Altschul et al. conducted a prospective study to investigate the association between blood pressure (BP) and cognitive functions across the eighth decade (1). Women with higher early-life cognitive function had lower BP during the eighth decade. In addition, prescribed antihypertensive medication was closely associated with lower BP, but antihypertensive medication had no effect on better cognitive function. Regarding no relationship between BP and cognitive decline, I have some concerns.
First, Ou et al. conducted a meta-analysis regarding the association between BP and cognitive impairment/dementia in prospective studies (2). The significant relationship of BP with cognitive impairment/dementia was observed in different BP variables, which were classified into midlife and late-life periods. In addition, prescribed antihypertensive medications exhibited a 21% reduction in dementia risk, which was different from data by Altschul et al. I suspect that long-term follow-up might change the relationship between BP and cognitive functions. Long survivors’ effect on BP and cognitive functions should be specified by further study.
Second, visit-to-visit variability in blood pressure was a significant predictor of subsequent cognitive decline in old subjects (3,4). But the association between BP variability and cognitive impairment was not mediated by BP lowering medication (5). As BP variables such as high systolic BP, low diastolic BP, excessive BP variability, and...
Altschul et al. conducted a prospective study to investigate the association between blood pressure (BP) and cognitive functions across the eighth decade (1). Women with higher early-life cognitive function had lower BP during the eighth decade. In addition, prescribed antihypertensive medication was closely associated with lower BP, but antihypertensive medication had no effect on better cognitive function. Regarding no relationship between BP and cognitive decline, I have some concerns.
First, Ou et al. conducted a meta-analysis regarding the association between BP and cognitive impairment/dementia in prospective studies (2). The significant relationship of BP with cognitive impairment/dementia was observed in different BP variables, which were classified into midlife and late-life periods. In addition, prescribed antihypertensive medications exhibited a 21% reduction in dementia risk, which was different from data by Altschul et al. I suspect that long-term follow-up might change the relationship between BP and cognitive functions. Long survivors’ effect on BP and cognitive functions should be specified by further study.
Second, visit-to-visit variability in blood pressure was a significant predictor of subsequent cognitive decline in old subjects (3,4). But the association between BP variability and cognitive impairment was not mediated by BP lowering medication (5). As BP variables such as high systolic BP, low diastolic BP, excessive BP variability, and orthostatic hypotension would interact with each other for increased dementia risk in later life (1), comprehensive analyses are needed to understand the effect of BP variables on subsequent cognitive decline.
Finally, Rajan et al. reported a U-shaped relationship between BP and Alzheimer disease (AD) (6), which was in agreement with data by Ou et al (2). These study present that non-linear relationships between BP and subsequent cognitive impairment/dementia might be existed.
References
1. Altschul D, Starr J, Deary I. Blood pressure and cognitive function across the eighth decade: a prospective study of the Lothian Birth Cohort of 1936. BMJ Open. 2020;10(7):e033990. doi:10.1136/bmjopen-2019-033990
2. Ou YN, Tan CC, Shen XN, et al. Blood pressure and risks of cognitive impairment and dementia: A systematic review and meta-analysis of 209 prospective studies. Hypertension. 2020;76:217-225. doi: 10.1161/HYPERTENSIONAHA.120.14993
3. Sabayan B, Wijsman LW, Foster-Dingley JC, et al. Association of visit-to-visit variability in blood pressure with cognitive function in old age: prospective cohort study. BMJ. 2013;347:f4600. doi: 10.1136/bmj.f4600
4. Qin B, Viera AJ, Muntner P. Visit-to-visit variability in blood pressure is related to late-life cognitive decline. Hypertension. 2016;68:106-113. doi: 10.1161/HYPERTENSIONAHA.116.07494
5. Wijsman LW, de Craen AJ, Muller M. Blood pressure lowering medication, visit-to-visit blood pressure variability, and cognitive function in old age. Am J Hypertens. 2016;29:311-318. doi: 10.1093/ajh/hpv101
6. Rajan KB, Barnes LL, Wilson RS, Weuve J, McAninch EA, Evans DA. Blood pressure and risk of incident Alzheimer's disease dementia by antihypertensive medications and APOE ε4 allele. Ann Neurol. 2018;83(5):935-944. doi:10.1002/ana.25228
We read with interest the paper entitled “Efficacy and safety of the pulsed electromagnetic field in osteoarthritis: a meta-analysis”.1 This paper concluded that “PEMF could alleviate pain and improve physical function for patients with knee and hand [osteoarthritis] OA, but not for patients with cervical [osteoarthritis] OA.” We have a few concerns with their conclusion.
The first concern is that the review reports very large effect sizes for some trials,2-5 but does not alert the reader to how atypical these results are. For example, Figure 3 of the manuscript1 contains three examples of effect sizes of ~3 and 4 standardised mean difference (SMD). Effect sizes this large are usually a red flag that something is amiss, either with the results of the review or the original trial. Unfortunately, both problems are present.
The review reported a SMD for the Nelson trial5 of -3.72; but this a mistake. The authors have confused the standard deviation (SD) with the standard error (SE) and when their error is corrected the true effect size is -0.74 [95% confidence interval (CI) -1.44 to -0.04] compared with -3.72 [95% CI -4.88 to -2.56] reported in the review. The correction also changes the pooled effect to -0.33 [-0.70 to 0.04] and would support the conclusion that the treatment is not effective for knee OA.
The other two large effect sizes are driven by outcomes in the treatment group and no change in the control group.2,3 For...
We read with interest the paper entitled “Efficacy and safety of the pulsed electromagnetic field in osteoarthritis: a meta-analysis”.1 This paper concluded that “PEMF could alleviate pain and improve physical function for patients with knee and hand [osteoarthritis] OA, but not for patients with cervical [osteoarthritis] OA.” We have a few concerns with their conclusion.
The first concern is that the review reports very large effect sizes for some trials,2-5 but does not alert the reader to how atypical these results are. For example, Figure 3 of the manuscript1 contains three examples of effect sizes of ~3 and 4 standardised mean difference (SMD). Effect sizes this large are usually a red flag that something is amiss, either with the results of the review or the original trial. Unfortunately, both problems are present.
The review reported a SMD for the Nelson trial5 of -3.72; but this a mistake. The authors have confused the standard deviation (SD) with the standard error (SE) and when their error is corrected the true effect size is -0.74 [95% confidence interval (CI) -1.44 to -0.04] compared with -3.72 [95% CI -4.88 to -2.56] reported in the review. The correction also changes the pooled effect to -0.33 [-0.70 to 0.04] and would support the conclusion that the treatment is not effective for knee OA.
The other two large effect sizes are driven by outcomes in the treatment group and no change in the control group.2,3 For example, in the trial by Kanat et al of hand OA,3 the group mean pain score in the active PEMF group was zero at 1-month follow-up; meaning that all 25 participants completely recovered. In contrast, in the sham group, pain did not change at all. These findings are quite unlike what normally happens in trials and clinical care. For a chronic episodic condition like OA, normally there is some improvement in the placebo group due to natural history, effects of testing, and the placebo (Hawthorne)6 effect. Typically, effective treatments have small or moderate effects; but not everyone is essentially “cured”. While these unusual results are not the fault of the review authors, there is a responsibility to alert readers to how unusual these results are.
Our final concern is that a Grading of Recommendations Assessment, Development, and Evaluation (GRADE) rating was not provided, which would have been useful to communicate to readers how confident they should be in the pooled estimate and whether further research is warranted.
We believe that this review provides a great example of the need to reflect upon large effect sizes; and to avoid simply publishing them without comment. Sometimes the problem is simply an error, and readily fixed. On other occasions there is something atypical about the trial and the reviewer is left with the challenge of what to do. At the least it would be helpful to communicate the issue to the readers. Another option may be to undertake a sensitivity analysis to see if the conclusion would change if the trial was removed. We understand that these are challenging issues, but nonetheless it is important to promote discourse in evidence-based medicine.
References
1. Wu Z, Ding X, Lei G, et al. Efficacy and safety of the pulsed electromagnetic field in osteoarthritis: a meta-analysis. BMJ Open. 2018;8(12):e022879.
2. Sutbeyaz ST, Sezer N, Koseoglu BF. The effect of pulsed electromagnetic fields in the treatment of cervical osteoarthritis: a randomized, double-blind, sham-controlled trial. Rheumatology international. 2006;26(4):320-24.
3. Kanat E, Alp A, Yurtkuran M. Magnetotherapy in hand osteoarthritis: A pilot trial. Complementary Therapies in Medicine. 2013;21(6):603-08.
4. Bagnato GL, Miceli G, Marino N, et al. Pulsed electromagnetic fields in knee osteoarthritis: a double blind, placebo-controlled, randomized clinical trial. Rheumatology. 2015;55(4):755-62.
5. Nelson FR, Zvirbulis R, Pilla AA. Non-invasive electromagnetic field therapy produces rapid and substantial pain reduction in early knee osteoarthritis: a randomized double-blind pilot study. Rheumatology International. 2013;33(8):2169-73.
6. McCambridge J, Witton J, Elbourne DR. Systematic review of the Hawthorne effect: new concepts are needed to study research participation effects. J Clin Epidemiol 2014;67(3):267-77.
Address correspondence to:
Dr Christina Abdel Shaheed
Institute for Musculoskeletal Health
P.O. Box M179, Missenden Road
Camperdown NSW 2050 Australia
Phone: +61 2 8627 6256
Fax: +61 2 8627 6262
Email: Christina.abdelshaheed@sydney.edu.au
We would like to thank RJ Aitken for presenting his basic scientist view on our clinical trial.
His first comment addresses the fact that we include “idiopathic infertility patients irrespective of their redox status “. He suggests that we should only include patients with proven oxidative stress. We would like to respond that, of course, we would prefer to follow his advice, on the condition that validated test are available to differentiate between men that do suffer (constantly) from oxidative stress and those that do not, or that are even at risk for reductive stress. If we could all agree on the reliability of such tests, then it would certainly be worthwhile to try and get additional funding for pre- and post-therapy testing in (a subset of) our patients, then analyze them separately according to their redox status. Such an addition might provide a more solid basis for the antioxidant therapy. However, sperm DNA fragmentation tests are very costly and there is as yet no international consensus on which sperm DNA fragmentation test should be used as becomes obviously clear when reading the extensive review of the literature composed by Agarwal et al and the extensive discussion it awakened with more than 50 commentary letters published.(1,2) As to the danger of causing reductive stress, we think this is limited, as Impryl does not contain direct and strong scavenging antioxidants such as vitamin C and E, but rather focuses on the homocysteine pathway and the 1...
We would like to thank RJ Aitken for presenting his basic scientist view on our clinical trial.
His first comment addresses the fact that we include “idiopathic infertility patients irrespective of their redox status “. He suggests that we should only include patients with proven oxidative stress. We would like to respond that, of course, we would prefer to follow his advice, on the condition that validated test are available to differentiate between men that do suffer (constantly) from oxidative stress and those that do not, or that are even at risk for reductive stress. If we could all agree on the reliability of such tests, then it would certainly be worthwhile to try and get additional funding for pre- and post-therapy testing in (a subset of) our patients, then analyze them separately according to their redox status. Such an addition might provide a more solid basis for the antioxidant therapy. However, sperm DNA fragmentation tests are very costly and there is as yet no international consensus on which sperm DNA fragmentation test should be used as becomes obviously clear when reading the extensive review of the literature composed by Agarwal et al and the extensive discussion it awakened with more than 50 commentary letters published.(1,2) As to the danger of causing reductive stress, we think this is limited, as Impryl does not contain direct and strong scavenging antioxidants such as vitamin C and E, but rather focuses on the homocysteine pathway and the 1 carbon cycle.(3,4)
His second comment addresses the fact that our primary outcome measure is pregnancy and that we do not search for increased mutational load or cancer-causing mutations in the offspring. Of course, we agree that preventing such mutations might be another important benefit of antioxidant therapy. However, for now we will adhere to pregnancy as our “real world situation” outcome measurement. Epigenetic changes in offspring are not within the scope of the SUMMER study.
We thank RJ Aitkin for presenting these critical notes and also for his positive comments. We surely hope that basic scientists will someday provide us with the technologies that reliably measure oxidative stress and more insight into the occurrence of cancer-causing mutations in offspring.
References
1. Agarwal A, Majzoub A, Esteves SC, Ko E, Ramasamy R, Zini A. Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios. Transl Androl Urol. 2016;5(6):935-950. doi:10.21037/tau.2016.10.03
2. Ward WS. Eight tests for sperm DNA fragmentation and their roles in the clinic. Transl Androl Urol. 2017;6(Suppl 4):S468-S470. doi:10.21037/tau.2017.03.78
3. Mohammadi, P., Hassani‐Bafrani, H., Tavalaee, M., Dattilo, M. and Nasr‐Esfahani, M.H. (2018), One‐carbon cycle support rescues sperm damage in experimentally induced varicocoele in rats. BJU Int, 122: 480-489. doi:10.1111/bju.14385
4. Gallo, A., Menezo, Y., Dale, B. et al. Metabolic enhancers supporting 1-carbon cycle affect sperm functionality: an in vitro comparative study. Sci Rep 8, 11769 (2018). https://doi.org/10.1038/s41598-018-30066-9
Cloth masks, while comforting to some, should not be implied to provide anything but marginal (at best) protection to this "epidemic". When referring to virus particles that can spread via droplets it is fairly apparent that cloth masks do little to nothing for protection (except piece of mine)...and sorry, but 3ish% is not even a nominal value, its a toss value when referring to health.
Take a covid 19 positive patient, have them where a cloth mask and exhale sharply, sneeze, or cough in front of a mirror....watch what happens. I understand this is an overly simplified example, but it gets the point across.
As a last ditch effort with nothing else? Sure, but as a primary line of active defense for at risk individuals? Not even close. These individuals should be protected, away from the "herd" community.
These look wonderful!
I wonder, though, if the filter placements could be moved or they could be reshaped to allow the wearer's mouth to show better for the hearing impaired.
Hughes-McCormack et al. investigated live birth, death rates and childhood hospitalisations in people with Down syndrome (1). Regarding childhood hospitalisations, adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of people with Down syndrome for hospital admission, readmission, and emergency admission were 1.84 (1.68, 2.01), 2.56 (2.08, 3.14), and 2.87 (2.61, 3.15), respectively. In addition, people with Down syndrome presented longer lengths of stays than controls. I have a query about their study.
Fitzgerald et al. described patterns of hospitalisations for children and young people with Down syndrome (2). Children with Down syndrome were at increased risk of morbidity for varied causes. Rate ratio (RR) (95% CI) of children with Down syndrome for overall hospitalisations was 5.2 (4.3, 6.2) by setting Silva data (3) as a control. I think that HR or RR would be changed according to control data, and hospitalisation rate would be changed with time. In addition, socioeconomic status would also be closely related to hospitalisation rate. Regarding the improved prognosis of people with Down syndrome, comprehensive analysis is needed by compiling information on medication and other social supporting systems.
References
1. Hughes-McCormack LA, McGowan R, Pell JP, et al. Birth incidence, deaths and hospitalisations of children and young people with Down syndrome, 1990-2015: birth cohort study. BMJ Open. 2020;10(4):e033770. Published 2020 Apr 1. d...
Hughes-McCormack et al. investigated live birth, death rates and childhood hospitalisations in people with Down syndrome (1). Regarding childhood hospitalisations, adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of people with Down syndrome for hospital admission, readmission, and emergency admission were 1.84 (1.68, 2.01), 2.56 (2.08, 3.14), and 2.87 (2.61, 3.15), respectively. In addition, people with Down syndrome presented longer lengths of stays than controls. I have a query about their study.
Fitzgerald et al. described patterns of hospitalisations for children and young people with Down syndrome (2). Children with Down syndrome were at increased risk of morbidity for varied causes. Rate ratio (RR) (95% CI) of children with Down syndrome for overall hospitalisations was 5.2 (4.3, 6.2) by setting Silva data (3) as a control. I think that HR or RR would be changed according to control data, and hospitalisation rate would be changed with time. In addition, socioeconomic status would also be closely related to hospitalisation rate. Regarding the improved prognosis of people with Down syndrome, comprehensive analysis is needed by compiling information on medication and other social supporting systems.
References
1. Hughes-McCormack LA, McGowan R, Pell JP, et al. Birth incidence, deaths and hospitalisations of children and young people with Down syndrome, 1990-2015: birth cohort study. BMJ Open. 2020;10(4):e033770. Published 2020 Apr 1. doi:10.1136/bmjopen-2019-033770
2. Fitzgerald P, Leonard H, Pikora TJ, Bourke J, Hammond G. Hospital admissions in children with down syndrome: experience of a population-based cohort followed from birth. PLoS One. 2013;8(8):e70401. Published 2013 Aug 13. doi:10.1371/journal.pone.0070401
3. Silva D, Palandri G, Bower C, Gill L, Codde J, et al. Specific child and adolescent health problems in Western Australia. East Perth, Western Australia: Health Department of Western Australia and TVW Telethon Institute for Child Health Research, 1999.
We do not see how the cost data has been adjusted for Taiwanese inflation, considering that the data collected covers a long period. If this has not been done, we may have underestimated cost data. We understand that this needs to be reviewed when considering the data.
When 85% of the viruses found in laboratory tests were rhinoviruses, which are about four times smaller than SARS-CoV2, no conclusion from this article can be applied to COVID-19/SARS-CoV2. No coronaviruses of any kind were found even though the tests were performed. Finally, their claim that "Penetration of cloth masks by particles was almost 97%" is of no value when the particles sizes are not stated. Furthermore, since many viruses, such as influenza, herpes simplex, and coronaviruses are surrounded by a fatty layer, called a "lipid envelope," one wonders about the choice of sodium chloride particles instead of oil particles, taking in consideration that the instrument used (TSI 8110 Filter tester) can use either.
We read the response to our systematic review by Henk Giele with great interest. The respondent stated:
“An uncritical reading of this and other reviews on the subject suggest that intra-articular steroid injections should not be used as no beneficial effect is demonstrated”
No such suggestion is made in our article and our conclusion is very clear in stating that the current evidence is equivocal regarding the use of injection therapy in base of thumb osteoarthritis. An absence of evidence is not an evidence of absence. The respondent also touches on some interesting aspects of the complexity of injection therapy as an intervention, such as the type of steroid and dosage, while there are many other elements which merit consideration such as the education given concomitantly, the period of rest, splint use, the type of injection guidance, the use of local anaesthetic, and patient factors such as stage of osteoarthritis and degree of synovitis. One of the key flaws in the current evidence base as highlighted by our review was the minimal regard paid to the overall package of care, and even something as simple as the advice and education given with a steroid injection may have a significant influence on outcome.
Without a large adequately powered methodologically robust RCT, we simply cannot be confident of what to tell our patients, both in terms of the degree of potential short term benefits, but also in terms of the potential longer term harms....
We read the response to our systematic review by Henk Giele with great interest. The respondent stated:
“An uncritical reading of this and other reviews on the subject suggest that intra-articular steroid injections should not be used as no beneficial effect is demonstrated”
No such suggestion is made in our article and our conclusion is very clear in stating that the current evidence is equivocal regarding the use of injection therapy in base of thumb osteoarthritis. An absence of evidence is not an evidence of absence. The respondent also touches on some interesting aspects of the complexity of injection therapy as an intervention, such as the type of steroid and dosage, while there are many other elements which merit consideration such as the education given concomitantly, the period of rest, splint use, the type of injection guidance, the use of local anaesthetic, and patient factors such as stage of osteoarthritis and degree of synovitis. One of the key flaws in the current evidence base as highlighted by our review was the minimal regard paid to the overall package of care, and even something as simple as the advice and education given with a steroid injection may have a significant influence on outcome.
Without a large adequately powered methodologically robust RCT, we simply cannot be confident of what to tell our patients, both in terms of the degree of potential short term benefits, but also in terms of the potential longer term harms. Given the significant proportion of the treatment effect which is related to contextual factors and regression to the mean in chronically painful musculoskeletal conditions, lower quality evidence does not help us to better inform our patients, given the significant influence of bias and confounding factors.
Recently, Skou and collegues published a trial-based cost-utility analysis that evaluated the cost per quality-adjusted life year (QALY) gained for total knee replacement (TKR) in addition to non-surgical treatment compared to non-surgical treatment alone (Skou 2020). Fortunately, this study now adds economic data on TKR based on a high-level evidence. However, with regard to the intrepretation of the results, the reader is left with some open questions.
Clinical and economic data was based on a randomised-controlled trial which provided data on TKR at the same time (Skou 2015). According to the study design, regression analyses were used to estimate incremental costs and quality-adjusted life years (QALYs) and, data was analysed in accordance with the intention-to-treat principle. In the base-case-scenario, the regression analyses were adjusted for covariates (i.e., age, sex and baseline costs/QALY), while two additional scenarios did not take covariates into account (Scenario 1), and did not consider either covariates or missing values/imputations (Scenario 2). While the base-case-scenario resulted in additional costs of 6070€ with a QALY-gain of 0.186 (incremental cost-effectiveness ratio of 32,611 €/QALY), the additional scenarios showed cost-utility-ratios below 20,000€/QALY (and thus below the NICE-threshold of 22,665 €/QALY). However, the results provided and the claimed cost-effective potential of TKR raises two concerns:
First, for the base-case costs...
Recently, Skou and collegues published a trial-based cost-utility analysis that evaluated the cost per quality-adjusted life year (QALY) gained for total knee replacement (TKR) in addition to non-surgical treatment compared to non-surgical treatment alone (Skou 2020). Fortunately, this study now adds economic data on TKR based on a high-level evidence. However, with regard to the intrepretation of the results, the reader is left with some open questions.
Clinical and economic data was based on a randomised-controlled trial which provided data on TKR at the same time (Skou 2015). According to the study design, regression analyses were used to estimate incremental costs and quality-adjusted life years (QALYs) and, data was analysed in accordance with the intention-to-treat principle. In the base-case-scenario, the regression analyses were adjusted for covariates (i.e., age, sex and baseline costs/QALY), while two additional scenarios did not take covariates into account (Scenario 1), and did not consider either covariates or missing values/imputations (Scenario 2). While the base-case-scenario resulted in additional costs of 6070€ with a QALY-gain of 0.186 (incremental cost-effectiveness ratio of 32,611 €/QALY), the additional scenarios showed cost-utility-ratios below 20,000€/QALY (and thus below the NICE-threshold of 22,665 €/QALY). However, the results provided and the claimed cost-effective potential of TKR raises two concerns:
First, for the base-case costs and health utilities are presented in tables 2 and 3. Based on this information, incremental costs and health utilities are presented for all scenarios in table 4. However, the increments reported in table 4 do not correspond to the values of the prior tables. Applying data from tables 2 and 3 would increase the cost-utility ratio of the base-case to more than 60,000 e/QALY (incremenatl costs of 8562€ at a QALY-gain of 0.139). The difference might result from processing data on costs and QALYs in the regression or from discounting. However, lacking sufficient transparency the article does not include any information about the parameters used for the regression (e.g., beta coefficients, confidence intervals, p-values, R-squared) which would essential for readers to understand the calculation.
Second, the authors claimed to have calculated their analysis in accordance with the intention-to-treat principle. Following this principle would have required to include participants who died within the study period (three in the TKR plus non-surgical group compared to only one person in the non-surgical group). This was only considered in a subanalysis and - as conceded in the discussion - would further increase the cost-utility ratio (even if TKR was still more effctive).
To some extent, the lack of transparency with regard to the usage of input data and the exclusion of died participants in the base-case scenario undermines the credibility of this important analysis, particularly because the presented cost-utility ratios are in close proximity to the mentioned NICE-threshold. It remains unclear why further clinical analyses with a prolonged time horizon and a smarter dealing with adjustment for covariates and imputation of missing values may improve the cost-effectiveness of TKR.
References:
1) Skou ST, Roos E, Laursen M, Arendt-Nielsen L, Rasmussen S, Simonsen O, Ibsen R, Larsen AT, Kjellberg J. Cost-effectiveness of total knee replacement in addition to non-surgical treatment: a 2-year outcome from a randomised trial in secondary care in Denmark. BMJ Open. 2020 Jan 15;10(1):e033495. doi: 10.1136/bmjopen-2019-033495.
2) Skou ST, Roos EM, Laursen MB, Rathleff MS, Arendt-Nielsen L, Simonsen O, Rasmussen S. A Randomized, Controlled Trial of Total Knee Replacement. N Engl J Med. 2015 Oct 22;373(17):1597-606. doi: 10.1056/NEJMoa1505467.
Altschul et al. conducted a prospective study to investigate the association between blood pressure (BP) and cognitive functions across the eighth decade (1). Women with higher early-life cognitive function had lower BP during the eighth decade. In addition, prescribed antihypertensive medication was closely associated with lower BP, but antihypertensive medication had no effect on better cognitive function. Regarding no relationship between BP and cognitive decline, I have some concerns.
First, Ou et al. conducted a meta-analysis regarding the association between BP and cognitive impairment/dementia in prospective studies (2). The significant relationship of BP with cognitive impairment/dementia was observed in different BP variables, which were classified into midlife and late-life periods. In addition, prescribed antihypertensive medications exhibited a 21% reduction in dementia risk, which was different from data by Altschul et al. I suspect that long-term follow-up might change the relationship between BP and cognitive functions. Long survivors’ effect on BP and cognitive functions should be specified by further study.
Second, visit-to-visit variability in blood pressure was a significant predictor of subsequent cognitive decline in old subjects (3,4). But the association between BP variability and cognitive impairment was not mediated by BP lowering medication (5). As BP variables such as high systolic BP, low diastolic BP, excessive BP variability, and...
Show MoreDear Dr Aldcroft,
We read with interest the paper entitled “Efficacy and safety of the pulsed electromagnetic field in osteoarthritis: a meta-analysis”.1 This paper concluded that “PEMF could alleviate pain and improve physical function for patients with knee and hand [osteoarthritis] OA, but not for patients with cervical [osteoarthritis] OA.” We have a few concerns with their conclusion.
The first concern is that the review reports very large effect sizes for some trials,2-5 but does not alert the reader to how atypical these results are. For example, Figure 3 of the manuscript1 contains three examples of effect sizes of ~3 and 4 standardised mean difference (SMD). Effect sizes this large are usually a red flag that something is amiss, either with the results of the review or the original trial. Unfortunately, both problems are present.
The review reported a SMD for the Nelson trial5 of -3.72; but this a mistake. The authors have confused the standard deviation (SD) with the standard error (SE) and when their error is corrected the true effect size is -0.74 [95% confidence interval (CI) -1.44 to -0.04] compared with -3.72 [95% CI -4.88 to -2.56] reported in the review. The correction also changes the pooled effect to -0.33 [-0.70 to 0.04] and would support the conclusion that the treatment is not effective for knee OA.
The other two large effect sizes are driven by outcomes in the treatment group and no change in the control group.2,3 For...
Show MoreWe would like to thank RJ Aitken for presenting his basic scientist view on our clinical trial.
His first comment addresses the fact that we include “idiopathic infertility patients irrespective of their redox status “. He suggests that we should only include patients with proven oxidative stress. We would like to respond that, of course, we would prefer to follow his advice, on the condition that validated test are available to differentiate between men that do suffer (constantly) from oxidative stress and those that do not, or that are even at risk for reductive stress. If we could all agree on the reliability of such tests, then it would certainly be worthwhile to try and get additional funding for pre- and post-therapy testing in (a subset of) our patients, then analyze them separately according to their redox status. Such an addition might provide a more solid basis for the antioxidant therapy. However, sperm DNA fragmentation tests are very costly and there is as yet no international consensus on which sperm DNA fragmentation test should be used as becomes obviously clear when reading the extensive review of the literature composed by Agarwal et al and the extensive discussion it awakened with more than 50 commentary letters published.(1,2) As to the danger of causing reductive stress, we think this is limited, as Impryl does not contain direct and strong scavenging antioxidants such as vitamin C and E, but rather focuses on the homocysteine pathway and the 1...
Show MoreCloth masks, while comforting to some, should not be implied to provide anything but marginal (at best) protection to this "epidemic". When referring to virus particles that can spread via droplets it is fairly apparent that cloth masks do little to nothing for protection (except piece of mine)...and sorry, but 3ish% is not even a nominal value, its a toss value when referring to health.
Take a covid 19 positive patient, have them where a cloth mask and exhale sharply, sneeze, or cough in front of a mirror....watch what happens. I understand this is an overly simplified example, but it gets the point across.
As a last ditch effort with nothing else? Sure, but as a primary line of active defense for at risk individuals? Not even close. These individuals should be protected, away from the "herd" community.
These look wonderful!
I wonder, though, if the filter placements could be moved or they could be reshaped to allow the wearer's mouth to show better for the hearing impaired.
Hughes-McCormack et al. investigated live birth, death rates and childhood hospitalisations in people with Down syndrome (1). Regarding childhood hospitalisations, adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of people with Down syndrome for hospital admission, readmission, and emergency admission were 1.84 (1.68, 2.01), 2.56 (2.08, 3.14), and 2.87 (2.61, 3.15), respectively. In addition, people with Down syndrome presented longer lengths of stays than controls. I have a query about their study.
Fitzgerald et al. described patterns of hospitalisations for children and young people with Down syndrome (2). Children with Down syndrome were at increased risk of morbidity for varied causes. Rate ratio (RR) (95% CI) of children with Down syndrome for overall hospitalisations was 5.2 (4.3, 6.2) by setting Silva data (3) as a control. I think that HR or RR would be changed according to control data, and hospitalisation rate would be changed with time. In addition, socioeconomic status would also be closely related to hospitalisation rate. Regarding the improved prognosis of people with Down syndrome, comprehensive analysis is needed by compiling information on medication and other social supporting systems.
References
Show More1. Hughes-McCormack LA, McGowan R, Pell JP, et al. Birth incidence, deaths and hospitalisations of children and young people with Down syndrome, 1990-2015: birth cohort study. BMJ Open. 2020;10(4):e033770. Published 2020 Apr 1. d...
We do not see how the cost data has been adjusted for Taiwanese inflation, considering that the data collected covers a long period. If this has not been done, we may have underestimated cost data. We understand that this needs to be reviewed when considering the data.
When 85% of the viruses found in laboratory tests were rhinoviruses, which are about four times smaller than SARS-CoV2, no conclusion from this article can be applied to COVID-19/SARS-CoV2. No coronaviruses of any kind were found even though the tests were performed. Finally, their claim that "Penetration of cloth masks by particles was almost 97%" is of no value when the particles sizes are not stated. Furthermore, since many viruses, such as influenza, herpes simplex, and coronaviruses are surrounded by a fatty layer, called a "lipid envelope," one wonders about the choice of sodium chloride particles instead of oil particles, taking in consideration that the instrument used (TSI 8110 Filter tester) can use either.
We read the response to our systematic review by Henk Giele with great interest. The respondent stated:
“An uncritical reading of this and other reviews on the subject suggest that intra-articular steroid injections should not be used as no beneficial effect is demonstrated”
No such suggestion is made in our article and our conclusion is very clear in stating that the current evidence is equivocal regarding the use of injection therapy in base of thumb osteoarthritis. An absence of evidence is not an evidence of absence. The respondent also touches on some interesting aspects of the complexity of injection therapy as an intervention, such as the type of steroid and dosage, while there are many other elements which merit consideration such as the education given concomitantly, the period of rest, splint use, the type of injection guidance, the use of local anaesthetic, and patient factors such as stage of osteoarthritis and degree of synovitis. One of the key flaws in the current evidence base as highlighted by our review was the minimal regard paid to the overall package of care, and even something as simple as the advice and education given with a steroid injection may have a significant influence on outcome.
Without a large adequately powered methodologically robust RCT, we simply cannot be confident of what to tell our patients, both in terms of the degree of potential short term benefits, but also in terms of the potential longer term harms....
Show MoreRecently, Skou and collegues published a trial-based cost-utility analysis that evaluated the cost per quality-adjusted life year (QALY) gained for total knee replacement (TKR) in addition to non-surgical treatment compared to non-surgical treatment alone (Skou 2020). Fortunately, this study now adds economic data on TKR based on a high-level evidence. However, with regard to the intrepretation of the results, the reader is left with some open questions.
Show MoreClinical and economic data was based on a randomised-controlled trial which provided data on TKR at the same time (Skou 2015). According to the study design, regression analyses were used to estimate incremental costs and quality-adjusted life years (QALYs) and, data was analysed in accordance with the intention-to-treat principle. In the base-case-scenario, the regression analyses were adjusted for covariates (i.e., age, sex and baseline costs/QALY), while two additional scenarios did not take covariates into account (Scenario 1), and did not consider either covariates or missing values/imputations (Scenario 2). While the base-case-scenario resulted in additional costs of 6070€ with a QALY-gain of 0.186 (incremental cost-effectiveness ratio of 32,611 €/QALY), the additional scenarios showed cost-utility-ratios below 20,000€/QALY (and thus below the NICE-threshold of 22,665 €/QALY). However, the results provided and the claimed cost-effective potential of TKR raises two concerns:
First, for the base-case costs...
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