Feasibility and delivery of patient-reported outcomes in clinical practice among racially diverse bladder and prostate cancer patients

ObjectiveTo assess the feasibility of enrollment and collecting patient-reported outcome (PRO) data as part of routine clinical urologic care for bladder and prostate cancer patients and examine overall patterns and racial variations in PRO use and symptom reports over time.Subjects/Patients and MethodsWe recruited 76 patients (n = 29 Black and n = 47 White) with prostate or bladder cancer at a single, comprehensive cancer center. The majority of prostate cancer patients had intermediate risk (57%) disease and underwent either radiation or prostatectomy. Over half (58%) of bladder cancer patients had muscle invasive disease and underwent cystectomy.Patients were asked to complete PRO symptom surveys using their preferred mode [web- or phone-based interactive voice response (IVR)]. Symptom summary reports were shared with providers during visits. Surveys were completed at 3 time points and assessed urinary, sexual, gastrointestinal, anxiety/depression, and sleep symptoms. Feasibility of enrollment and survey completion were calculated, and linear mixed effects models estimated differences in outcomes by race and time.ResultsSixty three percent of study participants completed all PRO measures at all 3 time points. Black patients were more likely to select IVR as their survey mode (40% vs. 13%, P < 0.05), and less likely to complete all surveys (55% vs. 74%, P = 0.13). Patients using IVR were also less likely to complete all surveys (41% vs. 69%, P = 0.046).ConclusionsReported preferences for survey mode and completion rates differ by race, which may influence survey completion rates and highlight potential obstacles for equitable implementation of PROs into clinical care.     

Long-term rates of bladder dysfunction after decompression in patients with cauda equina syndrome

BACKGROUND CONTEXTCauda equina syndrome (CES) occurs due to compression of the lumbar and sacral nerve roots and is considered a surgical emergency. Although the condition is relatively rare, the associated morbidity can be devastating to patients. While substantial research has been conducted on the timing of treatment, the literature regarding long-term rates of bladder dysfunction in CES patients is scarce.PURPOSEThe aim of this study was to identify long-term rates of bladder dysfunction in CES patients and to compare those rates to non-CES patients who underwent similar spinal decompression.STUDY DESIGN/SETTINGRetrospective database study.PATIENT SAMPLEThe CES cohort was comprised of 2,362 patients who underwent decompression surgery following CES diagnosis with a 5-year follow-up. These patients were matched to 9,448 non-CES control patients who underwent spinal decompression without a diagnosis of CES.OUTCOME MEASURESDiagnosis of bladder dysfunction, surgical procedure to address bladder dysfunctionMETHODSUsing the national insurance claims database, PearlDiver, CES patients who underwent decompression surgery were identified and 1:4 matched to non-CES patients who underwent similar spinal decompression surgery. The 1-year, 3-year, and 5-year rates of progression to a bladder dysfunction diagnosis and surgical intervention to manage bladder dysfunction were recorded. The CES and non-CES groups were compared with univariate testing, and an analysis of risk factors for bladder dysfunction was performed with multivariate logistic regression analysis.RESULTSA total of 2,362 CES patients who underwent decompression surgery were identified and matched to 9,448 non-CES control patients. After 5 years, CES patients had a 10%–12% increased absolute risk of continued bladder dysfunction and a 0.7%–0.9% increased absolute risk of undergoing a surgical procedure for bladder dysfunction, as compared to matched non-CES patients. Multivariate analysis controlling for age, sex, obesity, tobacco use, and diabetes, identified CES as independently associated with increased 5-year risk for bladder dysfunction diagnosis (odds ratio [OR]: 1.72; 95% confidence interaval [CI] 1.56–1.89; p<.001) and procedure (OR: 1.40; 95% CI 1.07–1.81; p=.012).CONCLUSIONSUnderstanding the long-term risk for bladder dysfunction in CES patients is important for the future care and counseling of patients. Compared to non-CES patients who underwent similar spinal decompression, CES patients were observed to have a significantly higher long-term likelihood for both bladder dysfunction diagnosis and urologic surgical procedure.     

Application of Stable Isotopic Ratio Analysis to Identify the Cause of Acute Versus Chronic Lead Poisoning of a Tundra Swan (Cygnus columbianus): A Case Study

We utilized lead (Pb) stable isotopes to identify the source of acute Pb poisoning in a Tundra Swan (Cygnus columbianus) and evaluated overall Pb exposure. Upon necropsy, we obtained samples of blood, liver, kidney, heart, thigh, breast, femur, and metallic objects (i.e., fishing sinker, spring and swivels) from the gizzard for Pb isotopic analysis. Pb isotope ratios of blood and soft tissues were essentially identical to the Pb ratios of the sinker, the likely source of acute poisoning. The spring and swivels had lower Pb content and ratios distinct from tissue, suggesting no significant contribution to poisoning. Femur Pb isotopic composition was the most distinct biological sample and indicative of a combination of sources. These results demonstrate isotopic analysis as a viable method for determining the source of acute Pb poisoning, and that Pb isotope ratios in bone most likely record a lifetime-averaged metric of Pb exposure.

     

Measuring physician practice site characteristics: A comparison of data from SK&A and a practice site survey

ObjectiveTo evaluate the comparability of commercially available practice site data from SK&A with survey data to understand the implications of using SK&A data for health services research.Data sourcesResponses to the Comprehensive Primary Care Plus (CPC+) Practice Survey and SK&A data.Study designComparison of CPC + Practice Survey responses to SK&A information for 2698 primary care practice sites.Data collectionCPC + Practice Survey data collected through a web‐only survey from April through September 2017, and SK&A data purchased in November 2016.Principal findingsInformation was similar across data sources, although some discrepancies were common. For example, 56% of practice sites had differences in the reported number of practitioners, and larger sites tended to have larger differences. Among practice sites with 1 practitioner in the survey, only 1.3% had a difference of 3 or more practitioners between the data sources, whereas 63% of practice sites with 11 or more practitioners had a difference of 3 or more practitioners.ConclusionsDiscrepancies between data sources could reflect differences of interpretation when defining practice site characteristics, changes over time in those characteristics, or data errors in either SK&A or the survey. Researchers using SK&A data should consider possible ramifications for their studies.     

Identification of natural antibodies to interleukin-18 in the sera of normal humans and three nonhuman primate species

Natural antibodies to cytokines can be found in the sera of normal healthy individuals in the absence of specific immunostimulation. However, the function, impact, and purpose of natural antibody development have yet to be fully elucidated. Interleukin (IL)-18 is a cytokine that exerts proinflammatory activities and induces natural killer (NK) cell activity. Recombinant human IL-18 (rHuIL-18) is currently in development as a cancer immunotherapy. In this study, the presence of natural antibodies to IL-18 in the sera of normal humans and three nonhuman primate species was evaluated by electrochemiluminescence immunoassay (ECLIA). Of the human sera tested, 6 of 47 samples were positive for natural antibodies to IL-18. Of the nonhuman primate sera tested, 22 of 80 cynomolgus monkey samples, 4 of 31 rhesus monkey samples, and 2 of 20 chimpanzee samples were positive for natural antibodies to IL-18. Natural anti-IL-18 antibodies were neutralizing in 5 of 22 cynomolgus and 2 of 4 rhesus sera. None of the chimpanzee or human sera were able to neutralize IL-18 induction of interferon (IFN)-gamma in vitro. In vivo activity of rHuIL-18 was compared in IL-18 natural antibody-positive and -negative cynomolgus monkeys. The presence of natural antibodies to IL-18 did not alter rHuIL-18 systemic exposure levels, induction of neopterin, or induction of treatment-induced antibodies following intravenous administration of rHuIL-18. In conclusion, our data indicate that, as has been found with other cytokines, natural anti-IL-18 antibodies are relatively common. Moreover, natural anti-IL-18 antibodies do not appear to influence rHuIL-18 activity in vivo and are not predictive of a heightened immune response, suggesting that natural anti-IL-18 antibodies do not impact IL-18 therapy. Finally, our data suggest that the ability to detect natural anti-cytokine antibodies may be a useful measure of the adequacy of an assay for deployment in clinical trials.     

In vitro cellular immune responses to recombinant antigens of Mycobacterium avium subsp. paratuberculosis

Five recombinant antigens (Ags; 85A, 85B, 85C, superoxide dismutase [SOD], and 35-kDa protein) were purified from Mycobacterium avium subsp. paratuberculosis and evaluated for their ability to stimulate peripheral blood mononuclear cells (PMBCs) from fecal-culture-positive cows (low and medium shedders) and culture-negative healthy cows. Recombinant Ags 85A, 85B, and 85C induced significant lymphocyte proliferation as well as the production of gamma interferon (IFN-gamma), interleukin-2 (IL-2), IL-12, and tumor necrosis factor alpha (TNF-alpha), but not IL-4, from low and medium shedders. The 85 antigen complex did not stimulate PMBC proliferation from culture-negative healthy cows. The 35-kDa protein also induced significant lymphocyte proliferation as well as the production of IFN-gamma and IL-4 from low and medium shedders. CD4(+) T cells and CD25(+) (IL-2R) T cells were stimulated the most by 85A and 85B, while the 35-kDa protein primarily stimulated CD21(+) B cells involved in humoral immune responses. Interestingly, SOD was less immunostimulatory than other antigens but strongly induced gammadelta(+) T cells, which are thought to be important in the early stages of infection, such as pathogen entry. These data provide important insight into how improved vaccines against mycobacterial infections might be constructed.     

A placebo-controlled crossover study of ketanserin in elderly hypertensive patients

Summary The results of the European Working Party for Hypertension in the Elderly Study showed that treatment of high blood pressure reduced the morbidity and mortality from strokes and myocardial infarction and reduced the incidence of heart failure in elderly patients. The largest number of hypertensive patients are elderly, and it is in this group of patients that the maximum benefit of treatment might be expected. The present study was designed to study in detail the efficacy and tolerability of ketanserin in an elderly population. Seventeen elderly (> 70 years) patients with a lying systolic blood pressure of 160 mmHg and/or a diastolic blood pressure of 90 mmHg were included in the study. For the 12 patients who completed the study, the mean blood pressure was significantly reduced on ketanserin compared with placebo (p<0.001) in the supine and erect positions. The mean net changes in blood pressure after 8 weeks were 21/17 mmHg and 23/16 mmHg erect. Heart rate was also significantly reduced (p<0.001) by a mean of 8 beats/min lying and 9 beats/min erect. Analysis of ambulatory 24-hour ECG tapes showed no significant effect of ketanserin on heart rhythms. Ketanserin therapy had no significant effect on routine hematology, plasma electrolytes, biochemistry, or urinalysis. Total exchangeable sodium and potassium and body weight were also unchanged. On ketanserin treatment, the overall quality of life score was significantly improved (p=0.002; analysis of variance on log transformed data) compared with the placebo phase.