Supplementary appendix This appendix formed part of the original submission and has been peer reviewed. We post it as supplied by the authors. Supplement to: Williams CM, Maher CG, Latimer J, et al. Efficacy of paracetamol for acute low-back pain: a double-blind, randomised controlled trial. Lancet 2014; published online July 24, 2014. http://dx.doi.org/10.1016/s0140-6736(14)60805-9.
Figure S1. Kaplan-Meier survival curves for sensitivty analysis of recovery defintion (first recovery) adjusted for baseline pain score. Global p=0.55.
Table S1. Post hoc analysis - longitudinal models for effect of treatment on pain in first two weeks Daily pain (up to 2 weeks) vs Mean Difference (99%CI) vs Mean Difference (99%CI) vs Mean Difference (99%CI) Day 1 0.05 ( -0.31, 0.40) 0.03 ( -0.33, 0.38) 0.02 ( -0.33, 0.37) Day 2-0.17 ( -0.53, 0.19) -0.09 ( -0.45, 0.27) -0.09 ( -0.45, 0.27) Day 3-0.20 ( -0.56, 0.16) 0.01 ( -0.35, 0.37) -0.21 ( -0.57, 0.15) Day 4-0.16 ( -0.52, 0.20) 0.02 ( -0.34, 0.38) -0.18 ( -0.54, 0.18) Day 5-0.07 ( -0.43, 0.29) -0.03 ( -0.39, 0.33) -0.03 ( -0.39, 0.33) Day 6 0.05 ( -0.31, 0.41) 0.15 ( -0.21, 0.51) -0.10 ( -0.45, 0.26) Day 7-0.00 ( -0.36, 0.36) 0.20 ( -0.16, 0.56) -0.20 ( -0.56, 0.16) Day 8 0.14 ( -0.22, 0.50) 0.23 ( -0.13, 0.60) -0.09 ( -0.45, 0.27) Day 9 0.15 ( -0.21, 0.51) 0.22 ( -0.14, 0.58) -0.07 ( -0.43, 0.29) Day 10 0.11 ( -0.25, 0.47) 0.12 ( -0.24, 0.49) -0.01 ( -0.37, 0.35) Day 11 0.13 ( -0.24, 0.49) 0.25 ( -0.11, 0.62) -0.13 ( -0.49, 0.23) Day 12 0.14 ( -0.22, 0.50) 0.20 ( -0.16, 0.57) -0.07 ( -0.43, 0.30) Day 13 0.20 ( -0.16, 0.56) 0.22 ( -0.14, 0.59) -0.02 ( -0.39, 0.34) Day 14 0.07 ( -0.30, 0.43) 0.14 ( -0.23, 0.50) -0.07 ( -0.43, 0.29) Overall 0.01 ( -0.27, 0.30) 0.12 ( -0.17, 0.41) -0.11 ( -0.39, 0.18) Pain numerical pain rating scale for average pain in the last 24 hours; scored from 0 (no pain) to 10 (worst possible pain).
Table S2. Comparison of medication diary and table count Measure (N = 550) (N = 546) (N = 547) Total self-reported consumption; diary (n = 532) (n = 528) (n =529) Time-contingent tablets (diary) 78.0 (36.0, 126.0) 72.0 (32.0, 126.0) 72.0 (30.0, 126.0) As needed tablets (diary) 8.0 (0.0, 34.0) 8.0 (0.0, 33.0) 8.0 (0.0, 32.0) Count of consumed tablets (N) (n = 248) (n = 266) (n = 264) Time-contingent consumed 84.0 (34.0, 134.0) 72.0 (32.0, 132.0) 80.0 (29.5, 126.0) As needed consumed 8.0 (0.0, 40.0) 12.0 (0.0, 46.0) 14.0 (0.0, 32.0) Self-reported daily consumption; the number of tablets the participant reports they consumed per day until recovery or the end of the treatment period (28 days) as recorded in the daily medication diary. Count of consumed tablets - the total number of tablets consumed by a participant calculated as that total number of tablets provided minus the total number of tablets returned in sealed medicine packages.
Table S3. Details of adverse events by group ICD-10 codes (N = 550) (N = 546) Weeks 1 to 4 A09 Gastroenteritis and colitis (infectious and unspecified origin) 0 0 1 B02 Zoster 0 1 0 B09 Unspecified viral infection 0 1 0 B27 Infectious mononucleosis 0 0 1 B35 Dermatophytosis 0 0 1 B83 Other helminthiases 0 0 1 E11 Non-insulin-dependent diabetes mellitus 1 0 0 E28 Ovarian dysfunction 1 0 0 E78 Lipoprotein metabolism disorders and other lipidaemias 0 0 1 F32 Depressive episode 0 2 0 F33 Recurrent depressive disorder 0 2 0 G43 Migraine 0 2 0 G47 Sleep disorders 1 0 0 H44 Disorders of globe including multiple structures of eye 0 1 0 H57 Other disorders of eye and adnexa 0 1 0 H60 Otitis externa 0 0 1 H65 Nonsuppurative otitis media 0 0 1 H83 Other diseases of inner ear 2 1 0 I10 Essential (primary) hypertension 0 1 0 I46 Cardiac arrest 0 1 0 I86 Varicose veins of other sites 0 0 1 J00 Acute nasopharyngitis [common cold] 7 2 3 J01 Acute sinusitis 0 1 0 J02 Acute pharyngitis 1 2 1 J03 Acute tonsillitis 1 0 2 J11 Influenza, virus not identified 11 10 4 J20 Acute bronchitis 0 0 2 J21 Acute bronchiolitis 1 0 0 J22 Unspecified acute lower respiratory infection 2 0 2 J30 Vasomotor and allergic rhinitis 0 1 0 J32 Chronic sinusitis 0 0 1 J45 Asthma 3 0 1 K00 Disorders of tooth development and eruption 1 0 0 K03 Other diseases of hard tissues of teeth 0 1 0 K04 Diseases of pulp and periapical tissues 1 0 0 K08 Other disorders of teeth and supporting structures 0 1 1 K21 Gastro-oesophageal reflux disease 1 2 0 K31 Other diseases of stomach and duodenum 1 3 1 K59 Other functional intestinal disorders 0 2 5 K63 Other diseases of intestine 0 0 1 K85 Acute pancreatitis 0 0 1 L23 Allergic contact dermatitis 0 0 1 L25 Unspecified contact dermatitis 1 0 0 L40 Psoriasis 1 0 0 L50 Urticaria 0 0 1 M06 Other rheumatoid arthritis 0 0 1 M10 Gout 1 0 0 M15 Polyarthrosis 0 0 1 M25 Other joint disorders, not elsewhere classified 1 0 3 M46 Other inflammatory spondylopathies 1 0 0 M47 Spondylosis 0 0 1 (N = 547)
ICD-10 codes (N = 550) (N = 546) M51 Other intervertebral disc disorders 0 1 0 M54 Dorsalgia 11 11 15 M75 Shoulder lesions 0 1 0 M77 Other enthesopathies 0 1 0 M79 Other soft tissue disorders, not elsewhere classified 5 1 2 M85 Other disorders of bone density and structure 0 1 0 N39 Other disorders of urinary system 1 1 2 N71 Inflammatory disease of uterus, except cervix 1 0 0 N80 Endometriosis 1 0 0 N83 Noninflammatory disorders of ovary and fallopian tube 1 0 0 N94 Pain and other conditions associated with female menstrual cycle 0 0 1 R05 Cough 1 0 0 R07 Pain in throat and chest 0 2 0 R09 Other symptoms and signs of circulatory and respiratory systems 0 0 1 R10 Abdominal and pelvic pain 5 2 0 R11 Nausea and vomiting 4 4 1 R20 Disturbances of skin sensation 3 0 0 R40 Somnolence, stupor and coma 0 3 1 R50 Fever of other and unknown origin 0 1 1 R51 Headache 2 2 5 R60 Oedema, not elsewhere classified 0 0 1 R69 Unknown and unspecified causes of morbidity 0 1 0 S30 Superficial injury of abdomen, lower back and pelvis 0 1 0 S40 Superficial injury of shoulder and upper arm 0 1 1 S43 Dislocation, sprain and strain of shoulder girdle 0 0 1 S46 Injury of muscle and tendon at shoulder and upper arm level 0 1 0 S49 Other and unspecified injuries of shoulder and upper arm 0 1 0 S63 Dislocation, sprain and strain at wrist and hand level 1 0 0 S70 Superficial injury of hip and thigh 2 0 1 S76 Injury of muscle and tendon at hip and thigh level 1 1 0 S79 Other and specified injuries of hip and thigh 1 0 0 S80 Superficial injury of lower leg 1 1 2 S83 Dislocation, sprain and strain of knee 0 0 3 S86 Injury of muscle and tendon at lower leg level 2 0 2 S90 Superficial injury of ankle and foot 0 0 2 T14 Injury of unspecified body region 1 1 0 T79 Certain early complications of trauma, not elsewhere classified 1 0 0 Z03 Medical observation/evaluation for suspected disease/condition 0 0 1 Z04 Examination and observation for other reasons 0 0 1 Total weeks 1 to 4 85 77 85 Weeks 5 to 12 B34 Viral infection of unspecified site 1 0 0 C43 Malignant melanoma of skin 0 1 0 D05 Carcinoma in situ of breast 1 0 0 F33 Recurrent depressive disorder 0 0 1 F41 Other anxiety disorders 0 1 1 F48 Other neurotic disorders 0 0 1 G43 Migraine 0 2 0 I21 Acute myocardial infarction 0 0 2 I51 Complications and ill-defined descriptions of heart disease 0 1 0 J01 Acute sinusitis 1 0 0 J02 Acute pharyngitis 1 2 0 J03 Acute tonsillitis 1 0 1 J11 Influenza, virus not identified 5 1 1 (N = 547)
ICD-10 codes (N = 550) (N = 546) (N = 547) J44 Other chronic obstructive pulmonary disease 0 0 1 J45 Asthma 1 0 1 K04 Diseases of pulp and periapical tissues 0 0 1 K31 Other diseases of stomach and duodenum 2 1 0 K40 Inguinal hernia 0 1 1 K50 Crohn disease [regional enteritis] 1 0 0 K51 Ulcerative colitis 0 1 0 K56 Paralytic ileus and intestinal obstruction without hernia 1 0 0 K58 Irritable bowel syndrome 1 0 0 K72 Hepatic failure, not elsewhere classified 0 0 1 L90 Atrophic disorders of skin 1 0 0 M19 Other arthrosis (of distal joints) 0 0 2 M23 Internal derangement of knee 0 1 0 M25 Other joint disorders, not elsewhere classified 1 3 1 M51 Other intervertebral disc disorders 2 0 0 M54 Dorsalgia 5 13 2 M75 Shoulder lesions 1 1 0 M79 Other soft tissue disorders, not elsewhere classified 1 0 0 M80 Osteoporosis with pathological fracture 0 0 1 M81 Osteoporosis without pathological fracture 1 0 0 M85 Other disorders of bone density and structure 0 0 1 M99 Biomechanical lesions, not elsewhere classified 1 0 0 N20 Calculus of kidney and ureter 0 0 1 N23 Unspecified renal colic 1 0 0 N28 Other disorders of kidney and ureter, not elsewhere classified 0 1 0 N83 Noninflammatory disorders of ovary and fallopian tube 0 0 1 R07 Pain in throat and chest 1 0 0 R51 Headache 0 1 2 R52 Pain, not elsewhere classified 0 1 0 S13 Dislocation, sprain and strain at neck level 0 1 1 S22 Fracture of rib(s), sternum and thoracic spine 0 0 1 S32 Fracture of lumbar spine and pelvis 1 0 0 S42 Fracture of shoulder and upper arm 1 0 0 S46 Injury of muscle and tendon at shoulder and upper arm level 0 1 0 S62 Fracture at wrist and hand level 0 1 0 S72 Fracture of femur 0 1 0 S82 Fracture of lower leg, including ankle 1 0 1 S83 Dislocation, sprain and strain of knee 0 1 1 S93 Dislocation, sprain and strain at ankle and foot level 0 0 1 S99 Other and unspecified injuries of ankle and foot 0 1 0 W10 Fall on and from stairs and steps 0 0 1 Z96 Presence of other functional (joint) implants 0 1 0 Total weeks 5 to 12 34 39 29 Adverse event; any new medical condition or exacerbation of and old medical conditions during the defined reporting period.
Table S4. Details of serious adverse events Description Treatment group Hospitalization - inpatient hospitalization due to acute pancreatitis Hospitalization - inpatient hospitalization due to asthma attach Hospitalization - inpatient hospitalization due to cellulitis Hospitalization - inpatient hospitalization due to abdominal pain (abdominal adhesions and ruptured ovaries) Hospitalization - inpatient hospitalization due to Crohn s disease Hospitalization - inpatient hospitalization for mental health reasons Hospitalization - inpatient hospitalization due to a bleeding bowel Hospitalization - inpatient hospitalization due to endometriosis (scheduled surgery) Hospitalization Emergency department for severe back pain, discharged with analgesia and physiotherapy Hospitalization - inpatient hospitalization due to right knee pseudo gout Hospitalization - inpatient hospitalization due to emergency hernia Hospitalization - inpatient hospitalization due metastatic bony disease with a compression fracture of L1* Hospitalization - inpatient hospitalization due to chest infection Hospitalization - inpatient hospitalization due to severe back pain (prolapsed disc) Serious adverse event; any event causing hospitalization or death. Details provided by treating clinician. * Postrandomization exclusion.