RSS Feeds
Published letters
Displaying 1-10 letters out of 2265 published
-
Elimination of mammographic screening and breast self examination in women 40-50
Submit responseThe USPSTF recommendation that women in the age group 40-50 not have screening mammograms comes from poor judgment about breast cancer data and clinical understanding of breast cancer. Coupling this recommendation to the recommendation that women in this age group not examine themselves clearly indicates that the panel members have limited understanding of breast cancer detection. To be sure there is no good evidence that breast self-examination lowers the risk breast cancer death. However, by limiting themselves to the impact of self-examination on mortality, they failed to address a second question raised by their recommendation that these women not have mammographic screening. Who is it that most often diagnoses breast cancer in the age group of 40-50 years? In unscreened women it is overwhelmingly the women themselves. If one follows the USPSTF recommendations that women in this age should not be screened and should not perform self-examination, how are breast cancers to be diagnosed? Certainly this will not come from annual clinical breast examination.
Conflict of Interest:
None declared
-
The USPSTF Recommendations should consider quality of life for breast cancer patients
Submit responseThe US Preventive Services Task Force (USPSTF) acknowledges that mammography screening, beginning at the age of 40, is not indicated for lower risk patients. Their guidelines, however, ignore the fact that breast cancer screening nowadays has two aims, from our point of view as breast surgeons. The first, of course, is regarding breast cancer deaths, which was discussed and can be easily calculated. But, the second one is related to the benefits of earlier diagnosis to breast surgery. We can preserve the breast and the axilla in most of patients with their breast cancer diagnosed in screening programs. Our current index of breast conservation surgery in a well selected population of brazilian patients in Curitiba (south of Brazil) who have access to screening today, is over 60%. Most of them (about 80%) had no axillary dissection, since the sentinel node was negative. These facts are directly related to quality of life in this group of patients. So there is a strong relation between screening and more conservative surgeries. I think that we can change our current recommendations in the future only if we consider the benefits to breast cancer patients in both aims. Mortality cannot be the only tool to be considered in the future guidelines. To save lifes is important, but to preserve quality of life is our current aim too in times of sentinel node and oncoplastic surgery.
Conflict of Interest:
None declared
-
Appropriateness Criteria for Diagnosis of Pulmonary Embolism
Submit responseRoy at al(1) provided the important contribution to the literature by showing how diagnostic accuracy of pulmonary embolism (PE) can be improved using an handheld decision-support system (CDSS). However, diagnostic accuracy is not the same as the appropriateness criteria. The authors defined PE to be appropriately excluded if the calculated posttest probability of PE was less than 5% while PE was appropriately ruled-in if the posttest probability of PE was greater than 85%. Roy at el do not explain how these criteria were derived. The appropriateness criteria need not only to take into considerations data on the diagnostic tests accuracy but the consequences of management that follow the results of the tests. In case of PE, this means assessing benefits and harms of anticoagulant treatments. We recently showed that according to expected utility theory (EUT) model- the 'gold' criterion of rational decision-making(2)- the threshold below which PE can be ruled out is significantly lower than 5% (often as low as 0.07%!) for most tests used in Roy et al. CDSS. Depending on benefits and harms of anticoagulant treatment, we also showed that PE can be considered ruled-in for non- invasive tests such as spiral CT when the posttest probability exceeds 13- 62%, respectively.(3-5) Therefore, it appears, that in many cases, most rational decision for physicians would be to order a CT angiogram when the probability of PE exceeds 0.07% i.e. the moment PE enters the physician's mind as a differential diagnostic possibility(3-5). Both the current and the previous study by Roy and colleagues(6) demonstrated that vast majority of physicians do not act by ordering diagnostic work-up for PE at the probability less than 1% as rationally indicated by the EUT model.(4) We proposed an alternative explanation- the concept of acceptable regret(3- 5), which can explain both overtesting and undertesting, that dominates the practice of modern medicine. While solution to the 'appropriateness criteria' is not easy, we think that using arbitrary values may not be the most 'appropriate' way to assess physicians' performance.
References
1. Roy PM, Durieux P, Gillaizeau F, et al. A Computerized Handheld Decision-Support System to Improve Pulmonary Embolism Diagnosis: A Randomized Trial. Ann Intern Med. 2009;151(10):677-686.
2. Bell DE, Raiffa H, Tversky A. Decision making. Descriptive, normative, and prescriptive interactions. Cambridge: Cambridge University Press; 1988.
3. Hozo I, Djulbegovic B. When is diagnostic testing inappropriate or irrational? Acceptable regret approach. Med Decis Making. 2008;28(4):540- 53.
4. Hozo I, Djulbegovic B. Will insistence on practicing medicine according to expected utility theory lead to an increase in diagnostic testing?. . Medical Decision Making 2009;29:320-322.
5. Hozo I, Djulbegovic B. Clarification and corrections of acceptable regret model. Medical Decision Making 2009;29:323-324.
6. Roy P-M, Meyer G, Vielle B, et al. Appropriateness of Diagnostic Management and Outcomes of Suspected Pulmonary Embolism. Ann Intern Med. 2006;144(3):157-164.
Conflict of Interest:
None declared
-
The USPSTF Recommendations Are Not Scientifically Based - Underestimate the Benefit of Mammography and Admit That Lives Will Be Lost Unnecessarily
Submit responseThe US Preventive Services Task Force (USPSTF) acknowledges that mammography screening, beginning at the age of 40, significantly decreases breast cancer deaths. Their guidelines, however, ignore the science and direct measurements of benefit to limit access to screening.
1. None of the parameters of screening change abruptly at the age of 50 or any other age (1). The age of 50 is an arbitrary threshold. 2. The USPSTF correctly used the randomized, controlled trials (RCT) as scientific proof of benefit. However, since the RCT did not stratify by risk, there is no proof that screening based on risk will save lives, and no scientific support for recommending screening based on risk (2). Screening only women at high risk will miss the 75-90% of breast cancers that occur in women who are not at high risk. 3. The USPSTF chose the lowest possible reduction in breast cancer deaths (15%), unaware of the fact that the RCT underestimate benefit. Women allocated to be screened who refuse the invitation, and die of breast cancer, are still counted as having been screened (non-compliance). Women allocated to be controls whose lives are saved by mammograms that they obtain outside the trial, are still counted as unscreened controls (contamination). 4. The USPSTF recognizes a 30 % decrease in breast cancer deaths in the U.S. since 1990 but ignore it, and ignore the 40% decrease in breast cancer deaths reported in Sweden (3), predominantly due to screening, that applies to women in their forties. 5 Ignoring direct data they used a 15% reduction in deaths and estimated 1300 women needed to be screened (NTS) to save one life was a reasonable number to support recommending mammography. They would deny screening to women ages 40-49 because they estimated their NTS was 1900. In reality there is 30-40% decrease in deaths for women in their forties so, using their formula, the NTS is 950-705 for women in their forties putting them well below the threshold. 6 Most false positive mammograms are easily resolved with a few extra pictures. Most biopsies are needle biopsies. Over treatment is not the fault of mammography and should be addressed to the oncologists. 7. The Task Force admits that lives will be lost by increasing the time between screens to two years.
Before denying women access to screening, anyone advising women needs to be aware of the facts.
References
1. Kopans DB. Informed decision making: age of 50 is arbitrary and has no demonstrated influence on breast cancer screening in women. Am J Roentgenology 2005;185:177-82
2. Kopans DB. Screening mammography for women age 40 to 49 years. Ann Intern Med. 2007;147:740-1.
3. Swedish Organised Service Screening Evaluation Group. Reduction in breast cancer mortality from organized service screening with mammography: 1. Further confirmation with extended data. Cancer Epidemiol Biomarkers Prev. 2006;15:45-51.
Conflict of Interest:
None declared
-
Overdiagnosis with breast screening was seriously underestimated
Submit responseNelson et al. calculate the reduction in breast cancer mortality based on the randomised trials (1), but for the most important harm, overdiagnosis, they present no calculations. They quote a mixture of observational studies and results from statistical models with unverifiable and doubtful assumptions. Only for the Malmo trial do they quote real data, but these data were obtained 15 years after the trial ended, when many additional cancers had occurred in both arms of the trial. When we corrected for this dilution, and for the fact that 24% of the women in the control group were also screened during the trial, we found 25% overdiagnosis (2), rather than the 10% reported by the authors.
It is indefensible that Nelson et al. base their estimate of overdiagnosis on flawed studies when there are data from about 600,000 randomised women, which we pooled in our Cochrane systematic review in 2009 (3), and before that in 2006 and 2001. We found 31% more lumpectomies and mastectomies. In July, we reported 52% overdiagnosis in a systematic review of publicly organised mammography screening programmes, without using assumptions or statistical modelling (4). It is also curious that Nelson et al. do not quote our Cochrane review, as they searched the Cochrane Library.
Nelson et al. reported that most studies found between 1% and 10% overdiagnosis. However, systematic reviewing is not a consensus conference, it is a scientific discipline, and Nelson et al. overlook that the small estimates of overdiagnosis are based on poor science, mostly produced by researchers with vested interests in screening. If one opens one's eyes, unaided by any statistical tricks, one cannot escape seeing a huge amount of overdiagnosis, e.g. in the UK (4,5).
The U.S. Preventive Services Task Force now recommends against breast screening in women aged 40-49 years, but it may be the case for all age groups that the harms outweigh the benefits. An effect of 15% and an overdiagnosis of 30% mean that for every 2000 women invited for screening throughout 10 years, one will have her life prolonged and 10 healthy women, who would not have been diagnosed if there had not been screening, will be treated unnecessarily (3). Furthermore, in USA about 1000 women will have experienced a false positive diagnosis (3). The psychological strain until one knows whether or not it was cancer can be severe. The harms caused by overdiagnosis are life-long.
References
1. Nelson HD, Tyne K, Naik A, Bougatsos C, Chan BK, Humphrey L. Screening for Breast Cancer: An Update for the U.S. Preventive Services Task Force. Ann Intern Med 2009; 151: 727-37.
2. Gotzsche PC, Jorgensen KJ. Estimate of harm/benefit ratio of mammography screening was five times too optimistic. http://bmj.bmjjournals.com/cgi/eletters/332/7543/691, 2006.
3. Gotzsche PC, Nielsen M. Screening for breast cancer with mammography. Cochrane Database Syst Rev 2009;(4):CD001877.
4. Jorgensen KJ, Gotzsche PC. Overdiagnosis in publicly organised mammography screening programmes: systematic review of incidence trends. BMJ 2009; 339: b2587.
5. Jorgensen KJ, Gotzsche PC. It is time for a new paradigm for overdiagnosis with screening mammography. http://www.bmj.com/cgi/eletters/339/jul09_1/b2587 - 218754, 2009.
Conflict of Interest:
None declared
-
Comment to Editorial: Cost-Effectiveness of Biologics as First-Line Treatment of Rheumatoid Arthritis (Ann Intern Med 2009 151:668-669)
Submit responseDr Maarten Boers writes elegantly about our cost-effectiveness study. We appreciate his ideas but some require comment(1). He feels, "curiously, the investigators shy away from a firm conclusion, instead stating that the cost-effectiveness of early biologics is still uncertain." We feel that the case cannot be closed for at least three major reasons: 1. The long-term impact of very early initiation of aggressive antirheumatic therapy, and biologic therapy, in particular, is largely unknown. These include the long-term impact on mortality, the need for joint replacement and the rate of disability decades after the initiation of these therapeutic strategies. 2. Other parameters profoundly impact the cost-effectiveness ratio of these therapeutic strategies, the major ones being the availability of effective alternatives after failure of several biologics, the price of these agents, the induction of long-term drug-free remission and the ability to identify responders to biologics before treatment initiation. Because of these uncertainties, a firm conclusion is not justified. Rather, our findings support the use of aggressive DMARDs before biologics in very early RA from a cost-effectiveness perspective. The study identifies the key parameters that are uncertain and drive the results, and which should be studied to improve future decisions.
We calibrated estimates of the published literature against real patients from the National Data Bank for Rheumatic Diseases (NDB). Such calibration techniques are appropriate and commonly applied in cost- effectiveness studies. Calibration in an another unrelated data set would further validate the model. However, at present, significant circularity is unlikely given that the patient populations used to derive most of the parameters and those used to calibrate the model are largely different.
Finally, Dr Boers takes issue with the model and its treatment of glucocorticoids and feels that including them in only the NSAID strategy arm is "medically inappropriate." Glucocorticoids are effective and clinically useful. In the doses originally used for rheumatoid arthritis, the benefits were outweighed by serious and sometimes fatal long-term effects, increased susceptibility to infection, osteoporosis, obesity, hypertension, or glucose intolerance. The long-term risk/benefit ratio of lower doses is debated(2), and in North America, more likely to be used to put out "fires" rather than long-term. Adding steroids to the DMARD strategy would, as Dr Boers points out, likely to be a conservative bias with respect to the findings(3).
REFERENCES
1. Finckh A, Bansback N, Marra CA, Anis AH, Michaud K, Lubin S, et al. Treatment of very early rheumatoid arthritis with symptomatic therapy, disease-modifying antirheumatic drugs, or biologic agents: a cost- effectiveness analysis. Ann Intern Med 2009;151(9):612-21.
2. Da Silva JA, Jacobs JW, Kirwan JR, Boers M, Saag KG, Ines LB, et al. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data. Ann Rheum Dis 2006;65(3):285-93.
3. Maillefert JF. Appropriate and inappropriate use of oral glucocorticoid therapy in rheumatoid arthritis. Joint Bone Spine 2006;73(3):234-5.
Conflict of Interest:
None declared
-
Vaccination Against Pandemic Influenza (H1N1): Adjuvant does matter
Submit responseIn their study Khazeni et al. chose to examine an adjuvanted vaccine as a conservative estimate in light of potentially increased vaccine side effects and costs with an adjuvant (1). They assumed that severe pandemic (H1N1) vaccine side effects could occur in 1 in 100000 vaccinated individuals (2). They state that they examined vaccine efficacy consistent with nonadjuvanted pandemic (H1N1) trial results (3), so the decision to use nonadjuvanted vaccine would not affect their conclusions other than decreasing costs, as they described in sensitivity analysis. We believe that the question of adjuvanted versus nonadjuvanted vaccine pandemic (H1N1) is rather important. Not only concerning the issues that were addressed by Khazeni et al, but also concerning the acceptability of the vaccination among the population. In this respect, Germany currently experiences a dramatic public discussion. This is driven by the fact that the federal and state health departments ordered adjuvanted vaccine for the general population whereas some governmental employees and politicians receive nonadjuvanted vaccine. As a result, not only the public opinion but also the opinion of healthcare workers seems to be biased. In a survey supported by the state health department, the statuary accident insurance and the state chamber of physicians (4), it was found that only 29,9% of physicians providing outpatient medical care want to receive adjuvanted A/H1N1 vaccination. This low acceptability points to the importance of the emotional public safety discussion, even in healthcare professionals such as physicians. We thereofore believe that information politics should be improved.
References
1. Khazeni N, Hutton DW, Garber AM, Hupert N, Owens DK. Effectiveness and Cost-Effectiveness of Vaccination Against Pandemic Influenza (H1N1) 2009. Ann Intern Med. 2009 Oct 5. [Epub ahead of print]
2. Neustadt RE, Fineberg HV. The Swine Flu Affair: Decision Making on a Slippery Disease. Washington, DC: National Academies Press Online; 1978.
3. Greenberg ME, Lai MH, Hartel GF, Wichems CH, Gittleson C, Bennet J, et al. Response after one dose of a monovalent influenza A (H1N1) 2009 vaccine - preliminary report. N Engl J Med. 2009. [PMID: 19745216]
4. Berlin State Chamber of Physicians: http://www.aerztekammer- berlin.de/40presse/15_meldungen/00659_FOBI_Neue_Grippe/index.htm (last update: 2009-11-19)
-
The Editors' Response
Submit response"In response to media reports that imply otherwise, Annals of Internal Medicine did not schedule the publication of the US Preventive Services Task Force recommendations about breast cancer screening to coincide with a particular date or event. The background papers (which underwent several rounds of revision over about 5 months based on independent peer review comments and Annals' statistical editor's comments) and the recommendation statement were all in final, accepted form by September 10, 2009. Annals scheduled them to appear in the next available print issue, which was the November 17th issue. Our routine print production process takes about 2 months from final acceptance to print." The Editors
Conflict of Interest:
None declared
-
The Editors' Response
Submit response"In response to media reports that imply otherwise, Annals of Internal Medicine did not schedule the publication of the US Preventive Services Task Force recommendations about breast cancer screening to coincide with a particular date or event. The background papers (which underwent several rounds of revision over about 5 months based on independent peer review comments and Annals' statistical editor's comments) and the recommendation statement were all in final, accepted form by September 10, 2009. Annals scheduled them to appear in the next available print issue, which was the November 17th issue. Our routine print production process takes about 2 months from final acceptance to print." The Editors
Conflict of Interest:
None declared
-
The Editors' Response
Submit response"In response to media reports that imply otherwise, Annals of Internal Medicine did not schedule the publication of the US Preventive Services Task Force recommendations about breast cancer screening to coincide with a particular date or event. The background papers (which underwent several rounds of revision over about 5 months based on independentpeer review comments and Annals' statistical editor's comments) and the recommendation statement were all in final, accepted form by September 10, 2009. Annals scheduled them to appear in the next available print issue, which was the November 17th issue. Our routine print production process takes about 2 months from final acceptance to print." The Editors
Conflict of Interest:
None declared