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The objective of this study was to assess the relative influence of VKORC1 and CYP2C9 genetic variants on several clinical outcomes related to warfarin treatment. We conducted a retrospective cohort analysis of 172 anticoagulation clinic patients followed from warfarin initiation. We assessed the following clinical outcomes: time to stable dose; time in, above, and below therapeutic range; the probability of overanticoagulation (international normalized ratio [INR] >5); frequency of anticoagulation clinic visits; and the contribution of genetics to maintenance dose. Patients with CYP2C9 variants, compared to those without, achieved stable dose 48% later (p < 0.01), spent a higher proportion of time above range in the first month of therapy (14% vs. 25%, p = 0.07), and had a higher odds ratio (OR) of an INR >5 (OR: 4.15, p = 0.03). In contrast, the only statistically significant effect with VKORC1 was a higher odds of an INR >5 (OR: 4.47, p = 0.03) for patients homozygous for the VKORC1 low-dose haplotype (AA) compared to heterozygotes. We did not detect an influence of CYP2C9 nor VKORC1 on the frequency of clinic visits. CYP2C9 alone, VKORC1 alone, and a combination of genetic and clinical factors explained 12%, 27%, and 50%, respectively, of the variation in warfarin maintenance dose. In conclusion, genetic variation in VKORC1 appears to have a different influence than CYP2C9 on anticoagulation-related outcomes such as bleeding events and time in therapeutic range. This difference may be due, in part, to pharmacokinetics factors (e.g. drug half-life), which are influenced primarily by CYP2C9; these findings should be confirmed in additional studies.

Risk-sharing agreements, under which payers and pharmaceutical manufacturers agree to link payment for drugs to health outcomes achieved, rather than the volume of products used, offer an appealing payment model for pharmaceuticals. Although such agreements have been widely touted, the experience to date mainly demonstrates how hard they are to implement. Barriers include high implementation costs, measurement challenges, and the absence of a suitable data infrastructure. Risk-sharing arrangements could gain traction in the United States as payers and product manufacturers acquire experience with the concept and as measurement techniques and information systems improve. For the foreseeable future, they are likely to remain the exception as drug companies pursue payment models unconnected to data collection or performance assessment.

Our model, based on initial clinical studies to date, suggests that warfarin pharmacogenomic testing may provide a small clinical benefit with significant uncertainty in economic value. Given the uncertainty in the analysis, further updates will be important as additional clinical data become available.

Background: Direct-to-consumer genetic testing (DTC-GT) provides personalized genetic risk information directly to consumers. Little is known about how and why consumers then communicate the results of this testing to health-care professionals. Aim: To query specialists in clinical genetics about their experience with individuals who consulted them after DTC-GT. Methods: Invitations to participate in a questionnaire were sent to three different groups of genetic professionals, totaling 4047 invitations, asking questions about individuals who consulted them after DTC-GT. For each case reported, respondents were asked to describe how the case was referred to them, the patient's rationale for DTC-GT, and the type of DTC-GT performed. Respondents were also queried about the consequences of the consultations in terms of additional testing ordered. The costs associated with each consultation were estimated. A clinical case series was compiled based upon clinician responses. Results: The invitation resulted in 133 responses describing 22 cases of clinical interactions following DTC-GT.Most consultations (59.1%) were self-referred to genetics professionals, but 31.8% were physician referred. Among respondents, 52.3% deemed the DTC-GT to be ''clinically useful.'' BRCA1/2 testing was considered clinically useful in 85.7% of cases; 35.7% of other tests were considered clinically useful. Subsequent referrals from genetics professionals to specialists and/or additional diagnostic testing were common, generating individual downstream costs estimated to range from $40 to $20,600. Conclusions: This clinical case series suggests that approximately half of clinical geneticists who saw patients after DTC-GT judged that testing was clinically useful, especially the BRCA1/2 testing. Further studies are needed in larger and more diverse populations to better understand the interactions between DTC-GT and the health-care system.

Purpose We compared the clinical outcomes of patients with ureteral or renal stones treated with ureteroscopy, shock wave lithotripsy using HM3 (Dornier®) and nonHM3 lithotripters, and percutaneous nephrolithotomy. Materials and Methods A systematic literature search identified 6, 4 and 3 randomized, controlled trials of treatment of distal and proximal ureteral stones, and renal stones, respectively, published between 1995 and 2010. Overall stone-free, re-treatment and complication rates were calculated by meta-analytical techniques. Results Based on the randomized, controlled trials evaluated the treatment of distal ureteral stones with semirigid ureteroscopy showed a 55% greater probability (pooled RR 1.55, 95% CI 1.13–2.56) of stone-free status at the initial assessment than treatment with shock wave lithotripsy. Patients treated with semirigid ureteroscopy were also less likely to require re-treatment than those treated with shock wave lithotripsy (nonHM3) (RR 0.14, 95% CI 0.08–0.23). The risk of complications was no different between the 2 modalities. Only 2 of the 4 randomized, controlled trials identified for proximal ureteral stones evaluated flexible ureteroscopy and each focused specifically on the treatment of stones 1.5 cm or greater, limiting their clinical relevance. The degree of heterogeneity among the studies evaluating renal stones was so great that it precluded any meaningful comparison. Conclusions Semirigid ureteroscopy is more efficacious than shock wave lithotripsy for distal ureteral stones. To our knowledge there are no relevant randomized, controlled trials of flexible ureteroscopy treatment of proximal ureteral calculi of a size commonly noted in the clinical setting. Collectively the comparative effectiveness of ureteroscopy and shock wave lithotripsy for proximal ureteral and renal calculi is poorly characterized with no meaningful published studies.

SRSE is associated with high mortality and morbidity, which place a high burden on healthcare resources. Projections based upon the findings of this study suggest an estimated 25,821-41,959 cases of SRSE may occur in the US each year, but more in-depth studies are required.

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