Understanding the Termination of Urologic Cancer Clinical Trials: Insights and Challenges.

PURPOSE: Clinical trials are valuable evidence for managing urologic malignancies. Early termination of clinical trials is associated with a waste of resources and may substantially affect patient care. We sought to study the termination rate of urologic cancer clinical trials and identify factors associated with trial termination. METHODS: A cross-sectional search of ClinicalTrials.gov identified completed and terminated kidney, prostate, and bladder cancer clinical trials started. Trials were assessed for reasons for termination. Multivariable analyses were conducted to determine the significant factors associated with the termination. RESULTS: Between 2000 and 2020, 9,145 oncology clinical trials were conducted, of which 11.30% (n = 1,033) were urologic cancer clinical trials. Of the urologic cancer clinical trials, 25.38% (n = 265) were terminated, with low patient accrual being the most common reason for termination, 52.9% (n = 127). Multivariable analysis showed that only the university funding source odds ratio (OR) of 2.20 (95% CI, 1.45 to 3.32), single-center studies OR of 2.11 (95% CI, 1.59 to 2.81), and sample size of <50 were significant predictors of clinical trial termination OR of 5.26 (95% CI, 3.85 to 7.69); all P values are <.001. CONCLUSION: The termination rate of urologic cancer clinical trials was 25%, with low accrual being the most frequently reported reason. Trials funded by a university, single-center trials, and small trials (sample size <50) were associated with early termination. A better understanding of these factors might help researchers, funding agencies, and other stakeholders prioritize resource allocations for multicenter trials that aim to recruit a sufficient number of patients.

Multiplex polymerase chain reaction to identify and determine the toxigenicity of Corynebacterium spp with zoonotic potential and an overview of human and animal infections.

Corynebacterium diphtheriae, Corynebacterium ulcerans and Corynebacterium pseudotuberculosis constitute a group of potentially toxigenic microorganisms that are related to different infectious processes in animal and human hosts. Currently, there is a lack of information on the prevalence of disease caused by these pathogens, which is partially due to a reduction in the frequency of routine laboratory testing. In this study, a multiplex polymerase chain reaction (mPCR) assay that can simultaneously identify and determine the toxigenicity of these corynebacterial species with zoonotic potential was developed. This assay uses five primer pairs targeting the following genes: rpoB (Corynebacterium spp), 16S rRNA (C. ulcerans and C. pseudotuberculosis), pld (C. pseudotuberculosis), dtxR (C. diphtheriae) and tox [diphtheria toxin (DT) ]. In addition to describing this assay, we review the literature regarding the diseases caused by these pathogens. Of the 213 coryneform strains tested, the mPCR results for all toxigenic and non-toxigenic strains of C . diphtheriae, C. ulcerans and C. pseudotuberculosis were in 100% agreement with the results of standard biochemical tests and PCR-DT. As an alternative to conventional methods, due to its advantages of specificity and speed, the mPCR assay used in this study may successfully be applied for the diagnosis of human and/or animal diseases caused by potentially toxigenic corynebacterial species.

Altered redox homeostasis in human diabetes saliva.

BACKGROUND: Oxidative stress has been implicated in the pathogenesis of diabetes mellitus (DM). Levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-epi-prostaglandin-F(2α) (8-epi-PGF2α), and total protein carbonyls were measured to assess whether DM is associated with altered salivary redox homeostasis. METHODS: A total of 215 patients with diabetes and 481 healthy controls were recruited from the Department of Endocrinology at the Jewish General Hospital in Montreal. Levels of oxidative biomarkers were assayed using enzyme-linked immunosorbent assay (ELISA) in whole unstimulated saliva. Associations of the redox data with exposure to insulin, metformin and dietary control were assessed by logistic regression analyses. RESULTS: We observed (i) significantly higher mean levels of 8-OHdG and protein carbonyls in whole unstimulated saliva of patients with diabetes compared to controls, (ii) higher mean levels of protein carbonyls in type 1 diabetes as well as higher mean levels of 8-OHdG and protein carbonyls in type 2 diabetes compared to controls, (iii) elevated levels of protein carbonyls in diet-controlled patients and in patients with diabetes on insulin and metformin, (iv) elevated levels of 8-OHdG in patients on metformin, and (v) significant associations between subjects with DM and salivary 8-OHdG and protein carbonyls. CONCLUSION: DM is associated with increased oxidative modification of salivary DNA and proteins. Salivary redox homeostasis is perturbed in DM and may inform on the presence of the disease and efficacy of therapeutic interventions.

Health-related quality of life in type 2 diabetic patients.

BACKGROUND AND OBJECTIVES: Health-related quality of life (HRQOL) is an important health outcome, representing one of the most important goals of all health interventions. The objectives of this study were to determine HRQOL and the factors affecting it in type 2 diabetic patients. PATIENTS AND METHODS: This cross-sectional study was conducted in five primary health care (PHC) centers in the Al-Khobar area. From a random sample of 225 type 2 diabetic patients, 216 patients were included in the study along with 216 age- , sex- and nationality-matched controls. Nine patients refused to participate. Type 2 diabetic patients and controls were interviewed with the translated Arabic SF-12 questionnaire. RESULTS: The mean ages were 50.0A+/-10.0 years for cases and of 49.3+/-10.3 years for controls (P=.526). Type 2 diabetic patients had lower socioeconomic status and educational level than controls. Obesity was significantly higher in diabetics than controls. HRQOL in type 2 diabetic patients was significantly lower than controls. The mean physical component score was 41.3+/-8.9 for cases vs. 47.5+/-9.5 for controls (P<.001), and the mean mental component score 47.8+/-9.1 in cases vs. 51.5+/-9.4 in controls (P<.001). HRQOL was significantly lower in females than males (P<.001). HRQOL was impaired in uncontrolled patients (fasting plasma glucose [FPG]>130 mg/dL) in comparison with controlled patients (FPG

Temperature inaccuracies during cardiopulmonary bypass.

Cerebral hyperthermia caused by perfusate temperature greater than 37 degrees C during the rewarming phase of CPB has been linked to postoperative neurologic deficits. The purpose of this study was to determine the accuracy of the coupled temperature measurement system and the CDI 500 arterial temperature sensor. Seventeen patients undergoing CPB were divided into four groups, each with a different temperature probe coupled to the oxygenator. The coupled temperature measurement system and CDI temperature sensors were compared with an indwelling probe placed in direct contact with the arterial perfusate. Blood, bladder, room and water temperatures, arterial line pressure, blood flow, and hemoglobin were recorded while the patients were supported with CPB. The actual blood temperature was significantly higher than the coupled temperature measurement system for two of the four groups (mean = 1.61 degrees C and 0.91 degrees C, p < 0.0001). A significant positive correlation between the actual temperature and the coupled temperature measurement system error was observed for the same two groups (r = 0.44, p < 0.0001). The actual temperature was significantly higher than the CDI temperature in all patients (mean = 1.2 degrees C, p < 0.0001). The coupling mechanism on the oxygenator generates inconsistent temperature readings. The perfusionist should consider these inconsistencies when using coupled temperature measurements and may consider the use of a direct temperature measurement system. The CDI temperature error is probably the result of inadequate flow through the sensor. On the test circuit, the flow of 170 mL/min was inadequate for circuit temperature accuracy. The accuracy of the CDI temperature drastically improved when the flow-through the sensor was increased to approximately 400 mL/min. Thus, the perfusionist must ensure adequate flow through the sensor in order for the temperature mechanism to function properly. Finally, the perfusionist can prevent cerebral hyperthermia by not allowing water temperature to exceed 37 degrees C, when using a coupled temperature measurement system.

Periodontal disease is not associated with preeclampsia in Canadian pregnant women.

BACKGROUND: The findings from the studies on the relationship between periodontal disease and preeclampsia are inconsistent. The objective of this study is to examine the relationship between periodontal disease and preeclampsia. METHODS: A multicenter case-control study was conducted in Quebec, Canada. Preeclampsia was defined as blood pressure ≥140/90 mm Hg and ≥1+ proteinuria after 20 weeks of gestation. Periodontitis was defined as the presence of ≥4 sites with a probing depth ≥5 mm and a clinical attachment loss ≥3 mm at the same sites. RESULTS: A total of 92 preeclamptic women and 245 controls were analyzed. The percentage of periodontal disease was 18.5% in preeclamptic women and 19.2% in normotensive women (crude odds ratio [OR] = 0.96, 95% confidence interval [CI] = 0.52 to 1.77). After adjusting for confounding variables, periodontitis remained not associated with preeclampsia (adjusted OR = 1.13, 95% CI = 0.59 to 2.17). CONCLUSION: This study does not support the hypothesis of an association between periodontal disease and preeclampsia.

Comparison of gastric emptying parameters between asymptomatic volunteers and patients with functional dyspepsia in Middle Eastern population.

OBJECTIVE: To derive the normal reference values for Middle East population using a standard method, and to validate its performance in functional dyspepsia. METHODS: A prospective study was designed to derive gastric emptying parameters in 36 healthy control subjects. We measured the lag phase, half time, and gastric retention at the first, second, and third hours. Values were compared to 49 patients with functional dyspepsia. This study was carried out between July 2005 and August 2009 at Jordan University Hospital, Amman, Jordan. RESULTS: There were no statistically significant differences between the 2 groups at lag phase. Dyspeptic patients had significantly higher gastric retention at the first, second, and third hours (p=0.045, p=0.003, p=0.002). Gastric retention at the third hour was the most sensitive parameter detecting 16 patients (32.6%). Only 3 patients (6.1%) had increased gastric retention at the first hour and normal retention at the third hour. Twelve patients (24.5%) had delayed half time; these patients had increased gastric retention either at the first or third hour. CONCLUSION: Measurement of gastric retention at the first, second, and third hour is enough to identify delayed-early and late phases of gastric emptying in functional dyspepsia patients.

Thumb reconstruction by grafting skeletonized amputated phalanges and soft tissue cover - A new technique: A case series.

This study reports five cases of crush-avulsion injury to the thumb at different levels presented at our plastic and hand surgery unit between 2005 and 2007. All of the patients were male labors with machine injuries to the thumb with non-replantable amputations. Distal phalanx or proximal phalanx, or both, were used as a free cortical bone graft. The amputated part was skeletonized keeping the periosteum attached to the cortical bone of the phalanx fixing it to the stump and covering it by either local flap like dorsal metacarpal flap or regional flaps like the distally based pedicled radial forearm flap and neurovascular island sensate flap or groin flap. The results were functionally and cosmetically good and follow up X rays showed no osteoporotic resorption after one year.

Multiplex polymerase chain reaction to identify and determine the toxigenicity of Corynebacterium spp with zoonotic potential and an overview of human and animal infections

Corynebacterium diphtheriae, Corynebacterium ulcerans and Corynebacterium pseudotuberculosis constitute a group of potentially toxigenic microorganisms that are related to different infectious processes in animal and human hosts. Currently, there is a lack of information on the prevalence of disease caused by these pathogens, which is partially due to a reduction in the frequency of routine laboratory testing. In this study, a multiplex polymerase chain reaction (mPCR) assay that can simultaneously identify and determine the toxigenicity of these corynebacterial species with zoonotic potential was developed. This assay uses five primer pairs targeting the following genes: rpoB (Corynebacterium spp), 16S rRNA (C. ulcerans and C. pseudotuberculosis), pld (C. pseudotuberculosis), dtxR (C. diphtheriae) and tox [diphtheria toxin (DT) ]. In addition to describing this assay, we review the literature regarding the diseases caused by these pathogens. Of the 213 coryneform strains tested, the mPCR results for all toxigenic and non-toxigenic strains of C . diphtheriae, C. ulcerans and C. pseudotuberculosis were in 100% agreement with the results of standard biochemical tests and PCR-DT. As an alternative to conventional methods, due to its advantages of specificity and speed, the mPCR assay used in this study may successfully be applied for the diagnosis of human and/or animal diseases caused by potentially toxigenic corynebacterial species.

Levamisole Therapy as a Second-line Immunosuppressive Agent in Corticosteroid-sensitive Nephrotic Syndrome in Children.

To evaluate the effect of levamisole therapy combined with corticosteroid in children with nephrotic syndrome and frequent relapses (FR) or steroid dependence (SD), we studied retrospectively 24 children (18 boys and six girls) with a mean age of 32 months. Eleven (46%) patients had FR and 13 (54%) had SD. Levamisole was used for a mean period of 8.5 months. The relapse rate decreased from a mean of 4 relapses/year during steroid therapy alone to 1.3 relapses/ year during the combined therapy in 17 (71%) of the patients. Remission was sustained, after discontinuing levamisole, for more than six months in 11 of the 17 responders (65%), and six patients relapsed after discontinuing levamisole. Seven of the 24 study patients (29%) had no response to levamisole. The seven patients who failed to respond to levamisole and the six initial responders who could not maintain remission after discontinuing the drug were treated with cyclophosphamide for 12 weeks. Eight of these patients (61.5%) had remission sustained for a mean duration of 10 months. The FR patients sustained remission for a longer period of time than SD patients in both groups. Levamisole was more effective than cyclophosphamide in patients with the age of onset of the disease above 2 years (10 patients out of 11 (91%). The side effects of levamisole and cyclophosphamide in our patients were transient and manageable. We conclude that levamisole is a safe and effective drug if combined with corticosteroid therapy in children with nephrotic syndrome. Further studies may be required.