Flexor tendon injuries are some of the more common injuries, but the injuries hand surgeons manage are complex. The flexor tendon mechanism plays a key role in the function of the hand. Physiotherapists and occupational therapists are often involved and play a key role in post-surgery recovery Rehabilitation for flexor tendon repair. A good understanding of the clinically relevant anatomy of these injuries and the healing phases of the therapeutic program of rehabilitation are essential for satisfactory outcomes in patients with flexor tendon injuries.
The 8 minute video below provides a good overview of the main features of flexor tendon injury treatment and anatomy.
Epidemiology of Flexor Tendon Injuries
- 33.2 injuries per 100 00 person-years
- The age group with the highest incidence of injuries is 20-29 years old with an average age of 35 years
- Higher incidence in males
- Injuries are significantly associated with age
- Incidence is inversely proportional to age (injuries decrease with age) 
- Extensor tendon injuries are more frequent than flexor tendon injuries 
- Most cases involve a single tendon Extensor tendon injuries involve zone III of the index finger and flexor tendons involve zone II of the index finger 
- Common injuries of glass or metal cuts by saws used by those engaged in physical construction work 
- Also common in people who work in food preparation as a result of a knife injury
- In recent years, the media has highlighted the increase in tendon injuries due to poor avocado deseed technique. In studies, the number of avocado-related knife wounds to the hands has been reported to be increasing
Clinically Relevant Anatomy
Tendons that may be involved include:
- Flexor hallucis longus (flexed tip of the thumb)
- Finger flexors (finger flexors)
- superficial flexor digitorum (bends the middle joint of each finger)
- Flexor carpi ulnaris
- Flexor carpi radialis
For the purposes of this page, specific anatomical details regarding the flexion of the fingers and the major muscles and tendons most commonly injured will be provided.
Flexors of the Fingers
Flexor Digitorum Superficialis
- Located in the anterior fascia of the forearm deep to the pronator palmar longus teres and flexor carpi ulnaris and flexor carpi radialis.
- flexor digitorum deep and flexor hallucis longus superficial
- Muscle has a long linear origin but is thought to arise from two heads
- medial/ humeroulnar head:
- The medial epicondyle of the humerus passes through the common flexor tendon, the anterior part of the ulnar collateral ligament, and the ascending tubercle of the upper medial part of the coronoid process of the ulna
- lateral/radial head origin:
- Upper two-thirds of the anterior border of the radius
- medial/ humeroulnar head:
- Halfway down the forearm, the muscle narrows and forms four separate tendons that penetrate deep into the flexor retinaculum, where they line up in pairs to access the hand:
- Shallow pair passed to the middle and ring fingers
- Deep pair passed to the index and ring fingers
- volar surface of the base of the middle phalanx
- Flexion of metacarpophalangeal and proximal interphalangeal joints
- also contributes to flexion of the wrist
Flexor Digitorum Profundus
- Deep in the superficial flexor muscles of the medial forearm
- From the medial coronoid process of the ulna, the superior three-quarters of the anterior and medial surfaces of the ulna, and the medial middle third of the adjacent interosseous membrane
- Also arises from the aponeurosis that attaches the flexor carpi ulnaris to the posterior border of the ulna
- Part of the muscle arising from the interosseous membrane forms a separate tendon halfway up the forearm, which passes to the index finger
- The remaining tendon forms proximal to the flexor retinaculum
- Separate tendons pass below the flexor retinaculum and run side by side as deep as the superficial flexor digitorum tendon, but in the same synovial sheath
- The four tendons transmit to the respective fingers in the palm
- Base of the volar/volar surface of the distal phalanx
- flexion of distal interphalangeal joint
- Also contributes to the flexion of the proximal interphalangeal and wrist joints as it crosses several other joints in its course
Flexor Pollicis Longus
- outside of flexor digitorum profundus
- From the anterior surface of the radius between the superior radial tubercle and inferior pronator quadratus and the adjacent anterior surface of the coronoid process of the ulna
- Fibers almost reach the wrist before the tendon forms
- tendon passes below flexor retinaculum
- Volar/volar surface of the base of the distal phalanx of the thumb
- thumb interphalangeal joint flexor
- All gripping activities of the opponent are critical
- Also flexes the metacarpophalangeal joints of the thumb and wrist
Pulley System in the Hand
- The pulley system is an important anatomical structure for understanding the tendon system of the hand. 
- The function of the looped pulley system is to keep the tendon close to the bone so that the tendon does not bend during active flexion. 
- The cross pulley system is flexible and collapsible, allowing digital flexion without deforming the pulley system. 
- This is a key thing to keep in mind when treating patients with tendon repairs, as patients sometimes experience bowstring symptoms after tendon repairs. 
- Understanding the anatomy and function of the pulley system will assist the therapist in making clinical reasoning about why this occurs. 
For more information on hand pulley systems, read this Physiopedia page: Hand Pulleys
The tendon of the flexor digitorum superficialis provides an attachment to the vincula tentinum, which feeds blood vessels to the tendon. The flexor tendons are encased in a sheath. The flexor digitorum superficial and deep flexor digitorum each have two small protrusions.  These tendons are not Well vascularized, with some avascular areas receiving nutrients by diffusion. 
This mechanism puts the tendon at risk of adhesions. When adhesions are present, the tendon cannot slide freely, which can lead to limited range of motion and limited function. 
Tendon Injury Zones
It is important to know and have a good understanding of the different tendon areas as this will:
- inform treatment planning
- The type of splint design the patient needs
The tendon regions of the extensors and flexors are different. For the finger flexors, the regions are as follows :
- Zone I – Distal to the flexor fingers superficialis (FDS)
- Zone II – Insertion from the FDS to the distal portion of the A1 pulley
- Zone III – from the A1 pulley to the transverse carpal ligament
- Zone IV – the carpal tunnel
- Zone V – proximal to carpal tunnel
The thumb has its own zone distrubution:
- Zone I – distal to the interphalangeal joint (IP) of the thumb
- Zone II – between the metacarpophalangeal (MCP) and interphalangeal (IP) joints
- Zone III – near the metacarpophalangeal (MCP) volar/volar flexion crease
Mechanism of Injury
Flexor tendon injuries are usually caused by volar/hand lacerations. This may occur with neurovascular injury.  Patients usually present directly to the hospital because they likely have suffered severe lacerations.
Another injury mechanism is a rupture rather than a tear, such as a rupture of the FDP tendon from its insertion at the distal phalanx – usually this is caused by a blunt injury mechanism. This is usually caused by forceful extension during active flexion. this happened to the ball Movements in which the fingers are forced to extend when flexed, or in activities such as a player grabbing an opponent’s shirt (jersey fingers) or rock climbing. 
Depending on the location of the injury, symptoms may include:
- Loss of active flexion strength or movement of the involved fingers
- Pain when trying to bend the affected finger
- Clinical tests:
- Flexor digitorum profundus (FDP) tendon – Patient unable to flex distal interphalangeal joint (DIP) alone 
- Flexor digitorum superficialis (FDS) tendon – Isolate the involved/affected finger and ask the patient to flex the proximal interphalangeal joint (PIP)
- Flexor hallucis longus – the interphalangeal joint (IP) that flexes the thumb alone 
- X-rays – possibly with fractures
- Ultrasound – for evaluation of suspected lacerations 
- Grip strength
- Goniometer measurement
Severed or ruptured tendons require surgical repair. When a tendon ruptures, the ends separate due to tension in the tendon. Sometimes there may be a few centimeters between the cut or broken ends of the tendon. Surgical repair is necessary to restore function That has been lost. The repair can be done under general anesthesia or regional anesthesia (injection of a local anesthetic in the shoulder). During the procedure, the wound is widened so that the cut end of the tendon can be located and held together with sutures. hand after surgery The forearm is secured in a splint, the splint is placed over the bandages, and the wrist and fingers are in a slightly flexed position to protect the restoration. 
Tendon repair is a surgeon-dependent process, and the surgeon will determine the best technique for a particular tendon repair. Common restorations are four-strand or six-strand restorations.
Post-Surgical Tendon Healing
The healing phase of the tendon consists of three phases :
- the first phase
- From the first postoperative day to the seventh day
- During this phase, fibroblasts produce collagen type III and macrophages help initiate healing and remodeling
- this is the second phase
- This is from day 8 to about three weeks after surgery
- Tissue modeling through the bulk of disorganized collagen occurs at this stage
- Angiogenesis also occurs during this phase
- this is the third stage
- Occurs about 18 months after surgery
- During this stage, tension causes tissue remodeling and collagen type III is replaced by collagen type I
- This happens in a more linear fashion, which creates cross-links to strengthen the tendon
Post-Surgical Physiotherapy Management
The therapist needs knowledge of the anatomy of the pulley tendon injury zone and the stages of tendon healing, as this will inform the approach to treatment. For example, the area of the tendon injury will dictate the splint design and course of treatment. Tendon healing time and stage can affect The type of rehabilitation exercise initiated. For example, if a patient is referred for treatment 8 or 9 days after surgery, and the patient has not received any treatment, the therapist may not want to start active range of motion exercises because the tendon is at its weakest post-surgery Postoperative day 8 to 21. The therapist also needs to understand the importance of the flexor mechanism in the functional use of the hand and how flexor tendon injuries can affect the patient’s function. 
Wound and Scar Management
Postoperative wound management is the first step in resolution. Post-operative wounds can be covered with a basic silicone dressing (products such as Mepitel can be used). The fingers are wrapped in a breathable and convenient gauze material. Other products a therapist may use include Coban but A comfortable clean and dry dressing is also acceptable.
Compression dressings are used to control edema.
Once the wound has healed, scar management can begin. Silicone gel patches can be used on scars or paper strips or products used for scar management such as Fixomull. Scar massage can be done during treatment and at home to prevent adhesions. 
- Patient education is critical to the management of flexor tendon injuries. 
- Patients need to be aware of the necessary precautions.
- The wound needs to be kept clean and dry.
- The splint needs to stay in place 24 hours a day, 7 days a week.
- If the splint does need to be removed, the patient needs to be educated in safe hand positioning.
- For flexor injuries, the patient needs to keep the fingers in a neutral position on the wrist if the splint is off.
- This position does not put any stretch or tension on the tendon.
- Treatments are usually twice a week for the first two weeks after surgery.
- Weekly thereafter until about 10 weeks after surgery.
FDP and FDS Tendon Repair
- A metacarpophalangeal (MCP) extension block splint based on the forearm with the wrist in a neutral position and the MCP in approximately 30° flexion. 
- Zone I II and III injuries of the deep and/or superficial flexors
- This promotes the activation of the flexion arc by the long flexors rather than the intrinsic muscles 
- It allows for differential sliding between the FDP and FDS tendons because flexion is initiated by the FDP tendon in this position.
- If the therapist fixes the patient in a greater degree of MCP joint flexion, flexion will be initiated by the intrinsic muscles rather than the long flexor muscles. 
- Manchester short splint
- hand-based splint
- Allows for maximum wrist flexion preventing wrist extension of 45°
- MCP joints – 30° flexion
- IP joints – neutral
- The use of a Manchester sports splint appears to enhance the early digital flexion arc. This results in an improvement in DIP joint flexion and differential glide 
- Using this type of splint has shown improved results while still maintaining prosthetic integrity. 
- Dorsal forearm-based orthosis
- Reach the tip of the thumb and reach three-quarters of the length of the metacarpal bone on the back of the hand
- wrist in neutral
- Thumb slightly volarly flexed towards MCP, about 20° of flexion, IP joint in neutral
The type of orthosis/splint used by the patient is usually prescribed by the surgeon, and the therapist will need to discuss appropriate splint options with the cooperating surgeon.
The goals of rehabilitation after flexor tendon repair are :
- Preserves tendon gliding and promotes differential tendon gliding
- control early collagen deposition
- Easy to reinforce the maintenance site
- Prevents adhesive tendon gaps or re-rupture
- Provide patients with the best possible outcome after surgery
Various protocols have been developed for rehabilitation of flexor tendon repair. These procedures often use a combination of active and passive range of motion.
Practice FDS and FDP repair after surgery (first 6 weeks)
Place-and-hold Flexion Exercises
The place and hold flexion exercise involves the patient placing the finger in passive flexion and then holding it in active flexion. Many flexor tendon rehabilitation programs include placing and holding flexion exercises. However, recent studies have shown that this can lead to gaps and Force through the tendon when it suddenly needs to be activated after passive flexion. Hand therapists are ditching this exercise and instead prescribing active flexion to the half-punch and active extension to the back of the splint. 
This open-source article with video provides a good overview of why true active movement is preferred over full fist placement and hold flexion exercises: Rehabilitation after Flexor Tendon Repair: St. John’s Protocol  article.
Therapists now use more advanced protocols, rather than placement and hold exercises, and ask the patient to actively flex to half a fist and actively extend to the back of the splint. Active flexion can be initiated from the first postoperative day. However, if the patient sees only Therapists on day 8 postoperatively, and have not recovered before then, are best not to start active flexion exercises, as the tendon is at its weakest during this healing phase. 
Passive Flexion and Active Extension
- The patient can passively flex the fingers and then actively extend the fingers into the back of the splint.
- The way to prevent any PIP joint flexion adhesions is to place a ruler on the back of the splint and allow the patient to actively extend. 
Exercise Frequency and Precautions
- Patients should perform these exercises five times a day with 10 repetitions. 
- Patients always perform exercises with a splint so there is no risk of stretching fingers and breaking or putting tendons at risk.
Post-op practice FPL repair (first 6 weeks)
- Passive IP joint flexion exercises
- Passive thumb composite flexion
- Active flexion to approximately half of the patient’s active range of motion
- 10 repetitions, 5 times a day
Post-Operative Exercises after 6 weeks
For all postoperative tendon repairs – splint for 6 weeks
- After the initial 6 weeks, the patient will be off the splint to begin light functional use
- Gradually increase and grade the patient’s full active and full passive range of motion
- Strengthening can usually begin about 8 weeks after surgery
- Strengthening exercises can include the following activities:
- Squeeze Theraputty playdough or sponge in hot water
- Progress to wrist weights and Theraband if appropriate for complete upper body strengthening
- Once the patient is able to resume his/her leisure activities, is able to use hand function with few limitations, and the pain is under control, the patient can be discharged and continue with the home program of scar stretching and strengthening exercises. 
Evidence for different types of rehabilitation
In a recent systematic review by Nieduski and Powell (2019)  nine studies were compared. These studies investigated early active movement (EAM) or true active flexion, as opposed to early passive or maintained flexion, to determine which is the most appropriate and scientific approach support. The primary outcome measure was total active movement (TAM).
Early Active Motion
Two studies investigated progressive protocols that required modification of the hand’s position in a protective orthosis following flexor tendon repair. The metacarpophalangeal flexion is reduced to 30° and combined with the hand orthosis. 
In the study by Peck et al. (2014)  wrist mobilization and immobilization were compared and light use of the affected hand was allowed in the immediate postoperative period. At 12 weeks, no significant differences were found between the two study groups in terms of total voluntary movement or disruption. However The group using the hand-based orthosis did show significant improvements in DIP flexion and PIP extension compared to participants wearing the forearm-based splint.
Early Passive Flexion and Place-and-Hold
A total of four studies investigated and compared early passive flexion and placement and retention protocols. Moderate evidence was provided that holding exercises at 8 weeks significantly improved total active movement compared with passive flexion exercises. This is only the case with patients Double strand zone II restoration. 
Further Findings of Systematic Review
Tendon repair strength of at least four strands is required to withstand the forces of true active movement 
There is moderate to high level of evidence that place and hold exercises provide better outcomes than passive flexion protocols (including Kleinert and modified Kleinert protocols) in patients with two to six-strand repairs 
Among patients over 30 years of age who underwent double-strand repair, those who underwent a true active protocol achieved greater total active motion at 12 weeks compared to those who followed a passive flexion protocol 
Well-designed intervention studies are necessary to support movement towards progressive protocols with truly active movement and reduced wrist fixation. 
Some red flags for the therapist to be aware of when treating a patient with a flexor tendon injury include :
- Watch for ruptures, especially during the first session of six-week splinting.
- Signs of tendon rupture may include:
- FDP Tendon – When the joint is isolated, the patient may show signs of flexion of the DIP joint with no movement
- FDS tendon repair – when the PIP is isolated, the patient may not have any active flexion of the PIP joint
- FPL tendon repair – patient may not have any isolated IP joint flexion
- It is important to contact the surgeon immediately if there is any concern about a patient with a ruptured tendon.
- There is a risk of infection with any surgery, and it is important to contact your surgeon if you develop any signs of infection.
- Signs of infection to look out for:
- Redness of and around the wound
- Presence of pus or cloudy wound drainage
- Increased temperature or fever around the wound
- Bad odour coming from the wound
- Especially in patients who have undergone FDS and FDP tendon repair
- If patients develop contractures, they sometimes require dynamic splinting around 8-10 weeks post-op
- It is important that the patient exercises with a dorsal block splint during the first 6 weeks and encourages active extension, especially of the PIP joint into the back of the splint, to prevent contractures. It also prevents flexion adhesions and PIP joint contractures.
- Scar Adhesions
- Scar adhesions limit the arc of flexion and range of motion of the patient’s fingers for active and passive movement as well as flexion and extension.
- Massaging the scar as much as possible is necessary to allow the skin to slide freely over the underlying tendon
- It is important to prevent sticking from the start
- If there are significant adhesions, it is an indication that the patient may need tenolytic surgery or tenolytic surgery.
- Loss of sensation
- Sometimes, patients have some minor nerve damage at the time of the injury that does not require surgical repair, but develops symptoms of nerve damage during the six-week splinting process. These symptoms include:
- Numbness, tingling, or pins and needles in the affected finger
- It is important to discuss these signs and symptoms with your surgeon, as further surgery may be required if the nerve is torn and does not heal conservatively.
- Sometimes, patients have some minor nerve damage at the time of the injury that does not require surgical repair, but develops symptoms of nerve damage during the six-week splinting process. These symptoms include:
Key Concepts to Remember
Some key information to keep in mind in the management of flexor tendon injuries :
- Know your anatomy
- This helps with treatment planning and understanding of the patient’s injury.
- Familiarize yourself with the patient’s medical history
- Understand the mechanism of injury
- Learn about surgery dates and surgery details
- Is it delayed surgery? Are the tendons frayed?
- Knowing this information will guide your treatment approach.
- If the tendon is worn or repaired tightly – the patient may not be able to regain full range of motion. This is important in setting realistic expectations for the desired outcome for the therapist and patient
- Communicate with the surgeon
- This is important in designing joint treatment options for patients with flexor tendon repairs
- These patients can have quite complex injuries and good and clear communication with the surgeon will help in understanding the rehabilitation needed and will also benefit the patient
- keep the tendon gliding to prevent adhesions
- Aim for an active range of motion when possible
- Attempt to have the patient start rehabilitation exercises before postoperative day 7
- This will help prevent scar tissue formation and adhesions.
- Be aware of and look out for red flags
- possible complications
Other Examples of Rehabilitation Programs
After optimizing the repair, the team of therapists works with the surgeon to select a rehabilitation plan that will both protect the repair and help maintain tendon glide. Rehabilitation guidelines are useful, but clinical reasoning should always be an integral part of flexor tendon management Injuried. Many factors affect treatment decisions, such as:
- repair technique
- associated tendon healing
- passive versus active range of motion
- tendon adhesions
These factors can help guide rehabilitation progression and promote functional range of motion to safely move the repaired tendon and prevent gap rupture and adhesions. [twenty one]
Here are some examples of rehabilitation programs for flexor tendon injuries:
- Brigham and Women’s Hospital. Department of Rehabilitation Services. Zones 2-5 Flexor Tendon Repair Protocol
- Rehabilitation After Flexor Tendon Repair: The St. John’s Protocol
- Flexor Tendon Repairs
- Manchester Protocol
- Treatment protocols for the hands (this document outlines various protocols, including the Kleinert modified Kleinert and Duran protocols)
- ↑ J Knight Flexor tendon surgery Available from: https://www.youtube.com/watch?v=nrZdYJdrSCo&app=desktop (last accessed 8.12.2019)
- ↑ Jump up to:2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 de Jong JP, Nguyen JT, Sonnema AJ, Nguyen EC, Amadio PC, Moran SL. The incidence of acute traumatic tendon injuries in the hand and wrist: a 10-year population-based study. Clinics in orthopedic surgery. 2014 Jun 1;6(2):196-202.
- ↑ Jump up to:3.0 3.1 3.2 3.3 3.4 Manninen M, Karjalainen T, Määttä J, Flinkkilä T. Epidemiology of flexor tendon injuries of the hand in a Northern Finnish population. Scandinavian journal of surgery. 2017 Sep;106(3):278-82.
- ↑ Farley KX, Aizpuru M, Boden SH, Wagner ER, Gottschalk MB, Daly CA. Avocado-related knife injuries: describing an epidemic of hand injury. The American journal of emergency medicine. 2020 May 1;38(5):864-8.
- ↑ Jump up to:5.0 5.1 5.2 5.3 Palastanga NP, Field D, Soames R. Anatomy and Human Movement: Structure and Function. 5th Edition. Edinburgh: Butterworth Heinemann, Elsevier. 2006.
- ↑ Jump up to:6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 6.16 Thorn, K. Flexor Tendon Injury Management. Course, Plus. 2020.
- ↑ Jump up to:7.0 7.1 7.2 7.3 Klifto CS, Capo JT, Sapienza A, Yang SS, Paksima N. Flexor tendon injuries. JAAOS-Journal of the American Academy of Orthopaedic Surgeons. 2018 Jan 15;26(2):e26-35.
- ↑ Jump up to:8.0 8.1 8.2 Ortho bullets Flexion tendon injuries Available from: https://www.orthobullets.com/hand/6031/flexor-tendon-injuries (last accessed 8.12.2019)
- ↑ Cole KP, Uhl RL, Rosenbaum AJ. Comprehensive review of rock climbing injuries. JAAOS-Journal of the American Academy of Orthopaedic Surgeons. 2020 Jun 15;28(12):e501-9.
- ↑ Jump up to:10.0 10.1 10.2 Khor WS, Langer MF, Wong R, Zhou R, Peck F, Wong JK. Improving outcomes in tendon repair: a critical look at the evidence for flexor tendon repair and rehabilitation. Plastic and reconstructive surgery. 2016 Dec 1;138(6):1045e-58e.
- ↑ BSHH Flexor tendon injuries Available from: https://www.bssh.ac.uk/patients/conditions/26/flexor_tendon_injury#What_is_the_treatment_ (last accessed 8.12.2019)
- ↑ Jump up to:12.0 12.1 Klifto CS, Bookman J, Paksima N. Postsurgical Rehabilitation of Flexor Tendon Injuries. The Journal of hand surgery. 2019 Aug 1;44(8):680-6.
- ↑ Legrand A, Kaufman Y, Long C, Fox PM. Molecular biology of flexor tendon healing in relation to reduction of tendon adhesions. The Journal of hand surgery. 2017 Sep 1;42(9):722-6.
- ↑ Jump up to:14.0 14.1 Seaward JR, Peck F, Lees VC. Impact of Long Flexor Versus Intrinsic Dominance in the Generation of Arc of Finger Flexion. Hand. 2016 Sep;11(3):364-7.
- ↑ Jump up to:15.0 15.1 15.2 15.3 15.4 Peck FH, Roe AE, Ng CY, Duff C, McGrouther DA, Lees VC. The Manchester short splint: a change to splinting practice in the rehabilitation of zone II flexor tendon repairs. Hand Therapy. 2014 Jun;19(2):47-53.
- ↑ Jump up to:16.0 16.1 Higgins A, Lalonde DH. Flexor tendon repair postoperative rehabilitation: the Saint John protocol. Plastic and Reconstructive Surgery Global Open. 2016 Nov;4(11).
- ↑ Rehab My Patient. How to use putty to strengthen your fingers. Available from https://www.youtube.com/watch?v=zWN8qSIDGjQ. [last accessed 15 September 2020]
- ↑ Rehab My Patient. How to get your grip back after injury. Available from https://www.youtube.com/watch?v=4NZ2drULuzc [last accessed 15 September 2020]
- ↑ Rehab My Patient. How to improve finger strength using putty. Available from https://www.youtube.com/watch?v=wtSn4B8lKm4 [last accessed 15 September 2020]
- ↑ Jump up to:20.0 20.1 20.2 20.3 20.4 20.5 Neiduski RL, Powell RK. Flexor tendon rehabilitation in the 21st century: A systematic review. Journal of Hand Therapy. 2019 Apr 1;32(2):165-74.
- ↑ Kannas S, Jeardeau TA, Bishop AT. Rehabilitation following zone II flexor tendon repairs. Techniques in hand & upper extremity surgery. 2015 Mar 1;19(1):2-10. Available from: https://www.ncbi.nlm.nih.gov/pubmed/25700105 (last accessed 9.12.2019)