Displaying 1-10 letters out of 46 published
Maternal pertussis vaccination
We were pleased to read the commentary by Millar and Sanz(1) regarding our publication on Tdap safety in pregnancy from the Vaccine Safety Datalink.(2) We agree that policies regarding routine vaccination should be made after careful review of the risks and benefits of vaccination. For maternal vaccination, evaluations of risk-benefit profiles are complex, as both maternal and infant outcomes must be considered.
In our observational retrospective study of more than 25,000 women with singleton pregnancies who received Tdap during pregnancy in California, we found no increased risk of hypertensive disorders of pregnancy, preterm or small for gestational age births associated with maternal vaccination. We did observe a small, but statistically significant increased risk of chorioamnionitis diagnosis among vaccinated women. Chart review of a subset of women with a chorioamnionitis diagnosis revealed that only half met case definitions for probable chorioamnionitis. Furthermore, 95% of women with a chorioamnionitis diagnosis had an epidural during labor, providing a potential alternative explanation for fever during labor.(3)
Tdap vaccination during pregnancy remains the most effective available strategy for promoting maternal transfer of pertussis-specific antibodies and thus preventing severe disease in newborns. In a recent case-control study in England, Dabrera and colleagues estimated the effectiveness of maternal Tdap vaccination for preventing laboratory- confirmed pertussis infection in infants to be 91%.(4)
In the United States, policies to routinely administer Tdap during pregnancy came after widespread pertussis outbreaks, including 10 infant deaths in California.(5) In 2014, California once again reported an increase in pertussis cases. In both recent outbreaks, disease prevalence and severity has been highest in infants under 4 months.(6) We agree with Millar and Sanz that further monitoring of Tdap safety is important, with particular attention to fetal outcomes potentially associated with chorioamnionitis. However, given continued ongoing pertussis transmission, and the high of risk of morbidity in newborns, we support current guidelines from the Advisory Committee on Immunization Practices recommending the routine administration of Tdap during pregnancy.
1. Millar MR, Sanz MG. The administration of pertussis vaccine to pregnancy women was associated with a small increased risk of chorioamnionitis, but not an increased risk fo hypertensive disorders or preterm birth Evid Based Med. 2015 (in press).
2. Kharbanda EO, Vazquez-Benitez G, Lipkind HS, et al. Evaluation of the association of maternal pertussis vaccination with obstetric events and birth outcomes. JAMA 2014;312(18):1897-1904.
3. Abramovici A, Szychowski JM, Biggio JR, et al. Epidural Use and Clinical Chorioamnionitis among Women Who Delivered Vaginally. Am J Perinatol. Apr 4 2014.
4. Dabrera G, Amirthalingam G, Andrews N, et al. A case-control study to estimate the effectiveness of maternal pertussis vaccination in protecting newborn infants in England and wales, 2012-2013. Clin Infect Dis 2015;60(3):333-337.
5. Winter K, Harriman K, Zipprich J, et al. California pertussis epidemic, 2010. J Pediatr 2012;161(6):1091-1096.
6. Winter K, Glaser C, Watt J, Harriman K. Pertussis Epidemic - California, 2014. Morbid Mortal Wkly Rep. 2014;63(48):1129-1132.
Conflict of Interest:
Re:Further research in low dose CT scan for suspected appendicitis.
We share your enthusiasm for the current efforts to reduce radiation exposure associated with the use of CT scanning and agree with your assertion that performance of appendectomy without scanning will inevitably lead to more negative appendectomies. We are confident though based on the NHS laparoscopic appendectomy statistics reviewed by Omar and Clark in the Annals of Surgery that those negative appendectomies are associated with essentially no risk. In the NHS series 234,402 patients underwent laparoscopic appendectoy without a single death or major morbidity. CT scanning these 234 thousand patients on the other hand will cause more than 100 fatal cases of cancer.
Conflict of Interest:
Further research in low dose CT scan for suspected appendicitis.
We read with great interest the recent article written by William Rogers et al on the Harms of CT scanning prior to surgery for suspected appendicitis(1). It highlights the radiation risk of cancer while routinely performing an abdominal CT scan on an otherwise healthy patient with symptoms suggestive of appendicitis. This radiation risk of cancer becomes all the more important in patients with 'negative' appendectomy.
However, relying purely on clinical judgment for diagnosis of appendicitis can result either in increased 'negative' appendectomy or diagnostic delay which may cause appendiceal perforation. There are studies which show that negative appendectomy is associated with an appreciable degree of morbidity and mortality, including a significant increase in length of hospital stay, postoperative complications like wound infection and death(2). Also, it can increase health care costs. Perforated appendicitis is also related to increase in length of hospital stay(3). In-house mortality is high for perforated appendicitis(4).
During the last decade, there have been many advances in CT technology which have resulted in improved spatial resolution, rapid scan and increased use of multiplanar images enabling better visualization of appendix. Although the effective dose value for CT scan of abdomen and pelvis is taken as 8 - 11 mSv(5) , studies comparing low-dose CT group with standard-dose CT group have shown that low-dose CT was not inferior with regard to diagnosis of appendicitis(6) and negative appendectomy rates(7) . Neither the appendiceal perforation rate nor the diagnostic performance of CT for appendicitis differed significantly between the two groups. A randomized controlled trial, low-dose CT for appendicitis trial (LOCAT) is being undergone comparing the clinical outcomes following low vs standard-dose computed tomography as the first-line imaging test in adolescents and young adults with suspected acute appendicitis, where the effective dose of CT is reduced to 2 mSv(8). This greatly reduces the carcinogenic risk. Study using non-contrast focused abdominal CT scan has also shown to have a high sensitivity for diagnosis of appendicitis(9). Here, there is no risk of contrast nephropathy.
Further research in this field will enable us to use very low dose CT scan with significantly less radiation risk of cancer; at the same time significantly reducing negative appendectomy rate without an increase in the appendiceal perforation rate.
(1) Rogers, W., Hoffman, J., Noori, N. Harms of CT scanning prior to surgery for suspected appendicitis. Evidence Based Medicine 2015;20(1):3-4.
(2) Flum DR, Koepsell T. The clinical and economic correlates of misdiagnosed appendicitis: nationwide analysis. Arch Surg 2002;137:799-804.
(3) Al-Omran M, Mamdani M, McLeod RS. Epidemiologic features of acute appendicitis in Ontario, Canada. Can J Surg 2003;46:263-268.
(4) Wen SW, Naylor CD. Diagnostic accuracy and short-term surgical outcomes in cases of suspected acute appendicitis. CMAJ 1995;152:1617-1626.
(5) Furlow B. Radiation dose in computed tomography. Radiol Technol 2010;81:437-50.
(6) Keyzer, C., Tack, D., De Maertelaer, V., et al. Acute Appendicitis: Comparison of Low- Dose and Standard-Dose Unenhanced Multi-Detector Row CT 1. Radiology 2004;232(1):164-172.
(7) Kim, K., Kim, Y. H., Kim, S. Y., et al. (2012). Low-dose abdominal CT for evaluating suspected appendicitis. New England Journal of Medicine 2012;366(17):1596-1605.
(8) Ahn S. LOCAT (low-dose computed tomography for appendicitis trial) comparing clinical outcomes following low- vs standard-dose computed tomography as the first-line imaging test in adolescents and young adults with suspected acute appendicitis: study protocol for a randomized controlled trial.Trials. 2014;15:28. doi:10.1186/1745-6215-15-28.
(9) Akhtar, W., Ali, S., Arshad, M., Ali, F., Nadeem, N. (2011). Focused abdominal CT scan for acute appendicitis in children: can it help in need. Journal of the Pakistan Medical Association 2011; 61(5):474-6.
Conflict of Interest:
In Response to Windish D. "EBM apps that help you search for answers to your clinical questions."
We read with great interest the recent article by Dr. Windish  reviewing a number of Evidence-Based Medicine (EBM) smartphone apps. Immediate access to brief summaries of the literature is essential in bringing EBM knowledge to the bedside, as physicians are often busy and are presented with frequent interruptions which hinder their ability to perform detailed searches or read complete articles during the workday. Indeed, we note the success of the randomized trial by Pastori, et al. , where in the intervention group they provided a physician whose sole purpose was collecting relevant EBM evidence from the literature. This resulted in better patient outcomes, as assessed by ICU transfers and hospital readmissions.
We would like to highlight an EBM database of diagnostic accuracy that we have developed, entitled GetTheDiagnosis.org (http://www.getthediagnosis.org). This website, which has a mobile version suited to smartphones as well, contains a database of sensitivity and specificity of history questions, physical examination findings, and laboratory and imaging tests for nearly 300 diagnoses. The data is culled from primary literature and is maintained by physician-users, who can submit new entries or edit existing entries in the same manner as Wikipedia. The site displays citations and links to the literature for each entry, and the data is highly structured and allows for searching by diagnosis or finding. By using structured data, we can provide a post-test probability calculator based on the data for each diagnosis.
In this way, we have attempted to marry successful features of apps such as EBM Tools or MedCalc 3000 EBM with an actual database of EBM data from the literature. We hope that physicians will find our website helpful and easy to use while in the clinic, and we hope that many of them will help build the database by adding articles from the primary literature.
1. Windish D. EBM apps that help you search for answers to your clinical questions. Evid Based Med 2014;:ebmed-2013-101623. doi:10.1136/eb-2013- 101623
2. Pastori MM, Sarti M, Pons M, et al. Assessing the impact of bibliographical support on the quality of medical care in patients admitted to an internal medicine service: a prospective clinical, open, randomised two-arm parallel study. Evid Based Med 2014;19:163-8. doi:10.1136/ebmed-2014-110021
Conflict of Interest:
Opinion editorials: necessity of present times
This article brings into light the upcoming ways in which medical health care knowledge is disseminated between general population and the various pitfalls such an approach can have. Although such issues are in nascent stage in a developing country like India but its climbing up the ladder at a brisk rate. The new generation of physicians is media savvy but can get easily influenced by media based propaganda's.
There is no doubt Evidence based Medicine is the future of way medicine is going to be practiced be it in a developed country or a developing nation, but scientific and regulating authorities need to keep a keen and watchful eye on ways, quality and standard of literature that is being published and distributed to practitioners and public.
There needs to be a healthy and interactive communication between journalists and scholars so that the message intended reaches the public and students in a clear, concise and undisputed way.
We agree with the authors that development of such web based facilities is an inevitable need of the hour even from the point of view of a developing country. Such acts will bring about greater understanding of complex medical issues and practices followed in patient care thereby avoiding unnecessary litigation and panic created by outbreak of an infectious diseases, a prime example being epidemic of dengue fever and assumption of direct correlation of decreasing platelet count with hemorrhage and mortality which is absolutely not true as shown by number of studies.
The article brings about the required amalgamation of media and scientific community in a cohesive way to produce comprehensible medical knowledge and its dissemination in public domain.
Conflict of Interest:
I am very grateful to Ken Uchino for amplifying and clarifying the detail of some of the points I was trying to make within the word limits of a 'Perspectives' paper. I suggest there are four key elements:
1. The epidemiology is indeed complex and I am neither an academic nor an epidemiologist. However, it would appear that we can agree that there is indeed a difference between 'younger old' (i.e. 65-75) and 'older old' (i.e. 80+), both in relative and absolute risk - albeit in opposite directions. The key point here is not the strength of the associations with age, but the magnitude of impact of treating the risk factor at any given age. This is where interventional trials come in.
2. As I pointed out in my paper, the data about treating hypertension in 80+ year olds accumulated prior to HYVET were very suggestive of benefit; they predicted HYVET would give a definitive answer. HYVET - by far the largest trial looking at patients aged 80+ - failed to live up to this promise. Sadly, the premature termination of the trial (because of excess mortality in the placebo group) arguably raised more questions about the clinical applicability of its results, than the trial answered.
3. The PROSPER trial examined the use of statins in European patients initially aged 70-82 (mean 75), and followed up for an average of 3.2 years. Nearly 20% of patients entered into the 4-week single-blind placebo lead-in period failed to proceed to the randomised period (either for using <75% or more than 120% of placebo, or because they refused to participate). This raises questions as to generalisability. Whilst reducing cardiovascular events, the intervention failed to show a reduction in stroke. I fully accept that absence of evidence is not necessarily evidence of absence, but this must surely raise questions as to the magnitude of any true effect.
4. None of these trials looked into the patients' preferences and priorities re outcomes. I argue that these change significantly with advancing frailty and incapacity (which in turn increase disproportionately with, but are not confined to, increasing age).
If we cannot even be certain of the ostensibly simple quantitative aspect of the decision (the certainty of the magnitude of the treatment effects), how can we properly weigh that up against the much more difficult to define qualitative aspects (the beliefs, values, and priorities of my patient)?
My central point is that without robust evidence applicable to the patient in front of me - usually over 80, and often very frail - how can I help the patient to reach truly informed consent? I may well have some of the estimates of magnitude wrong, but the principle still stands. A treatment decision is only as strong as its weakest link. I suggest that there are so many weak links in this particular evidence chain that it is almost impossible to reach a decision that all doctors would support. Suggesting that a simple 'one size fits all' (i.e. algorithmic guideline- based) solution would be appropriate is simplistic. Without more data we cannot be sure.
For all these reasons I strongly urge that we undertake randomised trials of withdrawals of treatment in real life elderly patients (both frail and robust). This has the potential to find out how much impact these interventions have in clinical practice, as opposed to in the rarefied environment of scientific clinical trials.
In the UK NHS we arguably should have a real opportunity to use 'big data' in real life in this way to find out if there are any signals there amongst the noise. A simple pragmatic trial involving tens of thousands of people would surely have a good chance of giving us the information we need? If the NHS funded this with the money currently earmarked for hitting treatment targets in those over 80, it would not take long to answer this question.
Conflict of Interest:
Overreacting to possible over-treatment? Hypertension treatment in the very elderly.
While I agree with Dr Byatt that it is important to discuss with patients the choices of treating risk factors to prevent disease, the basis for the discussion needs to be clarified and fine-tuned.
Epidemiology: The attributable risk of hypertension in stroke decreases in the elderly. This phenomenon may be partly because other factors such as atrial fibrillation become more dominant factor. Framingham Study quoted in the paper is only one study. Pooling data from multiple studies, Prospective Studies Collaboration has reported that that higher risk of stroke mortality is observed with higher systolic and diastolic blood pressures across blood pressure ranges into age 80s. The relative risk conferred with higher blood pressure diminish with age, but still in age 80s, 20 mm Hg increase in systolic blood pressure (SBP) is associated with ~1.5 fold increase in stroke. That compares with ~2.8 fold increase in risk of stroke in age 40s. But the absolute risk difference with increase in SBP or DBP is greater in old age.
Even if Dr Byatt's reading of epidemiologic data is correct, a lack of observed association disease (stroke) with a risk factor (hypertension) does not necessarily translate that intervening on the factor would not reduce disease. This was clearly shown in case of cholesterol, where no consistent association with stroke risk has been shown in multiple studies. Yet, clinical trials using statin class of cholesterol lowering medications have shown that stroke is indeed reduced if the study size is large enough in both primary and secondary prevention settings.[3, 4] We cannot assume that because the contribution of hypertension is smaller as one gets older, that treatment would not reduce stroke.
Trial data: There is a consistent finding from clinical trials of blood pressure reduction comparing different targets or regimens that SBP reduction of 10-20 mm Hg confer a relative reduction stroke by about 30- 40%. Most studies confirm that stroke is very sensitive to blood pressure. The finding of the HYVET study mentioned consistent in relative risk reduction of fatal and nonfatal stroke by 30% (p=0.06) with SBP difference in 15 mm Hg between the groups. The study may have be underpowered to reach statistical significance.
One needs to keep in mind that the risk of stroke is low in the relatively healthy elderly individuals in clinical trials that mostly consists of persons free of cardiovascular disease. HYVET study with 80 years of age or older and found a rate of stroke of 1.7% per year in the placebo group. Active treatment results in a number needed to treat of 94 over 2 years to prevent one stroke. For comparison, in ALLHAT, with the mean age of 67, the annual stroke rate was ~1% per year.
Primary prevention is a challenge because the event rate and absolute risk reduction by intervention is low, even if relative risk reduction is large. In the elderly, the risk of events is higher, but the time horizon is also shorter. The discussion should not necessarily focus on the absolute risk reduction and the number needed to treat, but put the context of the outlook of the elderly individuals into the next several years, some of whom are living into elderly age in relative good health. Prioritizing may be important. What are the important diseases to prevent, screen, treat? While Dr Byatt focuses on stroke, treatment of hypertension reduces strokes, congestive heart failure, and myocardial infarction. While I agree with the recent JNC 8 recommendation to question the same blood pressure target across ages, hypertension cannot be simply viewed as over treated.
1) Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360(9349):1903-13.
2) Lewington S, Whitlock G, Clarke R, et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 2007;370(9602):1829-39.
3) Taylor FC1, Huffman M, Ebrahim S. Statin therapy for primary prevention of cardiovascular disease. JAMA 2013;310(22):2451-2.
4) Amarenco P, Labreuche J. Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. Lancet Neurol 2009;8(5):453-63.
5) Staessen JA1, Wang JG, Thijs L. Cardiovascular protection and blood pressure reduction: a meta-analysis. Lancet. 2001;358(9290):1305-15.
6) ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:2981-2997
7) James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 2014;311(5):507-20.
Conflict of Interest:
Comment on "Need for standardising adverse event reporting in testosterone trials" by Basaria
We are very grateful for the positive comments from Dr Basaria about our meta-analysis of randomized controlled trials (RCTs) showing that testosterone therapy among men increases the risk of a cardiovascular -related event (1;2). As per the Preferred Reporting Items for Systematic Reviews and meta-Analysis (PRISMA) guidelines (item 25) (3), we also highlighted the limitations of our review. We are surprised that a comment on compliance with the PRISMA guidelines is followed by the sentence "Therefore, firm conclusions regarding the association between testosterone therapy and CVD cannot be drawn from this study" (1). This line of reasoning would preclude firm conclusions being drawn from all well-conducted meta-analyses of RCTs, which inevitably each have limitations as well as strengths. In a recent update of the Competing Interests statement associated with his commentary, Dr Basaria, and the editor, have clarified a number of potential conflicts of interest including connections with pharmaceutical companies selling or developing testosterone therapy, which may affect readers' interpretation of the commentary. A separate report describes the way pharmaceutical companies have subtly promoted testosterone therapy (4) despite growing evidence of its harmful effects.
(1) Basaria S. Need for standardising adverse event reporting in testosterone trials. Evid Based Med 2013.
(2) Xu L, Freeman G, Cowling BJ, et al. Testosterone and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med 2013;11(1):108.
(3) Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6(7):e1000097.
(4) Braun SR. Promoting "Low T": A Medical Writer's Perspective. JAMA Intern Med 2013;173(15):1458-1460.
Conflict of Interest:
Potential aetiological significance of statin's raising glucose
Montori and Brito draw attention to the limited clinical significance of statins' raising glucose (1), consistent with the non-linear association of fasting glucose with cardiovascular disease (2). It is quite possible that the limited clinical significance of statins' minor effects on glucose also translates into limited aetiological significance. On the other hand, statins are not alone in having divergent effects on diabetes and cardiovascular disease. At least one other well-established therapy for preventing cardiovascular disease also has the same set of effects. Diuretics similarly both decrease the risk of cardiovascular disease but also increase the risk of diabetes. Conversely, some effective treatments for diabetes have been found to increase the risk of cardiovascular disease, such as rosiglitazone and sulphonureas. Notwithstanding, the very well-established relation between diabetes and cardiovascular disease, this consistent pattern from experimental evidence suggests the existence of an underlying exposure which may both protect against cardiovascular disease and cause diabetes.
In randomized controlled trials testosterone therapy improves glucose metabolism (3) but increases the risk of cardiovascular-related events (4). Moreover, evidence from randomized controlled trials shows that statins reduce testosterone (5). Taking all this experimental evidence together raises the possibility that the mechanism underlying the divergent effects of statins on both diabetes and cardiovascular disease could be androgen modulation. Whether such a mechanism could also be relevant to the other therapies which also have divergent effects on diabetes and cardiovascular disease has never been considered. Notably spironolactone, which is known to decrease androgens, also has divergent effects on cardiovascular disease and diabetes, preventing mortality in heart failure but adversely affecting glucose metabolism (6). A small mechanistic randomized controlled trial examining whether the effects of statins on key factors in the ischemic pathway, such as markers of endothelial function or clotting factors (7), could be mediated by androgens, would provide confirmation or refutation. Androgen modulation as a contributor to the mechanism of statins, and perhaps other therapies, not only potentially provides a unified explanation for paradoxical results from randomized controlled trials, but also is consistent with the higher age-standardized rates of cardiovascular disease among men than women.
(1) Montori VM, Brito JP. Statins induce hyperglycaemia of uncertain importance. Evid Based Med 2013;18(4):157-158.
(2) Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di AE et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 2010;375(9733):2215-2222.
(3) Jones TH, Arver S, Behre HM, Buvat J, Meuleman E, Moncada I et al. Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care 2011;34(4):828-837.
(4) Xu L, Freeman G, Cowling BJ, Schooling CM. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med 2013;11:108.
(5) Schooling CM, Au Yeung SL, Freeman G, Cowling B.J. The effect of statins on testosterone in men and women: a systematic review and meta- analysis of randomized controlled trials. BMC Medicine 2013;11:57.
(6) Swaminathan K, Davies J, George J, Rajendra NS, Morris AD, Struthers AD. Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles. Diabetologia 2008;51(5):762-768.
(7) Violi F, Calvieri C, Ferro D, Pignatelli P. Statins as antithrombotic drugs. Circulation 2013; 127(2):251-257.
Conflict of Interest:
Reply to DeFrank and Brewer
We would like to thank DeFrank and Brewer for their interest in our recently published paper: Long-Term Psychosocial Consequences of False- Positive Screening Mammography.(1)
In the Methods section DeFrank and Brewer write: "Brodersen and colleagues conducted a study of 454 adult women in Denmark screened in the same time period who had normal mammography screening results, false- positives or breast cancer diagnoses." We (Brodersen & Siersma) included 454 adult women in Denmark who had abnormal mammography screening results (false-positives or breast cancer diagnoses) and 864 women with normal screening results - all 1318 screened in the same time period.
In the Methods section DeFrank and Brewer also state that the questionnaire we used: the Consequences Of Screening in Breast Cancer (COS -BC), is a revised version of the question: the Psychosocial Consequences Questionnaire (PCQ). This is not the case. Together with the developer of the original Australian version of the PCQ - deceased Professor Jill Cockburn - we published a systematic reviewed on "The adequacy of measurement of short and long-term consequences of false-positive screening mammography".(2) Part of our conclusion was: "The PCQ is an adequate questionnaire for measuring short-term consequences, and the PCQ is preferable to other measures because of its higher sensitivity. However, there is little evidence that the PCQ is able to adequately detect all long-term consequences of screening mammography. Given the inadequacy of the measurement instruments used, any current conclusions about the long-term consequences of false-positive results of screening mammography must remain tentative". In a qualitative study including six focus interviews with women having false-positive screening mammography we found that the PCQ includes ambiguous items, does not cover all psychosocial consequences of false- positive screening mammography and three items from the PCQ were deleted because they were judged by interviewees to be irrelevant.(3) We also found that the women's experiences in the critical period from abnormal screening mammography until final false-positive diagnosis differed entirely from their experiences after the final diagnosis.(3) Therefore, fifteen new items were generated to cover the negative psychosocial consequences of abnormal and false-positive screening mammography comprehensively.(3) Five new items were produced that concerned the consequences of screening mammography during the period after being declared ''free from'' suspicion of cancer.(3) Response options for the positive items were changed to allow responses in both positive and negative directions. Our conclusion was: "Because of the major changes to both parts of the PCQ the measure derived from this study should be regarded as a new questionnaire with two parts: Consequences Of Screening in Breast Cancer (COS-BC). Part II focuses on the long-term consequences of a false-positive screening mammography".(3) Because we had developed a new questionnaire (based on Jill Cockburn's work) we conducted two psychometric studies using the Item Response Theory Partial Credit Rasch model for polytomous items plus Classical Test Theory to validate the COS-BC.(4;5) Therefore, it is slightly confusing that DeFrank and Brewer calls COS-BC for PCQr when it actually is a new measure. Due to this extensive qualitative and statistical psychometrical work we have provided robust high quality evidence that the subscales of the COS- BC measure each distinct constructs that are unidimensional. It is therefore wrong when DeFrank and Brewer in the Commentary section write that some "subscales mix multiple constructs". Furthermore, we have revealed that the PCQ lacks content validity and encompass ambiguous items. Because the COS-BC has high content validity and adequate psychometric properties we can conclude that the COS-BC and the PCQ do not measure the same thing. It is therefore not appropriate that DeFrank and Brewer compare the scores of the PCQ with the scores of the COS-BC. Furthermore, standard methods, like the correlation coefficients are different from our linear regression methods, and do not adjust for the differential dropout. As stated in our method section: "We used generalized estimating equations methods to account for repeated measurement on the same individual. To adjust for possible bias resulting from differential dropout from the study, the scores available at each follow-up time point were weighted by the inverse of an estimate of the probability of this score being observed at that time point".(1) Those people that are worse off have the tendency to drop out in surveys. In our case, women diagnosed with breast cancer and the women that are most affected by the false-positive screening result could have a higher tendency to drop out; analysing only the subjects that did not drop out will then artificially decrease effects. By using inverse probability weighing and correcting the confidence intervals accordingly using generalized estimating equations we have adjusted for this differential drop out. The relatively small effect sizes found and commented on by DeFrank and Brewer using our data may well be an artefact of not adjusting for dropout.
In the Commentary section DeFrank and Brewer also write that the COS -BC "has a subscale for breast self-examination, a behaviour that many guidelines now recommended against". However, the subscale has not anything to do with breast self-examination recommendations. In our qualitative study we found that women with false-positive screening mammography examined their breasts with their hands and examined their breasts in a mirror as a psychosocial consequence of the false-positive results and not because of any recommendation.
In the Commentary section DeFrank and Brewer also write: "The second half of the PCQr assesses how patients...". Most of these women are not patients. The main part of the women in our survey had a normal or a false -positive screening result and besides that they were healthy. In the same sentence DeFrank and Brewer continue:"....think the testing affected them and uses an uncommon scoring system." We do not find the scoring system as a limitation since the response categories and scoring system for part 2 of the COS-BC were developed during the previous mentioned focus group interviews.(3) Furthermore, part2 of the COS-BC was validated using the empirical knowledge from these interviews,(3) the theory of cognitive dissonance, the theory of sense of coherence, and as mentioned above Item Response Theory Partial Credit Rasch model for polytomous items. (4;6)
In the Commentary section DeFrank and Brewer lastly write: "Finally, the absence of analyses that demonstrate whether changes over time differed by test results, the internal consistency of measures and their reliability over time. Study findings would be strengthened by the inclusion of outcomes assessed before screening or learning of test results." Test for interaction between time and the three screening groups could have been added to the tables, but such test may not have been very informative because of the large differences between the trajectories in the start of follow-up: most tests for interaction were highly significant. Where items are shown to fit a Rasch model the measure can be shown to posses criterion-related construct validity,(7) to be objective (invariant),(8) sufficient(9) and, therefore, also reliable.(10) Furthermore, we have provided evidence that the items in the subscales do not posses differential item functioning in relation to time.
(1) Brodersen J, Siersma VD. Long-Term Psychosocial Consequences of False-Positive Screening Mammography. The Annals of Family Medicine 2013;11(2):106-15.
(2) Brodersen J, Thorsen H, Cockburn J. The adequacy of measurement of short and long-term consequences of false-positive screening mammography. J Med Screen 2004 Mar 1;11(1):39-44.
(3) Brodersen J, Thorsen H. Consequences Of Screening in Breast Cancer (COS-BC): development of a questionnaire. Scand J Prim Health Care 20081;26(4):251-6.
(4) Brodersen J. Measuring psychosocial consequences of false- positive screening results - breast cancer as an example. Department of General Practice, Institute of Public Health, Faculty of Health Sciences, University of Copenhagen: M?nedsskrift for Praktisk L?gegerning, Copenhagen. ISBN: 87-88638-36-7; 2006.
(5) Brodersen J, Thorsen H, Kreiner S. Validation of a condition- specific measure for women having an abnormal screening mammography. Value in Health 2007;10(4):294-304.
(6) Brodersen J, Thorsen H, Kreiner S. Consequences Of Screening in Lung Cancer: Development and Dimensionality of a Questionnaire. Value in Health 2010;13(5):601-12.
(7) Rosenbaum PR. Criterion-related construct validity. Psychometrika 1989 ;54(4):625-33.
(8) Rasch G. An Informal Report on a Theory of Objectivity in Comparisons. In: Van der Kamp LJTh, Vlek CAJ, editors. Psychological Measurement Theory.Leyden: University of Leyden; 1967:1-19.
(9) Andersen EB. Sufficient Statistics and Latent Trait Models. Psychometrika 1977;42:69-81.
(10) Bartholomew DJ. The Statistical Approach to Social measurement. San Diego: Academic Press; 1996.
Conflict of Interest:
This recent issue is free to all users to allow everyone the opportunity to see the full scope and typical content of EBM.
View free sample issue >>
Don't forget to sign up for content alerts so you keep up to date with all the articles as they are published.