Dear Editor,

We have read the respective article, and we agreed to all stated observations and recommendations. This is a very useful article for many researchers and especially for the scientists working with addiction sciences.

We would just like to emphasise on the use of quantitative assays for the cognitive molecules (Lee et al., 2009) beside doping test. Mental performance is the attribute of three different interconnected domains; namely, Memory, attention and creativity. Many of the neuro-circuits and different specific molecules, involved in such pathways have been reported in this modern era of technology. Millions of smart drugs or nootropic drugs have been reported targeting these specific molecules.

We believe even though the doping test as per its principle is a general test available but at the same time, there is a need of looking at the molecular mechanisms which may vary from one individual to other and yes, if there is no effect on the cognitive molecules, then as per stated in the title, depending on the use of specific smart drug for targeting either memory or attention or creativity must have raised the said molecule and such molecules are needed to be quantified in the executives inclusive of the coaches in the team for a better understudying of the specific fraction of mental performance Vs doping test.

Conflict of Interest:

None declared

Dear Editor,

We thank Dr. Bollen for his interest in our paper on knee arthroscopy for the middle-aged and older patient with a painful knee (Thorlund et al. 2015a,b).

The consistent high-level evidence (Thorlund et al. 2015a,b; Khan et al. 2015) questioning the benefit of arthroscopic surgery has so far had a very limited effect on the practice of arthroscopic surgery in middle-aged and older patients with a painful knee and suspected meniscus or cartilage lesion (Cullen et al. 2009, Bohensky et al. 2012, Dearing and Brenkel 2010, Lazic et al. 2014, Thorlund et al. 2014).

Yet, patients included in the randomized controlled trials analyzed in the recent systematic reviews (Thorlund et al. 2015a,b; Khan et al. 2015) comprise the dominant patient group routinely treated with arthroscopic knee surgery. Thus, 3 out of 4 patients arthroscopically treated for suspected meniscus rupture, cartilage lesion or osteoarthritis of the knee are reported to be older than 35 (Roos and Lohmander 2009, Cullen et al. 2009, Bohensky et al. 2012, Dearing and Brenkel 2010, Thorlund et al. 2014, Mattila et al. 2015). Further, a recent characterization of patients treated with arthroscopic surgery found that half had a diagnosis of old meniscus tear or osteoarthritis (Bergkvist et al. 2015). These studies collectively show that a large proportion of arthroscopic surgeries performed are done in patients where current high- level evidence does not support the benefit of arthroscopic surgery over non-surgical treatment.

Arguments that favor arthroscopy focus on patient subgroups among the middle-aged and older with a painful knee, such as those with "mechanical symptoms", where arthroscopic surgery is claimed to be effective. However, criteria for such subgroups remain to be defined, and the benefit of arthroscopic surgery over non-surgical intervention to be shown in well designed studies. Indeed, the devil lives in the details.

Dr. Bollen fails to recognize that even extensive clinical impressions can be very deceiving (Cobb et al. 1959, Wartolowska et al. 2014), and that multiple psychological mechanisms are activated when faith in clinical experience is questioned by systematically collected evidence. These mechanisms are inherently human, and are likely applicable also to orthopaedic surgeons. When high level evidence speaks against clinical experience and unquestioned routine, cognitive dissonance results. Defenders of questioned treatments focus on potential scientific flaws in the published trials to invalidate trial results to decrease their level of cognitive dissonance, while at the same time they ignore the inherent bias of clinical experience (Horton 1996, Miller & Kallmes 2010). Another universal human trait is confirmation bias that makes us ignore, or not want to be exposed to, information or opinions that challenge what we already believe, while we readily accept information and beliefs that confirm what we already believe. This leads to overconfidence in personal beliefs and reinforces beliefs in the face of contrary evidence. The effects are stronger for emotionally charged issues and deeply entrenched views (Prasad et al. 2012, Aspenberg 2014, Lohmander and Roos 2015). A further contributing factor to lacking implementation of high-level evidence contrary to unquestioned routine is the organization of the care pathway which can create perverse incentives to maintain procedure rates (Hamilton and Howie 2015).

References

Aspenberg P. Mythbusting in orthopedics challenges our desire for meaning. Acta Orthop 2014;85:547.

Bergkvist D, Dahlberg LE, Neuman P, et al. Knee arthroscopies: who gets them, what does the radiologist report, and what does the surgeon find? Acta Orthop 2015;in press.

Bohensky MA, Sundararajan V, Andrianopoulos N, et al. Trends in elective knee arthroscopies in a population-based cohort, 2000-2009. Med J Aust. 2012;197:399-403.

Cobb LA, Thomas GI, Dillard DH, et al. An evaluation of internal mammary artery ligation by a double-blind technic. N Engl J Med 1959;260:1115-18.

Cullen KA, Hall MJ, Golosinskiy A. Ambulatory surgery in the United States, 2006. Natl Health Stat Report 2009;11:1-25.

Dearing J, Brenkel IJ. Incidence of knee arthroscopy in patients over 60 years of age in Scotland. Surgeon 2010;8:144-50.

Hamilton DF, Howie CR. Knee arthroscopy: influence of systems for delivering healthcare on procedure rates. BMJ 2015;351:h4720.

Horton R. Surgical research or comic opera: questions, but few answers. Lancet 1996;347:984-5.

Khan M, Evaniew N, Bedi A, et al. Arthroscopic surgery for degenerative tears of the meniscus: a systematic review and meta-analysis. CMAJ 2014;186:1057-64.

Lazic S, Boughton O, Hing C, et al. Arthroscopic washout for the knee: a procedure in decline. Knee 2014;21:631-4.

Lohmander LS, Roos EM. The evidence base for orthopaedics and sports medicine. Scandalously poor in parts. BMJ 2015;350:g7835.

Mattila VM, Sihvonen R, Paloneva J, et al. Changes in rates of arthroscopy due to degenerative knee disease and traumatic meniscal tears in Finland and Sweden. Acta Orthop 2015;in press.

Miller FG, Kallmes DF. The case of vertebroplasty trials. Promoting a culture of evidence-based procedural medicine. Spine 2010;35:2023-6.

Prasad V, Cifu A, Ioannidis JPA. Reversals of established medical practices. Evidence to abandon ship. JAMA 2012;307:37-8.

Roos EM, Lohmander LS. Young patients--old knees. Knee problems in the middle age often osteoarthritis. Lakartidningen 2009;106:1645-8.

Thorlund JB, Hare KB, Lohmander LS. Large increase in arthroscopic meniscus surgery of middle-aged and older in Denmark from 2000 to 2011. Acta Orthop 2014;85:287-92.

Thorlund JB, Juhl CB, Roos EM, et al. Arthroscopic surgery for the degenerative knee: systematic review and meta-analysis of benefits and harms. BMJ 2015a;350:h2747.

Thorlund JB, Juhl CB, Roos EM, et al. Arthroscopic surgery for degenerative knee: systematic review and meta-analysis of benefits and harms. Br J Sports Med 2015b;49:1229-35.

Wartolowska K, Judge A, Hopewell S, et al. Use of placebo controls in the evaluation of surgery: systematic review. BMJ 2014;348:g3253.

Conflict of Interest:

None declared

I would like to comment on the conclusions of the recent published meta-analysis by Thorlund et al in the BMJ and the subsequent sensationalist editorial. The conclusions are at odds with my own personal experience and that of my peer group.

Although the methodology of the study is valid I would take issue with the conclusions reached.

The meta-analysis on benefit started with nearly 1800 studies and was reduced to 10 (although in the text of the article, only 9 references are cited after this statement). The meta-analysis on harm was on a separate series starting with 2330 studies reduced to 9.

The devil is in the detail and I will address each study individually. I review papers for journals and would certainly not have allowed some of the conclusions reached in the papers, past the peer review stage.

To start with, the 9 (or 10!) studies on benefit (or not) are a mixed bunch dealing with degenerative change (3), degenerative meniscal tears (6 - 2 of which are the same study at different time intervals) or a combination of the two (1). Two papers would never pass an ethics committee in the UK and would not be considered for publication in the UK. One of the papers on meniscal injury is related to depression and anxiety and in an obscure journal. I have excluded this from my analysis as I don't generally perform surgery to improve a patients psyche and commenting on this is outside my sphere of competence.

Benefits (or lack of!)

Partial Meniscectomy

Yim et al - well conducted study but in common with other papers, diagnosis had a large reliance on MRI findings and only 2/3 of eligible patients entered the study. Patients who had any form of bony surgery were excluded. This study was performed in South Korea in a population that is very different, culturally and biomechanically from patients in the West and its findings are only directly applicable to similar populations.

Gauffin et al - This paper states that patients having surgery had significantly less pain than the non-surgery group at 12 months.

Sihvonen et al - this paper includes a sham surgery arm, which would be regarded as unethical in the UK. Of 205 eligible patients 49 were excluded. Interventions were carried out in 5 centres meaning only 30 in each centre. The authors state only meniscal surgery was performed - "no other surgical procedure was carried out". Tucked away in the supplementary appendix is the "findings at arthroscopy" - only 20% of the intervention group had no or mild degenerative change and 33% of the sham surgery group. 54% of the intervention group had degenerative change and 40% of the sham surgery group and an equal number in each group were osteoarthritic. This study only addresses intervention for one part of the knee when the pathology is likely to be multifactorial and in particular where there was no clear identification of symptoms directly attributable to a meniscal tear.

Herrlins et al's 2 papers are also interesting, being a 2 and 5 year follow up in the same cohort of patients. It is perhaps the most disturbing, in that the authors of the meta-analysis neatly discard the results and conclusions of the 5 year study "as the other outcomes are only out to 2 years". Perhaps this is because the conclusions of the 5 year outcomes are very different from those of the 2 year outcomes. Specifically - in the 2007 paper (2 year follow up) the abstract states - "arthroscopic partial medial meniscectomy alone, followed by exercise therapy was not superior to supervised exercise alone". In the 2013 (5 year follow up) paper the authors make the same statement but add "however, one third of patients from the exercise group, still had disabling symptoms but improved to the same level after surgery".

Meniscal tear and Osteoarthritis.

There is only one, widely quoted, paper in this group by Katz et al. Once again there is a large reliance on MRI diagnosis for degenerative change and meniscal tearing. Enrollment was based on one symptom, of at least 4 weeks duration, that might suggest a meniscal tear and a positive MRI. There were 7 centres involved in the study with numbers per centre ranging from119 to 17 patients. Of 1330 patients eligible for the study only 351 were enrolled. Of the 150 patients in the physical therapy group 51 had crossed to the surgery group in the first 6 months and a further 8 did so between 6-12 months. After surgery these patients improved to the level of the initially operated on patients. At 6 months 67% of surgical patients improved by 8 points on the WOMAC scale compared with 43% patients in the physical therapy group (bear in mind a third of these had crossed over to the operated group). In the UK it is very unusual to see a patient with symptoms of only 4 weeks duration and one must ask the reason why 2/3 of the patients declined to enter the study (not defined by the authors). The most likely reason in my experience is many patients will already have had physiotherapy before referral and not surprisingly, wouldn't want to be randomized to a group receiving treatment that had already failed them.

Osteoarthritis

Chang et al's paper is a small series, with 18 in one group and 14 in the lavage group ie both had an intervention. About half of each group had significant improvement at 12 months, but the authors reach the conclusion that "arthroscopic surgery may be beneficial in certain subgroups". This study is smaller than a study by Hubbard and one has to ask why Hubbards paper (see below), with a larger number of patients, wasn't included despite being almost identical in design.

Kirkley et al, again compares conservative management with conservative management + meniscal surgery. Once again 26% of those eligible did not complete the trial. The authors excluded any patient with grade 1 radiographic changes and 50% of the patients had grade 3 or 4 osteoarthritis. Generally in the UK there would be little indication for surgical intervention in more advanced OA unless there are associated mechanical symptoms.

Moseley et al's paper would again not be accepted by an English orthopaedic journal as it includes a sham surgery arm. It has already had a fairly robust rebuttal in an editorial in "Arthroscopy". Of the 324 patients eligible for the trial 144 declined to be enrolled. 25% of the patients had "severe osteoarthritis" - a group that would generally not be considered for surgery in the UK. To quote Bob Jackson "This study was seriously flawed, first by the selection of patients with no clear indication as to how severe the arthritic state was in each case. Second, patients in the Veterans Affairs system do not represent the typical population, which consists of younger people and women (97% of study patients were men). Moreover, VA patients have a vested interest in getting continued benefits for a disability. Third, the statistics used in the paper have been strongly criticized by independent statisticians, as the authors changed their direction on 3 occasions, first using an established device to show superiority of one group over another (which it did not), then using another proven device to demonstrate "equivalence" (which it did not), and then finally using an unvalidated measurement device of their own making, which did prove equivalence of the 3 groups."

Adverse Events

The authors of the meta-analysis boldly state - "Arthroscopy is associated with harms" without any qualification of this statement.

Professor Andy Carr has also recently stated in the BMJ that the death rate from arthroscopic surgery is approximately 1/1000 and deep vein thrombosis as 4 per 1000. Perhaps most worrying is this statement has been published without being referenced and despite emailing him I have not had a reply as to where these figures come from. This is, quite frankly, irresponsible of the BMJ. In my immediate group we have performed approximately 50,000 arthroscopies without a death.

The authors of the meta-analysis have been disingenuous in that they have taken a separate series of studies on complications and then applied them to the separate series of surgical results they have analysed. This cannot be logical or scientifically valid.

There are some large studies but these generally include all arthroscopic surgery, including complex ligament surgery, arthroscopic washout for septic arthritis etc, and not just meniscectomy and debridement.

Maletis et al, analyzing some 21,800 cases , report only one surgically attributable death.

Hetsroni et al quote a 2.8 /10,000 rate of pulmonary embolism but this is strongly associated with increasing age, complexity of surgery and operating time ie is not directly related to simple arthroscopic surgery.

Jameson's study included all arthroscopic surgery including ligament reconstruction, with problems once again associated with more complex surgery. Perhaps the most relevant point in this series is that a lower rate of problems was associated with high volume units. The authors state "Complications following arthroscopy of the knee are rare. It is a safe procedure."

Hame et al's paper states "post operative complications are rare", and this is in a series of patients who were all over 65 - a noted risk factor.

The authors of the meta-analysis also include 2 papers from the analysed "benefit" series in their analysis of adverse events.

Although they include the paper by Sihvonen et al the only adverse event was a deep infection, which occurred 4 months after surgery following a dental procedure and surely can't be directly attributed to the operation.

Perhaps the most interesting paper in their series is the widely quoted paper by Katz et al , which compared surgery against physical therapy followed up for 12 months. They reported 2 deaths - however one occurred in the physical therapy group! Adverse events of mild to moderate severity occurred in 15 patients post surgery and 13 in the physical therapy group. Ie physical therapy seems just as dangerous to the patient.

Discussion

I do not believe the stated conclusions of the meta-analysis can be justified by the evidence provided, and the paper does not seem to have been robustly reviewed or edited in appropriate detail. I hope I have demonstrated this in the above commentary.

In my own experience, appropriate debridement in early osteoarthritis can produce pain relief and improved function for anything up to 4 to 10 years. This has been shown in the literature in a prospective randomized, single surgeon study on consecutive patients - Hubbard MJS JBJS 1996 (for some reason not included in the meta-analysis) - which reports 50% of patients with continued pain relief at 5 years. Aichcroth et al's paper in 1991 (large number with only a small number lost to follow up) showed 75% of patients had minimal discomfort and improved function at 4 years post surgery and only 14% of patients had had to progress to further surgery. Although this study is not randomized, it was prospective and for a group of patients who had significant symptoms of significant duration who had already failed conservative management.

As far as meniscal tear goes, from the papers presented, this would seem to be a valid intervention even in series where I would take issue with some of the diagnostic criteria. It has been clearly demonstrated that diagnosis of clinically relevant meniscal tears is more sensitive and specific in the hands of an experienced knee clinician than MRI. - O'Shea K.J., et al Am J Sports Med 1996, and Gelb et al Am J Sports Med 1996.

To make the diagnosis of meniscal tear based on joint line pain and a positive MRI is clinical laziness at best. Posteromedial tenderness and fullness (often associated with a small parameniscal cyst) which mimics the patients pain, decreased flexion, pain on crouching and pain on sleeping with the knees together, almost always results in immediate pain relief flowing arthroscopic resection of the tear.

Even despite the poor clinical discrimination, 30% of patients failed conservative management with "continuing disabling symptoms" and were provided with pain relief on surgical intervention. An intervention which, in skilled hands is quick, relatively painless, and has a very, very low morbidity.

The authors state "these finding do not support the practice of arthroscopic surgery for middle aged or older patients with knee pain with or without signs of osteoarthritis" without defining the cause of the pain. This statement is not supported by the evidence provided. A summation of erroneous conclusions does not equate to a new "evidence based" conclusion. To baldly state "arthroscopy is associated with harms" with having looked at the complication rate specifically for simple uncomplicated arthroscopic surgery is unacceptable and should not have been allowed through by the editorial team.

The worry is that symptomatic patients will be denied appropriate treatment based on the findings of this "scientific study" which are in reality not scientifically valid. As is so often the case, it is the surgeon performing the procedure and not the procedure itself that is critical in getting a good outcome.

Steve Bollen Consultant Orthopaedic Surgeon.

Conflict of Interest:

None declared

It is common practice to refer lower limb injuries as non-contact, in this paper the categories have been clearly defined. The term pressing needs defining which may help the non soccer community. All lower limb injuries in football ought to be categorised as contact or in-direct contact with respect to the ground or an opponent. The principles of the Laws of Motion from Newtonian mechanics and basic physics might add further an understanding of patterns of movement and relative contact with the ground and the opponent. References: Bunn, JW (1972) Scientific principles of coaching. Englewood Cliffs,New Jersey. Armenti,A (1992) The Physics of Sports. Springer-Verlag, New York.

Conflict of Interest:

None declared