Publications

OBJECTIVES

Hematuria is considered a marker of active renal disease in ANCA-associated glomerulonephritis (ANCA-GN) with induction immunosuppression often continued until hematuria has resolved. We aim to determine whether longer hematuria duration is associated with lower estimated glomerular filtration rate (eGFR) at 1 year.

METHODS

We conducted a retrospective study of 55 patients with biopsy-proven ANCA-GN. Linear regression models were constructed to determine predictors of eGFR at 1 year. The primary exposure was hematuria (>5 rbc/hpf) duration, defined as <90 days vs. ≥ 90 days following renal biopsy. Covariates included age, gender, ANCA type, baseline eGFR, and baseline proteinuria.

RESULTS

Mean age at diagnosis was 58 years (53% male, 80% Caucasian, 38% PR3-ANCA, and 45% MPO-ANCA). At baseline, all patients had hematuria, 95% had proteinuria, and mean serum creatinine was 3.1 [standard deviation (SD) = 2.3]mg/dL. Overall, 93% were treated with steroids in combination with either cyclophosphamide or rituximab. Mean hematuria duration was 92 (SD = 77) days with 34 (62%) patients having hematuria resolution within 90 days. Older age and lower baseline eGFR were associated with lower eGFR at 1 year (p = 0.03 and p < 0.001, respectively). Hematuria resolution (<90 days vs. ≥ 90 days) was not predictive of eGFR at 1 year (p = 0.93).

CONCLUSIONS

In ANCA-GN, hematuria duration does not predict eGFR at 1 year. Our findings provide support that among individuals who are otherwise considered to be in clinical remission, the persistence of hematuria should not delay transition from induction to maintenance immunosuppression.

Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. CRC incidence and mortality can be reduced through screening. However, in the United States, screening participation remains suboptimal, particularly among underserved populations such as the uninsured, recent immigrants, and racial/ethnic minority groups. Increasing screening rates among underserved populations will reduce the US burden of CRC. In this commentary focusing on underserved populations, we highlight the public health impact of CRC screening, list key challenges to screening the underserved, and review promising approaches to boost screening rates. We identify four key policy and research priorities to increase screening among underserved populations: 1) actively promote the message, "the best test is the one that gets done"; 2) develop and implement methods to identify unscreened individuals within underserved population groups for screening interventions; 3) develop and implement approaches for organized screening delivery; and 4) fund and enhance programs and policies that provide access to screening, diagnostic follow-up, and CRC treatment for underserved populations. This commentary represents the consensus of a diverse group of experts in cancer control and prevention, epidemiology, gastroenterology, and primary care from across the country who formed the Coalition to Boost Screening among the Underserved in the United States. The group was organized and held its first annual working group meeting in conjunction with the World Endoscopy Organization's annual Colorectal Cancer Screening Committee meeting during Digestive Disease Week 2012 in San Diego, California.

The biopharmaceutics classification system (BCS) and biopharmaceutics drug distribution classification system (BDDCS) are complementary classification systems that can improve, simplify, and accelerate drug discovery, development, and regulatory processes. Drug permeability has been widely accepted as a screening tool for determining intestinal absorption via the BCS during the drug development and regulatory approval processes. Currently, predicting clinically significant drug interactions during drug development is a known challenge for industry and regulatory agencies. The BDDCS, a modification of BCS that utilizes drug metabolism instead of intestinal permeability, predicts drug disposition and potential drug-drug interactions in the intestine, the liver, and most recently the brain. Although correlations between BCS and BDDCS have been observed with drug permeability rates, discrepancies have been noted in drug classifications between the two systems utilizing different permeability models, which are accepted as surrogate models for demonstrating human intestinal permeability by the FDA. Here, we recommend the most applicable permeability models for improving the prediction of BCS and BDDCS classifications. We demonstrate that the passive transcellular permeability rate, characterized by means of permeability models that are deficient in transporter expression and paracellular junctions (e.g., PAMPA and Caco-2), will most accurately predict BDDCS metabolism. These systems will inaccurately predict BCS classifications for drugs that particularly are substrates of highly expressed intestinal transporters. Moreover, in this latter case, a system more representative of complete human intestinal permeability is needed to accurately predict BCS absorption.

INTRODUCTION/BACKGROUND

Docetaxel or AA are therapeutic options for mCRPC. We retrospectively analyzed clinical outcomes with subsequent docetaxel in patients with mCRPC after disease progression (DP) with AA to evaluate cross resistance between these therapies.

PATIENTS AND METHODS

Patients with chemotherapy-naive mCRPC who were treated with AA in previously reported phase I to III trials, who had DP, and were subsequently treated (not on study) with docetaxel, were included. Acquired AA resistance was defined as: PSA decline > 50% from baseline or radiographically stable disease for ≥ 8 months, with subsequent DP. All other patients were defined as having primary AA resistance. Efficacy outcomes after docetaxel therapy were analyzed.

RESULTS

We identified 23 patients who were treated with docetaxel after DP with AA, including 14 (61%) with acquired and 9 (39%) with primary AA resistance. Median duration between discontinuation of AA and docetaxel initiation was 2.7 months (range, 0.2-14.7 months). Subsequent docetaxel therapy led to ≥ 30% PSA decline in 15 patients (65%) and ≥ 50% PSA decline in 11 patients (48%). Median OS from date of first docetaxel dose was 12.4 months (95% confidence interval, 8.2-19.6). Patients with previous primary versus acquired AA resistance had similar outcomes with subsequent docetaxel therapy.

CONCLUSION

In this retrospective analysis, the type of AA resistance did not appear to affect outcomes with subsequent docetaxel. The PSA response rates observed suggest a lack of cross-resistance between docetaxel and AA, but prospective studies are needed to evaluate for potential cross-resistance and optimize sequences of therapy in patients with mCRPC.

BACKGROUND

Rising use of computed tomography (CT) to evaluate patients with trauma has increased both patient costs and risk of cancer from ionizing radiation, without demonstrable improvements in outcome. Patient-centred care mandates disclosure of the potential risks, costs and benefits of diagnostic testing whenever possible.

OBJECTIVE

We sought to determine (1) patient preferences regarding emergency department (ED) real-time discussions of risks and costs of CT during their trauma evaluations; and (2) whether varying levels of odds of detection of life-threatening injury (LTI) were associated with changes in patient preferences for CT.

METHODS

Excluding patients already receiving CT and patients with altered mental status, we surveyed adult, English-speaking patients at four Level I verified trauma centres. After informing subjects of cancer risks associated with chest CT, we used hypothetical scenarios with varying LTIs to assess patients' preferences regarding CT.

RESULTS

Of 941 patients enrolled, 50% were male and their mean age was 42 years. Most patients stated they would prefer to discuss CT radiation risks (73.5%, 95% CI [66.1-80.8]) and costs (53.2%, 95% CI [46.1-60.4]) with physicians. As the odds of detecting LTI decreased, preferences for receiving CT decreased accordingly: LTI 25% (desire 91.2%, 95% CI [89.4-93.1]), LTI 10% (desire 79.3%, 95% CI [76.7-81.9]), LTI 5% (desire 69.1%, 95% CI [66.1-72.1]) and LTI <2% (desire 53.8%, 95% CI [50.6-57.0]). If the LTI was <2% and subjects were required to pay $1000 out-of-pocket, only 34.5% (95% CI 31.4-37.5) would opt for CT.

CONCLUSION

Most non-critically injured patients prefer to discuss radiation risks and costs of CT prior to receiving imaging. As the odds of detecting LTI decrease, fewer patients prefer to have CT; at an LTI threshold of 2%, approximately half of patients would prefer to forego CT. Adding out-of-pocket costs reduced this proportion to one-third of patients.