Jones 2007.

Methods	4 groups: (a) pyridostigmine + mixed exercise (AE+RT+FX+Balance+Relax), (b) pyridostigmine + diet monitoring, (c) placebo pyridostigmine + mixed exercise (AE+RT+FX+Balance+Relax), (d) placebo pyridostigmine + diet monitoring Length: 26 weeks. Follow‐up: none Study design: randomised clinical trial with parallel groups
Participants	Female:male: pooled: 160:5, (a) 40:0, (b) 39:0, (c) and (d) not specified Age, years (SD): pooled: 49.5 (8.1), (a) 49.1 (9.0), (b) 49.3 (7.9), (c) 49.6 (7.7), (d) 49.8 (7.9) Duration of illness, years (SD): (a) 15.0 (10.5), (b) 14.8 (9.7), (c) 16.9 (11.9), (d) 14.9 (10.6) Inclusion: adults ages 18 to 65, diagnosis of FM (ACR 1990), medically capable to participate in exercise programme Exclusion: other rheumatic disorder; current or past history of cardiovascular, pulmonary, neurological, endocrine, or renal disease that would preclude involvement in treadmill testing to VO2 max or alter the GH/IGF‐1 axis; use of the following medications: pyridostigmine, high‐dose beta‐blockers, systemic steroids; currently exercising more than 30 min per week; Beck Depression Scale score (modified for FM) ≥ 29; BMI > 45 kg/m²; pregnant or nursing women; planned surgery during study period; ongoing, unresolved disability litigation
Interventions	(a) Pyridostigmine + supervised group mixed exercise (AE+RT+FX+Balance+Relax) (n = 40) ‐ Frequency: 3/week; Duration: 60 min (30 min WU and AE, 10 min RT, 5 min FX, 5 min Balance, 10 min Relax); Intensity: AE classification both as light intensity (40% to 50% HRmax) and light to moderate intensity (10 to 12 on 0 to 20 scale on Borg's rating of perceived exertion); RT: intensity not specified; Mode: AE low‐impact, floor aerobics, RT dynamic exercise using elastic bands and free weights for all major muscle groups, FX static and non‐ballistic stretching of all major muscle groups, balance static and dynamic standing on foam and balance boards, Relax guided imagery with breathing awareness (b) Pyridostigmine + diet monitoring (diet monitoring by registered nurse) (n = 36) ‐ Frequency: 1 phone call/week, 1 visit/month; Duration: visit duration 2 hours (c) Placebo pyridostigmine + supervised group mixed exercise (AE+RT+FX+Balance+Relax) (n = 39) ‐ Frequency: 3/week; Duration: 60 min (30 min WU and AE, 10 min RT, 5 min FX, 5 min Balance, 10 min Relax); Intensity: AE at 40% to 50% HRmax or 10 to 12 out of 20 on Borg's rating of perceived exertion (light intensity); RT: intensity not specified; Mode: AE low‐impact, floor aerobics, RT dynamic exercise using elastic bands and free weights for all major muscle groups, FX static and non‐ballistic stretching of all major muscle groups, Balance static and dynamic standing on foam and balance boards, Relax guided imagery with breathing awareness (d) Placebo pyridostigmine + diet monitoring – diet monitoring by registered nurse (n = 39) ‐ Frequency: 1 phone call/week, 1 visit/month; Duration: visit duration 2 hours
Outcomes	Health‐related quality of life (FIQ Total, Quality of Life Scale), pain (FIQ), fatigue (FIQ), depression (BDI‐R, FIQ), sleep (FIQ), stiffness (FIQ), tenderness (TP count, Total Myalgic score), anxiety (FIQ), cardiorespiratory max (Treadmill Test Balke Protocol modified for FM‐VO2 max, time), muscle endurance (# sit‐to‐stand in 30 s), flexibility (forward reach in long sitting, overhead external rotation to behind back internal rotation), balance (Flamingo stand); other: side effects of med/placebo (count), % body fat (skin fold test, bioelectrical impedance), hormone levels Measurements: 0 and 26 weeks
Adherence	(a) and (c): analysis included only participants who attended > 50% of sessions (b) and (d): not specified
Congruence of EX protocol with ACSM criteria for aerobic, strength or flexibility	(a) and (c): AE: met criteria specified for moderately to highly deconditioned individuals; RT: not enough information to determine; FX: no (5 min duration/session too short)
Notes	Country: United States of America Language: English. Author contact: n/a Trial registry record or protocol available: none Funding source: National Institute of Nursing Research grant 5R01‐NR‐8150‐4, General Clinical Research Center grant M01‐RR‐000334, medications provided by Valeant Pharmaceuticals, exercise equipment provided by TheraBand Conflict of interest: none reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random assignment study team statistician, who had no contact with participants. Participants were randomised via stratified block (age in 5‐year blocks, BMI in 3‐point blocks, and sex)
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	Not enough information for clear judging. The PYD arm was double‐blinded but the EX vs attention control could not be double‐blinded. This instructor was not responsible for collecting outcomes
Detection Bias ‐ Subjective measures All outcomes	Unclear risk	Self‐report measures used for health‐related quality of life, pain intensity, fatigue, and stiffness, but placebo used as comparator. Not enough information to judge if participants were aware of study hypothesis and group assignment
Detection Bias ‐ Blinding of assessor reported outcomes All outcomes	Low risk	Not applicable; no assessor‐reported tests were applied to measure cardiorespiratory submaximal function or muscle strength
Incomplete outcome data (attrition bias) All outcomes	Low risk	ITT analysis not utilised (a) 3/43 (7%) ‐ all for medical reasons unrelated to intervention (b) 6/42 (14%) ‐ 3 were unwilling, 1 had relocated, and 2 dropped for medical reasons (c) 0/39 (0%) (d) 2/41 (5%) ‐ 1 was unwilling, 1 dropped out for medical reasons; medical reasons were not well described
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement of risk
Other bias	Low risk	Study appears to be free of other sources of risk of bias