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"highwire-comments-list-all-wrapper"><div class="hw-comments-filter-wrapper"><form class="hw-comments-filter" action="/eletters" method="post" id="highwire-comments-filters-form" accept-charset="UTF-8"><div><input type="hidden" name="custom_redirect" value="eletters" /> <input type="hidden" name="query_parameters" value="" /> <div class="form-item form-item-label-before form-type-select form-item-pager-limit"> <label for="edit-pager-limit">Results/page </label> <select id="edit-pager-limit" name="pager_limit" class="form-select"><option value="10" selected="selected">10</option><option value="25">25</option><option value="50">50</option><option value="75">75</option><option value="100">100</option></select> </div> <div class="form-item form-item-label-before form-type-select form-item-sort"> <label for="edit-sort">Order by </label> <select id="edit-sort" name="sort" class="form-select"><option value="ASC">Oldest First</option><option value="DESC" selected="selected">Newest First</option></select> </div> <input id="highwire_comments_filter_form_submit" type="submit" name="op" value="Submit" class="form-submit" /><input type="hidden" name="form_build_id" value="form-nOEHQSMdU2WXRhQhaWilltU7YN2Qd31d2RBx05GWSLs" /> <input type="hidden" name="form_id" value="highwire_comments_filters_form" /> </div></form></div><div class="highwire-list highwire-article-citation-list"><ul class="highwire-comments"><li class="first odd"><div class="highwire-article-citation highwire-citation-type-highwire-comment" data-node-nid="147684" id="node-1476841169301878"><div class="highwire-cite highwire-cite-highwire-comment highwire-citation-bmjj-comment highwire-comment-view highwire-comment-view-147684 clearfix"> <a href="https://ebm.bmj.com/content/28/6/400.responses#controlled-but-not-placebo-controlled" class="highwire-comment-anchor-title-link highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title highwire-comment-view-title">Controlled but not placebo controlled</span></a> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-date highwire-cite-metadata">22 August, 2024 </span></div> <div class="highwire-cite-snippet"><div class="highwire-comment-view-body"><p>It is misleading (as stated in “what this study adds”) to described this trial as placebo controlled. Although dummy capsules were used to blind participants to which combination of curcumin or omeprazole they were receiving, no group received placebo only. One interpretation of the findings therefore remains that they are due to a placebo effect. It is unfortunate that this misrepresentation of the study design has already been picked up by a UK National newspaper (Guardian 12 September)</p> </div> </div> </div> </div></li><li class="even"><div class="highwire-article-citation highwire-citation-type-highwire-comment" data-node-nid="147949" id="node-147949165932980"><div class="highwire-cite highwire-cite-highwire-comment highwire-citation-bmjj-comment highwire-comment-view highwire-comment-view-147949 clearfix"> <a href="https://ebm.bmj.com/content/28/6/400.responses#multiple-problems-with-reporting-and-interpretation-of-the-results-" class="highwire-comment-anchor-title-link highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title highwire-comment-view-title">Multiple problems with reporting and interpretation of the results </span></a> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-date highwire-cite-metadata">22 August, 2024 </span></div> <div class="highwire-cite-snippet"><div class="highwire-comment-view-body"><div class="highwire-showhide-toggle-short highwire-showhide-toggle"><p>Dear Editorial Office,</p> <p>I want to express my concern regarding “Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial” by Kongkam et al(1). It was published against the journal’s editorial policy and has serious issues with reporting and interpretation of results. </p> <p>The article shouldn’t have been published in the first place. It lacks prospective registration, which directly contradicts the BMJ Evidence-based medicine editorial policy stating that a prospective registration is mandatory for any clinical trials(2). The Thai Clinical Trials Registry(3) registration TCTR20221208003 is retrospective which is clearly stated in the registry. The registration was submitted on 07 December 2022, just before a preprint was posted on medRxiv on 09 December 2022, while the study was completed on 30 April 2020. </p> <p>On top of that, there are serious issues with the reporting and interpretation of results. </p> <p>According to the authors an equivalence design was used with the equivalence margin of 2 points in the SODA score. Nine comparisons of SODA scores in the curcumin plus omeprazole (C+O), curcumin only (C), and omeprazole only (O) groups were reported. For three of those confidence intervals include equivalence margin. The only available interpretation here is that the trial failed to demonstrate equivalence. To demonstrate equivalence the confidence intervals should be between the two equivalence margins rath...</p><a href="#" class="highwire-showhide-toggle-show-more highwire-showhide-toggle-link" data-icon-position="" data-hide-link-title="0">Show More</a></div> <div class="highwire-showhide-toggle-full highwire-showhide-toggle" style="display:none"><p>Dear Editorial Office,</p> <p>I want to express my concern regarding “Curcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trial” by Kongkam et al(1). It was published against the journal’s editorial policy and has serious issues with reporting and interpretation of results. </p> <p>The article shouldn’t have been published in the first place. It lacks prospective registration, which directly contradicts the BMJ Evidence-based medicine editorial policy stating that a prospective registration is mandatory for any clinical trials(2). The Thai Clinical Trials Registry(3) registration TCTR20221208003 is retrospective which is clearly stated in the registry. The registration was submitted on 07 December 2022, just before a preprint was posted on medRxiv on 09 December 2022, while the study was completed on 30 April 2020. </p> <p>On top of that, there are serious issues with the reporting and interpretation of results. </p> <p>According to the authors an equivalence design was used with the equivalence margin of 2 points in the SODA score. Nine comparisons of SODA scores in the curcumin plus omeprazole (C+O), curcumin only (C), and omeprazole only (O) groups were reported. For three of those confidence intervals include equivalence margin. The only available interpretation here is that the trial failed to demonstrate equivalence. To demonstrate equivalence the confidence intervals should be between the two equivalence margins rather than include them. The fact that “no significant differences were observed among the three groups” is also fully irrelevant, it does not demonstrate equivalence, as the latter cannot be claimed on the basis of nonsignificant tests(4).</p> <p>Another striking deficiency in reporting is the unexplained loss to follow-up difference between the study arms. While 17 participants were lost to follow-up in the curcumin plus omeprazole and 17 in the curcumin only groups, only 1 was lost to follow-up in the omeprazole only arm. At the same time, the numbers of subjects who withdrew consent were also noticeably different – 2, 2 and 18 respectively. This difference is unlikely to have arisen by chance alone. There are two possible explanations: either the numbers of subjects who withdrew consent and those lost to follow-up were mistakenly swapped, or the loss to follow-up was systematically different in the omeprazole only arm compared to the two arms with curcumin. The former would question the peer review, the latter would question the blinding. Given the taste and smell of curcumin the blinding should have been questioned even if there were no differences in attrition. </p> <p>It’s hard to believe that CONSORT requirements, explicitly stating that the interpretation must be consistent with the results and the primary and secondary outcome measures need to be completely defined and pre-specified, were sufficiently taken into consideration during the review process. I hope appropriate actions will be taken by the journal to correct for that.</p> <p>(1) Kongkam P, Khongkha W, Lopimpisuth C, et alCurcumin and proton pump inhibitors for functional dyspepsia: a randomised, double blind controlled trialBMJ Evidence-Based Medicine 2023;28:399-406.</p> <p>(2) <a href="https://bmjopen.bmj.com/pages/authors">https://bmjopen.bmj.com/pages/authors</a></p> <p>(3) <a href="https://www.thaiclinicaltrials.org/">https://www.thaiclinicaltrials.org/</a></p> <p>(4) Piaggio G, Elbourne DR, Pocock SJ, Evans SJW, Altman DG, CONSORT Group FT. Reporting of Noninferiority and Equivalence Randomized Trials: Extension of the CONSORT 2010 Statement. JAMA. 2012;308(24):2594–2604. doi:10.1001/jama.2012.87802</p> <a href="#" class="highwire-showhide-toggle-show-less highwire-showhide-toggle-link" data-icon-position="" data-hide-link-title="0">Show Less</a></div> </div> </div> </div> </div></li><li class="odd"><div class="highwire-article-citation highwire-citation-type-highwire-comment" data-node-nid="148100" id="node-148100606336977"><div class="highwire-cite highwire-cite-highwire-comment highwire-citation-bmjj-comment highwire-comment-view highwire-comment-view-148100 clearfix"> <a href="https://ebm.bmj.com/content/29/3/207.responses#health--equitable-healthcare-is-a-human-right" class="highwire-comment-anchor-title-link highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title highwire-comment-view-title">Health & equitable healthcare is a human right</span></a> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-date highwire-cite-metadata">22 May, 2024 </span></div> <div class="highwire-cite-snippet"><div class="highwire-comment-view-body"><div class="highwire-showhide-toggle-short highwire-showhide-toggle"><p>Health & healthcare is a human rights issue. Persons with intellectual disabilities use disproportionately more health care resources than the population without intellectual disabilities. In spite of this, they experience poorer health outcomes and they and their carers are significantly less satisfied with the quality of care provided to them by a variety of healthcare personnel. This can include doctors, pharmacists, nurses and other personnel.</p> <p>The right to health contains freedoms. These freedoms include the right to be free from non-consensual medical treatment, such as medical experiments and research or forced sterilization, and to be free from torture and other cruel, inhuman or degrading treatment or punishment. </p> <p>The right to health also contains entitlements. These entitlements include among others: The right to a system of health protection providing equality of opportunity for everyone to enjoy the highest attainable level of health; The right to prevention, treatment and control of diseases; Equal and timely access to basic health services; The provision of health-related education and information; Equal and timely access to basic health services etc.</p> <p>Human rights are interdependent, indivisible and interrelated. This means that violating the right to health may often impair the enjoyment of other human rights, such as the rights to education or work, and vice versa. Persons with disabilities face various challenges to the enjoy...</p><a href="#" class="highwire-showhide-toggle-show-more highwire-showhide-toggle-link" data-icon-position="" data-hide-link-title="0">Show More</a></div> <div class="highwire-showhide-toggle-full highwire-showhide-toggle" style="display:none"><p>Health & healthcare is a human rights issue. Persons with intellectual disabilities use disproportionately more health care resources than the population without intellectual disabilities. In spite of this, they experience poorer health outcomes and they and their carers are significantly less satisfied with the quality of care provided to them by a variety of healthcare personnel. This can include doctors, pharmacists, nurses and other personnel.</p> <p>The right to health contains freedoms. These freedoms include the right to be free from non-consensual medical treatment, such as medical experiments and research or forced sterilization, and to be free from torture and other cruel, inhuman or degrading treatment or punishment. </p> <p>The right to health also contains entitlements. These entitlements include among others: The right to a system of health protection providing equality of opportunity for everyone to enjoy the highest attainable level of health; The right to prevention, treatment and control of diseases; Equal and timely access to basic health services; The provision of health-related education and information; Equal and timely access to basic health services etc.</p> <p>Human rights are interdependent, indivisible and interrelated. This means that violating the right to health may often impair the enjoyment of other human rights, such as the rights to education or work, and vice versa. Persons with disabilities face various challenges to the enjoyment of their right to health. Non-discrimination and equality are fundamental human rights principles and critical components of the right to health in this population group.</p> <p>Healthcare professionals such as doctors, pharmacists and nurses and others should be mindful of the clinical effects associated with intellectual disabilities and how the individual patient's health and access to equitable healthcare is challenged and/or adversely affected. They must also take the time to understand the overall impact the condition has on the patient's life and on their carers and support network. Person centred care involves asking the right questions and listening carefully to patients with intellectual disability and their carers describing their unique challenges and experiences e.g. how to administer often complex medication regimens safely.</p> <p>The right to health is a fundamental part of our human rights and of our understanding of a life with dignity. Regardless of our age, gender, socio-economic or ethnic background, ability/disability level our health is our most basic and essential asset. Improving health care providers' ( doctors, pharmacists, nurses and others) knowledge of intellectual disabilities and ability to provide culturally competent person centred care can limit the health disparities experienced by this disadvantaged population i.e. help ‘close the gap’.</p> <p>Culturally competent doctors, pharmacists, nurses are important in eliminating health disparities experienced by people of all populations, including those with intellectual disabilities. Specialist pharmacists must be included in any multidisciplinary clinic as medication use is the main therapeutic intervention in the population with intellectual disabilities. Multidisciplinary teams with knowledge, expertise and experience provide ‘reasonable accommodations’ to the person with intellectual disability and equitable access to healthcare. The population with intellectual disabilities have a right to equitable access to healthcare leading to equal outcomes with the general population.</p> <p>Bibliography<br /> Disability in Cultural Competency Pharmacy Education<br /> <a href="https://www.ajpe.org/article/S0002-9459">https://www.ajpe.org/article/S0002-9459</a>(23)03588-X/fulltext</p> <p>The Right to Health <a href="https://www.ohchr.org/sites/default/files/Documents/Publications/Factsheet31.pdf">https://www.ohchr.org/sites/default/files/Documents/Publications/Factshe...</a></p> <a href="#" class="highwire-showhide-toggle-show-less highwire-showhide-toggle-link" data-icon-position="" data-hide-link-title="0">Show Less</a></div> </div> </div> </div> </div></li><li class="even"><div class="highwire-article-citation highwire-citation-type-highwire-comment" data-node-nid="148177" id="node-148177920391476"><div class="highwire-cite highwire-cite-highwire-comment highwire-citation-bmjj-comment highwire-comment-view highwire-comment-view-148177 clearfix"> <a href="https://ebm.bmj.com/content/29/3/156.responses#re-ecological-study-estimating-melanoma-overdiagnosis-in-the-usa-using-the-lifetime-risk-method" class="highwire-comment-anchor-title-link highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title highwire-comment-view-title">Re: Ecological study estimating melanoma overdiagnosis in the USA using the lifetime risk method</span></a> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-date highwire-cite-metadata">22 May, 2024 </span></div> <div class="highwire-cite-snippet"><div class="highwire-comment-view-body"><div class="highwire-showhide-toggle-short highwire-showhide-toggle"><p>February 28, 2024 </p> <p>To: Juan VA Franco, MD<br /> Editor-in-Chief<br /> British Medical Journal, Evidence-Based Medicine </p> <p>Dear Editor:<br /> The study on cutaneous melanoma overdiagnosis attempts to tackle an important issue. However, we wish to address several methodological concerns that may warrant a critical evaluation of its conclusions. </p> <p>First, one key study assumption is that the overdiagnosis of melanoma is due to over-screening by clinicians, including dermatologists. However, whether the patients were actually screened by clinicians is unknowable with the current study design. Thus, the lack of direct evidence to support this key assumption limits the study's capacity to attribute melanoma diagnoses to the prevalence of screening. </p> <p>Second, the study's ecological methodology does not sufficiently account for variables that could affect melanoma diagnosis and mortality rate over time, such as advancements in diagnostic technologies, treatments, public awareness, and healthcare access, all factors that dermatologists have worked to improve over time. These factors could independently influence trends in melanoma incidence and mortality. This limitation is critical as it underlines the difficulty in drawing definitive conclusions from the ecological data presented. </p> <p>Thirdly, the choice to manually input annual data from the SEER program into the DevCan software, deviating from the standard 3-year data aggregatio...</p><a href="#" class="highwire-showhide-toggle-show-more highwire-showhide-toggle-link" data-icon-position="" data-hide-link-title="0">Show More</a></div> <div class="highwire-showhide-toggle-full highwire-showhide-toggle" style="display:none"><p>February 28, 2024 </p> <p>To: Juan VA Franco, MD<br /> Editor-in-Chief<br /> British Medical Journal, Evidence-Based Medicine </p> <p>Dear Editor:<br /> The study on cutaneous melanoma overdiagnosis attempts to tackle an important issue. However, we wish to address several methodological concerns that may warrant a critical evaluation of its conclusions. </p> <p>First, one key study assumption is that the overdiagnosis of melanoma is due to over-screening by clinicians, including dermatologists. However, whether the patients were actually screened by clinicians is unknowable with the current study design. Thus, the lack of direct evidence to support this key assumption limits the study's capacity to attribute melanoma diagnoses to the prevalence of screening. </p> <p>Second, the study's ecological methodology does not sufficiently account for variables that could affect melanoma diagnosis and mortality rate over time, such as advancements in diagnostic technologies, treatments, public awareness, and healthcare access, all factors that dermatologists have worked to improve over time. These factors could independently influence trends in melanoma incidence and mortality. This limitation is critical as it underlines the difficulty in drawing definitive conclusions from the ecological data presented. </p> <p>Thirdly, the choice to manually input annual data from the SEER program into the DevCan software, deviating from the standard 3-year data aggregation, raises concerns about the accuracy and reliability of the findings. Such a departure from standardized methods without a robust justification may introduce bias or artifacts into the analysis. Furthermore, this approach complicates the interpretation of trends over time, as it may attribute undue significance to annual fluctuations that could be mere artifacts of random variation rather than indicative of meaningful trends. </p> <p>In light of these concerns, we urge a cautious interpretation of the study's conclusions regarding the overdiagnosis of cutaneous melanoma. It is essential for future research in this area to address these methodological issues and be inclusive of all racial and ethnic groups, ensuring a more robust and reliable basis for understanding rate of melanoma diagnosis. </p> <p>Sincerely, </p> <p>Anna McNay M.D.<br /> President</p> <p>Melissa Shive M.D., M.P.H.<br /> President Elect </p> <p>On behalf of the California Society of Dermatology and Dermatologic Surgery (CalDerm)</p> <a href="#" class="highwire-showhide-toggle-show-less highwire-showhide-toggle-link" data-icon-position="" data-hide-link-title="0">Show Less</a></div> </div> </div> </div> </div></li><li class="odd"><div class="highwire-article-citation highwire-citation-type-highwire-comment" data-node-nid="147772" id="node-147772278834622"><div class="highwire-cite highwire-cite-highwire-comment highwire-citation-bmjj-comment highwire-comment-view highwire-comment-view-147772 clearfix"> <a href="https://ebm.bmj.com/content/29/3/142.responses#addressing-the-challenges-in-researching-long--and-post-covid-" class="highwire-comment-anchor-title-link highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title highwire-comment-view-title">Addressing the Challenges in Researching Long- and Post COVID </span></a> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-date highwire-cite-metadata">22 May, 2024 </span></div> <div class="highwire-cite-snippet"><div class="highwire-comment-view-body"><div class="highwire-showhide-toggle-short highwire-showhide-toggle"><p>Dear Editor,</p> <p>we are writing in response to the article titled " How methodological pitfalls have created widespread misunderstanding about long COVID”(1).</p> <p>We agree with the authors, that the existing epidemiological research on long COVID has suffered from overly broad case definitions and a striking absence of control groups, which may have led in an overestimation of risk.<br /> It is important to acknowledge that Long- and Post-COVID syndrome are heterogeneous conditions, likely comprising different pathomechanistic groups such as autoimmunity, mitochondrial dysfunction, and virus persistence (2). This complexity, coupled with the lack of routine biomarkers, makes it difficult to accurately define and study this condition. Høeg et al et al. therefore raise some relevant points regarding the challenges faced in studying Long- and Post-COVID syndrome, particularly the need for properly matched control groups and internationally-established diagnostic criteria. Regarding the latter, the authors of the article themselves fail to use definitions accurately, particularly in distinguishing between the now consented WHO definitions of Long-COVID and Post-COVID (WHO/2019-nCoV/Post_COVID-19_condition/Clinical_case_definition/2021.1).<br /> It is true, that initial studies depicted a high prevalence of Post-COVID syndrome (PCS). However, more recent population-based studies present a different perspective. In assessing the clinical picture, the primary focus isn...</p><a href="#" class="highwire-showhide-toggle-show-more highwire-showhide-toggle-link" data-icon-position="" data-hide-link-title="0">Show More</a></div> <div class="highwire-showhide-toggle-full highwire-showhide-toggle" style="display:none"><p>Dear Editor,</p> <p>we are writing in response to the article titled " How methodological pitfalls have created widespread misunderstanding about long COVID”(1).</p> <p>We agree with the authors, that the existing epidemiological research on long COVID has suffered from overly broad case definitions and a striking absence of control groups, which may have led in an overestimation of risk.<br /> It is important to acknowledge that Long- and Post-COVID syndrome are heterogeneous conditions, likely comprising different pathomechanistic groups such as autoimmunity, mitochondrial dysfunction, and virus persistence (2). This complexity, coupled with the lack of routine biomarkers, makes it difficult to accurately define and study this condition. Høeg et al et al. therefore raise some relevant points regarding the challenges faced in studying Long- and Post-COVID syndrome, particularly the need for properly matched control groups and internationally-established diagnostic criteria. Regarding the latter, the authors of the article themselves fail to use definitions accurately, particularly in distinguishing between the now consented WHO definitions of Long-COVID and Post-COVID (WHO/2019-nCoV/Post_COVID-19_condition/Clinical_case_definition/2021.1).<br /> It is true, that initial studies depicted a high prevalence of Post-COVID syndrome (PCS). However, more recent population-based studies present a different perspective. In assessing the clinical picture, the primary focus isn't merely on the presence of symptoms but on the symptom-related reduction in quality of life. Our own study reveals that only 20% of symptomatic patients experience a significant reduction in their quality of life, indicating suffering from Post-COVID syndrome. This suggests a prevalence of Post-COVID syndrome at 5-6% for the entire population (3). The risk of developing Post-COVID syndrome after infection with currently circulating variants is notably lower than in patients from the initial waves of the infection (3). This aspect should be emphasized as part of a critical analysis of the issue, the authors can be expected to go into this in more depth and thus contribute to a more objective discussion. A systematic meta-analysis that considers different data collection times after infection and the method of symptom recording (self-reported versus documented through examinations) would have been more beneficial. This approach would provide a more comprehensive view rather than highlighting individual studies, thus avoiding polarized statements.</p> <p>Furthermore, Høeg et al. suggest the inclusion of infection-negative control groups in future research. While this may be ideal, it is not realistic in the current state of the pandemic, which is now in its third year and has reached an endemic stage (Rahman et al., 2021). Additionally, the absence of antibodies does not exclude the presence of infection, as demonstrated in the Conan study, where half of the patients with PCR-confirmed infection had no detectable antibodies six weeks later (4).</p> <p>Despite methodological limitations pointed out by Høeg et al. that apply to Post-COVID studies, it is crucial to recognize that Post-COVID syndrome is a relevant and frequent condition that requires further investigation in order to optimized diagnostic criteria and identify pathomechanism related biomarkers that may help to assign patients to appropriate randomized treatment studies according to the underlying mechanism. The findings regarding immune dysregulation described by A. Iwaski's working group are indeed promising and offer encouragement to many individuals affected by this condition (5). It is essential to continue studying and addressing post-COVID conditions to provide appropriate care and support for those affected.</p> <p>Sincerely,</p> <p>Mathias W. Pletz, MD and Andreas Stallmach, MD</p> <p>Bibliography</p> <p>1. Høeg TB, Ladhani S, Prasad V. How methodological pitfalls have created widespread misunderstanding about long COVID. BMJ Evid Based Med. 2023 Sep 25;<br /> 2. Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. 2023 Mar;21(3):133–46.<br /> 3. Giszas B, Trommer S, Schüßler N, Rodewald A, Besteher B, Bleidorn J, et al. Post-COVID-19 condition is not only a question of persistent symptoms: structured screening including health-related quality of life reveals two separate clusters of post-COVID. Infection. 2023 Apr;51(2):365–77.<br /> 4. Weis S, Scherag A, Baier M, Kiehntopf M, Kamradt T, Kolanos S, et al. Antibody response using six different serological assays in a completely PCR-tested community after a coronavirus disease 2019 outbreak-the CoNAN study. Clin Microbiol Infect. 2021 Mar;27(3):470.e1-470.e9.<br /> 5. Klein J, Wood J, Jaycox J, Dhodapkar RM, Lu P, Gehlhausen JR, et al. Distinguishing features of Long COVID identified through immune profiling. Nature. 2023 Sep 25;</p> <a href="#" class="highwire-showhide-toggle-show-less highwire-showhide-toggle-link" data-icon-position="" data-hide-link-title="0">Show Less</a></div> </div> </div> </div> </div></li><li class="even"><div class="highwire-article-citation highwire-citation-type-highwire-comment" data-node-nid="147816" id="node-147816279444083"><div class="highwire-cite highwire-cite-highwire-comment highwire-citation-bmjj-comment highwire-comment-view highwire-comment-view-147816 clearfix"> <a href="https://ebm.bmj.com/content/29/3/142.responses#correspondence-on-how-methodological-pitfalls-have-created-widespread-misunderstanding-about-long-covid" class="highwire-comment-anchor-title-link highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title highwire-comment-view-title">Correspondence on "How methodological pitfalls have created widespread misunderstanding about long COVID"</span></a> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-date highwire-cite-metadata">22 May, 2024 </span></div> <div class="highwire-cite-snippet"><div class="highwire-comment-view-body"><div class="highwire-showhide-toggle-short highwire-showhide-toggle"><p>Dr Juan Franco<br /> Editor-In-Chief<br /> BMJ Evidence Based Medicine<br /> BMA House<br /> Tavistock Square<br /> London WC1H 9JP<br /> UNITED KINGDOM</p> <p>31 October 2023</p> <p>Dear Editor-In-Chief,</p> <p>We read with interest the recent article by Høeg and colleagues that describes how methodological limitations in long COVID research distort risk and overestimate prevalence.[1] </p> <p>The authors propose criteria to improve epidemiological research of long COVID. We write in support of these criteria, and to suggest two additions. We recently compared outcomes three months after PCR-confirmed COVID-19 infection with PCR-confirmed influenza infection, and found no difference between these illnesses.[2] Our comparative observational study had limitations (which we acknowledged) but was noteworthy because it was conducted in an Australian population that was primarily exposed to the Omicron variant after achieving high vaccination rates (>90%). </p> <p>As a result, our two proposed additions to Høeg et al’s criteria relate to the exposed population which, as they suggest, should have diagnostic evidence of infection.</p> <p>The first addition is to document the COVID variant to which this population was exposed. Recent data from Sweden shows a progressive (and substantial) decrease in the risk of long COVID from the wild type to the Omicron variant.[3] In addition, the type and frequency of symptoms has changed as the virus evolves.[4] This inclusion would improv...</p><a href="#" class="highwire-showhide-toggle-show-more highwire-showhide-toggle-link" data-icon-position="" data-hide-link-title="0">Show More</a></div> <div class="highwire-showhide-toggle-full highwire-showhide-toggle" style="display:none"><p>Dr Juan Franco<br /> Editor-In-Chief<br /> BMJ Evidence Based Medicine<br /> BMA House<br /> Tavistock Square<br /> London WC1H 9JP<br /> UNITED KINGDOM</p> <p>31 October 2023</p> <p>Dear Editor-In-Chief,</p> <p>We read with interest the recent article by Høeg and colleagues that describes how methodological limitations in long COVID research distort risk and overestimate prevalence.[1] </p> <p>The authors propose criteria to improve epidemiological research of long COVID. We write in support of these criteria, and to suggest two additions. We recently compared outcomes three months after PCR-confirmed COVID-19 infection with PCR-confirmed influenza infection, and found no difference between these illnesses.[2] Our comparative observational study had limitations (which we acknowledged) but was noteworthy because it was conducted in an Australian population that was primarily exposed to the Omicron variant after achieving high vaccination rates (>90%). </p> <p>As a result, our two proposed additions to Høeg et al’s criteria relate to the exposed population which, as they suggest, should have diagnostic evidence of infection.</p> <p>The first addition is to document the COVID variant to which this population was exposed. Recent data from Sweden shows a progressive (and substantial) decrease in the risk of long COVID from the wild type to the Omicron variant.[3] In addition, the type and frequency of symptoms has changed as the virus evolves.[4] This inclusion would improve our understanding of post-viral impacts by variant, and add important context to Høeg et al’s sensible suggestion of a symptom-based approach to support patients. </p> <p>The second addition involves documenting the population’s vaccination status, including (if possible) the time since last dose. A systematic review found that COVID-19 vaccination could protect against long COVID, but also noted that study quality was generally low for the reasons argued by Høeg et al.[5] While ongoing reinfections and decreased diagnostic testing may cloud the benefits of vaccination, vaccination status offers important insights into the symptoms and impacts of each COVID variant. </p> <p>Finally, we concur with the article’s observations about the ongoing impact of regular negative reports about long COVID. We have heard people say they are “more afraid of getting long COVID than they are of getting COVID”. Høeg and colleagues have provided a framework to challenge the many inflated claims that may contribute to this fear and anxiety. While we believe and support those who experience post-viral effects, we must remember the most likely outcome after COVID-19 infection is a full recovery.</p> <p>Yours sincerely,<br /> Matthew Brown (Program Manager, Queensland Long COVID Response)<br /> John Gerrard (Chief Health Officer, Queensland)<br /> Ross Andrews (Senior Consultant Epidemiologist) </p> <p>References<br /> 1 Hoeg TB, Ladhani S, Prasad V. How methodological pitfalls have created widespread misunderstanding about long COVID. BMJ Evid Based Med 2023.<br /> 2 Brown M, Gerrard J, McKinlay L, et al. Ongoing symptoms and functional impairment 12 weeks after testing positive for SARS-CoV-2 or influenza in Australia: an observational cohort study. BMJ Public Health 2023; 1(1).<br /> 3 Hedberg P, Naucler P. Post COVID-19 condition after SARS-CoV-2 infections during the omicron surge compared with the delta, alpha, and wild-type periods in Stockholm, Sweden. J Infect Dis 2023.<br /> 4 Looi MK. How are covid-19 symptoms changing? BMJ 2023; 380: 3.<br /> 5 Byambasuren O, Stehlik P, Clark J, et al. Effect of covid-19 vaccination on long covid: systematic review. BMJ Medicine 2023; 2(1).</p> <a href="#" class="highwire-showhide-toggle-show-less highwire-showhide-toggle-link" data-icon-position="" data-hide-link-title="0">Show Less</a></div> </div> </div> </div> </div></li><li class="odd"><div class="highwire-article-citation highwire-citation-type-highwire-comment" data-node-nid="147936" id="node-1479361177284128"><div class="highwire-cite highwire-cite-highwire-comment highwire-citation-bmjj-comment highwire-comment-view highwire-comment-view-147936 clearfix"> <a href="https://ebm.bmj.com/content/29/3/142.responses#article-on-long-covid-study-methodology-is-not-evidence-based" class="highwire-comment-anchor-title-link highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title highwire-comment-view-title">Article on Long COVID study methodology is not evidence-based</span></a> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-date highwire-cite-metadata">22 May, 2024 </span></div> <div class="highwire-cite-snippet"><div class="highwire-comment-view-body"><div class="highwire-showhide-toggle-short highwire-showhide-toggle"><p>We were surprised that BMJ Evidence Based Medicine chose to publish the flawed article by Høeg and co-authors on methodological limitations of research on long COVID (1). This piece appears to be a ‘Trojan Horse’ article where a scientifically dubious proposition escapes proper scrutiny because it is cloaked in otherwise plausible research commentary.</p> <p>As the authors state, we need well designed studies to provide a valid measure of the long-term effects of acute COVID-19 infection (Long COVID). Such studies require robust case definitions, adequate duration of follow-up, and suitable comparison groups. </p> <p>But in a section titled “The most well-designed studies provide reassuring estimates”, the authors include just two studies to support that sweeping statement. This highly selective ‘mini meta-analysis’ subverts the very purpose of evidence-based medicine. The main message of the Høeg paper appears to be that there is a negligible risk of long COVID, based on the selection of papers they have cited. That message does not fit with the actual body of scientific evidence (2). There is now overwhelming research that SARS-CoV-2 infection carries a significant risk of long-term effects over and above the generic effects of post-ICU syndrome and pneumonia (3). </p> <p>The evidence of long-term effects comes from multiple sources, including epidemiological studies and basic science research looking at the severe and lasting pathological changes that occur in some pati...</p><a href="#" class="highwire-showhide-toggle-show-more highwire-showhide-toggle-link" data-icon-position="" data-hide-link-title="0">Show More</a></div> <div class="highwire-showhide-toggle-full highwire-showhide-toggle" style="display:none"><p>We were surprised that BMJ Evidence Based Medicine chose to publish the flawed article by Høeg and co-authors on methodological limitations of research on long COVID (1). This piece appears to be a ‘Trojan Horse’ article where a scientifically dubious proposition escapes proper scrutiny because it is cloaked in otherwise plausible research commentary.</p> <p>As the authors state, we need well designed studies to provide a valid measure of the long-term effects of acute COVID-19 infection (Long COVID). Such studies require robust case definitions, adequate duration of follow-up, and suitable comparison groups. </p> <p>But in a section titled “The most well-designed studies provide reassuring estimates”, the authors include just two studies to support that sweeping statement. This highly selective ‘mini meta-analysis’ subverts the very purpose of evidence-based medicine. The main message of the Høeg paper appears to be that there is a negligible risk of long COVID, based on the selection of papers they have cited. That message does not fit with the actual body of scientific evidence (2). There is now overwhelming research that SARS-CoV-2 infection carries a significant risk of long-term effects over and above the generic effects of post-ICU syndrome and pneumonia (3). </p> <p>The evidence of long-term effects comes from multiple sources, including epidemiological studies and basic science research looking at the severe and lasting pathological changes that occur in some patients following SARS-CoV-2 infection. This research shows that COVID-19 is a multisystem disease that can cause microclots, changes to the immune system, viral persistence in tissues, and other effects even in mild cases (4). These effects provide a basis for well-described sequelae of COVID-19 such as impaired brain function, extreme fatigue, and stroke. </p> <p>Furthermore, tissue-level effects can be clinically silent but they include known risk factors for heart disease and other conditions, raising concerns for future population health. Viral persistence suggests additional potential for long-term effects that may take years or decades to emerge, as we have seen with other infections (5).</p> <p>Even the research selectively cited in the Hoeg article is not as reassuring as the authors imply. Antonelli et al. reported an overall lower risk of Long COVID for Omicron compared with Delta infection (6). But they noted that Omicron variants have caused far higher case numbers and the conclusion of their article is that "future numbers with long COVID will inevitably rise". </p> <p>Full declaration of potential conflicts of interest is important in evidence-based medicine. Yet at least two of the authors here have made no secret of their unorthodox scientific views on the origins, transmission, severity and prevention of COVID-19 and appear to be associated with particular ideological positions and organisations (7, 8).</p> <p>Rather than the robust science we might reasonably expect from the highly regarded BMJ Evidence-Based Medicine, the Høeg paper serves to illustrate the very biases and errors which evidence-based medicine was established to challenge. It appears to be a ‘Trojan Horse’ from a partisan group. Its publication significantly damages the reputation of the journal as a platform for rigorous, principled, and balanced scientific debate. </p> <p>References<br /> 1. Hoeg TB, Ladhani S, Prasad V. How methodological pitfalls have created widespread misunderstanding about long COVID. BMJ Evid Based Med 2023 doi: 10.1136/bmjebm-2023-112338 [published Online First: 2023/09/26]<br /> 2. Altmann DM, Whettlock EM, Liu S, et al. The immunology of long COVID. Nature reviews Immunology 2023;23(10):618-34. doi: 10.1038/s41577-023-00904-7 [published Online First: 2023/07/12]<br /> 3. Bowe B, Xie Y, Al-Aly Z. Postacute sequelae of COVID-19 at 2 years. Nat Med 2023;29(9):2347-57. doi: 10.1038/s41591-023-02521-2 [published Online First: 2023/08/22]<br /> 4. Castanares-Zapatero D, Chalon P, Kohn L, et al. Pathophysiology and mechanism of long COVID: a comprehensive review. Annals of medicine 2022;54(1):1473-87. doi: 10.1080/07853890.2022.2076901 [published Online First: 2022/05/21]<br /> 5. Chen B, Julg B, Mohandas S, et al. Viral persistence, reactivation, and mechanisms of long COVID. eLife 2023;12 doi: 10.7554/eLife.86015 [published Online First: 2023/05/04]<br /> 6. Antonelli M, Pujol JC, Spector TD, et al. Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2. Lancet 2022;399(10343):2263-64. doi: 10.1016/S0140-6736(22)00941-2 [published Online First: 2022/06/20]<br /> 7. Bragman W. New scientist group calling for pandemic answers is tied to rightwing Dark Money. OptOut, 2023; <a href="https://www.optout.news/newsletters/norfolk-group">https://www.optout.news/newsletters/norfolk-group</a>.<br /> 8. Prasad V. Do not report COVID cases to schools & do not test yourself if you feel ill. Vinay Prasad's Observations and Thoughts, 2023; <a href="https://vinayprasadmdmph.substack.com/p/do-not-report-covid-cases-to-schools">https://vinayprasadmdmph.substack.com/p/do-not-report-covid-cases-to-sch...</a>.</p> <a href="#" class="highwire-showhide-toggle-show-less highwire-showhide-toggle-link" data-icon-position="" data-hide-link-title="0">Show Less</a></div> </div> </div> </div> </div></li><li class="even"><div class="highwire-article-citation highwire-citation-type-highwire-comment" data-node-nid="147415" id="node-1474151452485355"><div class="highwire-cite highwire-cite-highwire-comment highwire-citation-bmjj-comment highwire-comment-view highwire-comment-view-147415 clearfix"> <a href="https://ebm.bmj.com/content/28/6/426.responses#perrier-et-al-a-deeply-flawed-study-on-conflict-of-interests-in-homeopathy-meta-analyses" class="highwire-comment-anchor-title-link highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title highwire-comment-view-title">Perrier et al a deeply flawed study on Conflict of Interests in Homeopathy meta-analyses</span></a> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-date highwire-cite-metadata">24 April, 2024 </span></div> <div class="highwire-cite-snippet"><div class="highwire-comment-view-body"><p>We read with interest the study by Perrier et al on the Relationship between the conflicts of interest and the results of meta-analyses of homoeopathy trials. We want to briefly address issues we see with this paper.<br /> Firstly, the criteria for a study presenting a Conflict of Interest (CoI) include that a single author has a link with any research institution involved in homeopathy research. Translated to other fields of research, Oncology for example, this would mean that cancer studies emanating from Cancer Research institutes would have to be considered as conflicted and therefore unreliable. This is clearly an absurd way of defining CoIs.<br /> More importantly, the authors wrongly report the Odds Ratio (OR) data for the Shang et al paper as being OR = 0.88, CI 0.65-1.19, N=105, this OR corresponds to the N=8 ‘larger high-quality trials’ from that study, not N=105. The OR for N=105 was never published but the OR for the N=21 ‘high-quality trials’ is OR = 0.76; CI: 0.59-0.99, N=21 (Ludtke & Ruttem 2008). Ignoring the meaningless N=1 MAs in Fig 1, we end up with three CoI-free MAs, which all favour homeopathy. And this trend would only be accentuated by using the correct OR for the full N=105 trials. The overall picture painted by the data is thereby very different than reported by the authors. In particular there appears to be no statistical difference between their so-called CoI and CoI-free MAs in Homeopathy.</p> </div> </div> </div> </div></li><li class="odd"><div class="highwire-article-citation highwire-citation-type-highwire-comment" data-node-nid="147542" id="node-1475421729712070"><div class="highwire-cite highwire-cite-highwire-comment highwire-citation-bmjj-comment highwire-comment-view highwire-comment-view-147542 clearfix"> <a href="https://ebm.bmj.com/content/27/1/7.responses#moving-forward-on-hpv-vaccine-safety-concerns" class="highwire-comment-anchor-title-link highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title highwire-comment-view-title">Moving Forward on HPV Vaccine Safety Concerns</span></a> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-date highwire-cite-metadata">24 April, 2024 </span></div> <div class="highwire-cite-snippet"><div class="highwire-comment-view-body"><div class="highwire-showhide-toggle-short highwire-showhide-toggle"><p>Gøtzsche and Jørgensen claim that the European Medicines Agency (EMA) mishandled their investigation of the safety of the HPV vaccine regarding serious neurological adverse events from the administration of the HPV vaccine, such as postural orthostatic tachycardia syndrome (POTS) and chronic regional pain syndrome (CRPS). The authors highlight the insufficiency due to poor data analysis, conflicts of interest, poor research into aluminum adjuvants, and bias in analyzing the research 1. We want to discuss several key points on the safety of the HPV vaccine.<br /> Over 270 million doses of HPV vaccines have been administered since 2006. Many regulatory agencies have overseen the safety of the HPV vaccine, including the World Health Organization’s GACVS (Global Advisory Committee on Vaccine Safety) 2. Most regulatory agencies regard the HPV vaccine as safe and effective 3,4. The noted exception in this article is the Uppsala Monitoring Centre which identified safety signals for POTS and CRPS post-HPV vaccination 5.<br /> As of specific note from the paper, the majority of the evidence supporting an association with the HPV vaccine and POTS and CRPS in the article by Gøtzsche and Jørgensen was generated from data in Europe, including Denmark 1. A recent study showed no safety signal generally and specifically commented that the Denmark signal was not identified in their analysis, noting that 1,232,572 girls received the vaccine and 563 unique CRPS diagnoses (6). Concerns about...</p><a href="#" class="highwire-showhide-toggle-show-more highwire-showhide-toggle-link" data-icon-position="" data-hide-link-title="0">Show More</a></div> <div class="highwire-showhide-toggle-full highwire-showhide-toggle" style="display:none"><p>Gøtzsche and Jørgensen claim that the European Medicines Agency (EMA) mishandled their investigation of the safety of the HPV vaccine regarding serious neurological adverse events from the administration of the HPV vaccine, such as postural orthostatic tachycardia syndrome (POTS) and chronic regional pain syndrome (CRPS). The authors highlight the insufficiency due to poor data analysis, conflicts of interest, poor research into aluminum adjuvants, and bias in analyzing the research 1. We want to discuss several key points on the safety of the HPV vaccine.<br /> Over 270 million doses of HPV vaccines have been administered since 2006. Many regulatory agencies have overseen the safety of the HPV vaccine, including the World Health Organization’s GACVS (Global Advisory Committee on Vaccine Safety) 2. Most regulatory agencies regard the HPV vaccine as safe and effective 3,4. The noted exception in this article is the Uppsala Monitoring Centre which identified safety signals for POTS and CRPS post-HPV vaccination 5.<br /> As of specific note from the paper, the majority of the evidence supporting an association with the HPV vaccine and POTS and CRPS in the article by Gøtzsche and Jørgensen was generated from data in Europe, including Denmark 1. A recent study showed no safety signal generally and specifically commented that the Denmark signal was not identified in their analysis, noting that 1,232,572 girls received the vaccine and 563 unique CRPS diagnoses (6). Concerns about the media role increased in case count, and most cases were self-resolving and limited 1.<br /> So, the question is how to rectify the disparity of conclusions between Uppsala and other regulatory agencies. Or maybe the discussion is misdirected? Gøtzsche and Jørgensen claim bias and poor scientific rigor in the trial design. An alternative to this hypothesis was noted by Uppsala Monitoring Center when they said variability in diagnosis terms (i.e., the ontology of vaccine adverse events) might not provide a coherent diagnosing paradigm and monitoring approach across clinical, regulatory, and industry entities, which was only alluded to by the authors. The Uppsala manuscript has an excellent analysis focused on adversomics, which is completely missing in the Gøtzsche and Jørgensen paper. The adversomics is THE important part of the Uppsala manuscript.<br /> During COVID-19, numerous tools were developed and used to assess vaccine responses for safety and efficacy. These tools could potentially identify people who have adverse events after vaccination. Immunogenomics, transcriptomics, epitope mapping, machine learning, etc., are available and could be used to identify the safety profile of all vaccines 6. We strongly advocate that with these current technologies, risk factors for POTS and CRPS could be identified (> GRADE 3 SAEs (Serious Adverse Event)) through the study of existing and future cases. We strongly advocate developing diagnostic criteria for POTS and CRPS by Brighton Collaboration, including consistent GRADE analysis and ontology. Regulatory agencies could require monitoring using these tools in serious adverse events cases for any vaccine to improve vaccine safety for rare SAEs. Instead of asking whether HPV is safe, maybe we should ask how high-risk patients can be identified pre-vaccination. The COVID-19 analysis suggests we could identify potential risk factors that lead to adverse events to adjuvants and the vaccine in general. We advocate for these approaches through regulatory requirements, including improved phase IV trials, active monitoring, and proper analysis. </p> <p>1. Gøtzsche PC, Jørgensen KJ. EMA’s mishandling of an investigation into suspected serious neurological harms of HPV vaccines. BMJ Evid-Based Med. 2022;27(1):7-10. doi:10.1136/bmjebm-2020-111470<br /> 2. HPV Vaccine Safety, WHO. Accessed June 23, 2023. <a href="https://www.who.int/groups/global-advisory-committee-on-vaccine-safety/topics/human-papillomavirus-vaccines/safety">https://www.who.int/groups/global-advisory-committee-on-vaccine-safety/t...</a><br /> 3. HPV Dashboard. Accessed June 23, 2023. <a href="https://www.who.int/teams/immunization-vaccines-and-biologicals/diseases/human-papillomavirus-vaccines-">https://www.who.int/teams/immunization-vaccines-and-biologicals/diseases...</a>(HPV)/hpv-clearing-house/hpv-dashboard<br /> 4. Bonanni P, Bechini A, Donato R, et al. Human papilloma virus vaccination: impact and recommendations across the world. Ther Adv Vaccines. 2015;3(1):3-12. doi:10.1177/2051013614557476<br /> 5. Chandler RE. Safety Concerns with HPV Vaccines Continue to Linger: Are Current Vaccine Pharmacovigilance Practices Sufficient? Drug Saf. 2017;40(12):1167-1170. doi:10.1007/s40264-017-0593-3<br /> 6. Cotugno N, Ruggiero A, Santilli V, et al. OMIC Technologies and Vaccine Development: From the Identification of Vulnerable Individuals to the Formulation of Invulnerable Vaccines. J Immunol Res. 2019;2019:e8732191. doi:10.1155/2019/8732191</p> <a href="#" class="highwire-showhide-toggle-show-less highwire-showhide-toggle-link" data-icon-position="" data-hide-link-title="0">Show Less</a></div> </div> </div> </div> </div></li><li class="last even"><div class="highwire-article-citation highwire-citation-type-highwire-comment" data-node-nid="147930" id="node-1479301072632376"><div class="highwire-cite highwire-cite-highwire-comment highwire-citation-bmjj-comment highwire-comment-view highwire-comment-view-147930 clearfix"> <a href="https://ebm.bmj.com/content/29/1/37.responses#understanding-each-other" class="highwire-comment-anchor-title-link highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title highwire-comment-view-title">Understanding each other</span></a> <div class="highwire-cite-metadata"><span class="highwire-cite-metadata-date highwire-cite-metadata">24 April, 2024 </span></div> <div class="highwire-cite-snippet"><div class="highwire-comment-view-body"><p>I read this scoping review with great interest. In linguistics there is a term for the phenomenon that a word can have the capacity to have multiple related meanings in different contexts. This term is polysemy. In the context of defining "Evidence-based medicine". If we want to understand each other, it proved successful to define the words we use .Sackett et al. in their seminal article about" EBM what it is and what it isn't" also defined what they mean by "evidence", namely: "By best available external clinical evidence we mean clinically relevant research,often from the basic sciences of medicine, but especially from patient centred clinical research into the accuracy and precision of diagnostic tests (including the clinical examination), the power of prognostic markers, and the efficacy and safety of therapeutic, rehabilitative, and preventive regimens."<br /> Doesn't this render it irrelevant for the context of EBM if others define differently in other contexts? A bigger problem arises when the term evidence is misunderstood or even misused within the context of EBM. This problem might be approached by better teaching of the meaning originally meant. Evidence to my knowledge (as a non-english native speaker) is a juridical term and thus different to proof or fact. Juridically only the sum of evidence is leading to a court decision. And, this decision can be wrong especially if new evidence arises.</p> </div> </div> </div> </div></li></ul></div><h2 class="element-invisible">Pages</h2><div class="item-list"><ul class="pager"><li class="pager-current first">1</li> <li class="pager-item"><a title="Go to page 2" href="/eletters?page=1">2</a></li> <li class="pager-item"><a title="Go to page 3" href="/eletters?page=2">3</a></li> <li class="pager-item"><a title="Go to page 4" href="/eletters?page=3">4</a></li> <li class="pager-item"><a title="Go to page 5" href="/eletters?page=4">5</a></li> <li class="pager-ellipsis">…</li> <li class="pager-next"><a title="Go to next page" href="/eletters?page=1">next ›</a></li> <li class="pager-last last"><a title="Go to last page" href="/eletters?page=13">last »</a></li> </ul></div></div> </div> </div> </div> </div> </div> <div class="sidebar-right-wrapper grid-10 omega"> <div class="panel-panel panel-region-sidebar-right"> <div class="inside"><div class="panel-pane 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