Ondansetron rapidly dissolving film for the prophylactic treatment of radiation-induced nausea and vomiting-a pilot study.

INTRODUCTION: The purpose of the present study was to investigate the efficacy of an ondansetron rapidly dissolving film (rdf) in the prophylaxis of radiation-induced nausea and vomiting (rinv). Rapidly dissolving film formulations facilitate drug delivery in circumstances in which swallowing the medication might be difficult for the patient. METHODS: Patients undergoing palliative radiotherapy at risk for rinv were prescribed ondansetron rdf 8 mg twice daily while on treatment and were asked to complete a nausea and vomiting-specific daily diary, the Functional Living Index-Emesis (flie), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C15 Palliative (qlq-C15-pal). Patients were categorized as receiving primary or secondary prophylaxis based on whether they had already experienced emetic episodes. "Overall control" was defined as a maximum increase of 2 episodes of nausea or vomiting from baseline. "Acute phase" was defined as the days during radiation until the first day after radiation; "delayed phase" was defined as days 2-10 after radiation. RESULTS: The study accrued 30 patients. Rates of overall control for nausea and for vomiting during the acute phase in the primary prophylaxis group were 88% and 93% respectively; during the delayed phase, they were 73% and 75%. Rates of overall control for nausea and for vomiting during the acute phase in the secondary prophylaxis group were both 100%; during the delayed phase, they were 50%. The number of nausea and vomiting episodes was found to be significantly correlated with the flie and qlq-C15-pal questionnaires. CONCLUSIONS: Ondansetron rdf is effective for the prophylaxis of rinv.

Patterns of practice in the prescription of palliative radiotherapy for the treatment of bone metastases at the Rapid Response Radiotherapy Program between 2005 and 2012.

OBJECTIVE: We examined whether patterns of practice in the prescription of palliative radiation therapy for bone metastases had changed over time in the Rapid Response Radiotherapy Program (rrrp). METHODS: After reviewing data from August 1, 2005, to April 30, 2012, we analyzed patient demographics, diseases, organizational factors, and possible reasons for the prescription of various radiotherapy fractionation schedules. The chi-square test was used to detect differences in proportions between unordered categorical variables. Univariate logistic regression analysis and the simple Fisher exact test were also used to determine the factors most significant to choice of dose-fractionation schedule. RESULTS: During the study period, 2549 courses of radiation therapy were prescribed. In 65% of cases, a single fraction of radiation therapy was prescribed, and in 35% of cases, multiple fractions were prescribed. A single fraction of radiation therapy was more frequently prescribed when patients were older, had a prior history of radiation, or had a prostate primary, and when the radiation oncologist had qualified before 1990. CONCLUSIONS: For patients with bone metastasis, a single fraction of radiation therapy was prescribed with significantly greater frequency.

Continued success in providing timely palliative radiation therapy at the Rapid Response Radiotherapy Program: a review of 2008-2012.

OBJECTIVE: We set out to review the Rapid Response Radiotherapy Program (rrrp). METHODS: We retrospectively reviewed a prospective database of patients referred to the rrrp between August 1, 2008, and June 30, 2012, extracting patient demographics, case dispositions, and wait times in days from referral to consultation and from consultation to treatment. RESULTS: Of 2742 patients referred to the rrrp, 1458 (53%) were men, and 1284 (47%) were women. Median age was 64 years. The most prevalent primary cancer sites were lung (33%), breast (21%), and prostate (17%). The most common reasons for referral were bone metastases (53%) and brain metastases (21%). Palliative radiation therapy was given to 1890 patients. The median wait time from referral to consultation was 3 days. Among treated patients, 60% were treated on the day of their consultation, and 33%, within 1-6 days. CONCLUSIONS: The rrrp continues to deliver timely palliative radiation therapy to patients, comparable to earlier reviews. The continued success of the rrrp will remain a model for future rapid-access palliative radiation therapy clinics.

Incidence of skeletal-related events over time from solid tumour bone metastases reported in randomised trials using bone-modifying agents.

AIMS: Skeletal-related events (SREs) in patients with bone metastases decrease a patient's quality of life and functional status. Although bone-modifying agents have been found to reduce the time to first on-trial SRE and decrease the total incidence of SREs in randomised clinical trials, standard practice in the management of bone metastases has changed concurrently. The purpose of this study was to investigate if advances in bone-targeted therapies have decreased the incidence of individual types of SREs and to delineate the trend of SREs. MATERIALS AND METHODS: A literature review was conducted in MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials to identify phase III, randomised bisphosphonate and other bone-targeted therapy trials from 1980 to September 2011. For all studies, a mean year of enrolment ([start of enrolment + end of enrolment]/2) was calculated. The incidences of SREs were tabulated and expressed as percentages of on-trial patients. Generalised linear mixed models were used to search for the trends of SREs over time for all placebo and intervention arms. Regression coefficients were interpreted as the odds ratio, which was calculated using the exponential of the slope. Ninety-five per cent confidence intervals were also calculated. RESULTS: In total, 20 eligible studies were identified that reported SRE data from phase III trials, of which 11 were suitable for the quantitative analysis. Most of the articles included patients with breast cancer and the remaining involved patients with prostate, renal cell, bladder and lung cancer or other solid tumours. Enrolment periods for all included data ranged from 1990 to 2009. Statistically significant overall downward trends in pathological fractures and the need for surgery were seen over time. Also significant differences between intervention and placebo were seen with all SREs. CONCLUSION: The decrease in SREs over time may not only be a result of the development of new generation bone-targeted agents, but also due to better systemic management and awareness of events associated with bone metastases.

Systematic patients' hand disinfection: impact on meticillin-resistant Staphylococcus aureus infection rates in a community hospital.

The role of patients and their relatives as unidentified transient meticillin-resistant Staphylococcus aureus (MRSA) carriers and sources of dissemination in healthcare institutions has not been systematically addressed. Patients' and their relatives' hands may represent a substantial and 'unaccounted for' mode of transmission. This study aimed to verify this hypothesis in our 250-bed community hospital. The trial consisted of a systematic waterless washing and gel rinse disinfection of all patients' and visiting relatives' hands for a period of one year, along with retrospective comparison of the nosocomial infection rates. Under the supervision of infection control personnel, a team of four full-time and four part-time attendants was trained to meet all patients and visiting relatives and encourage them to clean their hands with an alcohol gel rinse twice a day on every weekday. Rates of MRSA infections per thousand admissions, cost-benefit analysis and staff hand hygiene compliance were audited throughout. From the comparative year, the rate of MRSA nosocomial infections per thousand admissions decreased by 51%. Assuming that the incidence of MRSA was maintained from comparative to study year, the intervention may have prevented 51 cases of MRSA infection and resulted in substantial savings. While focusing extensively on staff behaviour to prevent MRSA transmission, we may have overlooked hand hygiene practices by patients and their relatives as a potential mode of transmission. Systematic hand hygiene of patients and relatives appears to be an inexpensive and highly effective preventive measure against MRSA nosocomial transmission.

Hypersensitivity pneumonitis in peat moss processing plant workers.

A nonsmoking 54-yr-old man, employed in a peat moss packaging plant, developed dyspnea and recurrent fever. The diagnosis of hypersensitivity pneumonitis (HP) was made. Thirteen of 14 coworkers and 13 nonexposed control subjects were studied. Five workers were nonsmokers, two were minimal smokers, and six were smokers. HP was found in another subject. Monocillium sp. and Penicillium citreonigrum, 4.6 x 10(7) CFU/g, were found in the peat moss. Three nonsmokers, the two minimal smokers (including the subject with HP), and the index case had antibodies to these microorganisms; none of the six heavy smokers had antibodies. Serum TNF-alpha was higher in the workers than in the control subjects (0.930 +/- 0.177 versus 0. 350 +/- 0.076). Three of the four asymptomatic seropositive workers and two seronegative smokers were further evaluated. All three seropositive workers had normal lung functions and CT but they all had a lymphocytic alveolitis (30, 34, and 68% lymphocytes in their bronchoalveolar lavage [BAL]). The smokers had normal lung functions, CT, and percentage of BAL lymphocytes (3 and 13%). This study identified a previously unrecognized work environment that can lead to HP and documented a protective effect of smoking on the response to antigens.

Effect of route of breathing on response to exposure in a swine confinement building.

Exposure of naive subjects to swine buildings results in acute nasal, lung, and peripheral blood inflammatory responses with an increase in nonallergic airway responsiveness. Because nasal passages filter large particles and soluble gases and because swine building exposure results in an acute inflammatory response at this level, we questioned what effect breathing through or avoiding this route would have on local and systemic inflammation. Nine normal young men 23 to 37 yr of age were exposed for 5 h to a swine building, once breathing normally and once with the mouth occluded (n = 8) (Protocol 1) or the nose occluded (n = 4) (Protocol 2); three subjects participated in both protocols. For each protocol each subject underwent a methacholine challenge for PC20 measurement, a nasal lavage, venous blood puncture, and a bronchoalveolor lavage (BAL) once before and once after each swine building exposure. Bronchial responsiveness as measured by PC20 decreased in most subjects after swine building exposure and was not influenced by the route of breathing. Nasal lavage neutrophils increased tenfold after each swine exposure, except when the nose was occluded where no alteration was observed. Total BAL cells significantly increased after each exposure to the swine building, this increase was not modified by the route of breathing. In Protocol 1, white blood cells increased from a baseline level of 7.0 to 10.5 x 10(9) cells/L after exposure with normal breathing and to 10.7 x 10(9) cells/L during nasal breathing exclusively. For Protocol 2, these respective values were: 5.6, 11.7 and 10.4 x 10(9)/L. Interleukins 6 and 8 levels in BAL, nasal washes, and serum were increased by swine building exposure, except in the nasal wash when the nose was occluded. In conclusion, the lung and blood responses to exposure in a swine confinement building are not modified by the route of breathing, suggesting that nasal inflammation and filtration are not important in the process and that small respirable particles and/or gases may be responsible for these responses.

Effects of repeated swine building exposures on normal naive subjects.

Exposure to swine confinement buildings has a negative impact on respiratory health. A short exposure to this environment results in an acute airway inflammatory response. The present study was performed to confirm and further define the acute effects of working in a swine building, and to determine whether these effects are reproducible. Seven previously nonexposed normal subjects underwent evaluations that included hourly measurement of forced expiratory volume in one second (FEV1), methacholine challenge (the provocative concentration producing a 20% fall in FEV1 (PC20)), bronchoalveolar lavage (BAL), nasal lavage (NL), and blood analyses, before (control) and after each of two 5 h exposures to a swine building environment. The exposures were conducted 8 days apart. The levels of total dust, endotoxins, and ammonia (NH3) in the confinement building were measured on each day of exposure. Both exposures resulted in a significant reduction in FEV1 (mean+/-SEM change in FEV1: control = 7+/-2%; exposure 1 = 15+/-3%; exposure 2 = 23+/-3%), decrease in PC20 (median value (25th-75th percentile): 223 (23-256), 20 (15-198) and 20 (11-71), respectively; p=0.05) and increase in BAL cells (129+/-20, 451+/-43 and 511+/-103x10(3) cells x mL(-1), respectively) and NL cells (6+/-4, 126+/-58 and 103+/-26x10(3) cells x mL(-1), respectively), mostly neutrophils. Levels of interleukin-8 (IL-8), but not interleukin-1 (IL-1) or tumour necrosis factors (TNF-alpha), increased both in BAL and nasal fluids with exposure. In normal naive subjects, repeated exposure to the environment of a swine building induced a marked and reproducible reduction in forced expiratory volume in one second, increase in airway responsiveness, and increased neutrophilic inflammatory response. These results could not be accounted for by any of the environmental factors measured.

Diagnostic accuracy of urinary cytology, and deoxyribonucleic acid flow cytometry and cytology on bladder washings during followup for bladder tumors.

PURPOSE: We evaluated the diagnostic accuracy of cytology on urine and bladder washings, and deoxyribonucleic acid (DNA) flow cytometry on bladder washings compared to cystoscopy during followup for bladder tumors. MATERIALS AND METHODS: A cross-sectional analysis was performed on 166 patients with a history of bladder tumor for the initial visit when cytology and DNA flow cytometry results were available for urine and bladder washing samples. There were 114 bladder tumor events and 52 negative controls (normal cystoscopy). A prospective study was conducted among the 66 patients with no tumor detected by cystoscopy at the initial visit and for whom the 3 test results were available. The patients were followed from this visit until tumor recurrence or the end of the followup period. Cytological examination was considered positive only when interpreted as malignant. Suspicious examinations were considered negative for the purpose of our study. RESULTS: Sensitivity and specificity of urinary cytology were 59 and 85%, respectively. Sensitivity was increased to 66% using bladder washing cytology whereas specificity was moderately decreased to 83%. The sensitivity and specificity of DNA aneuploidy were 45 and 87%, respectively. Inclusion within the aneuploid category of hyperdiploid samples (defined as more than 7% of cells in the S + G2M phase) increased sensitivity to 77%, while specificity decreased to 42%. Kaplan-Meier analysis of tumor-free survival in patients initially free of bladder cancer at cystoscopy showed an inability of DNA flow cytometry to predict recurrence, whereas positive urine or bladder washing cytology predicted a shorter time to recurrence (log-rank test p <0.01). CONCLUSIONS: These results show that DNA flow cytometry and cytology on bladder washing samples add little information to that obtained from voided urine cytology.

[Ipsilateral adrenalectomy in the surgical treatment of renal carcinoma]. / La surrénalectomie ipsilatérale dans le traitement chirurgical du carcinome rénal.

OBJECTIVES: To assess the value of ipsilateral adrenalectomy during radical nephrectomy for the treatment of renal cell carcinoma as a function of preoperative computed tomography findings. METHODS: Between May 1985 and June 1994, 194 patients underwent radical nephrectomy for renal cell carcinoma in our institution. Preoperative radiological reports and postoperative pathological reports were reviewed for 185 patients. RESULTS: 148 patients underwent abdominal computed tomography before surgery. 94 adrenalectomies were performed in this group of patients. None of the 77 patients in whom computed tomography showed a normal adrenal gland had adrenal metastasis on the definitive histological examination. 17 patients had an adrenal mass on computed tomography, 3 of which proved to be neoplastic. Preoperative CT had a sensitivity of 100%, a specificity of 82%, a positive predictive value of 18% and a negative predictive value of 100%. The 185 files reviewed included 114 adrenalectomies, including 4 adrenal glands invaded by renal cell carcinoma (3.5%). In these 4 cases, the smallest diameter of the renal tumour was 4 cm and the minimum pathological stage was T3. CONCLUSIONS: It therefore appears justified not to perform adrenalectomy during nephrectomy, in the presence of a renal tumour and negative adrenal computed tomography.

Farmer's lung and variables related to the decision to quit farming.

An exploratory strategy was used to investigate why 55% of patients with farmer's lung (FL) disease quit farming. Three groups were recruited: 47 patients with FL disease who quit farming because of the disease (FLq), 76 patients with FL disease who continued farming (FLc), and 123 control farmers without a history of FL disease. The severity of FL disease at diagnosis was similar in both groups of patients. For example, single-breath carbon monoxide diffusion capacity predicted for FLq and FLc was 64.4 +/- 28.2 and 63.9 +/- 22.0, respectively. Relying on a cognitive-behavior theory, numerous physiological, behavioral, cognitive, affective, and social variables were assessed. Results showed that the decision to quit farming was based on cognitive and behavioral motives rather than physiological factors. Subjects in the FLq group showed more negative beliefs toward FL and had more fears of FL disease. FLq subjects also reported that family members, friends, and family doctors were more inclined to consider that FL disease could stop them from farming. However, self-efficacy to continue farming despite having FL disease and perceived hindrance caused by FL disease played the most important roles in the decision to quit farming.

Quality of life of subjects with occupational asthma.

BACKGROUND: The aim of the study was to assess the quality of life in subjects with occupational asthma after removal from exposure to the offending agent by comparison with a group of subjects paired for clinical and functional indices in order to show the separation between the two groups of subjects with a hypothesized different quality of life and relate the impairment in quality of life to anthropometric, clinical, and functional variables. METHODS: A previously described asthma quality of life questionnaire (Juniper EF, et al. Thorax 1992;47:76-83) was administered to two groups of subjects in a prospective manner. Information on the clinical and functional severity of asthma was obtained from each subject. Two groups of subjects were assessed: group 1, 134 subjects with occupational asthma who were seen more than 2 years after the diagnosis was confirmed, and group 2, 91 subjects who were seen in specialized asthma clinics of tertiary care hospitals for treatment of nonoccupational asthma and matched with 91 of the 134 subjects with occupational asthma from group 1 according to need for medication and (when available), baseline forced expiratory volume in 1 second (FEV1), and level of bronchial responsiveness. RESULTS: A statistically significant difference was seen in the four domains (asthma symptoms, limitation of activities, emotional dysfunction, environmental stimuli) and in the total score of the quality of life questionnaire between the two groups of matched subjects; the mean difference in the total score was 0.6 on a scale of 1 (no limitation or none of the time) to 7 (severe limitation or all the time). A weak but statistically significant correlation between the total score and several indices (FEV1, bronchial responsiveness and asthma severity) was generally obtained. CONCLUSION: The quality of life of subjects with occupational asthma is slightly less satisfactory than that of subjects paired for clinical and functional indices, although the magnitude of the difference is small; and quality of life is weakly correlated with clinical and functional indices.

[The Quebec system of indemnification for occupational asthma. Description, efficacy, and costs]. / Le système québécois d'indemnisation pour asthme professionnel. Description, efficacité et coûts.

This study describes the Quebec system of compensation for occupational asthma, assessing the functional and social outcome of claimants and estimating the efficiency and cost. Information was obtained on the clinical, functional and social outcome as well as the estimated costs for 134/211 subjects (participation rate of 64%), who received compensation between 1986 and 1988. At the time of assessment (2 years and more after the diagnosis), 93% of participants still demonstrated significant bronchial hyperresponsiveness and 84% required anti-asthma medication. None of the participants remained exposed to the offending agent: 67% were working for the same or another employer, 16% were retired, 8% were retraining for a new job and 8% were still unemployed. Quality of life was mildly affected, more so than for a control group of subjects. The mean interval between the time claims were addressed and the first medicolegal decision was 8.1 months. The mean total cost (including temporary and permanent disability indemnities, medical and technical costs) was $CAN 49,200 (minimum and maximum values of $2,100 and $330,900). We conclude that for subjects with occupational asthma in Quebec: 1) the mean interval for a medicolegal decision to be made is eight months: 2) a minority is still unemployed two to four years after being assessed; 3) the quality of life is more affected than in a control group; 4) the mean cost is close to $CAN 50,000.

Respiratory health of workers exposed to swine confinement buildings only or to both swine confinement buildings and dairy barns.

Swine building workers (N = 488) and nonfarming neighborhood referents (N = 216) were enrolled in this study. There was a slight but significant increase in the prevalence of chronic bronchitis (17.49 versus 11.57%) and more evidence of airflow obstruction (forced expiratory volume in 1 s/forced vital capacity 0.75 versus 0.78) among the swine workers when they were compared with the referents. The subjects who spent more than 3 h/d in the swine buildings had a higher prevalence of chronic bronchitis (21.94 versus 13.25%) and airflow obstruction (forced expiratory volume in 1 s/forced vital capacity 0.75 versus 0.76) than those with shorter daily contact. Swine building only workers had no precipitins to antigens found in their environment and no clinical evidence of extrinsic allergic alveolitis. The number of years on the farm, dual exposure with dairy cattle, positive skin prick tests, type of piggery, and type of feeding did not add to the respiratory health impact of swine buildings.

Influence of time of administration on allergic skin prick tests response.

This study evaluated influences of time of administration on the response to allergy skin prick tests. There was no significant difference between the mean +/- SEM wheal diameter of positive responses obtained in the morning, 2.98 +/- 0.19 nm, or in the evening, 3.14 +/- 0.18 mm (n = 175).