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The majority of the literature shows larger and more persistent effects on cancer-specific anxiety medicine 853 buy prometrium 200mg cheap, worry medications not to take when pregnant order 100 mg prometrium mastercard, or other quality-of-life domains;174 symptoms quad strain order cheapest prometrium,179 in a recent meta-analysis, anxiety was the only generalized domain that showed significant effects. The extent to which cancer-specific concerns affect overall quality of life is unclear. In both this study and others, having a false positive result increases the likelihood of future screening-one mechanism for this may be increased cancer concern prompted by the original false positive result. To the extent that having a false positive may identify someone at higher risk for future breast cancer,180 this may be a net beneficial outcome, although additional evidence (including use of models that incorporate individual variation in screening behavior) would be helpful. There are no data presented on whether women who underwent biopsy had higher levels of anxiety, or long lasting anxiety, than women who only had repeat examinations or imaging. Disaggregating the effects of false positive biopsies from repeat examinations is an important consideration for weighing the public health impact of false positives. Intuitively, a false positive biopsy is a "worse" harm than a false positive resulting only in repeat examinations because of the need for an invasive procedure with attendant risks of complications, and, presumably, greater anxiety/worry. Even if all of the women undergoing biopsy experienced "a lot" or "extreme" anxiety, this still means that an additional 9-10% of women with a false positive resulting in only a repeat examination had an emotional experience (at least as measured using these instruments) similar to the women undergoing biopsy. Given the much larger number of false positive recalls than biopsy, this is a large absolute number of women. In other words, even if the average response to a false positive that does not lead to biopsy is mild and transient, these data are consistent with the possibility that the emotional impact in some women is significant, and that using false positive biopsies alone as a metric for "significant" false positive results may miss clinically meaningful outcomes in a substantial number of women. Both the study authors and the editorial point out that women participating in a clinical research study may be different from the general population in attitudes about screening, education, comfort with risk, etc. In this specific study, there is an additional aspect of research participation that may affect generalizability. This discussion was likely much more comprehensive than many women experience given the time constraints of a typical office visit-if participants in the study had a better understanding of the possibility of a false positive result than many women undergoing screening in the community, then the level of anxiety prior to a final determination of no cancer may have been lower, and/or resolution of the anxiety faster, than would be expected in the general population. Finally, although the study provided evidence that minimizing false positives is important to women, as measured both by their willingness to travel for a procedure that reduced the risk of a false positive and in their preference for a new procedure that reduced false positives over reduction in examination discomfort, both of these questions were asked under the explicit presumption of no decline in the ability of the test to detect early cancers (and reduce mortality). When an incremental approach to comparing the published results is used, dominance or extended dominance eliminates several strategies-if biennial screening at age 50 is used as the reference threshold, extended dominance eliminates biennial screening at younger ages, and the next strategy for consideration is annual screening beginning at age 50. False positive biopsies are a more "severe" outcome because they carry the risk of complications, are associated with greater pain and discomfort than additional imaging, and, presumably, because patients may associate them with a greater probability of cancer, more severe anxiety consequences. Evidence on "willingness-to-pay" for the trade-off of false positives versus cancer death in the U. Overdiagnoses per Breast Cancer Death Prevented Estimates of overdiagnosis per death prevented have only recently become an outcome of interest, and there are relatively few available estimates; interpretation of these results is subject to all of the uncertainties discussed above, particularly regarding the estimation of overdiagnosis. Duffy and colleagues estimated ratios of overdiagnoses per death prevented over 20 years of biennial screening from 50-70 years of age of 0. From the confidence intervals reported for the individual components, we can estimate confidence intervals around the ratio, assuming that overdiagnosis and mortality are independent (an assumption that may not be valid-presumably, increasing the ability of the screening test to detect smaller lesions will both decrease mortality and increase the probability of detecting a lesion that would otherwise have gone undetected). For the base case, we used the adjusted confidence intervals reported in the paper; for the sensitivity analysis, where confidence intervals were not reported, we assumed that all 34 cases were in the non-attending group, and that median follow-up was 15 years. Subtracting these 34 cases from the number of incident cases among the non-attenders, and subtracting 34*15 = 510 person-years of follow-up, we recalculated an unadjusted risk ratio and confidence intervals, with a resulting point estimate for the risk ratio identical to the one reported in the paper (1. The number of deaths among this group was not reported, and the authors state that the mortality reduction for 60- to 69-year-olds was "essentially unchanged" at 0. For simplicity, we assumed that the width of the confidence interval for the ratio was also unchanged, and simply lowered the upper and lower bounds by 0. We then generated confidence intervals for the ratio by running 10,000 simulations, multiplying the incidence in non-attenders by the estimated relative risk, drawing the value for the relative risk from lognormal distributions characterized by the estimates in Table 35. Although the confidence intervals around the ratios are useful for illustrating the uncertainty around the estimate, another way to visualize the uncertainty is through the use of a harm-benefit acceptability curve (as we did with the estimates of false positives per death prevented). Harm-benefit Acceptability Curve for Overdiagnoses and Breast Cancer Deaths Prevented for Women 60-69 Years Old in Florence, Italy (Derived from Puliti, 2012 45), "Base Case" Estimates.
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