Deep inspirations attenuate postprandial airway inflammation in college-aged adults with elevated baseline exhaled nitric oxide: A pilot study.

Airway inflammation (assessed by exhaled nitric oxide (eNO)) increases after a single high-fat meal (HFM), yet this response may be modified by airway stretch and baseline eNO level.Purpose: The purpose of this study was to investigate whether deep inspirations (DIs) would attenuate airway inflammation post-HFM and whether this is modulated by baseline eNO level.Methods: A total of sixteen healthy college-aged participants completed a randomized cross-over study with 8 lower eNO (14.8 ± 2.0 ppb: 3 M/5F; age: 22.0 ± 2.2 yrs) and 8 higher eNO (29.3 ± 11.6 ppb 5 M/3F; age: 22.5 ± 2.6 yrs) participants. All participants completed a control (CON) condition (no DIs pre-HFM) and DI condition (60 DI's to total lung capacity immediately pre-HFM) after an overnight fast. The primary outcome was eNO. Participants had 20 minutes to consume the HFM (1 g fat/1 kg body weight) and eNO was performed at 2- and 4- hours post-HFM. To determine whether baseline eNO levels impacted the effect of DI's, a median split was performed on their baseline eNO level.Results: There was a significant increase in eNO as a main effect of time (p < 0.001). However when analyzing the potential effect of baseline eNO, there was no significant increase in eNO post-HFM in the higher eNO group in the DI condition (p = 0.54). DIs modified the eNO response to a HFM in the group with a higher baseline eNO value.Conclusions: These data display a possible bronchoprotective protect of DIs against postprandial airway inflammation in participants with higher initial eNO level.

Phase I clinical, pharmacokinetic and pharmacodynamic study of SB939, an oral histone deacetylase (HDAC) inhibitor, in patients with advanced solid tumours.

BACKGROUND: SB939 is an orally available, competitive histone deacetylase (HDAC) inhibitor selective for class I, II and IV histone deacetylases. Preclinical evaluation of SB939 revealed a profile suggesting improved efficacy compared to other HDAC inhibitors. This phase I study was carried out to determine the safety, dose-limiting toxicity, recommended phase II dose (RPTD), as well as pharmacokinetic (PK) and pharmacodynamic (PD) profiles of SB939 in a daily × 5 schedule in advanced solid tumours. METHODS: Sequential dose-escalating cohorts of patients were enrolled into 8 dose levels. At dose level 1, SB939 was taken on days 1-3 and 15-17 every 4 weeks, then on days 1-5 and 15-19 for other dose levels. Detailed PK sampling was performed in cycle 1, days 1 and 5. Peripheral blood mononuclear cells (PBMCs) were collected on cycle 1 at various time points for determination of acetylated histone H3 (AcH3) levels. RESULTS: In total, 38 patients received a total of 96 cycles of treatment. The maximal administered dose was 90 mg and the RPTD was 60 mg given 5 consecutive days every 2 weeks. The most frequent non-hematologic adverse events (AEs) of at least possible attribution to SB939 were fatigue, nausea, vomiting, anorexia and diarrhoea. Pharmacokinetic analysis showed dose-proportional increases in AUC across the doses evaluated. Elimination half-life was 5.6-8.9 h. There was no clear relationship between AcH3 changes and dose level or anti-tumour response. CONCLUSIONS: SB939 is well tolerated in patients with advanced solid tumours. The RPTD of this drug is 60 mg on a schedule of 5 consecutive days every 2 weeks. The toxicities of SB939 are consistent with other HDAC inhibitors.

Surgonomics: the cost dynamics of craniotomy.

Prospective payment systems using the diagnostic related group (DRG) mechanism are being phased in for Medicare inpatient hospital care. The purpose of this study was to examine a common neurosurgical procedure (001), craniotomy without trauma, and characterize the cost dynamics of this DRG. All patients (n = 50) treated in this DRG at the Long Island Jewish Medical Center during 1983 had their financial charges exclusive of physician fees examined. The findings were: (a) each hospital service category had wide charge variances around the mean; (b) emergency (ER) admissions were 200% more expensive than nonemergency (non-ER) admissions; (c) ER admissions seemed to have no greater severity of illness than non-ER admissions, but had a significantly different referral pattern (i.e., admission from the ER to a nonneurosurgical service with a subsequent neurosurgical referral); (d) this DRG when grouped into clinical "subproducts" (i.e., craniotomy for tumor, hematoma, hydrocephalus, aneurysm, benign cyst, and other) showed marked charge differences; and (e) the most expensive 25% of patients had five times higher charges than the least expensive 25% for both ER and non-ER admissions. This type of financial analysis may give surgeons a methodology with which to address the problems of cost containment in a more serious manner.

The psychosocial climate of families with suicidal pre-adolescent children.

A structured interview measure of suicidal behavior and a questionnaire measure of family psychosocial climate were administered to 43 pre-adolescent psychiatric inpatients and their parents. Results showed that suicidal behavior tended to be associated with greater family conflict and with less family organization, cohesion, and achievement orientation.

The relationship of suicidality and psychiatric diagnosis in hospitalized pre-adolescent children.

Two structured interview measures of suicidal behavior were administered to 43 child psychiatric inpatients between the ages of 7 and 11 and their parents. DSM-III-R diagnoses were assigned to the children, with twenty-six Axis I and Axis II diagnostic categories represented. Generally, the interview measures of suicidal behavior were found to be unrelated to psychiatric diagnosis. The results suggest that to better understand pre-adolescent suicidal behaviors, it may be more useful to examine associations between these behaviors and the biopsychosocial dimensions that underlie the diagnostic categories.

The prevalence of suicidal behavior among preadolescent children who are psychiatric inpatients.

The prevalence of suicidal behavior displayed by preadolescent children hospitalized on inpatient psychiatric units is estimated to range between 18% and 80% of the population. The current study provides an independent estimate of the prevalence of this problem. A semistructured interview was used to assess suicidal behavior displayed by 61 admissions to a child psychiatric inpatient unit between April 1988 and September 1989. According to the Pfeffer Spectrum of Suicidal Behavior Scale, 63% of the sample engaged in some form of suicidal behavior. Preadolescents and their parents reported similar rates of suicidal thoughts, threats and attempts. The dangerousness of recent suicidal behavior was not found to differ by age, sex, legal custody status or socioeconomic status.

Value of routine pathology in herniorrhaphy performed upon adults.

The value of routine pathologic study of specimens taken at herniorrhaphy performed upon adults was assessed. All 789 patients who underwent inguinal or femoral herniorrhaphy at the Long Island Jewish Medical Center from January 1983 through July 1984 were studied. Patients were classified into five groups; 1, no specimen was sent for pathologic evaluation; 2, confirmation of hernia sac; 3, confirmation of hernia sac with additional expected pathologic findings (such as lipoma or hydrocele); 4, unexpected additional pathologic findings which appeared abnormal at operation, and 5, unexpected additional pathologic findings which appeared normal at operation. During this time period there were 935 herniorrhaphy procedures performed. Three of 1,020 specimens examined contained unexpected pathologic findings (groups 4 and 5): non-Hodgkin's lymphoma, liposarcoma and atypical lipoma. Only one specimen (group 5) with an abnormal pathology report showed an atypical lipoma which appeared normal at operation (0.098 per cent). The outcome of the operation was not altered by the pathology results in these three patients from either group 4 or 5. Aggregate charges for all specimens was $30,528.00 (a mean charge per patient of $48.00). Annual savings to the health care system of the United States by omitting routine pathologic examination of specimens from groups 1, 2 and 3 would be $18 million. Although there may be some justification for routine tissue testing for medical and legal reasons and quality assurance purposes or for specimens which appeared abnormal at operation, these data suggest that for patients who undergo herniorrhaphy, little positive effect on the outcome is gained from routine pathologic examination of specimens which appeared normal at operation.

Preadolescent suicidal behavior: the role of cognitive functioning.

The recent suicidal behavior of fifty-three hospitalized preadolescents was assessed in interviews with children and their parents. Children described by their parents as more suicidal scored higher on measures of verbal intelligence and language production than their less suicidal counterparts, with unique variance predicted only by language production ability. The results suggest that parents of preadolescents with better language production skills may be more aware of their youngsters' suicidal thoughts than parents of children with poorer language production ability.

Source of admission and cost: public hospitals face financial risk.

We studied all admissions to the 11 acute care hospitals of the New York City Health and Hospitals Corporation (April 1983-September 1984) matching emergency room (ER) admitted diagnostic related group (DRG) subgroups in each hospital with at least five non-ER admitted patients (N = 222,961). Mean cost per ER patient ($8,385) was greater than non-ER mean cost per patient ($4,386) for Medicare and non-Medicare. Our data suggest that public hospitals with a high proportion of ER admissions may be at a financial disadvantage under DRG reimbursement.

Mode of admission and cost for surgical DRGs.

The purpose of this study was to confirm the hypothesis that emergency department admissions were more expensive than their nonemergency counterparts per diagnosis-related group (DRG) and to see if this characteristic was displayed across many hospitals. All surgical admissions (N = 39,682) to the 11 acute-care hospitals of the New York City Health and Hospitals Corporation were analyzed during an 18-month period to yield a study population (N = 26,569) of matched DRG subgroups (ED vs nonED) at each hospital of at least five patients per variable for that particular DRG. A cost-per-patient analysis was conducted for each admission. Total costs for the study population were $163,360,636. A total of 75.8% of surgical admissions (N = 20,143) were admitted in DRGs in which ED admissions were more costly than their nonED-matched counterparts. The following was the trend in percentage of total specialty admissions in DRGs in which ED admissions were more costly than nonED admissions: urology (88.4%); ear, nose, and throat (86.2%); general and vascular (80.1%); cardiothoracic (78.0%); orthopedics (75.6%); plastic surgery (62.1%); neurosurgery (60.5%); and ophthalmology (46.0%). Route of admission (ED vs nonED) was an identifier of higher-cost patients per DRG across hospitals in a large public hospital system. These data demonstrate that hospitals with substantial numbers of surgical ED admissions may face significant financial risk under DRG reimbursement, and suggests that the DRG system does not adequately compensate hospitals for the higher cost of the emergency surgical admission.

The financial effects of emergency department-generated admissions under prospective payment systems.

The purpose of this study was to assess the financial impact (revenues vs expenses) as measured by hospital charges and costs vs diagnosis-related group (DRG) revenues of prospective payment systems on emergency department-generated admissions for a large teaching hospital under two payment systems: Medicare and an all-payor system. All emergency department admissions were analyzed for the years 1983 (N = 4,273) and 1984 (N = 4,125) under both systems, using standard DRG methodology. Our findings were as follows: (1) With charges as a measure of expense under both payment schemes, all clinical departments had large groups of unprofitable patients: Medicare, $12,895,038; all-payor system, $15,553,893. (2) When costs were computed as the expense measure (using our hospital's cost-to-charge ratio), Medicare patients produced a deficit ($2,363,163); however, under an all-payor system there was a small net profit ($4,267,859). (3) The implementation of federalized DRG reimbursement rates increased our losses for this population from 1983 to 1984. (4) Reductions in outlier reimbursement (10%) and teaching costs (25%) caused our revenues to drop substantially, potentiating our losses. These findings suggest that hospitals with large emergency department admission populations, particularly Medicare patients, may be at a significant financial disadvantage under prospective payment systems.