Saluran saraf biokejuruteraan dan balutan untuk pembaikan saraf periferi anggota atas
Appendices
Appendix 1. Types of outcome measurement
Outcome measurements that currently prevail in the literature are British Medical Research Council (BMRC) motor and sensory grading system, Semmes Weinstein Monofilament (SWM) test, and static or moving 2‐point discrimination (s/m2PD). Neurophysiological and magnetic resonance imaging (MRI) assessment modalities are not routinely employed in the postoperative period at present (Chemnitz 2015). The Rosén Model Instrument is becoming increasingly recognised as a comprehensive assessment tool of integrated function, but is yet to be adopted throughout the literature. Ideally, following peripheral nerve surgery a holistic evaluation of outcome would be made. This would be performed at regular and defined postoperative periods and comprise an objective, sensitive analysis of integrative function (e.g. The Model Instrument, Rosén 2000), accurate biodynamic outcome analysis (Pruszynski 2014), or vibrotactile perception (Dahlin 2015). Combined with participant‐reported outcome measurements investigating the individual's perception of performance over a series of tasks, this would allow more detailed evaluation. Currently, resource limitations and clinical practicalities necessitate the pragmatic use of less rigorous measurements of outcome in most studies.
The BMRC Motor Grade assesses motor function on a 6‐point scale, with ability to overcome gravity and comparison to the contralateral limb providing important benchmarks.
| BMRC Motor Grade | Muscle strength |
|---|---|
| M0 | No movement is observed |
| M1 | Trace or flicker of movement or fasciculations seen |
| M2 | Muscle can exert movement when gravity is eliminated |
| M3 | Muscle can exert movement against gravity |
| M4 | Muscle strength is reduced but some movement against resistance |
| M5 | Normal movement |
The BMRC sensory grade assesses sensory recovery on a 7‐point scale, where S0 is absence of any sensory recovery and S4 is recovery of sensibility and two‐point discrimination (2‐PD) of 3–6 mm (S2 and S3 are further subdivided into S2+ and S3+) (Zachary 1954). Weighted pins (e.g. 5–10 g) may be used for testing pressure and pain, Von Frey's hairs are used to assess tactile sensation; these are available in various calibres, and 2‐PD is assessed with a fine caliper. The sensory scale will be interpreted critically and detailed methodology provided.
| BMRC Sensory Grade | Sensory recovery |
|---|---|
| S0 | Absence of sensibility in the autonomous area |
| S1 | Recovery of deep cutaneous pain sensibility |
| S2 | Return of some degree of some degree of superficial cutaneous pain and tactile sensibility within the autonomous area of the nerve |
| S3 | Return of some degree of some degree of superficial cutaneous pain and tactile sensibility within the autonomous area of the nerve with disappearance of any previous over reactivity |
| S3+ | Return of sensibility as in Stage 3 with the addition that there is recovery of 2‐PD within the autonomous area |
| S4 | Complete recovery |
The Model Instrument is one of the most well recognised and widely applied composite assessment tools for assessment of peripheral nerve function following repair at the distal forearm and wrist (Rosén 2000). This standardised tool correlates well with the Disability of the Arm Shoulder and Hand (DASH), a validated participant‐reported outcome measurement of perceived ability to carry out activities of daily living (Beaton 2001; Gummesson 2003). A detailed protocol of the components of the test has been published, allowing inter‐operator standardisation. Briefly, a quantitative assessment of:
-
Motor recovery – manual muscle testing and Jamar dynamometer to test motor innervation and grip strength;
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Sensory recovery – Semmes Weinstein Monofilaments (SWM) are used to assess touch/pressure thresholds, 2‐PD;
-
Tactile gnosis and dexterity – shape texture identification (STI) to assess as well as 3 selected tasks from the Sollerman grip test (Sollerman 1995);
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Pain/discomfort – 4‐point scale questionnaire focusing on cold sensitivity, hyperaesthesia, and allodynia is performed.
The score for each subtest is normalised by dividing by a 'normal' result – this may be predetermined or obtained by testing the uninjured, contralateral arm. The mean score is calculated for each domain and the sum of these 3 scores generates the overall score which is plotted against 'average results' and over time. This allows recording of functional recovery and a prediction of recovery, by comparison to values generated in participants with similar injuries ('average results'). As the Rosén method encompasses a spectrum of tests it requires availability of assessment tools, experienced staff, and protected time periods to conduct. This ideally would form part of ongoing routine assessment by a dedicated and experienced hand surgery team, unfortunately this limits its use in some settings. As such, although desirable, lack of this reporting outcome will not be used as exclusion criteria.
Appendix 2. Additional methods described in the protocol but not used in the review
Our protocol described additional methods that were not required for the review (Thomson 2017).
Types of studies
Where RCTs are unavailable, we will provide narrative discussion of large cohort studies that satisfy minimum quality criteria, namely adequate description of the following:
-
injury (mixed/motor/sensory nerve, adult/child/neonate, mechanism, location, size, and concomitant injuries sustained);
-
surgical procedure (gap length to be reconstructed, length of inserted nerve conduit or graft);
-
neurosynthesis technique (e.g. suture or fibrin glue);
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outcome assessment (timing relative to injury, blinding measures used, detail of measure(s) used and how applied);
-
rate of dropout from study.
We will not perform a formal non‐randomised studies meta‐analysis and we will describe the non‐randomised studies in the discussion section only.
Subgroup analysis and investigation of heterogeneity
Ideally, subgroup analysis would be performed evaluating the role of the clinical factors detailed below on outcome. However, it is anticipated that this may be limited by heterogeneity within studies that meet the inclusion criteria.
We will evaluate the clinical heterogeneity of studies prior to performing any meta‐analysis, with attention to the distribution of individuals belonging to the above subgroups between treatment arms. We will assess statistical heterogeneity using the I2 statistic (value > 50% represents substantial heterogeneity) and Chi2 test (significance level 0.1). In the case of low level of heterogeneity (I2 < 50% or P > 0.1), we will perform a meta‐analysis. In the case of significant heterogeneity among included trials, we will provide a systematic narrative synthesis instead.
We selected the following subgroup analyses as predicted and proven factors influencing nerve healing (Birch 2015; Camara 2015; Hart 2011; Hundepool 2015).
-
Length of nerve gap (none, less than 3 cm, greater than 3 cm) (Grinsell 2014).
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Nerve type (sensory, motor, or mixed) (Lundborg 1986).
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Delay from time of injury until repair (less than 48 hours, 48 hours to 2 weeks, 2 weeks to 2 months, over 2 months) (British Orthopaedic Association) (Hart 2008).
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Participant age in years (less than 12, 12 to 25, 26 to 40, and greater than 40). Younger age confers increased regenerative capacity and younger individuals may be less able to comply with assessment; therefore, where possible we will perform subgroup analysis to consider those under the age of 12 years and over the age of 40 years (Chemnitz 2013).
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Smoking status at time of surgery (smoker versus non‐smoker) (Hundepool 2015).
-
Biological versus synthetic scaffold for wrap or conduit (Hart 2011).
-
Gender (Stenberg 2014).
We will use the outcomes selected for inclusion in the summary of findings table in subgroup analyses.
We will use the formal test for subgroup interactions in Review Manager 5 (Review Manager 2020). If subgroup data were available a simple significance test to investigate differences between two or more subgroups can be performed (Borenstein 2013). This procedure consists of undertaking a standard test for heterogeneity across subgroup results rather than across individual study results and using the fixed‐effect model calculating an I2 statistic.
It is not expected that controlled studies would include participants with obstetric brachial plexus palsy; however, if they had done, we would have reported this, and considered such participants as a separate subgroup.
Sensitivity analysis
We plan to carry out the following sensitivity analyses to ensure results are robust and meaningful.
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Repeat the analysis excluding any unpublished studies.
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Repeat the analysis excluding studies at high risk of bias (non‐blinded trials, questionable randomisation methods, significant difference between treatment groups, non‐gold‐standard management in control group).
Appendix 3. Cochrane Neuromuscular Specialised Register via CRS‐Web search strategy
1 nerve* adj5 (wrap* or cuff* or tube or tubes or tubular or repair* or graft* or allograft* or autograft*) AND INREGISTER 41
2 nerve* and conduit* AND INREGISTER 7
3 #1 or #2 41
4 upper limb* or arm* or arms or hand or hands or finger* or upper extremit* AND INREGISTER 1247
5 MeSH DESCRIPTOR Upper Extremity Explode All AND INREGISTER 125
6 MeSH DESCRIPTOR Brachial Plexus Explode All AND INREGISTER 154
7 #4 or #5 or #6 1340
8 peripheral nerve injur* AND INREGISTER 49
9 injury or innervation:MH AND INREGISTER 388
10 #8 or #9 390
11 #3 and #7 and #10 22
12 INCENTRAL AND INREGISTER 7221
13 #11 NOT #12 0
Appendix 4. Cochrane Central Register of Controlled Trials (CENTRAL) via CRS‐Web search strategy
1 nerve* adj5 (wrap* or cuff* or tube or tubes or tubular or repair* or graft* or allograft* or autograft*) AND INREGISTER 41
2 nerve* and conduit* AND INREGISTER 7
3 #1 or #2 41
4 upper limb* or arm* or arms or hand or hands or finger* or upper extremit* AND INREGISTER 1247
5 MeSH DESCRIPTOR Upper Extremity Explode All AND INREGISTER 125
6 MeSH DESCRIPTOR Brachial Plexus Explode All AND INREGISTER 154
7 #4 or #5 or #6 1340
8 peripheral nerve injur* AND INREGISTER 49
9 injury or innervation:MH AND INREGISTER 388
10 #8 or #9 390
11 #3 and #7 and #10 22
12 INREGISTER 7877
13 #11 NOT #12 0
Appendix 5. MEDLINE (OvidSP) search strategy
Database: Ovid MEDLINE(R) ALL <1946 to January 25, 2022>
1 ((Randomized Controlled Trial or Controlled Clinical Trial or Pragmatic Clinical Trial).pt. or (Randomi?ed or Randomly or Placebo or Trial or Groups).ab. or Drug Therapy.fs.) not (Animals not (Humans and Animals)).sh. (4579543)
2 ((nerve*1 adj5 (wrap* or cuff* or tube or repair* or graft* or allograft* or autograft*)) or (nerve*1 and conduit*1)).mp. (13687)
3 (upper limb* or arm*1 or hand*1 or finger*1 or upper extremit*).mp. or exp upper extremity/ or exp Brachial plexus/in (903633)
4 Peripheral Nerve Injuries/ or (in or ir).fs. (394474)
5 1 and 2 and 3 and 4 (146)
6 limit 5 to ed=20201212‐20221231 (4)
7 limit 5 to dt=20201212‐20221231 (1)
8 6 or 7 (4)
Appendix 6. Embase (OvidSP) search strategy
Database: Embase <1974 to 2022 week 03>
1 Randomized controlled trial/ (691698)
2 Controlled clinical study/ (464804)
3 random$.ti,ab. (1744987)
4 randomization/ (92766)
5 intermethod comparison/ (278912)
6 placebo.ti,ab. (335163)
7 (compare or compared or comparison).ti. (554914)
8 ((evaluated or evaluate or evaluating or assessed or assess) and (compare or compared or comparing or comparison)).ab. (2430077)
9 (open adj label).ti,ab. (93908)
10 ((double or single or doubly or singly) adj (blind or blinded or blindly)).ti,ab. (252422)
11 double blind procedure/ (191507)
12 parallel group$1.ti,ab. (28712)
13 (crossover or cross over).ti,ab. (114316)
14 ((assign$ or match or matched or allocation) adj5 (alternate or group$1 or intervention$1 or patient$1 or subject$1 or participant$1)).ti,ab. (370900)
15 (assigned or allocated).ti,ab. (436768)
16 (controlled adj7 (study or design or trial)).ti,ab. (397303)
17 (volunteer or volunteers).ti,ab. (263950)
18 human experiment/ (561857)
19 trial.ti. (348228)
20 or/1‐19 (5632908)
21 (random$ adj sampl$ adj7 ("cross section$" or questionnaire$1 or survey$ or database$1)).ti,ab. not (comparative study/ or controlled study/ or randomi?ed controlled.ti,ab. or randomly assigned.ti,ab.) (8833)
22 Cross‐sectional study/ not (randomized controlled trial/ or controlled clinical study/ or controlled study/ or randomi?ed controlled.ti,ab. or control group$1.ti,ab.) (296038)
23 (((case adj control$) and random$) not randomi?ed controlled).ti,ab. (19353)
24 (Systematic review not (trial or study)).ti. (197153)
25 (nonrandom$ not random$).ti,ab. (17508)
26 "Random field$".ti,ab. (2632)
27 (random cluster adj3 sampl$).ti,ab. (1402)
28 (review.ab. and review.pt.) not trial.ti. (957287)
29 "we searched".ab. and (review.ti. or review.pt.) (39966)
30 "update review".ab. (119)
31 (databases adj4 searched).ab. (47817)
32 (rat or rats or mouse or mice or swine or porcine or murine or sheep or lambs or pigs or piglets or rabbit or rabbits or cat or cats or dog or dogs or cattle or bovine or monkey or monkeys or trout or marmoset$1).ti. and animal experiment/ (1134805)
33 Animal experiment/ not (human experiment/ or human/) (2381946)
34 or/21‐33 (3870082)
35 20 not 34 (4993846)
36 ((nerve*1 adj5 (wrap* or cuff* or tube or tubes or tubular or repair* or graft* or allograft* or autograft*)) or (nerv* and conduit*)).mp. (19638)
37 (upper limb* or arm*1 or hand*1 or finger*1 or upper extremit*).mp. or exp upper limb/ (1301168)
38 peripheral nerve injury/ or (nerve*1 adj5 injur*3).mp. (76405)
39 35 and 36 and 37 and 38 (199)
40 limit 39 to (conference abstracts or embase) (162)
41 limit 40 to em=202050‐202203 (14)
Appendix 7. ClinicalTrials.gov search strategy
Advanced search
Condition: Nerve Injury
Study Type: select Interventional/clinical trial
Intervention: Wrap OR Tube OR Scaffold OR Cuff OR Conduit OR Bridge
First posted on or after 12/13/2020
2 studies found
Appendix 8. WHO ICTRP search strategy
On 13 December 2020, this resource was inaccessible. The following strategy is for previous search:
Advanced search
Nerve Injury in the Condition
Wrap OR Tube OR Scaffold OR Cuff OR Conduit OR Bridge in the Intervention
Recruitment status: select ALL
8 records for 8 trials found
Study PRISMA flow diagram.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Forest plot of comparison: 1 Repair using bioengineered device versus standard nerve repair, outcome: 1.5 Integrated functional outcome, assessed with Rosén Model Instrument.
Forest plot of comparison: 1 Repair using bioengineered device versus standard nerve repair, outcome: 1.9 Adverse events.
Forest plot of comparison: 1 Repair using bioengineered device versus standard nerve repair, outcome: 1.10 Device removal or revision.
Comparison 1: Repair using bioengineered device versus standard nerve repair, Outcome 1: Sensory recovery at ≥ 24 months
Comparison 1: Repair using bioengineered device versus standard nerve repair, Outcome 2: Muscle strength, assessed with BMRC motor grading at 12–24 months
Comparison 1: Repair using bioengineered device versus standard nerve repair, Outcome 3: Motor Rosén at 12–24 months
Comparison 1: Repair using bioengineered device versus standard nerve repair, Outcome 4: Sensory recovery, assessed with BMRC sensory grading at 12–24 months
Comparison 1: Repair using bioengineered device versus standard nerve repair, Outcome 5: Integrated functional outcome, assessed with Rosén Model Instrument
Comparison 1: Repair using bioengineered device versus standard nerve repair, Outcome 6: Touch threshold, measured by Semmes‐Weinstein Monofilament
Comparison 1: Repair using bioengineered device versus standard nerve repair, Outcome 7: Cold intolerance
Comparison 1: Repair using bioengineered device versus standard nerve repair, Outcome 8: Sensory nerve action potential (SNAP)
Comparison 1: Repair using bioengineered device versus standard nerve repair, Outcome 9: Adverse events
Comparison 1: Repair using bioengineered device versus standard nerve repair, Outcome 10: Device removal or revision
| Repair using bioengineered devices versus standard techniques | ||||||
| Patient or population: people undergoing peripheral nerve repair of the upper limb | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | № of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Risk with standard repair | Risk with bioengineered devices | |||||
| Muscle strength at ≥ 24 months | Not reported | |||||
| Sensory recovery at ≥ 24 months | The mean sensory recovery assessed with BMRC sensory grading in the standard repair group at 2 years was 2.75 points | The mean sensory recovery assessed with BMRC sensory grading at 2 years with bioengineered devices was 0.03 points higher | — | 28 (1 RCT) | ⊕⊝⊝⊝ | There may be no difference in therapeutic effect on sensory recovery with bioengineered devices compared to standard repair at 24 months, but the evidence is very uncertain. |
| Integrated functional outcome at ≥ 24 months Follow‐up: 2 years | The mean integrated functional outcome (RMI score) in the standard repair group was 1.875 | The mean integrated functional outcome (RMI score) with bioengineered devices was 0.17 lower (0.38 lower to 0.05 higher) | — | 60 | ⊕⊕⊝⊝ | There may be little or no difference in RMI with bioengineered devices compared to standard repair at 24 months to 5 years. At 5 years, the RMI may be slightly better after device repair than standard repair (MD 0.23, 95% CI 0.07 to 0.38; 1 RCT, 28 participants). |
| Touch threshold (score 0–1, where higher score is better) | Mean touch threshold score in the standard repair group was 0.81 | The mean touch threshold score with bioengineered devices was 0.01 higher (0.06 lower to 0.08 higher) | — | 32 (1 RCT) | ⊕⊝⊝⊝ | There may be little or no difference in touch threshold measured by Semmes‐Weinstein monofilament test with bioengineered nerve conduits compared to standard repair at 24 months. Semmes‐Weinstein monofilament test contributed to RMI data in 2 studies at 12 months. 1 further study planned to use this outcome measure but found it to be imprecise and did not report data. |
| Impact on daily living | No studies employed DASH PROM. | |||||
| Adverse events assessed as: adverse events (serious and non‐serious) Follow‐up: range 3 months to 5 years | 10 per 1000 | 68 per 1000 (17 to 280) | RR 7.15 (1.74 to 29.42) | 213 participants | ⊕⊝⊝⊝ | Use of bioengineered devices may increase adverse events compared to standard repair techniques, but the evidence is very uncertain. 2 studies included in this analysis had no adverse events. 1 study provided no information on adverse events in the standard repair group. |
| Specific serious adverse events: further surgery (device removal or revision)i assessed as: any unplanned secondary surgery to remove device Follow‐up: range 3 months to 5 years | 12/129 devices required further surgery (device removal) in the bioengineered devices group; 0/127 procedures required further surgery in the standard repair group | RR 7.61 (1.48 to 39.02) | 256 repairs | ⊕⊝⊝⊝ | The use of bioengineered devices may require more revision (device removal or revision) than standard repair but the evidence is uncertain. Unplanned removal of 12/44 devices (1/21 poly(DL‐lactide‐caprolactone) (Neurolac) devices, 8/17 silicone devices and 3/6 polyglycolic acid devices. 2 studies included in this analysis required no device removal. | |
| *The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). BMRC: British Medical Research Council; CI: confidence interval; DASH PROM: Disability of Arm Shoulder and Hand Patient‐Reported Outcome Measure; MD: mean difference; RCT: randomised controlled trial; RMI: Rosén Model Instrument; RR: risk ratio. | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded twice for imprecision, because of the very small sample size. | ||||||
| Device trade name | Material | Cost for device to repair 10 mm gap, 2 mm diameter |
|---|---|---|
| NeuroTube | Polyglycolic acid | GBP 580 exc of VAT (November 2018) |
| Neurogen PNG220 | Type I collagen | GBP 689.26 exc of VAT (Nov 2018) |
| Neurolac (Polyganics) | poly(DL‐lactide‐ε‐caprolactone) | No reply November 2018 [email protected] and info@polyganics emailed further 7 January 2019 further 18 May 2019 |
| Salubridge | Polyvinyl alcohol | No reply November 2018 [email protected] emailed further 7 January 2019 further 18 May 2019 |
| Axoguard | Porcine small intestine submucosa | USD 1000 equivalent to GBP 789.04 (April 2019) |
| Avance Axogen | Decellularised cadaveric nerve | USD 1800 equivalent to GBP 1420.28 (April 2019) |
| RevoInerv (NG02‐0203) | Porcine Type I and III collagen, bovine Type I | GBP 348 exc of VAT (January 2019) |
| exc: exclusive; GBP: Great British pounds; USD: United States dollars; VAT: value added tax. | ||
| Conduit/name | Study detail | Outcomes measured | Status | Study design |
|---|---|---|---|---|
| Registry of Avance Nerve Graft Evaluating utilization and outcomes for the Reconstruction of peripheral nerve discontinuities (RANGER) Avance, Axogen Inc. | Avance vs standard practice (epineurial suture or autologous nerve graft). Aim 5000 participants, 36 months' follow‐up | Adverse events, "improvement in function, return of meaningful recovery" | Recruiting, estimated completion December 2020, extended to December 2025 | Observational retrospective registry |
| Polynerve University of Manchester (UK) | Polynerve repair of nerve gaps 5–20 mm Aim 16 participants, 12 months' follow‐up | Adverse reactions (Clavien‐Dindo classification), 2‐PD, SWM | Recruitment complete, 17 participants, estimated completion August 2019 | Prospective observational cohort |
| Fibrin wrap or conduit University Hospital Basel (Switzerland) | Fibrin wrap or conduit vs standard practice (epineurial suture or autologous nerve graft) direct repair or > 5 mm gap digital nerves. Aim 48 participants, 6 months' follow‐up | 2‐PD, SWM, electroneurography | Recruiting, estimated completion December 2022 | Interventional case control |
| Hydrophilic polymers at repair site Vanderbilt University (Nashville, Tennessee) | Repair and topical polyethylene glycol (MiraLAX (MERCK) at repair site vs repair alone (epineurial suture or autologous nerve graft)). Within 48 hours of injury. Aim 18 participants 12 months' follow‐up | Return of nerve function as measured by BMRC classification. | Recruiting, estimated completion March 2020 | Interventional RCT |
| Reaxon Siemers, Medovent, GmBH (Germany) | Reaxon vs standard practice (epineurial suture or autologous nerve graft) < 26 mm gap digital nerves. Within 3 months of injury. Aim 76 participants, study terminated | 2‐PD, cold intolerance, Hoffmann‐Tinel‐Test, adverse reactions | Recruiting, estimated completion December 2018. January 2019 update Terminated (study was stopped due to slow participant recruitment and insufficient participant compliance) | Interventional RCT |
| Comparison of processed nerve allograft and collagen nerve cuffs for peripheral nerve repair (RECON) Axogen Inc. | Human nerve allograft vs bovine collagen repair cuff Aim 220 participants 12 months' follow‐up | 2‐PD | Recruiting Estimated completion November 2021 | Interventional RCT |
| A multicentre prospective observational study of nerve repair and reconstruction associated with major extremity trauma Johns Hopkins (Baltimore, Maryland) | Partial or complete upper extremity nerve injury, all repair types. Aim 250 participants 24 months' follow‐up | Extensive list of primary and secondary outcome measures with 2‐year follow‐up period – detail available | Active, not recruiting Estimated completion September 2022 | Prospective observational cohort |
| Chitosan nerve tube for primary repair of traumatic sensory nerve lesions of the hand (CNT) BG Unfallklinik (Frankfurt, Germany) | Chitosan nerve tube vs standard repair sensory nerves of the hands Aim 100 participants 24 months' follow‐up | 2‐PD, DASH, grip strength, range of motion, pain, cold intolerance, hypersensitivity, existence of neuromas, adverse events | Recruiting Last update July 2017 | Interventional RCT |
| Mid‐term effect observation of biodegradable conduit small gap tubulisation repairing peripheral nerve injury Peking University People's Hospital (Beijing, China) | Repair of peripheral nerve injury in the upper extremities using a biodegradable conduit Aim 150 participants 36 months' follow‐up | BMRC grading SHEN Ning‐jiang score | Active Estimated completion December 2021 | Prospective observational cohort |
| Preliminary evaluation of the clinical safety and effectiveness of the bionic nerve scaffold Xijing Hospital (China) | Preliminary evaluation of the clinical safety and effectiveness of the bionic nerve scaffold Aim 10 participants 6 months' follow‐up | 2‐PD, joint position sense and haematological tests | Recruiting Last update December 2018 | Prospective observational cohort |
| Pilot study to evaluate the reconstruction of digital nerve defects in humans using an implanted silk nerve guide Klinik für Plastische Chirurgie und Handchirurgie – UniversitätsSpital Zürich (Switzerland) | Prospective, unblinded, single‐group assignment silk nerve guide Aim 15 participants 12 months' follow‐up | Adverse events, sensory recovery 2‐PD, VAS, patient satisfaction Patient Global Impression of Change questionnaire | Recruiting Estimated completion March 2021 | Prospective observational cohort |
| CoNNECT (Conduit Nerve approximation versus Neurorrhaphy Evaluation of Clinical Outcome Trial): a study of sutureless nerve repair Queen Elizabeth Hospital Birmingham (UK) | Digital nerve injuries in upper limb, direct repair vs poly(DL‐lactide‐caprolactone) (Neurolac) nerve guide sutured vs Neurolac nerve guide no sutures Aim 240 participants 12 months' follow‐up | Static and moving 2‐PD, monofilament pressure testing, DASH, EQ‐5D, Tinel sign, pain, cold intolerance, hyperaesthesia, site, and quality of repair | Active Estimated completion January 2021 | Interventional RCT |
| Expanded access for single patient treatment of autologous human Schwann cells (ahSC) for peripheral nerve repair | Autologous, culture expanded Schwann cells seeded in Duragen collagen matrix used to repair a sciatic nerve defect | Not provided | Single participant study, 5 years' follow‐up | Single participant study |
| BMAC Nerve Allograft Study | Decellularised cadaveric nerve graft combined with unexpanded autologous bone marrow cells. Aim 15 participant recruitment, comparison to historical outcome measures obtained for Avance nerve graft. | Adverse events, Rosén Model Instrument, motor and sensory nerve conduction studies, pinch and grip strength, 1‐PD and 2‐PD | Recruiting | Single group, interventional clinical trial |
| 1‐PD: 1‐point discrimination; 2‐PD: 2‐point discrimination; DASH: disability of the arm, shoulder and hand; EQ‐5D: Euro‐Qol 5 Dimension; BMRC: British Medical Research Council; RCT: randomised controlled trial; SWM: Semmes‐Weinstein monofilament; VAS: visual analogue scale. | ||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Sensory recovery at ≥ 24 months Show forest plot | 1 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.1.1 At 5 years | 1 | 28 | Mean Difference (IV, Fixed, 95% CI) | 0.03 [‐0.43, 0.49] |
| 1.2 Muscle strength, assessed with BMRC motor grading at 12–24 months Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 1.2.1 At 18 months | 1 | 11 | Mean Difference (IV, Random, 95% CI) | 0.40 [‐0.38, 1.18] |
| 1.3 Motor Rosén at 12–24 months Show forest plot | 2 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 1.3.1 At 24 months | 2 | 60 | Mean Difference (IV, Random, 95% CI) | ‐0.09 [‐0.24, 0.05] |
| 1.3.2 At 12 months | 1 | 35 | Mean Difference (IV, Random, 95% CI) | ‐0.15 [‐0.18, ‐0.12] |
| 1.4 Sensory recovery, assessed with BMRC sensory grading at 12–24 months Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 1.4.1 At 18 months | 1 | 11 | Mean Difference (IV, Random, 95% CI) | 0.93 [‐0.09, 1.95] |
| 1.5 Integrated functional outcome, assessed with Rosén Model Instrument Show forest plot | 2 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.5.1 At 5 years | 1 | 28 | Mean Difference (IV, Fixed, 95% CI) | 0.23 [0.07, 0.38] |
| 1.5.2 At 24 months | 2 | 60 | Mean Difference (IV, Fixed, 95% CI) | ‐0.17 [‐0.38, 0.05] |
| 1.5.3 At 12 months | 2 | 65 | Mean Difference (IV, Fixed, 95% CI) | ‐2.29 [‐2.49, ‐2.09] |
| 1.6 Touch threshold, measured by Semmes‐Weinstein Monofilament Show forest plot | 2 | Mean Difference (IV, Fixed, 95% CI) | Subtotals only | |
| 1.6.1 At 24 months | 1 | 32 | Mean Difference (IV, Fixed, 95% CI) | 0.01 [‐0.06, 0.08] |
| 1.6.2 At 12 months | 2 | 65 | Mean Difference (IV, Fixed, 95% CI) | 0.05 [‐0.07, 0.17] |
| 1.7 Cold intolerance Show forest plot | 1 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 1.7.1 At 24 months | 1 | 32 | Mean Difference (IV, Random, 95% CI) | 0.11 [‐0.08, 0.30] |
| 1.8 Sensory nerve action potential (SNAP) Show forest plot | 2 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 1.8.1 At 24 months | 2 | 60 | Mean Difference (IV, Random, 95% CI) | ‐0.08 [‐1.89, 1.73] |
| 1.8.2 At 12 months | 2 | 61 | Mean Difference (IV, Random, 95% CI) | 0.23 [‐0.58, 1.03] |
| 1.9 Adverse events Show forest plot | 5 | 213 | Risk Ratio (M‐H, Fixed, 95% CI) | 7.15 [1.74, 29.42] |
| 1.10 Device removal or revision Show forest plot | 5 | 256 | Risk Ratio (M‐H, Fixed, 95% CI) | 7.61 [1.48, 39.02] |
