Sevim 2004.

Methods	Randomised, single‐blind controlled trial Blinded assessors Ethics approval and informed consent obtained
Participants	Total N = 120 participants (120 wrists) Intervention group 1 N =30 wrists randomised, 28 wrists completed Intervention group 2 N = 30 wrists randomised, 29 wrists completed Intervention group 3 N = 60 wrists randomised, 28 wrists completed Intervention group 4 N = 23 wrists completed* 16 males, 92 females** Mean ± SD (range) age:** Total sample: 46.27 ± 10.24 yrs (range 23 to 71 yrs) Intervention group 1: 43.89 ± 10.54 yrs (range not reported) Intervention group 2: 45.45 ± 11.60 yrs (range not reported) Intervention group 3: 49.71 ± 9.75 yrs (range not reported) Intervention group 4: 46.00 ± 7.90 yrs (range not reported) Mean ± SD (range) duration of CTS symptoms: Total sample: Range 5 months to 30 years (mean ± SD not reported) Inclusion criteria: 1. Referred to the electroneuromyography (ENMG) laboratory for the evaluation of CTS with symptoms including nocturnal paraesthesias, pain in the median nerve distribution during activity, or numbness in the median nerve distribution. 2. Abnormal median sensory nerve conduction values.  Exclusion criteria: 1. Patients with secondary CTS (i.e. those with diabetes mellitus, hypothyroidism, rheumatic disease, previous wrist trauma) 1. Patients with coincident cervical radiculopathy or ulnar‐radial neuropathy 2. Patients younger than 18 years 3. Patients who had previous surgical treatment of CTS, used splints in the last 6 months or received steroid injections for CTS 4. Patients with a median motor distal latency longer than 6 ms on ENMG examination 5. Pregnant women. 6. Patients with a median nerve distal motor latency longer than the reference values underwent needle electromyography of the abductor pollicis brevis muscle, and those with fibrillation potentials, positive sharp waves or chronic neuropathic changes (decreased recruitment pattern, long duration or high amplitude of motor unit potentials) at needle electromyography were excluded 7. Patients with both normal motor and normal sensory conduction values
Interventions	Intervention group 1: Proximal steroid injection containing 3 mg betamethasone disodium phosphate and 3 mg betamethasone acetate suspension (Celestone Chronodose), mixed with 0.5 cc of a lidocaine HCl solution (Aritmal ampul 2%, 5 cc). The injection site was the volar side of the forearm 4 cm proximal to the wrist crease between the tendons of the radial flexor muscle; the long palmar muscle and the needle was inserted with an angle of 10º to 20º before injection of the solution. All the participants were injected once.  Intervention group 2: Distal steroid injection containing 3 mg betamethasone disodium phosphate and 3 mg betamethasone acetate suspension (Celestone Chronodose), mixed with 0.5 cc of a lidocaine HCl solution (Aritmal ampul 2%, 5 cc). The needle was inserted at the anterior wrist flexion crease just near to ulnar side of the palmaris longus tendon and angulated 45º distally as well as 45º radially. All the participants were injected once.  Intervention group 3: Splinting was performed by placing a standard lightweight wrist splint with a metal strip extending across the wrist to the midpalm region. The splint was bent so the wrist would be in neutral position (0° to 5° extended). The participants were instructed to wear the splints every night and to mark each night that they had worn the splints on a calendar. Splints were instructed to be worn every night until the 1‐year follow‐up (average 11 months, range 9 to 14).  Intervention group 4: Control group formed by the subset of participants who were randomised to the splint group but who did not comply with wearing the splint 6 to 7 days per week during the 1 year treatment period (average 11 months, range 9 to 14), and instead wore the splint less than 1 night per week.
Outcomes	Outcomes assessed at baseline and at the end of 12 months treatment (average of 11 months post start of treatment, range 9 to 14 months):  1. Neurological symptoms measured by two clinicians using a structured questionnaire regarding possible symptoms of CTS: numbness, pain, paraesthesia, swelling, sense of swelling, drying or/and colour change in the related hand; numbness, pain, paraesthesia of the forearm and arm; provocation of symptoms by housework, reading and driving; existence of night symptoms; awakening due to night symptoms; frequency of night symptoms; numb hand upon awakening in morning; and mean duration of any symptom throughout the day. The severity of each symptom was graded from 0 to 3 (0, no symptom; 1, mild; 2, moderate; 3, severe). The sum of all complaint scores gave a total neurologic symptom score (NSS) for each participant. The authors do not indicate what the possible total NSS was.  2. Nerve conduction studies: median antidromic sensory nerve conduction studies of digits I, II and III (m/s), ulnar sensory nerve conduction study of digit V (m/s), median‐versus‐ulnar digit IV antidromic sensory distal latency difference (ms), mean antidromic median sensory action potential amplitude of the 3 digits (digits I, II and III) (uV)***, median motor nerve conduction (m/s)***, ulnar motor nerve conduction (m/s)***, median second lumbrical‐versus‐ulnar interossei distal motor latency (ms). 3. Adverse effects: the authors did not report how and when adverse effects were recorded.
Notes	*Control group was formed by the subset of participants who were randomised to the splint group but who did not comply with wearing the splint 6 to 7 days per week during the treatment period, and instead wore the splint less than one night per week. As a result, we chose not to include any outcome data from this study in the review, due to the high risk of bias associated with breaking the randomisation schedule. **Data only reported for participants available for follow‐up analysis (n = 108). ***Data not reported in the publication. Each participant contributed only one CTS‐affected wrist to the study, so a unit of analysis error resulting from the correlation between two wrists in bilateral CTS participants could not have occurred.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were randomly assigned to one of the 3 groups: splint group (60 patients), distal injection group (30 patients) and proximal injection group (30 patients)." Comment: Not enough information to determine the adequacy of the randomisation sequence generation.
Allocation concealment (selection bias)	Unclear risk	Quote: "Patients were randomly assigned to one of the 3 groups: splint group (60 patients), distal injection group (30 patients) and proximal injection group (30 patients)." Comment: Not enough information to determine whether the allocation sequence was adequately concealed until interventions were assigned.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: Due to the nature of the interventions, participants and personnel were aware of which treatment they received.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "Two authors (HK and MA), blinded to the electrophysiologic findings and treatment methods of the patients throughout the study, assessed the patients using a structured questionnaire regarding possible symptoms of carpal tunnel syndrome." Quote: "Electrophysiological examinations were performed on the chosen hand of each patient before and after the treatment, by the same author (SS) who was blinded to treatment methods and historical data throughout the study." Comment: Outcome assessors were probably blind to treatment allocation.
Incomplete outcome data (attrition bias) 3 months or less	High risk	Quote: "At the end of 11 months (range, 9 to 14 months), contact with one patient from the proximal injection group and one from the distal injection group were lost for follow‐up. Another patient from the proximal injection group refused the electrophysiologic follow‐up examination. These 3 patients were dropped from the final analysis. Of the 60 participants in the splint group, 9 wore the splints on average 1‐5 nights per week and were excluded. Twenty‐three from this group wore the splints less than 1 night per week and were considered to form a control group. The remaining 28 patients wore the splints 6‐7 nights per week and they were taken as the properly used splint group. Thus, follow‐up evaluation was performed on 28 patients from the proximal injection group, 29 from the distal injection group, 28 from the splint group and 23 from the control group. These 108 participants were re‐evaluated by the same methods used at baseline and by the same physicians." Comment: Withdrawals and reasons for these were clearly reported. Participants who did not adhere to the splint protocol were either excluded from the analysis or entered into a 'control' group. The rationale for this method was not reported, and this 'as‐treated' analysis is likely to have biased the results
Selective reporting (reporting bias)	High risk	Comment: Median nerve motor distal latency, F wave latency, F wave persistency, median nerve compound action potential and median nerve sensory action potential amplitudes were not pre‐specified in the Methods section, but were reported in Results as being either significantly or non‐significantly reduced compared with baseline in the splint group (but no data were reported, and the result of this outcome for the remaining three groups was not reported at all). Ulnar sensory nerve conduction of digit V and ulnar motor nerve conduction were pre‐specified in the Methods section, but were not reported for any group in the Results.
Other bias	Low risk	Comment: No other sources of bias identified.