Preliminary psychometric evaluation of the Child Health Ratings Inventory (CHRIs) and Disease-Specific Impairment Inventory-Hematopoietic Stem Cell Transplantation (DSII-HSCT) in parents and children.

PURPOSE: To describe the initial results of the Child Health Ratings Inventory (CHRIs), 20-item generic health-related quality of life (HRQL) instrument and the 10-item disease-specific (DS) module, the Disease Specific Impairment Inventory-Hematopoietic Stem Cell Transplantation (DSII-HSCT), for children and adolescents, ages 5-18 years and their parents following HSCT. STUDY DESIGN: Using cross sectional design, 122 children with a median age of 11 years (range 5.0-18 years) completed the questionnaire (CHRIs + DSII-HSCT) with research assistance. Seventy-four parents independently completed a parallel version of the questionnaire; health care providers assigned a global clinical severity rating. RESULTS: The generic core includes four domains: physical, role, and emotional functioning, and energy. The DS module has three domains: worry, hassles, and body image. The Cronbach's alpha for parents and for older children (8 years and over) exceeded 0.70 for all generic and DS domains. While the range of alpha coefficients was lower for younger children, ages 5-7 year, only the alpha coefficient for one domain (energy) was less than 0.70. The instrument satisfactorily discriminated between clinically important groups: those early in the transplant process (< 6 months) versus those later (> 12 months) and by provider-assigned clinical severity ratings. CONCLUSION: results suggest that the CHRIs generic core and its DSII-HSCT module is a promising measure of HRQL after pediatric HSCT. Although parent and child reports were moderately correlated and revealed complementary results, the unique perspectives of both raters provide a more complete picture of HRQL. Longitudinal application is underway to further characterize the measurement properties of the CHRIs and to determine the instrument's responsiveness and sensitivity to change over time in this vulnerable population.

Association of human herpesvirus 6 reactivation with severe cytomegalovirus-associated disease in orthotopic liver transplant recipients.

To explore the possible interaction between human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) in patients who have undergone organ transplantation, stored serum samples from 139 orthotopic liver transplant recipients were tested for HHV-6 immunoglobulin (Ig) G and IgM antibodies. HHV-6 reactivation occurred in 87 patients (62.6%) and was associated with CMV disease (P=.01), severe CMV-associated disease (P=.01), older age (P=.005), and use of muromonab-CD3 (Orthoclone; Orthobiotech) as treatment for rejection (P=.02). Trends for an association between HHV-6 reactivation and invasive fungal disease (P=.12), bacteremia (P=.10), and graft loss (P=.12) were seen. In a multivariate analysis of risk factors for severe CMV-associated disease, HHV-6 reactivation (relative risk [RR], 3.5; 95% confidence interval [CI], 1.2-10.2; P=.02), CMV donor-positive-recipient-negative match (RR, 5.7; 95% CI, 2.5-13.2; P<.001), and elevated serum creatinine level (P<.0001) were independent predictors. HHV-6 reactivation is associated with severe CMV-associated disease in liver transplant recipients.

Mood changes in adolescents using depot-medroxyprogesterone acetate for contraception: a prospective study.

STUDY OBJECTIVE: Depot-medroxyprogesterone acetate (DMPA) is thought to cause changes in mood among patients using it for contraception. The purpose of this study was to evaluate changes in negative and positive affect among adolescent females using DMPA as a contraceptive agent. DESIGN, SETTING, PARTICIPANTS: This prospective study was set in an urban hospital adolescent clinic. Thirty-nine adolescents choosing DMPA as a contraceptive agent and 24 adolescents not using any hormonal contraception were enrolled as subjects and controls, respectively. Two standardized questionnaires, the Beck Depression Inventory (BDI) and the Multiple Affect Adjective Checklist-Revised (MAACL-R), were administered at baseline to all participants and readministered at 3, 6, and 12 months. MAIN OUTCOME MEASURES: Changes in negative affect from baseline to 3, 6, and 12 months were evaluated by the BDI and by "dysphoria" subscale scores of the MAACL-R. Paired t-tests were used to measure these changes in subjects and controls separately. RESULTS: The mean change in BDI scores from baseline to one year for those who completed one year was -4.8 for subjects (P =.02) and +.3 (P =.84) for controls. The mean change in the dysphoria subscale scores was -5.7 (P =.21) for the subjects and -.1 (P =.98) for the controls while the change in the positive affect scores over a period of one year were -2.1 (P =.46) and +.1 (P =.98) for subjects and controls, respectively. CONCLUSIONS: Adolescents using DMPA do not show depressive symptoms when using DMPA as a contraceptive agent over a period of 12 months as measured by the BDI and show no significant changes in negative or positive affect as measured by the MAACL-R.

High dose radiation therapy and chemotherapy as induction treatment for stage III nonsmall cell lung carcinoma.

BACKGROUND: The current study was conducted to review the authors' experience in treating consecutive patients with American Joint Committee on Cancer (1997 revision) Stage III nonsmall cell lung carcinoma with aggressive preoperative chemoradiation followed by surgical resection. METHODS: The records of all patients who received preoperative chemoradiation were evaluated. Patients received 2 cycles of concurrent cisplatin and etoposide with 5940 centigrays of radiation therapy. They then were reevaluated to determine whether they were surgical candidates. If so, resection of the primary tumor with mediastinal lymph node dissection was performed 4-6 weeks after the completion of preoperative treatment. After adequate healing, an additional four cycles of cisplatin/etoposide or carboplatin/paclitaxel was given. RESULTS: Forty-two patients received preoperative chemoradiation, 33 of whom underwent surgical resection (79%), including 9 patients who underwent pneumonectomies. Complete pathologic responses were observed in 27% of these patients. Postoperative complications were noted in 21% of the patients and included persistent air leak, supraventricular arrhythmia, and empyema. There were no reported treatment-related deaths. The median follow-up was 26 months. The overall 5-year survival rate for all patients was 36.5% and was 45. 3% for patients who underwent resection. A trend toward increased 5-year survival was observed in patients who had a complete pathologic response (57.1%). Univariate analysis revealed the N stage classification to be significant for predicting a complete response. Patterns of failure revealed the brain to be the most common site of first recurrence (50%) and the only site of recurrence in 36% of patients. There was only one case of local failure. CONCLUSIONS: Preoperative chemoradiation using high radiation doses is feasible with acceptable toxicity. The results of the current study suggest an increased complete pathologic response rate and increased overall survival rate compared with reports in the published literature.

Early ECG abnormalities associated with transcatheter closure of atrial septal defects using the Amplatzer septal occluder.

UNLABELLED: Conduction abnormalities and arrhythmias may occur in patients following secundum atrial septal defect (ASD) closure using the Amplatzer septal occluder (ASO). Therefore, the aim of this study was to prospectively perform ambulatory ECG monitoring to assess the electrocardiographic effects of transcatheter closure (TCC) of ASD using the ASO device. From 5/97 to 3/99, 41 patients with secundum ASD, underwent TCC using the ASO device at a median age of 9.2[emsp4 ]y. (0.5-87[emsp4 ]y.) and median weight of 34[emsp4 ]kg (5. 6-88[emsp4 ]kg.). Ambulatory Holter monitoring was performed pre- and immediately post TCC. Holter analysis included heart rate (HR), ECG intervals, supraventricular ectopy (SVE), ventricular ectopy (VE), and AV block. No change in baseline rhythm was noted in 37 patients (90%). Changes in AV conduction occurred in 3 patients (7%), including intermittent second degree AV block type II, and complete AV dissociation post closure. SVE was noted in 26 patients (63%) post closure, ranging from 5-2207 supraventricular premature beats (SVPB), including 9 patients (23%) with non-sustained supraventricular tachycardia (SVT), 3 of whom had short runs of SVT prior to closure. A significant increase in post-closure number of SVPB per hour (p=0.047) was noted. No significant difference was noted in PR interval, ventricular premature beats per hour, or QRS duration. CONCLUSIONS: Based on ambulatory ECG analysis, TCC of ASD with the ASO device is associated with an acute increase in SVE and a small risk of AV conduction abnormalities, including complete heart block. Long term follow-up studies will be necessary to determine late arrhythmia prevalence and relative frequency compared with standard surgical ASD repair.

Comparative in vitro activities of clinafloxacin and trovafloxacin against 1,000 isolates of bacteroides fragilis group: effect of the medium on test results.

The in vitro antibacterial activities of clinafloxacin, trovafloxacin, ciprofloxacin, and cefoxitin against 1,000 clinical isolates of Bacteroides fragilis group were compared by agar dilution in brucella blood agar (BBA) and Wilkins Chalgren agar (WCA). Significantly higher geometric mean MICs for the three quinolones and cefoxitin (P<0.001) were obtained in BBA than in WCA. Regardless of medium, clinafloxacin was slightly more active than trovafloxacin. The activity of clinafloxacin and trovafloxacin was greater than that of cefoxitin against B. distasonis, B. ovatus, and B. thetaiotaomicron but lower against B. vulgatus. High cross resistance between trovafloxacin and clinafloxacin was observed.

Assessment of physician responses to abnormal results of bone densitometry studies.

OBJECTIVE: To assess how physicians who have ordered bone densitometry studies respond to abnormal results. METHODS: We conducted a retrospective review of cases from physicians affiliated with a community teaching hospital. The study sample consisted of 142 female patients with abnormal bone mineral density (BMD) who had been referred by 50 physicians (internists or gynecologists). A questionnaire was completed for each patient, providing data about further investigations, treatment interventions, and frequency of referral to a specialist in bone diseases. RESULTS: Of the patients diagnosed with osteoporosis on the basis of BMD studies, 20.4% had no further investigations, and 27.8% underwent only mammography. Of all the patients with osteoporosis, 10.6% received no therapy (calcium and vitamin D excluded). The majority of all patients (71.8%) received a combination of calcium and vitamin D. The most common treatment modality was hormone replacement therapy. The second most common treatment strategy was bisphosphonates. The percentage of all referrals to specialists in metabolic bone diseases was low--11.3% in the patients of internists and 14.5% in the patients of gynecologists. CONCLUSION: In this study, the information provided by bone densitometry did not affect management in a substantial percentage of patients. A considerable percentage of patients underwent no further investigations to rule out secondary causes of osteoporosis.

Tumor necrosis factor genetic polymorphisms correlate with infections after renal transplantation.

BACKGROUND: Nonimmunosuppressed individuals possessing a NcoI restriction enzyme site in the tumor necrosis factor (TNF) gene locus produce less TNF-alpha in vitro and in vivo than do individuals lacking this site. We have previously shown that this NcoI+/low TNF-alpha genotype is independently associated with increased rates of infection for liver transplant recipients. METHODS: In this study, we performed polymerase chain reaction amplification and restriction fragment length polymorphism analysis of the TNF locus from 45 renal transplant recipients to determine whether the presence of the NcoI site is associated with the frequency of rejection, infection, time to rejection or infection, and patient or graft survival. RESULTS: Twenty-six recipients were typed with the NcoI+/low TNF-alpha genotype, whereas 19 recipients had the NcoI-/high TNF-alpha genotype. Age, sex, donor type, secondary immunosuppression, use of anti-lymphocyte preparations, graft ischemia time, and year of transplant were evenly distributed in the two groups. There was no difference between the genotype groups in the rate of, or time to, rejection. In contrast, significantly more patients with the NcoI+/low TNF-alpha site developed infections (46% vs. 10% P=0.01). In bivari able models, each controlling for donor type, ischemia time, recipient age, use of antilymphocyte agents, and secondary immunosuppression, the NcoI+/low TNF-alpha genotype was still independently associated with increased numbers of infections (relative risk, 5.38; confidence interval, 1.20-23.8). Conclusion. We conclude that in individuals genetically predetermined to be low TNF-alpha producers, the additional inhibition of TNF-alpha production by routine immunosuppression may be excessive, rendering these individuals less able to respond to infectious stimuli. These patients may benefit from lower doses or withdrawal of corticosteroids, which are known inhibitors of TNF-alpha transcription.

Outcome of transplantation of organs procured from bacteremic donors.

BACKGROUND: Transplantation of organs from donors who are bacteremic is controversial. We examined the outcome of recipients of solid organs from donors with bacteremia and/or fungemia at the time of organ recovery. METHODS: All organ donors from a single organ procurement organization between January 1990 and December 1996 were retrospectively analyzed. We calculated rates of transmission from bacteremic or fungemic donors to their recipients and compared the graft and patient survival rates for recipients of these organs with those for recipients of organs from non-bacteremic donors. RESULTS: There were 95 (5.1%) bacteremic donors from a total of 1775, from whom 212 recipients received organs. Forty-six (48%) of the bacteremic donors had pathogens in their blood. Among the 101 recipients of organs from these, no evidence of transmission could be documented. (0% transmission rate, 95% CI 0-3). The remaining 49 donors had either Staphylococcus epidermidis or other unlikely pathogens recovered from the blood. Examination of the 111 recipients of organs from these donors also found no evidence for transmission (0% transmission rate, 95% CI 0-3). Of the 212 recipients, 193 (91%) received a mean of 3.8+/-2.5 days of antibiotics postoperatively. The 30-day graft and patient survival for recipients of organs from bacteremic donors was not significantly different from recipients of organs from nonbacteremic donors (P = 0.695 for patient survival, and P = 0.310 for graft survival). CONCLUSIONS: Organs transplanted from bacteremic donors do not transmit bacterial infection or result in poorer outcomes. Use of organs from these donors could help increase organ availability.

Multicenter study of in vitro susceptibility of the Bacteroides fragilis group, 1995 to 1996, with comparison of resistance trends from 1990 to 1996.

Antimicrobial resistance, including plasmid-mediated resistance, among the species of the Bacteroides fragilis group is well documented. An analysis of the in vitro susceptibility of B. fragilis group species referred between 1995 and 1996 as well as during a 7-year (1990 to 1996), prospective, multicenter survey of over 4,000 clinical isolates of B. fragilis group species was undertaken to review trends in the percent resistance to and geometric mean MICs of the antibiotics tested. There was a trend toward a decrease in the geometric mean MICs of most beta-lactam antibiotics, while the percent resistance to most agents was less affected. Within the species B. fragilis, the geometric mean MICs showed significant (P < 0.05) decreases for piperacillin-tazobactam, ticarcillin-clavulanate, piperacillin, ticarcillin, ceftizoxime, cefotetan, and cefmetazole; a significant increase was observed for clindamycin and cefoxitin. For the non-B. fragilis species, a significant decrease in the geometric mean MICs was observed for meropenem, ampicillin-sulbactam, ticarcillin-clavulanate, piperacillin, ticarcillin, ceftizoxime, and cefmetazole; a significant increase was observed for cefoxitin. Significant increases in percent resistance were observed within the B. fragilis strains for ticarcillin and ceftizoxime and within the non-B. fragilis isolates for cefotetan. Significant increases in percent resistance among all B. fragilis group species were observed for clindamycin, while imipenem showed no significant change in resistance trends. The trend analysis for trovafloxacin was limited to 3 years, since the quinolone was tested only in 1994, 1995, and 1996. During the 7 years analyzed, there was no resistance to metronidazole or chloramphenicol observed. The data demonstrate that resistance among the B. fragilis group species has decreased in the past several years, the major exception being clindamycin. The majority of the resistance decrease has been for the beta-lactams in B. fragilis, compared to other species. The reasons for these changes are not readily apparent.

Tumor necrosis factor genetic polymorphisms correlate with infections after liver transplantation. NEMC TNF Study Group. New England Medical Center Tumor Necrosis Factor.

Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory mediator of the immune response to allogenic and infectious stimuli. Non-immunosuppressed individuals possessing a NcoI restriction enzyme site in the TNF gene locus produce less TNF-alpha in vitro and in vivo compared with individuals lacking this restriction site. We performed polymerase chain reaction amplification and restriction enzyme fragment length analysis of the TNF locus from 86 liver transplant recipients to determine if presence of the NcoI site is associated with the frequency of rejection or infection, time to rejection or infection, and patient and graft survival. We controlled for recipient primary diagnosis, age, sex, United Network for Organ Sharing status, year of transplant, type of immunosuppression, use of anti-lymphocyte agents, and graft ischemia time. Fifty-six recipients possessed the NcoI+/low TNF-alpha genotype and 30 were NcoI-/high TNF-alpha genotype. In the first year after transplant, there were no significant differences in the frequency, or time to first rejections or the overall number of rejection episodes between the two genotypes. NcoI+/low TNF-alpha genotype recipients had significantly more infections (1.52 vs. 0.87, P=0.014). In a linear regression, multivariate model controlling for all marginally significant variables, the NcoI+/low TNF-alpha genotype was still associated with significantly more infections (P=0.0031). Patient and graft survival were equal for the two groups. One implication of this study, in individuals genetically predetermined to be low TNF-alpha producers, is that additional inhibition of TNF-alpha production by routine immunosuppression may be excessive, rendering these individuals less able to respond to infectious stimuli. These patients may benefit from lower doses or withdrawal of corticosteroids.

Early infection in bone marrow transplantation: quantitative study of clinical factors that affect risk.

Infections remain common life-threatening complications of bone marrow transplantation. To examine clinical factors that affect infection risk, we retrospectively studied patients who received bone marrow transplants (53 autologous and 51 allogeneic). Over a median of 27 hospital days, 44 patients developed documented infections. Both autologous transplantation and hematopoietic growth factor use were associated with less prolonged neutropenia and decreased occurrence of infection (P < or = .05). In a survival regression model, variables independently associated with infection risk were the log10 of the neutrophil count (hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.32-0.75), ciprofloxacin prophylaxis (HR, 0.42; 95% CI, 0.19-0.95), empirical intravenous antibiotic use (HR, 0.09; 95% CI, 0.03-0.32), and an interaction between neutrophil count and intravenous antibiotic use (HR, 1.86; 95% CI, 1.06-3.29). In this model, infection risk increases steeply at low neutrophil counts for patients receiving no antibiotic therapy. Ciprofloxacin prophylaxis and particularly intravenous antibiotic therapy provide substantial protection at low neutrophil counts. These results can be used to model management strategies for transplant recipients.

Health-related quality of life in pediatric bone marrow transplant survivors: according to whom?

Historically, health-related quality of life (HRQL) assessment in pediatrics, including the few validated instruments in pediatric oncology, has been based on proxy reporting, relying primarily on parental assessment. Children have been deemed incapable of providing consistent and reliable information about their level of functioning or state of well-being. Previous studies have been hampered by either limited or poor correlation among the proxy reporters, i.e., teachers, parents and physicians, and in comparisons to disease severity. Simply stated, proxy reporters have greater agreement about what the child can do vs. what the child thinks or feels. Comparisons among proxy reporters have been hindered also by a lack of parallel content in the instruments used, which may result in poorly congruent assessments simply because the instruments measure different constructs. In addition to the measurement issues, the emotional milieu of the parent, particularly the mother, has been shown to influence assessments of the child's functioning. Maternal distress, marital adjustment and health locus of control all co-vary with reports of the child's behavior. What, then, is the proxy reporter telling us about the child? We conducted a cross-sectional study of school-aged pediatric bone marrow transplant (BMT) patients at our institution to evaluate children's self-reported HRQL and functional status. We formally tested the Child Health Rating Inventories (CHRIs), a recently developed generic health-status measure, with its companion measure, the Disease Impairment Inventories-Bone Marrow Transplant (DSII-BMT). Separate questionnaires were administered to patients, parents and physicians at a scheduled outpatient visit after BMT. The questionnaires were designed to have parallel content. All responses were confidential. The psychometric properties of the CHRIs and DSII-BMT are reported elsewhere. In brief, the responses of all raters were reliable, based on measurements of internal consistency. The children's self-reported health status was correlated significantly with the physicians' disease severity rating (DSR) across all generic and disease-specific domains. In contrast, parental reports of child health status were not correlated significantly with the DSR for disease-specific problems or the child's pain. Parental ratings deviated most from the children's ratings within the dimensions of mental health and quality of life (p < 0.001). For the entire sample, parental ratings were significantly lower than the children's ratings. Within the subgroup "early after transplant (<6 months)", parental ratings were significantly lower than the children's self-reports in all categories. In the subgroup ">12 months after transplant", with the exception of mental health and quality of life, parental scores were the same as or higher than the children's ratings. Our results confirm previous studies that the parental reporting of children's health status is a complex construct and that valuable information can be elicited directly from the children. Further research is needed to substantiate these findings, particularly in longitudinal applications with adequate sample sizes.

Human herpesvirus 6 reactivation is associated with cytomegalovirus infection and syndromes in kidney transplant recipients at risk for primary cytomegalovirus infection.

A potential association between human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) following kidney transplantation was explored by retrospectively testing serial serum specimens for HHV-6 IgG and IgM antibody. HHV-6 reactivation occurred in 35 (66%) of 53 transplant recipients. Fungal or parasitic opportunistic infections, graft rejection or loss, and mortality were not associated with HHV-6 reactivation. HHV-6 reactivation was associated with primary CMV infection (P=.001) and CMV syndrome (P=.003) and with trends for CMV-related hepatitis (P=.095), CMV-related neutropenia (P=.104), and serious CMV disease (P=.085). After controlling for CMV immune globulin (CMVIG) prophylaxis, the association between HHV-6 reactivation and primary CMV infection and syndrome remained significant (P=.002 and 0.006, respectively). The reduction in CMV syndrome among those receiving CMVIG prophylaxis remained significant (P=.007) after controlling for HHV-6 reactivation. HHV-6 reactivation in kidney transplant recipients at risk for primary CMV infection is associated with CMV infection and CMV-related disease, and these effects are independent of CMVIG prophylaxis.

New insights and observations in three-dimensional echocardiographic visualization of ventricular septal defects: experimental and clinical studies.

BACKGROUND: The positions, sizes, and shapes of ventricular septal defects (VSDs) can be difficult to assess by 2-dimensional echocardiography (2DE). Volume-rendered 3-dimensional echocardiography (3DE) can provide unique views of VSDs from the left ventricular (LV) side, allowing complete assessment of their circumference and spatial orientations to other anatomic structures. METHODS AND RESULTS: Seventeen experimentally created defects of various locations, sizes, and shapes were imaged and reconstructed in 9 explanted porcine hearts. From an en face projection, major and minor axis diameters of the defects were measured, and these data were compared with direct anatomic measurements. Optimal reconstructions of the VSDs were obtained in all heart specimens, accurately depicting their positions and shapes. The correlations between 3DE and anatomy for the VSD major and minor axis diameters were y=1.0x+0.3 (r=0.88, P<0.001) and y=1.0x-1.4 (r =0.89, P<0.001), respectively. Good agreement between the 2 methods was demonstrated for all measurements. Our experience from the in vitro model was then applied to patient studies. Optimal LV en face reconstructions were obtained in 45 of 51 patients, permitting detailed assessment of the positions, sizes, and shapes of the VSDs. In the 25 patients with comparative surgical measurements, the correlations between 3DE and surgery for the VSD major and minor axis diameters were y =0. 81x+2.1 (r=0.92, P<0.001) and y=0.73x+2.0 (r=0.91, P<0.001), respectively. Good agreement was demonstrated between measurements made by 3DE and those obtained at surgery. CONCLUSIONS: 3DE provides excellent visualization of various types of VSDs. From an LV en face projection, the positions, sizes, and shapes of VSDs can be accurately determined. Such precise imaging will be beneficial for surgical and catheter-based closure of difficult perimembranous and singular or multiple muscular VSDs.