Patient-centered prioritization of bladder cancer research.

BACKGROUND: Patient-centered research requires the meaningful involvement of patients and caregivers throughout the research process. The objective of this study was to create a process for sustainable engagement for research prioritization within oncology. METHODS: From December 2014 to 2016, a network of engaged patients for research prioritization was created in partnership with the Bladder Cancer Advocacy Network (BCAN): the BCAN Patient Survey Network (PSN). The PSN leveraged an online bladder cancer community with additional recruitment through print advertisements and social media campaigns. Prioritized research questions were developed through a modified Delphi process and were iterated through multidisciplinary working groups and a repeat survey. RESULTS: In year 1 of the PSN, 354 patients and caregivers responded to the research prioritization survey; the number of responses increased to 1034 in year 2. The majority of respondents had non-muscle-invasive bladder cancer (NMIBC), and the mean time since diagnosis was 5 years. Stakeholder-identified questions for noninvasive, invasive, and metastatic disease were prioritized by the PSN. Free-text questions were sorted with thematic mapping. Several questions submitted by respondents were among the prioritized research questions. A final prioritized list of research questions was disseminated to various funding agencies, and a highly ranked NMIBC research question was included as a priority area in the 2017 Patient-Centered Outcomes Research Institute announcement of pragmatic trial funding. CONCLUSIONS: Patient engagement is needed to identify high-priority research questions in oncology. The BCAN PSN provides a successful example of an engagement infrastructure for annual research prioritization in bladder cancer. The creation of an engagement network sets the groundwork for additional phases of engagement, including design, conduct, and dissemination. Cancer 2018. © 2018 American Cancer Society.

Refractory migraine in a "just world".

The "just world hypothesis" is the belief that a poor outcome to treatment always implies patient noncompliance. However, all disease states have a spectrum of severity, with the most severe end representing treatment failures despite compliant patients and excellent care. Some refractory headache patients represent this group of compliant patients, who had excellent care but who have bad disease.

Influence of apolipoprotein E genotype on progression of diabetic nephropathy.

AIMS: Diabetic nephropathy progresses at a variable rate part of which may be explained by genetic polymorphisms. ApoE polymorphisms are associated with progression of atherosclerosis and because of the similarities between atherosclerosis and glomerulosclerosis, we chose to examine apoE and its role in progression of diabetic nephropathy. METHODS: The apoE genotypes of 90 patients with type 2 diabetes and nephropathy who were recruited into a 2-year prospective randomised controlled study comparing intensive medical management with routine clinical care were analysed. The primary endpoint was the rate of progression of renal disease in the second year. RESULTS: The apoE genotype frequencies were 49 with E3/3, 20 with E2/3, 17 with E3/4 and 4 with of E2/4. There were no significant differences in age, degree of renal failure, BP, albuminuria or glycaemic control between any genotype. The rate of progression of renal failure of patients with the E3/4 genotype was 0.80 ml/min/month compared to 0.30 ml/min/month for E2/3 and 0.18 ml/min/month for those with E3/3. Patients with E3/4 genotype had significantly faster rates of progression in the second year when compared with the other 3 genotypes (0.80 vs. 0.25 ml/min/month, p = 0.012). There was no difference in mortality according to apoE genotype. CONCLUSION: Patients who possess the apoE3/4 genotype had significantly faster rates of progression of renal failure.

A prospective open-label randomised trial of quinapril and/or amlodipine in progressive non-diabetic renal failure.

BACKGROUND: Treatment of hypertension slows the progression of non-diabetic nephropathies, but the optimal regimen is unknown. Angiotensin-converting enzyme inhibitors are more effective than beta-blockers, but their merits relative to calcium channel blockers are less clear. METHODS: 73 hypertensive patients with progressive non-diabetic nephropathies were prospectively randomised to open-label quinapril (Q, n = 28), amlodipine (A, n = 28) or both drugs (Q&A, n = 17). Therapy was increased to achieve a diastolic blood pressure < 90 mm Hg. Patients were followed for 4 years or until death. The primary outcome was the combined endpoint of doubling serum creatinine, starting renal replacement therapy or death. RESULTS: There was no significant difference in the primary outcome, or in the change of glomerular filtration rate. Blood pressure was equally controlled throughout the study period. 29 (40%) patients were withdrawn from the allocated therapy (Q 39%, A 36%, Q&A 47%). Because of the large crossover between trial arms, the data were re-analysed per protocol. The effect on preventing the need for renal replacement therapy then approached significance between the groups (p = 0.089) and the combined quinapril-containing groups were less likely than the amlodipine group to achieve the primary endpoint (p = 0.038), or the individual endpoints of renal replacement therapy (p = 0.030) or doubling creatinine (p = 0.051). CONCLUSIONS: Quinapril is more effective than amlodipine at reducing the incidence of dialysis in patients with progressive renal failure, but only if they can tolerate the drug. The tolerability of these drugs in patients with advanced renal failure is poor.

Comparative effects of cerivastatin and fenofibrate on the atherogenic lipoprotein phenotype in proteinuric renal disease.

Patients with nephrotic-range proteinuria have impaired clearance of triglyceride-rich lipoproteins. This results in the atherogenic lipoprotein phenotype (mild hypertriglyceridemia, low high-density lipoproteins [HDL], and excess small, dense low-density lipoproteins [LDLIII]). Excess remnant lipoproteins (RLP) are linked to hypertriglyceridemia and may contribute to the atherogenicity of nephrotic dyslipidemia. A randomized crossover study compared the effects of a statin (cerivastatin) and a fibrate (fenofibrate) on LDLIII and RLP in 12 patients with nephrotic-range proteinuria. Cerivastatin reduced cholesterol (21%, P: < 0.01), triglyceride (14%, P: < 0.05), LDL cholesterol (LDL-C; 23%, P: < 0.01), total LDL (18%, P: < 0.01), and LDLIII concentration (27% P: < 0.01). %LDLIII, RLP-C, and RLP triglyceride (RLP-TG) were unchanged. Plasma LDLIII reduction with cerivastatin treatment correlated with LDL-C reduction (r(2) = 34%, P: < 0.05). Fenofibrate lowered cholesterol (19%), triglyceride (41%), very low-density lipoprotein cholesterol (52%), LDLIII concentration (49%), RLP-C (35%), and RLP-TG (44%; all P: < 0.01). Fenofibrate also reduced %LDLIII from 60 to 33% (P: < 0.01). HDL-C (19%, P: < 0.01) increased with fenofibrate treatment; LDL-C and total LDL were unchanged. The reduction in LDLIII concentration and RLP-C with fenofibrate treatment correlated with plasma triglyceride reduction (LDLIII r(2) = 67%, P: < 0.001; RLP cholesterol r(2) = 58%, P: < 0.005). Serum creatinine increased with fenofibrate treatment (14%, P: < 0.01); however, creatinine clearance was unchanged. LDLIII concentration was 187 +/- 85 mg/dl after cerivastatin treatment and 133 +/- 95 mg/dl after fenofibrate treatment. Cerivastatin and fenofibrate reduce LDLIII concentration in nephrotic-range proteinuria. However, atherogenic concentrations of LDLIII remain prevalent after either treatment. Fenofibrate but not cerivastatin reduces remnant lipoproteins. The two treatments seem to reduce LDLIII by different mechanisms, suggesting a potential role for combination therapy to optimize lowering of LDLIII and RLP.