published between 2019 and 2022
I suggest the basis of the Ezzatvar, et al., report is increased dehydroepiandrosterone (DHEA). It is known exercise increases DHEA. It is my hypothesis of 2020 that low DHEA is linked to the severity of Covid-19 infection and subsequent pathology (© Copyright 2020, James Michael Howard, Fayetteville, Arkansas, U.S.A.) New research, 2022, regarding DHEA has been published that supports my hypothesis that severe Covid-19 illness is associated with low DHEA: “COVID-19 patients with altered steroid hormone levels are more likely to have higher disease severity,” ( 2022 Jul 30. doi: 10.1007/s12020-022-03140-6.) “DHEA was an independent indicator of the disease severity with COVID-19.”
Tarp et al. evaluated the associations of total and intensity-specific physical activity and all-cause mortality (1). Compared with the obese-low total physical activity reference, the hazard ratios (HRs) (95% confidence intervals [CIs]) of subjects with normal weight-high total activity and obese-high total activity for mortality were 0.59 (0.44 to 0.79) 0.67 (0.48 to 0.94), respectively. In contrast, the HR (95% CI) of subjects with normal weight-low total physical activity for mortality was 1.28 (0.99 to 1.67). Physical activity has a preventive effect on mortality regardless of obesity, and I have some comments about the study with special reference to sedentary time and aging.
Li et al. reported that the adjusted HRs (95% CIs) of daily sedentary time per 1 hour increase for all-cause mortality was 1.03 (1.01-1.05) and significant increase of the adjusted HR was observed in subjects with daily sedentary time of 8 or longer (2). This means that physically inactive lifestyle has an effect on increased risk in mortality, and physical activity and sedentary behaviour should be checked simultaneously. In addition, I suppose that the content of physical activity should be specified; such as leisure-time and work-related activity.
Yang et al. conducted a meta-analysis to evaluate the effect of physical activity and sedentary behaviour over adulthood on all-cause and cause-specific mortality (3). They clarified that active subjects over adulthood was significantl...
Yang et al. conducted a meta-analysis to evaluate the effect of physical activity and sedentary behaviour over adulthood on all-cause and cause-specific mortality (3). They clarified that active subjects over adulthood was significantly associated with lower all-cause and cardiovascular-disease mortality compared with inactive subjects. Lowering sedentary time is important for the risk reduction of mortality, and physical activity in adults with daily sedentary job may be effective to avoid the mortality risk. To evaluate the beneficial health effects of keeping activity and avoiding sedentary time, health-related behaviours such as smoking, alcohol consumption, sleeping habit and diet, should be appropriately adjusted. In addition, socioeconomic differences might mediate the effect of these health behaviours on subsequent risk of all-cause and cause-specific mortality (4).
Aging is closely related to subsequent comorbidities and status of medical cares may influence the risk of mortality (5). This means that age-related factors, including the level of frailty, would interact with the association between physical activity, sedentary behaviour and mortality (6). Recommendation of desirable health habits should be made to reduce the mortality risk among older subjects.
1. Tarp J, Fagerland MW, Dalene KE, et al. Device-measured physical activity, adiposity and mortality: a harmonised meta-analysis of eight prospective cohort studies. Br J Sports Med 2022;56:725-32.
2. Li Y, Zhou Q, Luo X, et al. Association between sedentary time and 6-year all-cause mortality in adults: The rural Chinese cohort study. J Nutr Health Aging 2022;26:236-42.
3. Yang Y, Dixon-Suen SC, Dugué PA, et al. Physical activity and sedentary behaviour over adulthood in relation to all-cause and cause-specific mortality: a systematic review of analytic strategies and study findings. Int J Epidemiol 2022;51:641-67.
4. Petrovic D, de Mestral C, Bochud M, et al. The contribution of health behaviors to socioeconomic inequalities in health: A systematic review. Prev Med 2018;113:15-31.
5. Dugravot A, Fayosse A, Dumurgier J, et al. Social inequalities in multimorbidity, frailty, disability, and transitions to mortality: a 24-year follow-up of the Whitehall II cohort study. Lancet Public Health 2020;5:e42-e50.
6. Hanlon P, Nicholl BI, Jani BD, et al. Frailty and pre-frailty in middle-aged and older adults and its association with multimorbidity and mortality: a prospective analysis of 493 737 UK Biobank participants. Lancet Public Health 2018;3:e323-e332.
I read with great interest the study by Atakan et al., (2022) where they summarize existing evidence regarding the effect of high intensity interval training (HIIT) and sprint interval training (SIT) over fat oxidation during sub-maximal intensity exercise. An impaired fat oxidation is a common feature of patients with obesity and type 2 diabetes. Thus, this meta-analysis provides novel information that could be used by physicians and personal trainers to improve the metabolic health of the above mentioned populations. In this rapid response, I discuss several issues regarding data collection process, statistical modelling and interpretation of the reported findings that raised up after a deep analysis of the studies included in this meta-analysis.
The first meta-analysis of this study evaluated the effect of HIIT/SIT over exercise fat oxidation, summarizing the data from nine studies (Fig. 1). The findings of this meta-analysis are reported in g/min, nevertheless, Arad et al. (60) reported fat oxidation (Fox) relative to fat-free mass (mg∙kg FFM-1∙ min-1), Nybo et al. (30) reported Fox in kJ/min while Zapata-Lamana et al. (64) reported the relative contribution of lipids to energy expenditure. Of note, the authors do not report to request the fat oxidation in g/min from these studies (see data extraction section). Then, ¿How did the authors computed Fox in g∙min-1?
Otherwise, Astorino et al. (44) and Schubert et al (33), evaluated the effect of both HIIT a...
Otherwise, Astorino et al. (44) and Schubert et al (33), evaluated the effect of both HIIT and SIT over fat oxidation. According to the study selection criteria employed by the authors, data from both training regimes must be included in the meta-analysis, giving a total of 11 data for the forest plot. Nevertheless, only the data from 9 studies is reported.
With regard to the first analysis reported in this study (Fig. 1), the authors stated that a random effects meta-analysis was performed. According to the description of the reported data “, a positive value indicates a larger increase in fat oxidation as a result of interval training compared with no exercise”, which suggest that authors employed the inverse-variance approach (not specified by the authors). If this is true, the forest plot suggest that 8/9 studies reported a larger increment of Fox in the experimental group when compared to observed modifications in the control group. Nevertheless, from 9 studies investigating the effects of HIIT/SIT over Fox (including 6 studies that evaluated maximal fat oxidation, MFO), only Jabbour and Lancu (47) and Zapata-Lamana et al. (64) reported a significant increment of Fox. Thus, there is a disagreement between the data reported by the studies and the data presented in the meta-analysis. Moreover, because Fox is reported in different units across studies, authors must employ standardized mean difference instead of mean difference. In addition, three of the included studies (44, 56, 64) performed the assessments of fat oxidation on three or more separate occasions. However, the authors do not describe how did they adjusted for repeated measures/multiple comparisons in their analysis. In this sense it would be more appropriate to employ the reported effect size reported or computed by each study (Cohens d for studies that performed only 2 measurements and n2p for studies that performed 3 measurements).
In agreement with the authors, criteria for interpreting whether the enhancement of Fox was substantial or poor remains undefined. However, from the analytical point of view, the observed increment of Fox must be higher than inter-day Fox variation. For example, previous studies report that MFO shows an inter-day variation between 11-26%1-3. Thus the increment of MFO must be larger than such variation, otherwise, authors are only reporting the variation in MFO between exercise test performed at baseline and after training intervention.
Finally, I would like to highlight that in spite HIIT/SIT induced a larger increment on fat oxidation rates in comparison to moderate intensity training (MOD), HIIT/SIT is not better for burning fat in comparison to MOD as equivocally interpreted by many readers who shared the findings from this study in different websites (see altmetric). Indeed, enhancing Fox would be useless if people keep training at high intensity (>85% of VO2max or %PPO) where fat oxidation became negligible. Of note, this meta-analysis does not discuss whether HIIT/SIT improves Fox in different intensity domains, including vigorous intensity. On the contrary, the results from this meta-analysis, suggest that HIIT/SIT and MOD must be combined; the HIIT/SIT will increase Fox during MOD which might contribute to reach a negative fat balance and prevent lipid accumulation in the sarcolemma which impairs insulin signaling.
Note: numbers in the parenthesis correspond to the reference number of the studies included in the meta-analysis.
1. Croci I, Borrani F, Byrne NM, et al. Reproducibility of Fatmax and fat oxidation rates during exercise in recreationally trained males [published correction appears in PLoS One. 2014;9(11):e114115. Byrne, Nuala [corrected to Byrne, Nuala M]; Wood, Rachel [corrected to Wood, Rachel E]; Hickman, Ingrid [corrected to Hickman, Ingrid J]]. PLoS One. 2014;9(6):e97930. Published 2014 Jun 2. doi:10.1371/journal.pone.0097930
2. Dandanell S, Præst CB, Søndergård SD, et al. Determination of the exercise intensity that elicits maximal fat oxidation in individuals with obesity. Appl Physiol Nutr Metab. 2017;42(4):405-412. doi:10.1139/apnm-2016-0518
3. Robles-González L, Gutiérrez-Hellín J, Aguilar-Navarro M, et al. Inter-Day Reliability of Resting Metabolic Rate and Maximal Fat Oxidation during Exercise in Healthy Men Using the Ergostik Gas Analyzer. Nutrients. 2021;13(12):4308. Published 2021 Nov 29. doi:10.3390/nu13124308
Dr Araujo and colleagues have demonstrated the utility for mortality risk assessment of the 10-second one leg standing (10s-OLS) test,1 colloquially known as the “flamingo test” (although every amateur ornithologist will know that the 10s-OLS test posture, illustrated in Figure 1 of Araujo et al., is different from that adopted by a flamingo, and that many other birds adopt a single-legged stance when roosting). The 10s-OLS test is easily administered, safe, and simply categorised (binary yes/no), so should be easy to apply in clinical practice. Failure to achieve 10s-OLS (“NO 10s-OLS”) was found to be associated with patient age, high waist-height ratio, and prevalence of diabetes mellitus.
Contrary to the view expressed by Dr Araujo and colleagues that "balance assessment is not routinely incorporated in the clinical examination",1 we suggest that most neurologists would include such an assessment in the neurological examination, particularly in older patients,2 and invariably if there is a complaint of imbalance or falling. Hence for neurologists, the findings of the study beg questions about underlying neurobiological mechanisms. Aside from speculating that "subclinical central or autonomic nervous system dysfunction" might contribute, the authors do not specifically address these issues, other than to indicate the exclusion from the study of patients with unstable gait or with signs of acute vestibular or otoneuro...
Contrary to the view expressed by Dr Araujo and colleagues that "balance assessment is not routinely incorporated in the clinical examination",1 we suggest that most neurologists would include such an assessment in the neurological examination, particularly in older patients,2 and invariably if there is a complaint of imbalance or falling. Hence for neurologists, the findings of the study beg questions about underlying neurobiological mechanisms. Aside from speculating that "subclinical central or autonomic nervous system dysfunction" might contribute, the authors do not specifically address these issues, other than to indicate the exclusion from the study of patients with unstable gait or with signs of acute vestibular or otoneurological disturbance.1
Age-related changes in balance-control are common, involving both sensory systems (somatosensory [proprioceptive], visual, and vestibular inputs) and motor systems (strength, range of motion, coordination), as well as cognitive functions (sensory adaptation, attention).2 Any or all of these factors might contribute to the clinical finding of NO 10s-OLS. Whilst associated with factors which might suggest that cerebrovascular disease is a significant contributor, such as high waist-height ratio and prevalence of diabetes mellitus, and hence potentially amenable to intervention, this will not be the case for all patients.
Fractionation of NO 10s-OLS patients by means of screening and/or formal neurological examination will surely be necessary if the findings of Araujo et al. are to lead to meaningful, individualised, interventions to reduce mortality. This examination might include the modified Romberg test to assess proprioceptive, visual, and vestibular inputs, as well as assessment of motor strength and coordination.
1. Araujo CG, de Souza e Silva CG, Laukkanen JA et al. Successful 10-second one-legged stance predicts survival in middle-aged and older individuals. British Journal of Sports Medicine Published Online First: 21 June 2022. doi: 10.1136/bjsports-2021-105360
2. Schott JM, Larner AJ. Neurological signs of ageing. In: Sinclair AJ, Morley JE, Villas B, Cesare M, Munshi M (eds). Pathy’s Principles and Practice of Geriatric Medicine. 6th edition. Wiley Blackwell, 2022: 563-569. https://doi.org/10.1002/9781119484288.ch44
Reply to: ‘Comment on: Isometric exercise versus high-intensity interval training for the management of blood pressure: a systematic review and meta-analysis by Edwards et al.’ by Wewege et al.
Edwards, J.J., Wiles, J.D., & O’Driscoll, J.M.
School of Psychology and Life Sciences, Canterbury Christ Church University, Kent, CT1 1QU
Correspondence to Dr Jamie O’Driscoll, School of Psychology and Life Sciences, Canterbury Christ Church University, North Holmes Road, Canterbury, Kent, CT1 1 QU. Email: firstname.lastname@example.org; Telephone: 01227922711.
We thank Wewege et al. (1) for their assessment and comments on our recent work (2), highlighting their concerns over the employed statistical analysis approach, which they suggest may “invalidate the results”.
We take these comments seriously and have therefore re-performed the analysis as suggested by Wewege et al. (1) and individually addressed the points raised within this rapid response.
Wegewe et al. (1) state that the marked differences found in our study “contrast previous findings”, with reference to a previous large-scale network meta-analysis by Naci et al. (3). As detailed, Naci et al. (3) did not include high intensity interval training (HIIT), and the lower blood pressure (BP) changes observed can be attributed to a combination of differences to the present study, including a smaller pool of lower quality iso...
Wegewe et al. (1) state that the marked differences found in our study “contrast previous findings”, with reference to a previous large-scale network meta-analysis by Naci et al. (3). As detailed, Naci et al. (3) did not include high intensity interval training (HIIT), and the lower blood pressure (BP) changes observed can be attributed to a combination of differences to the present study, including a smaller pool of lower quality isometric exercise training (IET) trials. Specifically, our analysis includes 8 trials that would not have been published at the time Naci et al. (3) performed their systematic search and we contrarily ensured the omission of older trials that did not meet today’s standards of methodological rigour. We would also strongly recommend a full exploration of the supplementary file of Naci et al. (3) (appendix 8) which clearly supports the comparative efficacy of IET.
The next concern raised by Wegewe et al. states that: “None of the included trials in this review appear to contain both isometric and HIIT interventions; therefore, the authors are unable to ‘directly compare’ the interventions”. As the authors (1) are probably aware, there is currently no direct randomised control trial data on the effects of IET versus HIIT. Consequently, the only available statistical approach to meta-analysing the current data is via indirect means, as performed in the present study. We agree that our wording within the first paragraph of the discussion, where we refer to “directly comparing” these modes, should not be interpreted in an analytical context but rather this statement was made in consideration of the relevant limitations of the wider literature. In hindsight, we agree that this could have been overtly explained for those not fully conversant with the current literature.
The primary concern raised by Wegewe et al. (1) questions whether the chosen statistical approach is “correct”, citing the potential of being misleading and prone to bias. We agree that there are limitations of this method of analysis; however, to label the employed statistical approach as “incorrect” is far too simplistic and implies that the process of this type of analysis selection can only be viewed in terms of black-and-white. There are advantages and limitations to all employed statistical analyses and the decision for employing the current method was informed based on the available data. As stated by Wegewe et al. (1), many of the HIIT studies (6 to be exact) did not utilise a non-intervention control group, but instead included a moderate-intensity training group. Thus, to follow the statistical method advised by Wegewe et al. (1) would mean the omission of 6 effects sizes from the final HIIT analysis, which would carry its own bias implications. However, to remove any doubt regarding the validity of our published findings, we have performed the alternative method of analysis as recommended by Wegewe et al. (1), following a between-group random-effects (exercise versus non-intervention control only) analysis. The results are as follows:
Results from the current approach
IET - sBP: -8.50 (95% CI: 6.49-10.52, p<0.001) dBP: -4.07 (95% CI: 3.04-5.10, p<0.001)
HIIT - sBP: -2.86 (95% CI: 1.11-4.62, p=0.001) dBP: -2.48 (95% CI: 1.49-3.48, p<0.001)
Results from the alternative approach suggested by Wegewe et al
IET - sBP: -8.04 (95% CI: 6.37-9.72, p<0.001) dBP: -3.23 (95% CI: 1.91-4.55, p<0.001)
HIIT - sBP: -3.33 (95% CI: 1.17-5.48, p=0.003) dBP: -2.15 (95% CI: 0.53-3.78, p=0.009)
As such, following the statistical technique proposed by Wegewe et al. (1), IET still produces statistically and clinically significant reductions in BP compared to HIIT. Importantly, regardless of whether our original, or their proposed statistical approach is employed, the primary results do not meaningfully change. Thus, any concern presented by Wegewe et al. (1) regarding changes in exercise guideline recommendations for the incorporation of IET for the management of BP can now be removed.
1 Wewege MA, Hansford HJ, Jones MD. Comment on: ‘Isometric exercise versus high-intensity interval training for the management of blood pressure: a systematic review and meta-analysis’ by Edwards et al. Br J Sports Med Published Online First: 2022. https://bjsm.bmj.com/content/56/9/506.responses#comment-on-‘isometric-exercise-versus-high-intensity-interval-training-for-the-management-of-blood-pressure-a-systematic-review-and-meta-analysis’-by-edwards-et-al
2 Edwards J, Caux A De, Donaldson J, et al. Isometric exercise versus high-intensity interval training for the management of blood pressure: a systematic review and meta-analysis. Br J Sports Med 2021;:bjsports-2021-104642. doi:10.1136/BJSPORTS-2021-104642
3 Naci H, Salcher-Konrad M, Dias S, et al. How does exercise treatment compare with antihypertensive medications? A network meta-analysis of 391 randomised controlled trials assessing exercise and medication effects on systolic blood pressure. Br. J. Sports Med. 2019;53:859–69. doi:10.1136/bjsports-2018-099921
Conflicts of Interest
We are the authors of the published work.
As a general practitioner and specialist in the musculoskeletal system, I have read the article
“Small Steps, strong shield: directly measured moderate physical activity in 65361 adults is associated with significant protective affects from severe COVID-19 outcomes” from Steenkamp et al with great interest. The covid epidemic has put a huge burden of disease on the entire world and is weighing heavily on the capacity of healthcare. More and more is known about risk and protective factors for individuals to become severely ill from COVID-19 and this study contributes to this. In addition, prevention of disease is becoming an increasingly important task of health care, partly in order to curb rising healthcare costs.(1) Good physical condition can help prevent certain diseases as mentioned in the article.
The authors have collected a large dataset from a very large group of people in South Africa. What is missing in the analysis, however, is data on BMI. Studies show that BMI is an important risk factor for severe course of COVID-19. A high BMI, or adiposity, is one of the strongest reported risk factors for severe COVID-19. (2). In this study, the BMI was available in only 50% of the study population. Authors claim that when adding BMI to the model it did not alter the outcome for severe COVID-19 disease for the different physical activity groups. The authors attribute this to associated diseases such as hypertension and DM2, however researc...
The authors have collected a large dataset from a very large group of people in South Africa. What is missing in the analysis, however, is data on BMI. Studies show that BMI is an important risk factor for severe course of COVID-19. A high BMI, or adiposity, is one of the strongest reported risk factors for severe COVID-19. (2). In this study, the BMI was available in only 50% of the study population. Authors claim that when adding BMI to the model it did not alter the outcome for severe COVID-19 disease for the different physical activity groups. The authors attribute this to associated diseases such as hypertension and DM2, however research suggests that adipocytes and adipocyte-like cells likely play a major role. (2) If you consider this collinearity between x and x, then why did the authors choose to analyze hypertension and DM2 and not BMI? It is an omission not to share the BMI data, for example the mean and distribution in de different physical activity groups. It is likely that the people with a high physical activity level have a lower BMI and that this explains the difference in the course of covid infection.
The study reports on the physical activity patterns/levels that patients had for 3 months in the 2 years before the start of the COVID pandemic. It is very likely that the degree of exercise has changed during the pandemic and lockdown, therefor data on 2 years prior to the exposure to COVID-19 cannot automatically be translated to the physical activity directly before the exposure. It is known that training effect on -among others- VO2 max (stroke volume and oxygen extraction; physical capacity) have almost completely worn off after approximately 5 weeks after stopping training. (3,4). It would have been interesting to see report on the physical activity shortly prior to infection with COVID-19 and during the lockdown and what effect this had on the severity of COVID-19 illness.
The study shows that a medical history of HIV positive and rheumatic arthritis has a protective effect. Authors conclude that the disease generates that effect. However, there is no data on medication use available in the study. Virus inhibitors and immunosuppressants are used specifically in these groups of patients. Research shows that these drugs can have a beneficial effect on the course of COVID-19. (5)
In conclusion, the analysis Steenberg et al made, is a small step towards more knowledge about the preventive possibilities of physical activities, however the conclusions drawn for a strong shield is likely based on the wrong interpretation of associated diseases and protective factors.
Marieke van Hemert, MD, GP
2. Ilja L. Kruglikov The role of adipocytes and adipocyte-like cells in the severity of COVID-19 infections Obesity (Silver Spring)2020 Jul;28(7):1187-1190.doi: 10.1002/oby.22856. Epub 2020 Jun 10
3. Sara Maldonado-Martín, Jesús Cámara, David V.B. James, Juan Ramón
Fernández-López & Xabier Artetxe-Gezuraga (2016): Effects of long-term training cessation in
young top-level road cyclists, Journal of Sports Sciences, DOI: 10.1080/02640414.2016.1215502
I read with great appreciation the study “Exercise prehabilitation during neoadjuvant chemotherapy may enhance tumour regression in oesophageal cancer: results from a prospective non-randomised trial” . The authors aimed to evaluate the clinical impact of a structured exercise intervention in patients with operable oesophageal cancer during Neoadjuvant chemotherapy compared with those on a standard treatment pathway (p. 1); and for that, they carried out a prospective non-randomised trial. The paper has an elegant rationale and I am sure that will generate new research, however, exist some methodological fragile that may compromise the results.
1st, as this study specifically assessed the impact of exercise on measures of chemotherapy response (p. 1), the exercise program should be clearly described (e.g., exercise volume, time under tension, duration, cadence and range of motion, heart and respiratory rate). 2nd, the authors established moderate intensity for exercise, based on WHO recommendations for physical activity level (p. 2), however, physical activity is different of physical exercise; besides, they did not use the repetition-maximum  test to assess the strength of the patients and plan the intensity individually.
3rd, the authors added aerobic exercise (p. 2) to the structured program, but it was unclear how patients were assessed for this intervention (what velocity? Incline? Heart rate? Vo2?). 4th, the strategy for sample...
3rd, the authors added aerobic exercise (p. 2) to the structured program, but it was unclear how patients were assessed for this intervention (what velocity? Incline? Heart rate? Vo2?). 4th, the strategy for sample calculation is not enlightening (p. 3), impossible assessment of sampling errors; the results of this study are relevant, but we need a detailed sample calculation to evaluate statistical power (exist also no citation on the statistics of the study).
5th, the Minimal Clinically Important Difference (MCID) is omitted in the comparisons (what do the comparisons mean without the MCID?). 6th, intergroup comparisons should be evaluated through performed using the linear mixed models . The results are relevant a lot! But do these outcomes present themselves in the same way through the linear mixed models?
1. Zylstra J, Whyte GP, Beckmann K, Pate J, Santaolalla A, Gervais-Andre L, et al. Exercise prehabilitation during neoadjuvant chemotherapy may enhance tumour regression in oesophageal cancer: results from a prospective non-randomised trial. Br J Sports Med. 2022;56(7):402-409. doi:10.1136/bjsports-2021-104243
2. ACSM. American College of Sports Medicine. American College of Sports Medicine position stand. Progression models in resistance training for healthy adults. Med Sci Sports Exerc. 2009;41(3):687-708. doi:10.1249/MSS.0b013e3181915670
3. Casals M, Girabent-Farrés M, Carrasco JL. Methodological quality and reporting of generalized linear mixed models in clinical medicine (2000-2012): A systematic review. PLoS One. 2014;9(11):1-10. doi:10.1371/journal.pone.0112653
On behalf of the PTED study group, we would like to thank the authors for the rapid response on our recently published paper “Cost-effectiveness of Full Endoscopic versus Open Discectomy for Sciatica . The authors mention that they don’t agree with the conclusion of this study and have several comments. Below we will respond to these comments.
Firstly, the authors suggest that “another study design is needed to investigate cost-effectiveness of PTED above conventional microdiscectomy.” We strongly disagree. The study design was an economic evaluation alongside a pragmatic randomized controlled trial examining the cost-effectiveness of full-endoscopic versus open discectomy for sciatica. An economic evaluation alongside a pragmatic randomised controlled trial is considered an adequate design, because it provides timely information on an intervention’s cost-effectiveness with high internal and sufficient external validity . Furthermore, the study design was peer reviewed by the grant agency (ZONMW in the Netherlands) and we have pre-published our study protocol in an open access, peer reviewed journal , supported in a covenant agreement including the Dutch Neurosurgical Society (NVvN), Dutch Orthopedical Society (NOV), Dutch Spine Society and the Dutch Association for patients with low back pain (NVVR).
Secondly, the authors comment that “costs associated with endoscope equipment and disposables were not included in their cost measur...
Secondly, the authors comment that “costs associated with endoscope equipment and disposables were not included in their cost measurements. The direct costs only included time of the operating room, costs of medications and overnight hospital stay.” This is not entirely correct. In the article we wrote “Costs of the interventions include the time of the operating room used, the costs of the medications used during the surgery and for open microdiscectomy also the cost for one overnight hospital stay.” We didn’t state ‘only’. The PTED and OM prices were based on the corresponding so-called Diagnosis- Treatment Combinations (DBC) prices that are being used in the Netherlands. The cost associated with endoscope equipment and disposables are included, as DBCs include all costs related to the procedure (i.e. the whole package). [Note: In the Dutch health care system, treatment costs and related hospital reimbursement encompass a fixed price for each patient, defined as DBC. However, these reimbursements can differ between hospitals depending on the agreement with the health insurer.] As the PTED price was not set in stone yet, because it was not yet included in the Netherlands public health system, we also conducted sensitivity analyses in which two scenarios of PTED intervention costs were considered. In the high-cost scenario, the cost of PTED was €5000/patient, that is, €500 more than in the main analysis. In the low-cost scenario, the cost of PTED and open microdiscectomy were equal, that is, €4095 per patient. In both sensitivity analyses, the result is that PTED is dominant compared with OM. This shows that the findings are robust and hence not influenced by surgical costs but more based on productivity-related costs.
Thirdly, the authors state that for adequate comparison of costs, it should have been better when both groups had the same postoperative strategy, either both treatments in daycare, or both treatments with overnight stay. This study was funded by ZONMW’s program Healthcare Efficiency in which new interventions are typically compared with usual care. When we started this study, the most commonly used surgical technique in the Netherlands for this population was open microdiscectomy with mostly one night at the hospital. This was acknowledged by peer review. During the last couple of years more clinics/surgeons have started offering open microdiscectomy and consequently a relevant question for future research might be whether PTED is cost-effective compared with ‘daycare’ open microdiscectomy. However, the cost of one day of hospitalization in the Netherlands is approximately euro 500. We conducted a sensitivity analysis in which the cost of PTED was increased with euro 500, which is similar to one day of hospitalization. So, even if both PTED and open microdiscectomy would be associated with one day of hospitalization, the results and conclusion would be the same.
Fourthly, the authors state that the study “ultimately did not reach the initial sample size of 682 patients.” This is right and we have discussed this in the effectiveness paper in BMJ . The pre-estimated sample size of 682 patients was not reached. Of the 382 patients calculated to be necessary in the final sample size of the trial (i.e., excluding learning curve cases), we were able to include 179 instead of 191 of the patients who would undergo PTED. We argue that it is unlikely that the results would have been different with 682 instead of the 613 patients that were finally included. It may have resulted in a more precise effect estimate (slightly smaller confidence interval), but not in a clinically relevant change in the effect estimate itself. The sensitivity analysis including the learning curve (N= 613) confirms the robustness of our findings.
Fifthly, the authors state that “long-term outcome data is needed to determine whether treatment with PTED will have the same revision rate as standard microdiscectomy.” We agree that long-term data are needed and therefore we have extended the follow-up of our trial to 5 years. We will analyze and publish these data once they are available.
In summary, we don’t agree with the authors of the letter who stated that they don’t agree with the conclusion of this study. The methods are state-of-the art, the results are robust, and the conclusion of this large study reflects the results. The results of our study suggest that PTED can be considered as a cost-effective alternative to open microdiscectomy in treating sciatica.
1 Gadjradj PS, Broulikova HM, van Dongen JM, et al. Cost-effectiveness of full endoscopic versus open discectomy for sciatica. Br J Sports Med 2022;:bjsports-2021-104808. doi:10.1136/BJSPORTS-2021-104808
2 Ramsey SD, Willke RJ, Glick H, et al. Cost-Effectiveness Analysis Alongside Clinical Trials II—An ISPOR Good Research Practices Task Force Report. Value Heal 2015;18:161–72. doi:10.1016/J.JVAL.2015.02.001
3 Seiger A, Gadjradj PS, Harhangi BS, et al. PTED study: Design of a non-inferiority, randomised controlled trial to compare the effectiveness and cost-effectiveness of percutaneous transforaminal endoscopic discectomy (PTED) versus open microdiscectomy for patients with a symptomatic lumbar disc he. BMJ Open Published Online First: 2017. doi:10.1136/bmjopen-2017-018230
4 Gadjradj PS, Rubinstein SM, Peul WC, et al. Full endoscopic versus open discectomy for sciatica: randomised controlled non-inferiority trial. BMJ 2022;376:e065846. doi:10.1136/bmj-2021-065846
We read with great interest the article by Gronwald et al. that investigated the injury inciting events of moderate and severe acute hamstring injuries in professional male football (soccer) players with systematic video analysis.1 Despite the pain-taking reviewing of videos and motion analyses by the authors, there are still some practical concerns over injury severity and subject recruitment.
Taking into account the importance of injury severity assessment that served as the basis for study subject enrollment in that study, the use of time loss to represent the severity of injury may not be optimal when considering other factors that may contribute to a prolonged rest after injury. For instance, pre-existing hamstring conditions including hamstring strings, proximal hamstring tendinopathy, or referred posterior thigh pain are not uncommon among soccer players.2 Following this argument, the recruitment of study subjects based on club or physician registration without meeting more objective criteria and without excluding those with previous hamstring injuries through a medical record review may introduce bias regarding the determination of injury severity. In this aspect, magnetic resonance imaging (MRI), which was available in 87% (45 out of 52 cases for pattern hamstring injury categorisation), may be a more reliable tool for evaluation because of its ability to show the extent of injury and the reported correlation between the size of injury a...
Taking into account the importance of injury severity assessment that served as the basis for study subject enrollment in that study, the use of time loss to represent the severity of injury may not be optimal when considering other factors that may contribute to a prolonged rest after injury. For instance, pre-existing hamstring conditions including hamstring strings, proximal hamstring tendinopathy, or referred posterior thigh pain are not uncommon among soccer players.2 Following this argument, the recruitment of study subjects based on club or physician registration without meeting more objective criteria and without excluding those with previous hamstring injuries through a medical record review may introduce bias regarding the determination of injury severity. In this aspect, magnetic resonance imaging (MRI), which was available in 87% (45 out of 52 cases for pattern hamstring injury categorisation), may be a more reliable tool for evaluation because of its ability to show the extent of injury and the reported correlation between the size of injury and the time lost from sport.3 Besides, the readers would benefit from knowledge of the severity of injury based on MRI, including grading (i.e., Grade 1–3) as well as the presence (or absence) of more serious conditions such as hamstring tendon avulsions or ischial apophyseal avulsions, which was not mentioned in the study.
1. Gronwald T, Klein C, Hoenig T, Pietzonka M, Bloch H, Edouard P, et al. Hamstring injury patterns in professional male football (soccer): a systematic video analysis of 52 cases. Br J Sports Med 2022;56(3):165-71.
2. Sherry MA, Johnston TS, Heiderscheit BC. Rehabilitation of acute hamstring strain injuries. Clin Sports Med 2015;34(2):263-84.
3. Slavotinek JP, Verrall GM, Fon GT. Hamstring injury in athletes: using MR imaging measurements to compare extent of muscle injury with amount of time lost from competition. AJR Am J Roentgenol 2002;179(6):1621-8.
I would like to commend the authors on highlighting the risk factors for concussion in Rugby Football Union. This type of research is essential for current and future guidance and therefore to be referenced it must be of the highest academic standard.
Don Gatherer and David Hamilton have published several papers on cervical assessment in rugby and have huge experience in the biomechanical function, action, rehabilitation, and measurement of the cervical spine especially at International Rugby Football Union level.
It is with regret that we are writing to express our great concerns regarding the recent study published in BJSM in particular the prudence of the Testing Protocols and how the findings may be misleading and the results mis-interpreted.
There are a number of methodological issues with this study which will have contributed to the misinterpretation of their results and subsequent conclusions.
The scientific methodology construct of isometric testing of the Head, Neck, and Upper Shoulder Girdle (HNS) must be based upon the correct application of the principles defined in Newton’s Laws of Motion.
The Aim of this study is to produce and measure a validated ISOMETRIC FORCE MAXIMA
To clarity, the test action can be precisely stated as ‘the measurement of a one isometric voluntary muscle contraction repetition maxima’ - 1IVMCmax
Principles and Forces related to this study.
• Head, Neck, and Upper S...
• Head, Neck, and Upper Shoulder Girdle are held in the neutral test position by Intrinsic Forces
• Intrinsic Force is defined as the Biomechanical properties of the NMSK system of the HNS
• Intrinsic Force – In this experiment is UNKNOWN and is the force to be measured and defined.
• HNS held in test position isometrically in a defined position for each action
• Intrinsic Force MUST be LESS than the Extrinsic Force for test completion and validity.
• Extrinsic Force is defined as an external force applied to the Head affecting the HNS.
• Extrinsic Force application is via auto means of manual hand compression through a load cell.
• Extrinsic Force – In this experiment IS KNOWN as the force Maxima must be defined by compression of the load cell in each test action.
• Extrinsic Force test position, once defined, will set the Test Maxima of that test.
• Extrinsic Force application is via single or double action arm actions and thus of different magnitude.
• Extrinsic Force application must be directed at right angles to the point of contact with a controlled rate of force development that allows maximal motor unit recruitment whilst avoiding jerking.
• Extrinsic Force MUST be GREATER than Intrinsic Force for test completion and validity.
• If an Extrinsic force is applied, the HNS will remain in the neutral test position unless the Intrinsic Force is exceeded by the Extrinsic Force.
• An Extrinsic Force overload will result in Loss of the neutral test position, and this defines the test End Point.
• The End Point represents the HNS Isometric Force Maxima of the Intrinsic Force relative to that test set up and position which can be measured and recorded.
• If the HNS Isometric Force Maxima End Point is not achieved by an applied extrinsic force, the HNS will not move. The resultant Extrinsic force measurement therefore does NOT represent a Force Maxima but an Isometric Force Sub Maxima of the Intrinsic Force.
• Timing out a held Sub Maxima Force also does NOT define or represent a Force Maxima.
• Auto Testing
• Compression load cell
• Timed End Point i.e. Load cell bleep when the input does not increase for 3 seconds.
The TEST must have three basic reproducible elements:
1. A defined Start Point
2. An appropriate application of an Extrinsic force Maxima
3. A defined End Point
Failure to adhere to any one of these basic elements will invalidate the test data
This paper fails on points 2 and 3.
It is important to note that the extrinsic force maxima of all test positions cannot be shown to be GREATER than the Intrinsic force maxima on any of the tests shown in this paper and therefore the input data is flawed and invalid.
Please try the Side Flexion test with your hand and see if you can exert sufficient force to overcome the cervical side flexors by moving the head out of the test position.
You simply cannot because our research shows that the extrinsic force maxima of this test set up is at least 25% lower than the intrinsic force maxima.
Therefore, all tests will register a sub maxima intrinsic score that is equates to the extrinsic force maxima.
Don Gatherer MCSP