Decreasing Radiation Exposure to the Abdomen in Children with Chronic Constipation.

Background: Bowel management for children with chronic constipation may include repeated single-view abdomen radiographs (AXR) to monitor treatment success. Only one image of the abdomen is needed to include most of the colon, but technologists often make a second (or even third) exposure to be sure they have imaged the entire abdomen. Our quality improvement project aimed to reduce radiation exposure by decreasing the frequency of >1 exposure performed for AXR orders in children with chronic constipation from 27% to <10% by December 2022 and sustain. Methods: We counted baseline (01/2020-11/2020) and intervention (12/2020-5/2023) examinations with >1 exposure. Initial interventions were a structured communication to technologists and an article in the monthly department newsletter and later, a technologist education module. Additional interventions included communication to radiologists, project updates and encouragement to all technologists, and individual technologist feedback. A statistical process control chart tracked data to study process changes over time. Results: During the baseline and intervention periods, 525/1944 and 1329/8334 examinations, respectively, had >1 exposure performed for AXR orders. Interventions created 2 centerline shifts. Overall, examinations with >1 exposure decreased from 27% to 13.5%. Conclusions: Frequency of >1 exposure performed for AXR orders in children with chronic constipation decreased from 27% to 13.5% through education and communication. This was sustained. We plan to assign training modules for all new technologists, policy reminders (annual training in odd years) for all technologists, and continue individualized learning opportunities.

Knowledge of the Genetic Information Nondiscrimination act among individuals affected by Huntington disease.

The Genetic Information Nondiscrimination Act (GINA) of 2008 was the first US legislation to address genetic discrimination. We sought to assess understanding of GINA among individuals affected by the autosomal dominant condition, Huntington disease (HD). We conducted a cross-sectional survey of individuals with varying risk of HD to assess their familiarity with GINA. As a control, individuals were surveyed about their familiarity with the Health Insurance Portability and Accountability Act (HIPAA). Those who reported familiarity with GINA were asked about their knowledge of specific provisions of the legislation. The survey was offered to 776 participants and completed by 410 (response rate 53%). Respondents across all groups were less familiar with GINA (41% slightly, somewhat, or very familiar) than with HIPAA (65%; p < 0.0001). Of individuals with or at risk for HD who reported some familiarity with GINA, less than half correctly identified GINA's protections, and less than 15% correctly identified its limitations. Thus, among individuals affected by HD, familiarity with and knowledge of GINA are low. The effectiveness of the legislation may be limited by this lack of knowledge.

Erythropoietin for patients with malignant disease.

BACKGROUND: Anaemia associated with cancer and cancer therapy is an important clinical factor in the treatment of malignant diseases. Therapeutic alternatives are recombinant human erythropoietin (EPO) and red blood cell transfusions. OBJECTIVES: The aim of this systematic review was to assess the effect of erythropoietin to either prevent or treat anaemia in cancer patients. SEARCH STRATEGY: We searched the Central Register of Controlled Trials, MEDLINE (01/1985 to 12/2001), EMBASE (01/1985 to 12/2001), other databases and reference lists of articles. We also contacted experts in the field and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials comparing the use of recombinant human erythropoietin (plus transfusion if needed) with red blood cell transfusions alone for the treatment or prevention of anaemia in cancer patients. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. All authors from included studies were contacted for additional information. MAIN RESULTS: Twenty seven trials with 3,287 adults were included. Use of erythropoietin significantly reduced the relative risk of red blood cell transfusions (RR 0.67; 95% CI 0.62 to 0.73, 25 trials, n = 3,069). On average participants in the erythropoietin group received one unit of blood less than the control group (WMD -1.00; 95% CI-1.31 to -0.70, 13 trials, n = 2,056). For participants with baseline haemoglobin below 10 g/dL haematological response was observed more often in participants receiving EPO (RR 3.60; 95% CI 3.07 to 4.23, 14 trials, n = 2,347). There was inconclusive evidence whether EPO improves tumour response (fixed effect RR 1.36; 95% CI 1.07 to 1.72, seven trials, n = 1,150; random effects: RR 1.21; 95% CI 0.92 to 1.59) and overall survival (adjusted data: HR 0.81; 95% CI 0.67 to 0.99; unadjusted data: HR 0.84; 95% CI 0.69 to 1.02, 19 trials, n = 2,865). There were no statistically significant adverse effects. Evidence was inconclusive with respect to quality of life and fatigue. REVIEWERS' CONCLUSIONS: There is consistent evidence that the administration of erythropoietin reduces the risk for blood transfusions and the number of units transfused in cancer patients. For patients with baseline haemoglobin below 10 g/dL there is strong evidence that erythropoietin improves haematological response. There is inconclusive evidence whether erythropoietin improves tumour response and overall survival. Research on side effects is inconclusive.

Economic analysis of a phase III study of G-CSF vs placebo following allogeneic blood stem cell transplantation.

Hematopoietic colony-stimulating factors (CSF) decrease the duration of neutropenia following stem cell transplantation (SCT). With CSF-mobilized allogeneic blood SCT (alloBSCT), the yields of CD34+ cells are several-fold higher than in other SCT settings, raising concern that post-transplant CSF use may be unnecessary. In this study, we estimate the resource and cost implications associated with CSF use following alloBSCT. A cost identification analysis was conducted for 44 patients on a randomized, double-blind placebo-controlled trial of G-CSF following alloBSCT. Study drug was given daily until an absolute neutrophil count (ANC) > or = 1000 cells/microl. Billing information from the time of transplant to day +100 was analyzed. The median number of days to an ANC > or = 500 cells/microl was shorter in the G-CSF arm, 10.5 days vs 15 days (P < 0.001), while platelet recovery and rates of acute graft-versus-host disease (GVHD) and survival were similar. Resource use was similar, including days hospitalized, days on antibiotics, blood products transfused and outpatient visits. Total median post-transplant costs were $76577 for G-CSF patients and $78799 for placebo patients (P = 0.93). G-CSF following allogeneic blood SCT decreased the median duration of absolute neutropenia and did not incur additional costs, but did not result in shorter hospitalizations, or less frequent antibiotic use.

Initial observations on the efficacy of highly active antiretroviral therapy in the treatment of HIV-associated autoimmune thrombocytopenia.

BACKGROUND: Immune thrombocytopenic purpura (ITP) occurs in as many as 40% of patients infected with the human immunodeficiency virus (HIV). We sought to evaluate the effect of highly active antiretroviral therapy (HAART) on platelet counts in such patients. METHODS: Data collected from 11 homosexual men with HIV-associated ITP and < or = 50 x 10(9) platelets were analyzed after they were placed on HAART. At initial evaluation, 7 patients were antiretroviral naive, 2 were taking zidovudine alone, and 2 were receiving combination antiretroviral therapy for known HIV infection. For 6 patients with <30 x 10(9) platelets, prednisone was initially coadministered with HAART. The primary outcome measure was the platelet count response to HAART, which was measured weekly until counts had normalized on 3 consecutive occasions, then every 3 months while on HAART. Secondary outcome measures were HIV-viral RNA levels and CD4+ cell counts. RESULTS: One month after the initiation of HAART, 10 evaluable patients had an increase in mean platelet count. This improvement was sustained at 6 and 12 months' follow-up for 9 of 10 evaluable patients. Increases in mean platelet count at 6 and 12 months of the 9 responders were statistically significant. The range of follow-up in the 9 responders is 21 to 46 months (median, 30 months), with no thrombocytopenic relapses. The 9 long-term platelet responders have been maintained on HAART and at 12 months had a mean reduction of > 1.5 log10 in HIV viral RNA serum levels and a marked improvement in CD4+ T-lymphocyte cell count. CONCLUSION: HAART seems to be effective in improving platelet counts in the setting of HIV-associated ITP, enhancing CD4+ cell counts, and reducing HIV viral loads.

Reporting and dissemination of industry versus non-profit sponsored economic analyses of six novel drugs used in oncology.

PURPOSE: Our prior study found that pharmaceutical-sponsored and non-profit sponsored analyses differed in their published assessments of the economic value of six new oncology drugs. In this study, we expand on our earlier findings and evaluate the association between funding source and 1) characteristics of the published study report and 2) journal type for dissemination of the previously evaluated economic studies. METHODS: We reviewed the published cost-effectiveness literature for hematopoietic colony stimulating factors, 5-HT3 antagonist antiemetics. and taxanes. Two blinded investigators rated specific aspects of study reporting based on the US Public Health Service Panel on Cost-effectiveness in Health and Medicine criteria. Dissemination strategies were evaluated using impact factor scores from the Science Citation Index. RESULTS: The operational aspects of pharmaceutical-sponsored study reporting were better overall than those associated with non-profit sponsored studies. Specifically, pharmaceutical-sponsored studies were more likely to be reported based on data obtained from randomized clinical trials or detailed cost-models (90% vs. 70%), to include descriptions of the source of cost differences (90% vs. 79%), to state whether the study was carried out from a societal, governmental, or insurer perspective (70% vs. 42%), and to clearly indicate the time-period over which costs were evaluated (65% vs. 50%). Nonprofit sponsored studies were more likely than pharmaceutical sponsored studies to report the generalizability of the findings, including being more likely to include information about how the data could be extrapolated to other clinical settings (58% vs. 35%), to include statements on the statistical significance of the findings (38% vs. 20%), and to clearly outline the cost per unit and data sources for the cost analyses (67% vs. 45%). A similar percent of pharmaceutical and non-profit sponsored studies reported background and conclusions with about 80% providing literature comparisons of the results (about 80%) and two thirds to three fourths discussing the limitations of the finding (75% for pharmaceutical-sponsored and 67% for non-profit sponsored studies). Most studies were published in low impact factor peer-reviewed journals, and journal impact factor scores were similar between pharmaceutical and nonprofit sponsored studies. CONCLUSIONS: Upon reviewing the entire pharmacoeconomic literature for six new oncology drugs, we identified differences in study reporting, but not in types of journals where studies were published, between pharmaceutical-sponsored and non-profit sponsored studies. These results, particularly the observed differences in data generalizability, may account in part for our previous finding of lower likelihood of reporting unfavorable conclusions in pharmaceutical-sponsored studies.

Optimisation of a polarised X-ray source for the in vivo measurement of platinum in head and neck tumours.

There is a continuing need to improve the understanding of kinetics of platinum-based chemotherapeutic agents, such as cisplatin and paraplatin. Although these agents demonstrate highly effective anti-cancer activity, they also have associated, often dose-limiting, side-effects such as nephrotoxocity. In vivo X-ray fluorescence (XRF) has been proven to be a suitable technique for measuring the uptake of these agents in tumour and critical organs, but radioisotope based systems have not found their way into routine clinical use due to their rapid increase in minimum detection limit (MDL) with depth. Polarised X-rays offer a solution to this problem by reducing the scattered background, which not only reduces the MDL, but also allows the intensity of the source to be increased without saturating the detector electronics. This paper describes the development and optimisation of a polarised XRF system for in vivo measurement of platinum in head and neck tumours, whose response to cisplatin is often unpredictable. The polarised X-ray source comprises a clinical X-ray therapy unit (the Pantak DXT-300) with removable purpose-built collimators. Optimisation studies have concentrated upon the operating voltage, polariser material and additional filtering. The optimum voltage was found to lie within the range 200-300 kV for all polarising materials. There was no significant difference using copper, aluminium or iron as the polariser. Increasing the additional filtering improved the MDL for a preset number of counts, but decreased the count-rate significantly, resulting in unacceptably long counting times. An MDL of 9 ppm was achieved for a phantom depth of 2 cm, using a copper polariser, 0.25 mm of tin filtering and an operating voltage of 220 kV. TLD measurements showed that the corresponding skin dose was 6 mGy. These results indicate a factor of improvement in the MDL from the previous 99mTc system, for a factor of two lower skin dose. The detection limit achieved is the lowest reported to date, and is considered adequate for a comprehensive patient study. It is anticipated that this will yield better information and the pharmacokinetics of platinum compounds and will lead to optimisation of both chemo and radiotherapy treatment. Additionally this technique can be easily integrated into any radiotherapy based department.

Penetration of ceftazidime into the human prostate gland following intravenous injection.

The concentration of ceftazidime in human prostatic tissue obtained by transurethral resection was measured by microbiological assay in 24 patients after the intravenous administration of one 2 g dose. The average concentration of ceftazidime in the tissue was 10.1 micrograms/g 70 min after injection and 6.1 micrograms/g 140 min after injection; these levels were each approximately 14% of the corresponding serum levels. The concentration of ceftazidime achieved in the prostatic tissue was greater than the minimum inhibitory concentrations of ceftazidime for Gram-negative pathogens.

Ceftazidime compared to tobramycin and ticarcillin in immunocompromised haematological patients.

Tobramycin and ticarcillin has been compared to ceftazidime in a clinical study on immunocompromised patients with febrile episodes. In the tobramycin and ticarcillin group (A) 70 febrile episodes occurred (10 being unassessable) in 43 patients of which 16 (23%) were bacteriologically positive. Forty-three episodes occurred during neutropenia. In the ceftazidime group (B) 54 febrile episodes (6 being unassessable) were treated in 34 patients. Eleven (20%) were bacteriologically positive and 30 episodes occurred during neutropenia. Clinical cure in group A occurred in 39 episodes, 65% of assessable cases. Cures in group B numbered 27 out of 54 episodes (56% of assessable cases). Clinical failure among evaluable cases, that is no decrease in fever in three days, was 22% in group A and 31% in group B. These results, within the limitation of the study, suggest that ceftazidime given alone at a dosage of 1 g tds is not significantly worse than tobramycin 120 mg tds plus ticarcillin 2 g tds.

Long-term treatment of severe hypertension with minoxidil, propranolol and furosemide.

Thirteen patients with severe hypertension were treated with combined minoxidil, propranolol, and furosemide (mean daily doses 33 mg, 475 mg, and 578 mg, respectively) for nine to twenty-five months (mean 13.8). Average mean blood pressure while on aggressive therapy with conventional medication was 144 +/- 14 mm Hg; on minoxidil and propranolol it was 108 "/- 10 mm Hg (P less thator to optimum blood pressure control and required large doses of furosemide to control. Propranolol blunted the reflex tachycardia associated with arteriolar dilator therapy but all patients continued with a clinically hyperdynamic circulation. Seven of seven had elevated ejection fractions on echocardiogram, and two of three had elevated cardiac indices. Three of three who had heart catheterization had pulmonary hypertension which was aggravated by exercise. An additional three patients on hydralazine, propranolol, and furosemide also had pulmonary hypertension suggesting this is not unique to minoxidil. Two of thirteen developed pericardial effusions. Renal function improved in three and worsened in three.