODS: Using the HMO's electronic medical record, we identified 1,747 persons with evidence of new or recurrent asthma. Interviews with 352 of them elicited information about workplace exposures, symptoms, and home environment. Industrial hygienists rated the potential asthmagenicity of the respondents' work environments. RESULTS: Based on the industrial hygienist ratings and self-reported work-relatedness of asthma symptoms, we classified 33% of those interviewed as having potentially work-related asthma, suggesting an overall work-related asthma incidence/recurrence rate of 28 cases per 10,000. CONCLUSIONS: The contribution of occupation to the occurrence of adult onset asthma may be much higher than typically suggested in the literature.

Caesarean section delivery and the risk of allergic disorders in childhood.

BACKGROUND: The composition of the intestinal flora in young children, if unfavourable, may increase the susceptibility to allergic disorders. Beneficial intestinal microbes originate from the maternal vaginal tract and thus are more likely to be transferred during vaginal births than during Caesarean sections (C-sections). OBJECTIVE: To determine whether children born by C-section have a different risk of allergic disorders compared with those delivered vaginally. We also tested the hypothesis that the risk of allergic disorders is highest for children born after 'repeat C-sections'. METHODS: A retrospective cohort study of 8,953 children aged 3-10 years. Children diagnosed with allergic rhinoconjunctivitis (AR), asthma, atopic dermatitis (AD), or food allergies were identified from the Kaiser Permanente Northwest Region electronic records. The children's sex, birth weight, birth order, postnatal exposure to antibiotics as well as the mothers' age, ethnicity, education, marital status, smoking status during pregnancy, and use of asthma or hayfever medications were identified through the mothers' medical records or through the Oregon Birth Registry. RESULTS: The risk of being diagnosed with AR was significantly higher in the children born by C-section than in those delivered vaginally: adjusted odds ratio (OR)=1.37%, 95% confidence interval (CI)=1.14-1.63. Delivery by C-section was also associated with the subsequent diagnosis of asthma (OR=1.24%, 95% CI=1.01-1.53); this association was gender specific, with a positive association restricted to girls (OR for asthma in girls: OR=1.53%, 95% CI=1.11-2.10; in boys: OR=1.08%, 95% CI=0.81-1.43). There was no significant association between mode of delivery and AD. If children born in a 'repeat C-section' were considered separately the risk of being diagnosed with AR increased further (OR=1.78%, 95% CI=1.34-2.37). The same increase was noted for asthma in girls (OR=1.83%, 95% CI=1.13-2.97) but not in boys. CONCLUSION: Caesarean sections may be associated with an increased risk of developing AR in childhood.

Incidence of Churg-Strauss syndrome in asthma drug users: a population-based perspective.

OBJECTIVE: To estimate the incidence of Churg-Strauss syndrome (CSS) among a large population of asthma drug users. METHODS: A retrospective study was conducted among patients who had been dispensed asthma drugs at 3 managed care organizations. Adults who received >or =3 dispensings of an asthma drug during any consecutive 12-month period between January 1, 1995 and June 30, 2000 were identified. Information on patient age, gender, enrollment status, asthma drugs dispensed, and inpatient and outpatient diagnoses and procedures was obtained from automated databases. Chart reviews were performed on persons identified by combinations of diagnostic and billing codes indicative of CSS. A rheumatologist reviewed abstracted information on all subjects; those who met >or =2 American College of Rheumatology criteria for CSS were reviewed by 2 clinical experts. Each clinical expert independently rated the cases; disagreements were resolved by consensus. Cases classified as having "probable/definite" CSS were included in these analyses. The incidence of CSS was estimated overall and according to patient gender, age, and calendar year. RESULTS: From a population of 184,667 asthma drug users contributing 606,184 person-years of exposure, 21 incident cases of CSS were identified (overall incidence of 34.6 per million person-years; 95% confidence interval 21.4 to 53.0). Incidence rates did not differ by gender and age group. The incidence rates for 1995, 1996, 1997, 1998, 1999, and the first 6 months of 2000 were 0, 22, 52, 75, 14, and 14 per million person-years respectively. CONCLUSIONS: Results from this population-based study suggest a somewhat lower incidence of CSS in asthma drug users than previously reported and provides important information as to the risk of developing CSS from a population-based perspective.

Identification of patients with Churg-Strauss syndrome (CSS) using automated data.

PURPOSE: Our aim was to identify individuals with Churg-Strauss syndrome (CSS) among asthma drug users, based on patterns of diagnostic and procedural codes (termed 'algorithms') contained in automated claims data. METHODS: A retrospective study was conducted among patients who had been dispensed asthma drugs at three HMOs. Individuals who received > or =3 dispensings of an asthma drug during any consecutive 12-month period beginning 1 January 1994 through 20 June 2000 were identified. Information on patient age, gender, enrollment status, asthma drugs dispensed, inpatient and outpatient diagnoses and procedures were obtained from the HMO automated databases. Twelve combinations of diagnostic and billing codes ('algorithms') were developed using the claims data to identify potential cases of CSS. Chart reviews blinded to drug exposure were performed using a standardized abstraction form. A rheumatologist reviewed abstracted information on all subjects, and those who met two or more American College of Rheumatology (ACR) criteria for CSS were further reviewed by two clinical experts. Cases were classified as unlikely, possible, or probable/definite CSS. Each clinical expert independently rated the cases; disagreements were resolved by consensus. RESULTS: A total of 185 604 patients who had been dispensed asthma drugs were identified. Three hundred fifty subjects were selected for chart review, and 15 were classified as having 'probable/definite' CSS. The algorithms that were most successful in identifying patients with CSS were as follows: (1) two or more codes for vasculitis (13 confirmed cases from 129 reviewed; positive predictive value 10%); (2) codes for both vasculitis and neurologic symptoms (6 confirmed cases from 15 reviewed; positive predictive value 40%) and (3) codes for both eosinophilia and vasculitis (4 confirmed cases from 5 reviewed; positive predictive value 80%). CONCLUSION: Automated claims data can be used to identify patients with CSS. This approach can facilitate better epidemiologic study of the risk factors for the condition.

Searching multiple clinical information systems for longer time periods found more prevalent cases of asthma.

OBJECTIVE: The development of a reliable asthma registry is an important first step for conducting population-based asthma disease management. This study developed a computerized algorithm for defining prevalent asthma, identified operational difficulties, and summarized data on asthma prevalence in the study population. STUDY DESIGN AND SETTING: As part of a study of the incidence of occupational asthma, we used the electronic databases of a large health maintenance organization to develop a computerized algorithm for defining prevalent asthma and validated it against chart review. The predictive values of eight health care utilization profiles were validated by chart review to establish the algorithm. RESULTS: The 1-year treated prevalence of asthma was 4.1% among members aged 15-55; the pharmacy database identified 61% of cases, and the outpatient care database 66%. Extending the outpatient care window from 1 year to 2 years increased estimated prevalence to 5.3%, with 81% now found in the outpatient care database. CONCLUSION: This analysis illustrates the benefit of using multiple databases for more accurate enumeration of cases and the impact of extending the search in time. These results are useful for researchers who can use such databases in selecting algorithms to define and identify asthma for their own purposes.

Orexigenic action of peripheral ghrelin is mediated by neuropeptide Y and agouti-related protein.

Ghrelin, a stomach-derived orexigenic hormone, has stimulated great interest as a potential target for obesity control. Pharmacological evidence indicates that ghrelin's effects on food intake are mediated by neuropeptide Y (NPY) and agouti-related protein (AgRP) in the central nervous system. These include intracerebroventricular application of antibodies to neutralize NPY and AgRP, and the application of an NPY Y1 receptor antagonist, which blocks some of the orexigenic effects of ghrelin. Here we describe treatment of Agrp(-/-);Npy(-/-) and Mc3r(-/-);Mc4r(-/-) double knockout mice as well as Npy(-/-) and Agrp(-/-) single knockout mice with either ghrelin or an orally active nonpeptide ghrelin agonist. The data demonstrate that NPY and AgRP are required for the orexigenic effects of ghrelin, as well as the involvement of the melanocortin pathway in ghrelin signaling. Our results outline a functional interaction between the NPY and AgRP pathways. Although deletion of either NPY or AgRP caused only a modest or nondetectable effect, ablation of both ligands completely abolished the orexigenic action of ghrelin. Our results establish an in vivo orexigenic function for NPY and AgRP, mediating the effect of ghrelin.

Incidence of Norwalk-like viruses, rotavirus and adenovirus infection in patients with acute gastroenteritis in Jakarta, Indonesia.

Norwalk-like viruses (NLVs), rotavirus and adenovirus are reportedly responsible from 4 to 42% of non-bacterial acute sporadic gastroenteritis. The incidence of NLVs, adenovirus and rotavirus infections in Indonesia is unclear. A total of 402 symptomatic cases from Indonesian patients with acute gastroenteritis and 102 asymptomatic controls that tested negative for bacteria and parasites were screened for the presence of NLVs, rotavirus and adenovirus using the reverse transcriptase-polymerase chain reaction (RT-PCR), Rotaclone kits and Adenoclone kits. Specific prototype probes were used to ascertain which NLV prototypes were present in the area. NLVs were detected in 45/218 (21%), rotavirus was detected in 170/402 (42%) and adenovirus was detected in 11/273 (4%) samples examined. Genetic analysis of the RT-PCR products using specific prototype probes for NLVs indicated that the prototypes were 42% Taunton agent and 58% Hawaii/Snow Mountain agent. Comparative data on patients showed that the incidence of rotavirus infections was two times greater than the NLVs infections, and that adenovirus infections were the least prevalent. All of the control samples tested were negative for NLVs and adenoviruses, however 8/70 (11%) of the samples were positive for rotaviruses. The high incidence of enteric viral-related infections is a threat among acute diarrheic patients in Jakarta, Indonesia.

Association of asthma control with health care utilization: a prospective evaluation.

Population-based disease management should be enhanced by good risk assessment models and instruments. We prospectively evaluated the ability of a simple measure of short-term asthma control (scored 0 to 4) to predict asthma 12-mo health care utilization (HCU). A total of 5,172 adult asthma patients completed a brief questionnaire in fall 1997 to assess current level of asthma control. We then evaluated HCU for calendar year 1998. Ninety-three percent had health plan eligibility in 1998 and were included in this analysis. Both acute and routine asthma utilization increased with increasing numbers of asthma control problems. Rates of acute care episodes were 3.5 (95% confidence interval [CI] = 2.9, 4.3) times more likely for those with 3 to 4 control problems versus those with no control problems. Lesser, but statistically significant, increases were seen for those with two (relative risk [RR] = 1.7, 95% CI = 1.4, 2.2) or one (RR = 1.4, 95% CI = 1.1, 1.8) control problems. These patterns were similar for men and women, and diminished with increasing age. The asthma control index contributed significantly to prospective prediction models even after adjusting for administrative data such as medication use and prior HCU. These data reinforce the usefulness of measures of short-term asthma control both for the individual clinician and for those interested in population-based asthma management.

Trends in anemia at initiation of dialysis in the United States.

BACKGROUND: Anemia almost invariably develops in patients with chronic renal insufficiency (CRI) and is associated with a wide range of complications. The anemia of CRI can be effectively treated with recombinant human erythropoietin (rHuEPO). Recent studies suggest that the management of anemia of CRI is suboptimal in the United States. METHODS: We examined the trends in hematocrit and rHuEPO use among all patients who started chronic dialysis therapy between April 1, 1995, and December 31, 1999, from the End-stage Renal Disease Medical Evidence Form 2728 submitted to the Health Care Financing Administration of the United States. Follow-up data containing hematocrit levels after initiation were obtained from the Medicare Part A institutional outpatient dialysis provider claims for 1990 to 1998 prevalent patients. RESULTS: From June 1995 to June 1999, the mean hematocrit at initiation of dialysis increased from 28.1 to 29.3%. Likewise, the annual percentage of patients receiving pre-dialysis rHuEPO increased from 21.8 to 28.1%. Patients receiving predialysis rHuEPO had a higher mean hematocrit than patients without predialysis rHuEPO. The annual percentage of patients with hematocrit <24% fell 6.6% and the percentage with hematocrit > or =30% increased 9.2%. The trend toward higher hematocrit levels has been consistent across all age, gender, and race categories. Older patients, males, whites, and those who selected peritoneal dialysis had higher hematocrit levels than their counterparts. There were significant geographic differences in the prevalence of predialysis rHuEPO use. CONCLUSION: There has been a slight improvement in the management of anemia of CRI in the United States. However, a considerable fraction of patients still have hematocrit levels that are significantly lower than the currently recommended target. Furthermore, improvement in the management of anemia could result in improved clinical outcomes among patients with CRI.

A family study of psychiatric comorbidity in girls and boys with attention-deficit/hyperactivity disorder.

BACKGROUND: Because attention-deficit/hyperactivity disorder (ADHD) is relatively infrequent among girls, little is known about the nature and causes of psychiatric comorbidity in girls and the reason for gender differences in the prevalence of these comorbidities. METHODS: Using blinded, structured psychiatric interviews, we studied two groups of boys: 140 ADHD probands and 120 non-ADHD comparisons. These groups had 454 and 368 first-degree biological relatives, respectively. We also studied two groups of girls: 140 ADHD probands and 122 non-ADHD comparisons. These groups had 417 and 369 first-degree biological relatives, respectively. RESULTS: The co-occurrence of ADHD and comorbid psychopathology in families was the same for families ascertained through boy and girl probands. CONCLUSIONS: Our results suggest that boys and girls do not differ in the familial risk factors that mediate comorbid psychopathology and the familial aggregation of comorbid disorders in ADHD families. Although this is consistent with prior work suggesting more similarities than differences in the nature of psychiatric comorbidity in ADHD boys and girls, we cannot make strong conclusions, owing to the possibility of cohort effects.

Invasive pneumococcal infections in pediatric cardiac transplant patients.

BACKGROUND: Bacterial infections cause significant morbidity and mortality in cardiac transplant patients. Because Streptococcus pneumoniae is the most prominent bacterial pathogen of childhood, the objective of this study was to define the role of S. pneumoniae as a pathogen in the cardiac transplant population. METHODS: Medical records of cardiac transplant patients from March, 1990, through November, 2000, were reviewed to identify invasive pneumococcal infections after transplantation. Demographic, clinical and microbiologic data were reviewed. RESULTS: Nine (11%) of 80 patients had 12 episodes of pneumococcal bacteremia for an incidence rate of 39 cases/1,000 patient years. Patients who were African-American, transplanted before 2 years of age and transplanted because of idiopathic dilated cardiomyopathy were at increased risk of invasive pneumococcal disease (P < 0.05). Six patients were eligible for the 23-valent pneumococcal polysaccharide vaccine before their first invasive infection, but only 1 had received it at the recommended age. Most isolates (82%) were penicillin-susceptible, and no single serotype predominated. There were 2 deaths in the study group, but each was unrelated to infection. Three patients (33%) had recurrent invasive disease with a second serotype an average of 12 months after the first infection. CONCLUSIONS: The incidence of pneumococcal bacteremia in cardiac transplant patients is higher than in the general pediatric population. Risks for infection were being African-American, being younger than 2 years at the time of transplant and being transplanted because of idiopathic cardiomyopathy. It is plausible that pneumococcal vaccine would decrease this risk.

Bacteriology and beta-lactamase activity in acute exacerbation of chronic bronchitis.

OBJECTIVES: To assess the bacteriology of beta-lactamase (BL) enzyme activity in sputum of 40 patients with acute exacerbation of chronic bronchitis (AECB). METHODS: The microbiology, BL production by the different isolates, and BL contents in the sputum were determined. RESULTS: Eighty-four isolates were recovered (2.1 isolates per specimen), 44 aerobic and facultative (1.1 isolates per specimen), and 40 anaerobic (1.0 isolate per specimen). Aerobic bacteria were recovered in only 9 (22.5%) specimens, anaerobic bacteria in 9 (22.5%), and mixed aerobic and anaerobic bacteria were found in 22 (55%). The predominant aerobic isolates were Streptococcus pneumoniae (15 isolates), Haemophilus influenzae (11), Moraxella catarrhalis and Klebsiella pneumoniae (4 each). The predominant anaerobes were Peptostreptococcus sp. (19), Prevotella sp. (11), and Fusobacterium sp.(6). Mixed flora were present in 25 (62.5%) specimens, and the number of isolates varied from 2 to 5 per specimen. Thirty-nine beta-lactamase-producing bacteria (BLPB) were isolated in 33 (82.5%) of the 40 cases. The predominant aerobic BLPB were H. influenzae, M. catarrhalis, K. pneumoniae, Staphylococcus aureus, and Escherichia coli. The predominant anaerobic BLPB were Prevotella sp. and Fusobacterium sp. Beta-lactamase activity was detected in 26 (79%) of 33 of specimens in which BLPB were isolated, and in none of the seven specimens that did not harbor BLPB. CONCLUSIONS: The rapid detection of BL activity in sputum specimens may have implications for the antimicrobial management with AECB.

Death after rejection with severe hemodynamic compromise in pediatric heart transplant recipients: a multi-institutional study.

BACKGROUND: Rejection with severe hemodynamic compromise results in high mortality in adult transplant patients. This study determines the incidence, outcome and risk factors for rejection with severe hemodynamic compromise in a multi-institutional study of pediatric heart transplant recipients. METHODS: Data from 847 patients transplanted between 1/1/93 and 12/31/98 at 18 centers in the Pediatric Heart Transplant Study were analyzed. Rejection with severe hemodynamic compromise was defined as a clinical event occurring beyond 1 week postoperatively, which led to augmentation of immunosuppression and use of inotropic therapy. Actuarial freedom from such rejection and death after rejection were determined and risk factors sought. RESULTS: Among 1,033 rejection episodes in 532 patients, 113 (11%) episodes were associated with severe hemodynamic compromise in 95 patients. The highest risk for severe rejection was in the first year. Risk factors were older recipient age (p >.05) and non-white race (p >.001). Survival after an episode was poor (60%), and biopsy score did not affect outcome. Deaths were due to rejection (n = 14), other cardiac causes (n = 17), infection (n = 5), lymphoma (n = 2), pulmonary causes (n = 2), and thrombosis (n = 1). CONCLUSIONS: Rejection with severe hemodynamic compromise occurs in 11% of pediatric patients, irrespective of age, sex or biopsy score, and mortality is high. Non-white race and older recipient age are independent risk factors for rejection with severe hemodynamic compromise. Aggressive treatment and close surveillance should be crucial components of protocols aimed at reducing the high mortality.