For more than 30 years, our organization, the Institute for Patient- and Family-Centered Care (IPFCC) has been a leader in helping other organizations develop and sustain effective partnerships with patients and families to improve the quality, safety, and the experience of care. During that same time, the patient safety movement has affirmed the important roles of patients and their families in safety.
We are concerned about the recent BMJ Open article, “Explaining the negative effects of patient participation in patient safety,” and the very different message it conveys. Our concerns center on the authors’ misunderstanding of what true partnership means in health care and the inherent bias in the structure of the research. Additionally, there was no patient or partner involvement in the “design, conducting, reporting, or dissemination plans of the research.”
The questions in the “topic guide” were leading and reflected bias; therefore, they could only elicit negative views from respondents. The sample size of 8 professionals and 8 patients is small in establishing such strong conclusions.
A patient in labor having the responsibility for checking the accuracy of medications was not an appropriate example of patient participation in safety nor of an understanding of partnership. Authentic partnership would entail a discussion about patient safety as a team responsibility and a determination from the patient on how she wishes to participate on that...
For more than 30 years, our organization, the Institute for Patient- and Family-Centered Care (IPFCC) has been a leader in helping other organizations develop and sustain effective partnerships with patients and families to improve the quality, safety, and the experience of care. During that same time, the patient safety movement has affirmed the important roles of patients and their families in safety.
We are concerned about the recent BMJ Open article, “Explaining the negative effects of patient participation in patient safety,” and the very different message it conveys. Our concerns center on the authors’ misunderstanding of what true partnership means in health care and the inherent bias in the structure of the research. Additionally, there was no patient or partner involvement in the “design, conducting, reporting, or dissemination plans of the research.”
The questions in the “topic guide” were leading and reflected bias; therefore, they could only elicit negative views from respondents. The sample size of 8 professionals and 8 patients is small in establishing such strong conclusions.
A patient in labor having the responsibility for checking the accuracy of medications was not an appropriate example of patient participation in safety nor of an understanding of partnership. Authentic partnership would entail a discussion about patient safety as a team responsibility and a determination from the patient on how she wishes to participate on that team. Further, the article made no mention of care partners/family members and their important, additional, role in patient safety.
Over the years, the BMJ has published many articles that have furthered the understanding of and commitment to sound patient safety practices and partnerships with patients and families. Many readers remember the 9/18/99 theme issue, “Embracing Patient Partnership,” and its dramatic cover of the tango dancers. Unfortunately, this current article seems like an anomaly.
To Prof Forrest and the authors of the Chaudhary et al paper(1): Thank you for your response to our review(2) in which you highlight that there was a significant reduction in alcohol-related liver disease (ALD) discharges following the introduction of minimum unit pricing (MUP) at your unit. This is an important point to highlight as a misrepresentation of the Chaudhary et al study in our review.
In our review, we reported the outcome measure of mean weekly ALD discharges before and after MUP for 'All hospital episodes' which did not reach pre-defined significance (6.2 versus 5.2; p = 0.123) in the Chaudhary et al study, however the outcomes for 'individual patients' and those 'actively drinking' did indeed reach pre-defined significance and should have been included in our review. These outcomes from the Chaudhary et al study would certainly be consistent with the overall conclusion of our review, adding further support to the impact of MUP reducing alcohol-related hospital burden as you have highlighted.
We would also like to correct the reference to your study in the main text of our review which should read “Chaudhary et al” and not “Ferguson et al” (found under ‘Results’, subheading ‘Natural experiments’).
References
1. Chaudhary S, MacKey W, Duncan K, Forrest EH. Changes in Hospital Discharges with Alcohol-Related Liver Disease in a Gastroenterology and General Medical Unit Following the...
To Prof Forrest and the authors of the Chaudhary et al paper(1): Thank you for your response to our review(2) in which you highlight that there was a significant reduction in alcohol-related liver disease (ALD) discharges following the introduction of minimum unit pricing (MUP) at your unit. This is an important point to highlight as a misrepresentation of the Chaudhary et al study in our review.
In our review, we reported the outcome measure of mean weekly ALD discharges before and after MUP for 'All hospital episodes' which did not reach pre-defined significance (6.2 versus 5.2; p = 0.123) in the Chaudhary et al study, however the outcomes for 'individual patients' and those 'actively drinking' did indeed reach pre-defined significance and should have been included in our review. These outcomes from the Chaudhary et al study would certainly be consistent with the overall conclusion of our review, adding further support to the impact of MUP reducing alcohol-related hospital burden as you have highlighted.
We would also like to correct the reference to your study in the main text of our review which should read “Chaudhary et al” and not “Ferguson et al” (found under ‘Results’, subheading ‘Natural experiments’).
References
1. Chaudhary S, MacKey W, Duncan K, Forrest EH. Changes in Hospital Discharges with Alcohol-Related Liver Disease in a Gastroenterology and General Medical Unit Following the Introduction of Minimum Unit Pricing of Alcohol: The GRI Q4 Study. Alcohol and Alcoholism 2022; 57(4): 477–482.
2. Maharaj T, Angus C, Fitzgerald N, et al. Impact of minimum unit pricing on alcohol-related hospital outcomes: systematic review. BMJ Open 2023; 13: e065220. doi: 10.1136/bmjopen-2022-065220
I'm a 68 year old male with parox AF so am very interested in ablation data. I applaud the authors for their work and look forward to the results. One sentence in this paper confused me---" The benefits of ablation may not be fully realised among elderly patients." I wasn't sure what they meant by that. Elderly patients may be unable to appreciate the benefits? There may not be any benefits in elderly patients? Something else?
Again, very good work, thanks to the authors.
Declan Fox
Family physician
Dear Editor,
The article by Yang et al. (2022) is fundamentally flawed due to a number of serious methodological shortcomings. These deficits are of such crucial relevance that it is in our view highly doubtful whether the conclusions the authors draw from their research are valid.
1) Data extraction is not transparent and sometimes false:
We were not able to replicate any of the values included in the main analysis of pain (Figure 4). In at least one study, values were extracted from the wrong group. In two further studies, the given values are incompatible with the values reported in the study. In at least three studies, sample sizes were falsely extracted.
Specifically:
Only in one of the included studies (Bishop et al., 2016) the values given in Figure 4 (Mean, SD) were found (Table 6, Bishop et al., 2016). However, the values of the control group were extracted from the false group (see below). For all other included studies, the values (Mean, SD) given in Figure 4 were not found. We were not able to find a description of how the authors may have transformed the values to explain the disagreement. In some studies, the given values in Figure 4 are not only not replicable but are incompatible with the values reported in the studies:
o In Bishop et al. (2016), values were extracted from the false group. Values were taken from standard care group but Yang et al. stated in Table 1 to have used the placebo acupuncture group as control g...
Dear Editor,
The article by Yang et al. (2022) is fundamentally flawed due to a number of serious methodological shortcomings. These deficits are of such crucial relevance that it is in our view highly doubtful whether the conclusions the authors draw from their research are valid.
1) Data extraction is not transparent and sometimes false:
We were not able to replicate any of the values included in the main analysis of pain (Figure 4). In at least one study, values were extracted from the wrong group. In two further studies, the given values are incompatible with the values reported in the study. In at least three studies, sample sizes were falsely extracted.
Specifically:
Only in one of the included studies (Bishop et al., 2016) the values given in Figure 4 (Mean, SD) were found (Table 6, Bishop et al., 2016). However, the values of the control group were extracted from the false group (see below). For all other included studies, the values (Mean, SD) given in Figure 4 were not found. We were not able to find a description of how the authors may have transformed the values to explain the disagreement. In some studies, the given values in Figure 4 are not only not replicable but are incompatible with the values reported in the studies:
o In Bishop et al. (2016), values were extracted from the false group. Values were taken from standard care group but Yang et al. stated in Table 1 to have used the placebo acupuncture group as control group. The placebo acupuncture group actually had better pain scores than the experimental group. This is the opposite effect of what is used in Figure 4.
o Elden et al. (2005) reported morning and evening pain values post treatment in three groups. For all three groups and both measures (morning, evening), Elden et al. (2005) reported different medians. However, in Figure 4, equal means are given for experimental and control group for Elden et al. (2008) (which is a follow-up publication of the same study as Elden et al., 2005; see below).
o Lund et al. (2006) compared deep and superficial acupuncture. They did not report mean values but concluded that, regarding pain levels, "according to our study, there is not enough evidence of different treatment effects between the two stimulation modes of acupuncture". However, in Figure 4, the effect estimate presented for Lund et al. (2006) strongly favors the experimental group und the confidence interval does not include 0.
o In at least three studies, the extracted sample sizes were too large. Here, Yang et al. seemed to have used the number of participants that were included in the beginning of the study but failed to recognize that the analysis was done for a smaller number of patients. In the following, actual and falsely reported numbers are given for the groups Yang et al. presented in Table 1 (experimental group / control group): Bishop et al. (2016) reported 32 / 27, Yang et al. used 42 / 41; Ekdahl and Petersson (2010) reported 16 / 16, Yang et al. used 20 / 20; Elden et al. (2005) reported 107 / 108, Yang et al. used 130 / 125.
2) The same study is included twice:
Yang et al. included two publications of the same study (Elden et al., 2008; Elden et al., 2005) and presented them as two different studies in Table 1 and throughout the manuscript. Elden et al. (2005) reported pain endpoints whereas Elden et al. (2008) did not report values of pain. In contrast to that, in Figure 4, pain values are assigned to Elden et al. (2008).
3) The choices of the comparator group are not comprehensible:
Five of the nine included studies analyzed more than two groups (e.g. true acupuncture, placebo acupuncture, and standard care). Yang et al. did not give reasons for their choices of which group is used as control group. When three- or four-armed studies included both a placebo acupuncture group and a standard care group, Yang et al. sometimes chose the placebo acupuncture group as control (Bishop et al., 2016) and sometimes the standard care group (Jorge et al., 2019; Wang et al., 2009). One study (Ekdahl and Petersson, 2010) compared two acupuncture groups where the intervention was equal but began at different gestational weeks. It is not transparent why one of the groups was chosen as experimental group and the other one as control group.
3) Effects were pooled and interpreted as significant results with staggering heterogeneity and scarcity of data:
Despite the major heterogeneity observed, studies were pooled and effects were presented as statistically significant. This is contrary to the Cochrane recommendations for dealing with large heterogeneity (Cochrane Handbook Section 10.10.3 “Strategies for addressing heterogeneity” (https://training.cochrane.org/handbook/current/chapter-10#section-10-10-3): “1. Check again that the data are correct / 2. Do not do a meta-analysis”)
4) Choice between fixed-effect-model and random-effects-model was done in hindsight:
The authors stated “If p<0.1 or I**2 >50% we combined results using a random-effect model (29).” This is considered as bad practice, see, e.g. Borenstein et al. (2010) (https://doi.org/10.1002/jrsm.12): “In some circles, researchers tend to start with the fixed-effect model, and then switch to the random-effects model if there is a compelling reason to do so. Usually, this means that the test for heterogeneity across studies is statistically significant. This is a bad idea for many reasons.”
Furthermore, the cited reference (29) gives no justification for the applied approach.
In addition to the above points, some further issues came to our attention:
Figure 6 is falsely labelled. The left side of the forest plot should favor experimental.
The choice of the pain endpoint is not transparent: The included studies collected multiple different measures of VAS-pain. Two studies (Wedenberg et al., 2000; Elden et al., 2005) collected morning and evening values. One study (Kvorning et al., 2004) collected minimal and maximal pain. Yang et al. did not describe or explain which values they used.
In summary, due to its serious weaknesses in conduct, methods, and reporting, the article by Yang et al. does in our view not contribute to clarify the value of acupuncture for low back and/or pelvic pain during pregnancy but is misleading and thus does a disservice to physicians and patients.
Dear Editor,
The recent systematic review by Maharaj et al on the impact of minimum unit pricing on alcohol-related hospital outcomes is a welcome addition to the literature on this subject1. The mirroring of real-world experience of minimum pricing of alcohol with modelling studies provides yet further support for this public health measure.
As part of their review, the authors cite our study which assessed the impact of minimum pricing of alcohol specifically on alcohol-related liver disease hospital episodes2. In the review it is stated that our study showed ‘no change in ALD hospital discharge rate’ after the introduction of minimum pricing. This conclusion is reiterated in the discussion. However I fear this is a misrepresentation of our study. When we reviewed patients discharged from the specialist Gastroenterology wards at Glasgow Royal Infirmary before and after the introduction of minimum unit pricing, we did find that there was a significant reduction in alcohol-related liver disease discharges. What did not change was the proportion of those patients with specific complications of liver disease such as ascites, hepatic encephalopathy or alcoholic hepatitis. Neither was there any change in mortality. Whilst accepting the limitations of our study as raised in the discussion, these results indicate that minimum unit pricing did reduce the number of hospital episodes with alcohol-related liver disease. However for those fewer patients who did require ho...
Dear Editor,
The recent systematic review by Maharaj et al on the impact of minimum unit pricing on alcohol-related hospital outcomes is a welcome addition to the literature on this subject1. The mirroring of real-world experience of minimum pricing of alcohol with modelling studies provides yet further support for this public health measure.
As part of their review, the authors cite our study which assessed the impact of minimum pricing of alcohol specifically on alcohol-related liver disease hospital episodes2. In the review it is stated that our study showed ‘no change in ALD hospital discharge rate’ after the introduction of minimum pricing. This conclusion is reiterated in the discussion. However I fear this is a misrepresentation of our study. When we reviewed patients discharged from the specialist Gastroenterology wards at Glasgow Royal Infirmary before and after the introduction of minimum unit pricing, we did find that there was a significant reduction in alcohol-related liver disease discharges. What did not change was the proportion of those patients with specific complications of liver disease such as ascites, hepatic encephalopathy or alcoholic hepatitis. Neither was there any change in mortality. Whilst accepting the limitations of our study as raised in the discussion, these results indicate that minimum unit pricing did reduce the number of hospital episodes with alcohol-related liver disease. However for those fewer patients who did require hospitalisation, their outcomes and presentations were similar to hospital episodes prior to the introduction of minimum pricing.
Therefore our study is supportive of the conclusions of the systematic review rather than being ‘inconsistent’ with the other studies.
Prof Ewan Forrest
Consultant Hepatologist and Honorary Professor, Department of Gastroenterology, Glasgow Royal Infirmary and University of Glasgow.
References
1. Maharaj T, Angus C, Fitzgerald N, et al. Impact of minimum unit pricing on alcohol-related hospital outcomes: systematic review. BMJ Open 2023; 13: e065220. doi: 10.1136/bmjopen-2022-065220
2. Chaudhary S, MacKey W, Duncan K, Forrest EH. Changes in Hospital Discharges with Alcohol-Related Liver Disease in a Gastroenterology and General Medical Unit Following the Introduction of Minimum Unit Pricing of Alcohol: The GRI Q4 Study. Alcohol and Alcoholism 2022; 57(4): 477–482.
The question raised by Juan Ervriti and Colleagues (1) whether the obvious benefit of evolocumab is offset by a currently unknown risk is justified and of high clinical relevance. We know active ingredients that effectively lower the atherogenic lipopoproteins, but have an unfavorable benefit-risk ratio under the bottom line (2). Therefore, the raised concerns must be addressed.
The chosen methodology by Ervriti and Colleagues seems to me feasible, although not perfect. For a comprehensive reanalysis the raw data are required. Unfortunately they never received such data, although they have made many efforts to do so.
To my opinion, scientific misconduct – as intended by Sabatine et. al. (3) - is not the case with Evriti et al. but rather with the FOURIER authors and the study sponsor, who apparently never answered the questions that were put to them repeatedly and publicly (4).
The announcement by the FOURIER authors that they will respond to the accusations now promptly (3) is no longer sufficient. They are biased in a number of ways, but primarily because their scientific reputation is at stake. There is no other way to understand their rude reaction.
From my point of view, it is also highly irritating that neither EMA nor Health Canada seem to have scrutinized the case report forms (CRF) when they approved this new drug. It looks like they've never laid their hands on a FOURIER-CRF. If that is the case, then they trusted the investigators bl...
The question raised by Juan Ervriti and Colleagues (1) whether the obvious benefit of evolocumab is offset by a currently unknown risk is justified and of high clinical relevance. We know active ingredients that effectively lower the atherogenic lipopoproteins, but have an unfavorable benefit-risk ratio under the bottom line (2). Therefore, the raised concerns must be addressed.
The chosen methodology by Ervriti and Colleagues seems to me feasible, although not perfect. For a comprehensive reanalysis the raw data are required. Unfortunately they never received such data, although they have made many efforts to do so.
To my opinion, scientific misconduct – as intended by Sabatine et. al. (3) - is not the case with Evriti et al. but rather with the FOURIER authors and the study sponsor, who apparently never answered the questions that were put to them repeatedly and publicly (4).
The announcement by the FOURIER authors that they will respond to the accusations now promptly (3) is no longer sufficient. They are biased in a number of ways, but primarily because their scientific reputation is at stake. There is no other way to understand their rude reaction.
From my point of view, it is also highly irritating that neither EMA nor Health Canada seem to have scrutinized the case report forms (CRF) when they approved this new drug. It looks like they've never laid their hands on a FOURIER-CRF. If that is the case, then they trusted the investigators blindly and failed to do their job. This would disqualify theses institutions for a trusting reanalysis of the data.
Ultimately, only another independent reanalysis of the FOURIER raw data by a recognized independent institution should clarify the facts as soon as possible.
References:
1. Erviti J, Wright J, Bassett K, Ben-Eltriki M, Jauca C, Saiz LC, Leache L, Gutierrez-Valencia M and Perry TL. Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data. BMJ open. 2022;12:e060172.
2. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J, Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA. 2002;288(3):321.
3. Marc S. Sabatine, MD, MPH, Stephen D. Wiviott, MD, Anthony C. Keech, MD, Peter S. Sever, PhD, FRCP and Robert P. Giugliano, MD, SM. Letter to the Editor RE: "Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data". BMJ Open. 2022;12:3060172.
Published on: 11 January 2023
4. Erviti J, et al. Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data. BMJ Open 2022;12:e060172. doi: 10.1136/bmjopen-2021-060172
Most of the studies in the literature propagate that the incidence of frozen shoulder is higher in people with diabetes. According to the American Diabetic Association, the average age of people with frozen shoulder is 52 years. Among people 40 and over, the condition affects 2 to 4 percent of the general population and up to 25 percent of people with diabetes. But no definite pathophysiological mechanism to support the data has been postulated.
Several questions remain unanswered.
Do people with diabetes experience worse outcomes from frozen shoulders than those without diabetes?
Does uncontrolled diabetes have a higher risk or severity of disease?
Do people with diabetes develop frozen shoulder at an earlier age than non-diabetics?
Does Diabetes delay the recovery from a frozen shoulder?
Answers to the above questions may be yes in several studies in scientific literature. However, the certainty in evidence in most such studies is moderate to low. In our experience of more than 30 years, we also don't find any such correlation.
Frozen shoulder undoubtedly has a higher incidence among patients with Myocardial Infarction, but the incidence, duration of disability, severity of symptoms, and age of onset are not remarkably different from the general population.
Most of the studies in the literature propagate that the incidence of frozen shoulder is higher in people with diabetes. According to the American Diabetic Association, the average age of people with frozen shoulder is 52 years. Among people 40 and over, the condition affects 2 to 4 percent of the general population and up to 25 percent of people with diabetes. But no definite pathophysiological mechanism to support the data has been postulated.
Several questions remain unanswered.
Do people with diabetes experience worse outcomes from frozen shoulders than those without diabetes?
Does uncontrolled diabetes have a higher risk or severity of disease?
Do people with diabetes develop frozen shoulder at an earlier age than non-diabetics?
Does Diabetes delay the recovery from a frozen shoulder?
Answers to the above questions may be yes in several studies in scientific literature. However, the certainty in evidence in most such studies is moderate to low. In our experience of more than 30 years, we also don't find any such correlation.
Frozen shoulder undoubtedly has a higher incidence among patients with Myocardial Infarction, but the incidence, duration of disability, severity of symptoms, and age of onset are not remarkably different from the general population.
hi-
This seems like a really interesting, and potentially very important study. I'm concerned though that you are not listing as a primary objective improving the CD4/CD8 ratio. While a home run could be decreasing the reservoir, whether you decrease the reservoir or not, you might improve the ratio and this by itself could alter future cancer susceptibility (anal, colon, lung) and may avoid zoster, or tb acquisition (if in India for example) and could improve immune response to vaccines. I'm not saying all of this naturally follows, but if you beat down CMV it is at least as likely that you make the immune system less distracted then it is you decrease the reservoir. Thanks for getting this together though and I look forward to the outcomes. Rob Striker UW Madison
This research by Mooghali and team provide valuable and disturbing data on the problem of financial conflicts of interest (COI) in clinical practice guidelines.(1) Failure of authors and committee members to accurately disclose potential COI raises concerns about lack of transparency in the process, bias in the resulting guidelines, and ultimately harm to patients.
The pioneering work in this area was done by the American Academy of Family Physicians, which published in 1994 the first international call for an explicit declaration of conflicts of interest in the development of clinical practice guidelines.(2) This has been followed by policies on COI by other groups of primary care physicians in the US(3,4), the UK(5,6) and Canada(7,8).
Primary care physicians have been early champions of evidence-based medicine and explicit clinical practice guidelines. They are also the clinicians working at the point of care, partnering with patients to make shared decisions. The best in care requires the best guidance based on the best evidence. Therefore, potential COIs must be fully disclosed and critically managed by all involved in producing, disseminating, and implementing clinical practice guidelines.
REFERENCES
1.Mooghali M, Glick L, Ramachandran R, et al. Financial conflicts of interest among US physician authors of 2020 clinical practice guidelines: a cross- sectional study. BMJ Open 2023;13:e069115. doi:10.1136/ bmjopen-2022-069115
2. Phillips...
This research by Mooghali and team provide valuable and disturbing data on the problem of financial conflicts of interest (COI) in clinical practice guidelines.(1) Failure of authors and committee members to accurately disclose potential COI raises concerns about lack of transparency in the process, bias in the resulting guidelines, and ultimately harm to patients.
The pioneering work in this area was done by the American Academy of Family Physicians, which published in 1994 the first international call for an explicit declaration of conflicts of interest in the development of clinical practice guidelines.(2) This has been followed by policies on COI by other groups of primary care physicians in the US(3,4), the UK(5,6) and Canada(7,8).
Primary care physicians have been early champions of evidence-based medicine and explicit clinical practice guidelines. They are also the clinicians working at the point of care, partnering with patients to make shared decisions. The best in care requires the best guidance based on the best evidence. Therefore, potential COIs must be fully disclosed and critically managed by all involved in producing, disseminating, and implementing clinical practice guidelines.
REFERENCES
1.Mooghali M, Glick L, Ramachandran R, et al. Financial conflicts of interest among US physician authors of 2020 clinical practice guidelines: a cross- sectional study. BMJ Open 2023;13:e069115. doi:10.1136/ bmjopen-2022-069115
2. Phillips WR. Clinical policies: making conflicts of interest explicit. JAMA 1994; 272(19):1479. doi:10.1001/jama.1994.03520190021010
3. Schünemann HJ, Al-Ansary LA, Forland F, Kersten S, Komulainen J, Kopp IB, et al. Guidelines International Network: Principles for disclosure of interests and management of conflicts in guidelines. Ann Intern Med. 2015;163:548-553. doi:10.7326/M14-1885Ann Int Med 2016
4. Phillips WR. American Academy of Family Physicians pioneered full disclosure in clinical
guidelines. (eLetter 7 January) Ann Intern Med. 2015;163:548-553. doi:10.7326/M14-1885Ann Int Med 2016
5. Moore, Ainsley, et al. Financial conflict of interest among clinical practice guideline-producing organisations. British J General Practice 70.700 (2020): 530-531. Web. 30 Oct. 2020. doi: 10.3399/bjgp20X713177
6. Phillips WR. General practice leads in transparency of clinical guidelines. (eLetter 30 OPct 2020) British J General Practice 70.700 (2020): 530-531. https://bjgp.org/content/70/700/530/tab-e-letters
7. Allan GM, Cauchon M, Katz A, Kuling PJ, Moore S, Scrimshaw C, Stalker P. Endorsement of clinical practice guidelines. Criteria from the College of Family Physicians of Canada. Can Fam Physician 2021;67:499-502. doi: 10.46747/cfp.6707499
“Re: Letter to the Editor RE: "Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data". BMJ Open. 2022;12:3060172.”
Dear editor,
In their letter to the editor, Sabatine et al. comment on the restoration study of the FOURIER trial by Erviti et al.1 We agree that some discrepancies in locally established and adjudicated causes of deaths can be expected as part of the adjudication process. However, the trial investigators do not explain why there were so many discrepancies in FOURIER: 41.4% of locally established causes of deaths were not confirmed after central adjudication by the clinical-events committee. The site investigators attributed 358 of 870 deaths (41.1%) to a cardiovascular cause, and the committee 491 (56.4%): a difference of +15.3%. The high rate of discrepancies is surprising because both groups had all detailed clinical information at their disposal as well as the study protocol with definitions for cardiovascular events, and were blinded to the treatment status of the participants. Moreover, several previous studies have shown much lower discrepancy rates in other clinical outcomes trials that tested a drug for the prevention of cardiovascular disease. One recent study concerned the COMPASS trial among 27,395 patients that received rivaroxaban with aspirin, rivaroxaban monotherapy or aspirin monotherapy.2 There were 552 investiga...
“Re: Letter to the Editor RE: "Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data". BMJ Open. 2022;12:3060172.”
Dear editor,
In their letter to the editor, Sabatine et al. comment on the restoration study of the FOURIER trial by Erviti et al.1 We agree that some discrepancies in locally established and adjudicated causes of deaths can be expected as part of the adjudication process. However, the trial investigators do not explain why there were so many discrepancies in FOURIER: 41.4% of locally established causes of deaths were not confirmed after central adjudication by the clinical-events committee. The site investigators attributed 358 of 870 deaths (41.1%) to a cardiovascular cause, and the committee 491 (56.4%): a difference of +15.3%. The high rate of discrepancies is surprising because both groups had all detailed clinical information at their disposal as well as the study protocol with definitions for cardiovascular events, and were blinded to the treatment status of the participants. Moreover, several previous studies have shown much lower discrepancy rates in other clinical outcomes trials that tested a drug for the prevention of cardiovascular disease. One recent study concerned the COMPASS trial among 27,395 patients that received rivaroxaban with aspirin, rivaroxaban monotherapy or aspirin monotherapy.2 There were 552 investigator-reported (52.2%) and 558 (52.8%) adjudicated cardiovascular deaths among 1057 deaths (difference +0.6%).
A second study investigated the events of the REDUCE-IT trial.3 This trial assessed the effects of icosapent ethyl versus placebo in 8,179 patients with elevated triglycerides that used a statin. The number of investigator-reported and adjudicated cardiovascular deaths was the same: 387 of 592 (65.4%) deaths (difference 0.0%).
A third study analysed the STABILITY trial that compared darapladib to placebo in 15,828 patients with stable coronary disease.4 There were 667 (62.7%) investigator-reported and 638 (60.0%) adjudicated cardiovascular deaths of 1064 deaths (difference -2.7%).
A fourth paper concerned the SOCRATES trial that evaluated the effects of ticagrelor versus aspirin in 13,199 patients after stroke or transient ischemic attack.5 There were 87 (58.8%) investigator-reported and 93 (62.8%) adjudicated cardiovascular deaths among 148 all-cause deaths (difference +4.0%).
The four cited studies demonstrate a high concordance in the number of cardiovascular deaths reported by local investigators and adjudicated by central adjudication committees. Similar results were found for the primary composite outcomes of the investigated trials, which included non-fatal myocardial infarcts and strokes. Hence, the question remains why there was such a large discrepancy in investigator-reported and adjudicated cardiovascular deaths in FOURIER, and whether the non-fatal cardiovascular events show the same discrepancy. If Sabatine et al. have “complete confidence in the adjudicated events”, then why not share the raw data for independent restoration and reanalysis?
F.H. van Bruggen, H. J. Luijendijk
Department of General Practice, UMCG, PO Box 196, 9700 AD Groningen, The Netherlands. E-mail: h.j.luijendijk@umcg.nl
1. Erviti J, Wright J, Bassett K, et al. Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data. BMJ Open. 2022;12(12):e060172. doi:10.1136/bmjopen-2021-060172
2. Gaba P, Bhatt DL, Dagenais GR et al. Comparison of Investigator-Reported vs Centrally Adjudicated Major Adverse Cardiac Events: A Secondary Analysis of the COMPASS Trial. JAMA Netw Open. 2022;5(11):e224. doi:10.1001/jamanetworkopen.2022.43201
3. Gaba P, Bhatt DL, Giugliano RP, et al. Comparative Reductions in Investigator-Reported and Adjudicated Ischemic Events in REDUCE-IT. J Am Coll Cardiol. 2021. doi:10.1016/j.jacc.2021.08.009
4. Held C, White HD, Stewart RAH, et al. Characterization of cardiovascular clinical events and impact of event adjudication on the treatment effect of darapladib versus placebo in patients with stable coronary heart disease: Insights from the STABILITY trial. Am Heart J. 2019. doi:10.1016/j.ahj.2018.10.010
5. Easton JD, Denison H, Evans SR, et al. Estimated treatment effect of ticagrelor versus aspirin by investigator-assessed events compared with judgement by an independent event adjudication committee in the SOCRATES trial. Int J Stroke. 2019. doi:10.1177/1747493019851282
For more than 30 years, our organization, the Institute for Patient- and Family-Centered Care (IPFCC) has been a leader in helping other organizations develop and sustain effective partnerships with patients and families to improve the quality, safety, and the experience of care. During that same time, the patient safety movement has affirmed the important roles of patients and their families in safety.
We are concerned about the recent BMJ Open article, “Explaining the negative effects of patient participation in patient safety,” and the very different message it conveys. Our concerns center on the authors’ misunderstanding of what true partnership means in health care and the inherent bias in the structure of the research. Additionally, there was no patient or partner involvement in the “design, conducting, reporting, or dissemination plans of the research.”
The questions in the “topic guide” were leading and reflected bias; therefore, they could only elicit negative views from respondents. The sample size of 8 professionals and 8 patients is small in establishing such strong conclusions.
A patient in labor having the responsibility for checking the accuracy of medications was not an appropriate example of patient participation in safety nor of an understanding of partnership. Authentic partnership would entail a discussion about patient safety as a team responsibility and a determination from the patient on how she wishes to participate on that...
Show MoreDear Editor,
To Prof Forrest and the authors of the Chaudhary et al paper(1): Thank you for your response to our review(2) in which you highlight that there was a significant reduction in alcohol-related liver disease (ALD) discharges following the introduction of minimum unit pricing (MUP) at your unit. This is an important point to highlight as a misrepresentation of the Chaudhary et al study in our review.
In our review, we reported the outcome measure of mean weekly ALD discharges before and after MUP for 'All hospital episodes' which did not reach pre-defined significance (6.2 versus 5.2; p = 0.123) in the Chaudhary et al study, however the outcomes for 'individual patients' and those 'actively drinking' did indeed reach pre-defined significance and should have been included in our review. These outcomes from the Chaudhary et al study would certainly be consistent with the overall conclusion of our review, adding further support to the impact of MUP reducing alcohol-related hospital burden as you have highlighted.
We would also like to correct the reference to your study in the main text of our review which should read “Chaudhary et al” and not “Ferguson et al” (found under ‘Results’, subheading ‘Natural experiments’).
References
Show More1. Chaudhary S, MacKey W, Duncan K, Forrest EH. Changes in Hospital Discharges with Alcohol-Related Liver Disease in a Gastroenterology and General Medical Unit Following the...
I'm a 68 year old male with parox AF so am very interested in ablation data. I applaud the authors for their work and look forward to the results. One sentence in this paper confused me---" The benefits of ablation may not be fully realised among elderly patients." I wasn't sure what they meant by that. Elderly patients may be unable to appreciate the benefits? There may not be any benefits in elderly patients? Something else?
Again, very good work, thanks to the authors.
Declan Fox
Family physician
Dear Editor,
The article by Yang et al. (2022) is fundamentally flawed due to a number of serious methodological shortcomings. These deficits are of such crucial relevance that it is in our view highly doubtful whether the conclusions the authors draw from their research are valid.
1) Data extraction is not transparent and sometimes false:
Show MoreWe were not able to replicate any of the values included in the main analysis of pain (Figure 4). In at least one study, values were extracted from the wrong group. In two further studies, the given values are incompatible with the values reported in the study. In at least three studies, sample sizes were falsely extracted.
Specifically:
Only in one of the included studies (Bishop et al., 2016) the values given in Figure 4 (Mean, SD) were found (Table 6, Bishop et al., 2016). However, the values of the control group were extracted from the false group (see below). For all other included studies, the values (Mean, SD) given in Figure 4 were not found. We were not able to find a description of how the authors may have transformed the values to explain the disagreement. In some studies, the given values in Figure 4 are not only not replicable but are incompatible with the values reported in the studies:
o In Bishop et al. (2016), values were extracted from the false group. Values were taken from standard care group but Yang et al. stated in Table 1 to have used the placebo acupuncture group as control g...
Dear Editor,
Show MoreThe recent systematic review by Maharaj et al on the impact of minimum unit pricing on alcohol-related hospital outcomes is a welcome addition to the literature on this subject1. The mirroring of real-world experience of minimum pricing of alcohol with modelling studies provides yet further support for this public health measure.
As part of their review, the authors cite our study which assessed the impact of minimum pricing of alcohol specifically on alcohol-related liver disease hospital episodes2. In the review it is stated that our study showed ‘no change in ALD hospital discharge rate’ after the introduction of minimum pricing. This conclusion is reiterated in the discussion. However I fear this is a misrepresentation of our study. When we reviewed patients discharged from the specialist Gastroenterology wards at Glasgow Royal Infirmary before and after the introduction of minimum unit pricing, we did find that there was a significant reduction in alcohol-related liver disease discharges. What did not change was the proportion of those patients with specific complications of liver disease such as ascites, hepatic encephalopathy or alcoholic hepatitis. Neither was there any change in mortality. Whilst accepting the limitations of our study as raised in the discussion, these results indicate that minimum unit pricing did reduce the number of hospital episodes with alcohol-related liver disease. However for those fewer patients who did require ho...
The question raised by Juan Ervriti and Colleagues (1) whether the obvious benefit of evolocumab is offset by a currently unknown risk is justified and of high clinical relevance. We know active ingredients that effectively lower the atherogenic lipopoproteins, but have an unfavorable benefit-risk ratio under the bottom line (2). Therefore, the raised concerns must be addressed.
Show MoreThe chosen methodology by Ervriti and Colleagues seems to me feasible, although not perfect. For a comprehensive reanalysis the raw data are required. Unfortunately they never received such data, although they have made many efforts to do so.
To my opinion, scientific misconduct – as intended by Sabatine et. al. (3) - is not the case with Evriti et al. but rather with the FOURIER authors and the study sponsor, who apparently never answered the questions that were put to them repeatedly and publicly (4).
The announcement by the FOURIER authors that they will respond to the accusations now promptly (3) is no longer sufficient. They are biased in a number of ways, but primarily because their scientific reputation is at stake. There is no other way to understand their rude reaction.
From my point of view, it is also highly irritating that neither EMA nor Health Canada seem to have scrutinized the case report forms (CRF) when they approved this new drug. It looks like they've never laid their hands on a FOURIER-CRF. If that is the case, then they trusted the investigators bl...
Most of the studies in the literature propagate that the incidence of frozen shoulder is higher in people with diabetes. According to the American Diabetic Association, the average age of people with frozen shoulder is 52 years. Among people 40 and over, the condition affects 2 to 4 percent of the general population and up to 25 percent of people with diabetes. But no definite pathophysiological mechanism to support the data has been postulated.
Several questions remain unanswered.
Do people with diabetes experience worse outcomes from frozen shoulders than those without diabetes?
Does uncontrolled diabetes have a higher risk or severity of disease?
Do people with diabetes develop frozen shoulder at an earlier age than non-diabetics?
Does Diabetes delay the recovery from a frozen shoulder?
Answers to the above questions may be yes in several studies in scientific literature. However, the certainty in evidence in most such studies is moderate to low. In our experience of more than 30 years, we also don't find any such correlation.
Frozen shoulder undoubtedly has a higher incidence among patients with Myocardial Infarction, but the incidence, duration of disability, severity of symptoms, and age of onset are not remarkably different from the general population.
References: 1.https://www.sciencedirect.com/science/article/pii/S259010952100051...
Show Morehi-
This seems like a really interesting, and potentially very important study. I'm concerned though that you are not listing as a primary objective improving the CD4/CD8 ratio. While a home run could be decreasing the reservoir, whether you decrease the reservoir or not, you might improve the ratio and this by itself could alter future cancer susceptibility (anal, colon, lung) and may avoid zoster, or tb acquisition (if in India for example) and could improve immune response to vaccines. I'm not saying all of this naturally follows, but if you beat down CMV it is at least as likely that you make the immune system less distracted then it is you decrease the reservoir. Thanks for getting this together though and I look forward to the outcomes. Rob Striker UW Madison
This research by Mooghali and team provide valuable and disturbing data on the problem of financial conflicts of interest (COI) in clinical practice guidelines.(1) Failure of authors and committee members to accurately disclose potential COI raises concerns about lack of transparency in the process, bias in the resulting guidelines, and ultimately harm to patients.
The pioneering work in this area was done by the American Academy of Family Physicians, which published in 1994 the first international call for an explicit declaration of conflicts of interest in the development of clinical practice guidelines.(2) This has been followed by policies on COI by other groups of primary care physicians in the US(3,4), the UK(5,6) and Canada(7,8).
Primary care physicians have been early champions of evidence-based medicine and explicit clinical practice guidelines. They are also the clinicians working at the point of care, partnering with patients to make shared decisions. The best in care requires the best guidance based on the best evidence. Therefore, potential COIs must be fully disclosed and critically managed by all involved in producing, disseminating, and implementing clinical practice guidelines.
Show MoreREFERENCES
1.Mooghali M, Glick L, Ramachandran R, et al. Financial conflicts of interest among US physician authors of 2020 clinical practice guidelines: a cross- sectional study. BMJ Open 2023;13:e069115. doi:10.1136/ bmjopen-2022-069115
2. Phillips...
“Re: Letter to the Editor RE: "Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data". BMJ Open. 2022;12:3060172.”
Dear editor,
Show MoreIn their letter to the editor, Sabatine et al. comment on the restoration study of the FOURIER trial by Erviti et al.1 We agree that some discrepancies in locally established and adjudicated causes of deaths can be expected as part of the adjudication process. However, the trial investigators do not explain why there were so many discrepancies in FOURIER: 41.4% of locally established causes of deaths were not confirmed after central adjudication by the clinical-events committee. The site investigators attributed 358 of 870 deaths (41.1%) to a cardiovascular cause, and the committee 491 (56.4%): a difference of +15.3%. The high rate of discrepancies is surprising because both groups had all detailed clinical information at their disposal as well as the study protocol with definitions for cardiovascular events, and were blinded to the treatment status of the participants. Moreover, several previous studies have shown much lower discrepancy rates in other clinical outcomes trials that tested a drug for the prevention of cardiovascular disease. One recent study concerned the COMPASS trial among 27,395 patients that received rivaroxaban with aspirin, rivaroxaban monotherapy or aspirin monotherapy.2 There were 552 investiga...
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