Traumatic SCI

Much of the following epidemiology data on traumatic spinal cord injury in Canada has been extracted from the 2006 Canadian Institute of Health Information Report on Traumatic SCI (CIHI 2006a) using 2003-2004 data from the Canadian National Trauma Registry (NTR).  Over 950 traumatic spinal cord injuries occurred in 2003-2004 (CIHI 2006a).  Reports of the annual incidence vary in part due to differing methods of identifying and tracking injuries, and due to regional differences.  The annual incidence has been estimated at 52.5 per million population (1997-2006) in Alberta (Dryden et al. 2003), 40 per million population (1981-1984) in Manitoba (Hu et al. 1996), and 49 per million population in Ontario in the year 2000 (Pickett et al. 2006). Pickett et al. (2006) also found annual increases in the incidence of SCI from 1997 to 2000. In 1997, the annual incidence was reported at 21 per million population, and increased to 26, 44, and 49 million in 1998, 1999, and 2000 respectively. See SCIRE’s review on the epidemiology of traumatic SCI for a global perspective on the incidence and prevalence of SCI. 

In Canada, males comprise over three-quarters of these traumatic injuries with the majority occurring in those under 35 years of age.  Motor vehicle accidents are commonly reported as the leading cause of SCI injury (with reports ranging from 35.1 to 56.4%), while falls are the second leading cause (with reports ranging from 19.1 to 36%) (NTR 1999; Dryden et al. 2003; Pickett et al. 2006).  The number of SCIs resulting from falls are increasing due to the growing older adult segment of the population. This has contributed to the increase in age of a person with traumatic SCI (from average age 46 in 1994 to average 49 in 1998).  In fact, we are now seeing a bimodal distribution of SCI in the population with one mode centralizing at approximately 30 years of age and another mode centralizing at 60 years of age.  Not surprisingly, falls are the primary cause of SCI admissions in seniors, while motor vehicle crashes are the leading cause in young adults (NRT 1999).  Fractures of the vertebral column, in addition to injuries of the spinal cord represent 71% of all SCI hospital admissions (NTR 1999).  Of the SCI admissions, 44% result in paraplegia and 56% tetraplegia (NTR 1999). 

Traumatic SCI can be complex as motor vehicle accidents or other violent incidents often result in more than injury to the spinal cord.  In particular, patients with the dual diagnosis of traumatic brain injury and spinal cord injury present a challenge to the rehabilitation professional as they are often agitated and have poor concentration.  The percentage of SCI injuries which are accompanied by a traumatic brain injury are substantial, for example, Lida et al. (1999) reported that 35% of SCI had a traumatic brain injury, and in a more recent US study, Macciocchi et al. (2008) found 60% of their SCI sample to have co-occurring traumatic brain injury.

There appears to be a trend towards more severe injuries in Canada. In the 1970s, the Canadian Paraplegic Association (CPA) reported that about 25% of injuries resulted in tetraplegia and 75% paraplegia.  Of the new injuries reported to CPA during 1999, 47% resulted in tetraplegia and 53% resulted in paraplegia.  This increase in tetraplegic injuries concurs with the findings of the US National Spinal Cord Injury Statistical Center (NSCISC)  that, since 2000, tetraplegia has accounted for 52.4% of the injuries, and paraplegia 41.5% (NSCISC 2008). A survey of the epidemiology literature (Wyndaele and Wyndaele 2006) suggests increasing proportions of tetraplegia with a global proportion of approximately two-thirds tetraplegia.

There have been some suggestions that there are increasing numbers of incomplete lesions in some regions (Calancie et al. 2005).  However, these finding are not consistent.  The Model Spinal Cord Systems in the US (Jackson et al. 2004) reported an increase in complete injuries in the 1990s which has since dropped back to pre-1990 levels with just less than half of the injuries being complete, and since 2000, the NSCISC reports complete injuries on average have accounted for 41.3% (NSCISC 2008). The Australian Spinal Cord Injury Registry reported increasing rates in elderly males, fall-related injury and incomplete tetraplegia and complete paraplegia over an eleven year period (O’Connor 2006).

Although the precise relationship between gender and SCI is difficult to determine, it is generally acknowledged that men and women exhibit different patterns with respect to SCI etiology, recovery, and lived experience.  For example, according to data from Model Spinal Cord Injury Care System records, men are 4 times more likely to sustain a SCI than women, although this has slightly decreased since 2000 where 77.8% of injuries are sustained by males compared to pre-1980 rates where males accounted for 81.8% of the spinal cord injuries (NSCISC 2008).  When women do incur a SCI, it is more likely to be incomplete and occur later in life.  Men, in contrast, are more likely to incur a complete injury and do so during their young adult years (Nobunaga et al. 1999).   While the three leading causes of injury do not differ between men and women (motor vehicle crashes, falls, and gunshot wounds), medical/surgical complications occur more frequently among women, whereas violence-related SCI occurs more frequently among men.  Differences in SCI etiology reach peak disparity during the ages of 16 to 30, and become less relevant in later adult years (Nobunaga et al. 1999).

Non-traumatic SCI

There are many different causes of non-traumatic SCI, the more common conditions include spinal stenosis (narrowing of the spinal canal), tumor compression and vascular ischemia.   Individuals with a non-traumatic SCI do not necessarily enter major trauma or rehabilitation centres and thus are not easily tracked in SCI registries or databases.  Non-traumatic SCI has different demographics than traumatic SCI as spinal stenosis and spinal tumors are more common in adults over 50 years of age.  In addition, specific diseases such as multiple sclerosis, paediatric spina bifida or poliomyelitis can also contribute to non-traumatic spinal cord injury and each has demographics specific to the condition.

Overall, compared to traumatic SCI, individuals with non-traumatic SCI tend to be older with less severe injuries, more likely to be female, married, retired, and have an incomplete paraplegic injury (McKinley et al. 1999, 2002a, 2002b). Differences in demographics, clinical presentation and rehabilitation outcomes have important implications for management of non-traumatic SCI.

Neuroplasticity

Spontaneous neuronal plasticity occurs through various mechanisms and has been demonstrated primarily in animal models.  Recovery mechanisms following complete injuries may include recovery of nerve roots beside the lesion level, changes in the gray matter of the spinal cord at the lesion level, reorganization of existing spinal circuits and peripheral changes (Bradbury & McMahon 2006; Kern et al. 2005; Ding et al. 2005; Hagg & Oudega 2006; Ramer et al. 2005).  The evidence for spontaneous axonal regeneration is limited as a small proportion of fibres regenerate and over a modest distance (Bradbury & McMahon 2006). However, cortical re-organization can occur, for example, Lotze et al. (2006) showed that cortical representation of elbow movements following a complete thoracic injury in humans was moved toward cortical areas which represented the injured thoracic regions.  There is evidence that a pattern-generating spinal circuitry (also known as a central pattern generator) is retained following a complete injury which can produce stepping-like movements and activation patterns with epidural lumbar cord stimulation (Kern et al. 2005) or treadmill stimulation (Dietz et al. 2002). However, the functional consequences of these observations are yet to be determined.

Incomplete injuries may have a greater extent of axonal sprouting and axonal growth (Ding et al. 2005; Hagg & Oudega 2006).  In incomplete spinal cord injury in rats, transected hindlimb corticospinal tract axons sprouted into the cervical gray matter to contact short and long propriospinal neurons (Bareyre et al. 2004).  Following cervical lesions of the rat dorsal corticospinal motor pathway which contains more than 95% of all corticospinal axons, there was spontaneous sprouting from the ventral corticospinal tract onto medial motoneuron pools (Weidner et al. 2001).  This sprouting was paralleled by functional recovery.  Ramer et al. (2005) suggested that if axonal regeneration occurs or if synaptic spaces become occupied with different axons, functional recovery will require retraining to optimize these new circuits.  The neuroplastic changes which underlie spontaneous recovery may be enhanced by physical interventions (e.g., exercise, electrical stimulation) and pharmacological agents (Ramer et al. 2005).

Measures of Recovery

The American Spinal Injury Association (ASIA) International Classification of Spinal Cord Injury, neurological level of injury and completeness of injury are often used to indicate human neurological recovery.

ASIA International Standards for Neurological Classification of Spinal Cord Injury consists of 1) 5 category ASIA Impairment Scale (AIS A-E), 2) motor score and 3) sensory score (ASIA 2002). Twenty-eight dermatomes are assessed bilaterally using pinprick and light touch sensation for the sensory score (maximum of 112 for pinprick and 112 for light touch sensation).  Ten key muscles are assessed bilaterally with manual muscle testing for the motor score (maximum of 50 for lower limbs and 50 for upper limbs). The results are used in combination with evaluation of anal sensory and motor function as a basis for the determination of the AIS and the 5 categories are summarized below (ASIA 2002).

Table 1: Descriptions of Categories from ASIA Impairment Scale (AIS)

AIS A:Complete injury where no sensory or motor function is preserved in sacral segments S4-S5.
AIS B:Incomplete injury where sensory, but not motor, function is preserved below the neurologic level and extends through sacral segments S4-S5.
AIS C:Incomplete injury where motor function is preserved below the neurologic level, and most key muscles below the neurologic level have muscle grade less than 3 (active full-range movement against gravity).
AIS D:Incomplete injury where motor function is preserved below the neurologic level, and most key muscles below the neurologic level have muscle grade greater than or equal to 3.
AIS E:Normal sensory and motor functions.

Neurological level of injury is the most caudal level at which both motor and sensory levels are intact and has been shown to change in some individuals over recovery.

Completeness of  injury are based on the ASIA standards where the absence of sensory and motor functions in the lowest sacral segments indicates a complete injury and preservation of sensory or motor function below the level of injury, including the lowest sacral segments indicates an incomplete injury. Sacral-sparing is an important indicator of motor recovery and provides evidence of the physiologic continuity of spinal cord long tract fibers with the sacral fibers at the end of the cord.  The requirement of sacral sparing to identify an incomplete injury provides a more rigorous definition and less patients will convert from incomplete to complete injury over time when using this definition.

Stauffer (1976) proposed that individuals with tetraplegia would recover one neurological level, although this has been revised in recent years to qualify that recovery of one neurologic level in subjects with tetraplegia depends on severity, initial level of the injury and the strength of muscles below the level of injury (Dittuno et al. 2005).  Dittuno et al. (1992) reported that 70 to 80% of motor-complete tetraplegia subjects with some motor strength at the injury level would recover to the next neurologic level within 3 to 6 months.  Although those with complete lesions are generally limited to improvements of one or two levels, subjects with incomplete lesions may exhibit recovery at multiple levels below the injury site (Dittuno et al. 2005).  Triceps elbow extension (C7) is a significant determinant for functional independence in self-care for community-living individuals with tetraplegia (Welch et al. 1986).

For those with complete paraplegia, Waters et al. (1992) reported that 73% of 108 patients (T2-L2) did not change in neurological level at one year post-injury compared to the rehabilitation admission assessment.  18% recovered to the next neurological level, while 7% had 2 levels of recovery.  For incomplete paraplegia, 78% of 45 cases (T1-L3) had no changes in neurological level between the first and 12^th month but there was substantial improvement in motor function particularly within the first 3 months (Waters et al. 1994). 70% of this sample were able to ambulate within 1 or 2 years post-injury (27% without any devices).  Patients with initial grade 2 hip flexor and knee extensor motor strength achieved community ambulation. In terms of function, individuals with a T2-T9 injury have some trunk control and may be able to stand using braces and an assistive device such as a walker.  Although injuries below T11 have increased potential for ambulation with bracing, successful community ambulation often involves individuals with an injury at the L3 level or below.

Marino et al. (1999) assessed data from 21 Model System SCI systems with 3585 individuals with SCI over the first year of recovery.  They found that 10 to 15% of those with initial complete AIS A injuries converted to incomplete injuries.  For AIS B injuries, 1/3 converted to AIS C and 1/3 to AIS D or E.  For AIS C injuries, over 2/3 converted to AIS D.  However, the accurate prediction of AIS conversion can be fraught with problems.  Burns et al. (2003) found that individuals with cognitive factors (e.g., traumatic brain injury, alcohol intoxication, analgesic administration, psychological disorders) and communication barriers (e.g., language barriers, ventilatory dependency) had a higher percent of AIS conversion over the first year likely due to an inaccurate initial assessment.

Literature Search Strategy

Quality Assessment Tool and Data Extraction

Methodological quality of individual RCTs was assessed using the Physiotherapy Evidence Database (PEDro) tool (http://www.pedro.fhs.usyd.edu.au/scale_item.html). PEDro was originally developed for the purpose of accessing bibliographic details and abstracts of randomized-controlled trials (RCT), quasi-randomized studies and systematic reviews in physiotherapy. PEDro has been used to assess both pharmacological and non-pharmacological studies with good agreement between raters at an individual item level and in total PEDro scores (Foley et al. 2006).  Maher et al. (2003) found the reliability of PEDro scale item ratings varied from "fair" to "substantial," while the reliability of the total PEDro score was "fair" to "good. 

The PEDro is an 11-item scale, in which the first item relates to external validity and the other ten items assess the internal validity of a clinical trial. One point was given for each satisfied criterion (except for the first item, which was given a YES or NO), yielding a maximum score of ten. The higher the score, the better the quality of the study and the following cut-points were used: 9-10 (excellent); 6-8 (good); 4-5 (fair); <4 (poor).  A point for a particular criterion was awarded only if the article explicitly reported that the criterion was met.  The scoring system is detailed in Appendix 2. Two independent raters reviewed each article. Scoring discrepancies were resolved through discussion.

All other studies were assessed with the Downs and Black Tool (Downs and Black 1998) for methodological quality.  This tool consists of 27 questions in the following sub-sections: Reporting, External Validity, Internal Validity (bias and confounding). Total scores using the original tool range from 0 to 32.  However, we modified the last question from a scale of 0 to 5 to a scale of 0 to 1 where 1 was scored if a power calculation or sample size calculation was present while 0 was scored if there was no power calculation, sample size calculation or explanation whether the number of subjects was appropriate.  Thus, our modified version ranged from 0 to 28, with a higher score indicating higher methodological quality. The Downs and Black tool is attached in Appendix 3.

Data were extracted to form tables.  Sample subject characteristics (Population), nature of the treatment (Intervention), measurements (Outcome Measures) and key results are presented in the tables.  In cases, where a single study overlapped into multiple chapters (e.g., treadmill training has effects on the cardiorespiratory, lower extremity and bone health), the results focus on the outcomes relevant to that chapter.

Appendix 1: Specific Search Terms

Specific SCI rehabilitation topics were identified by a multi-disciplinary team of expert scientists, clinicians, consumers with SCI and policy-makers.  These specific topics were searched with additional keywords generated from expert scientists and clinicians in SCI rehabilitation familiar with the topic and more titles and abstracts are reviewed. MeSH headings were used with the keywords.  Key words were paired with spinal cord injury, tetraplegia, quadriplegia or paraplegia.  The reference lists of previous review articles, systematic reviews and clinical practice guidelines were hand searched.  It is known that hand searching may provide higher rates of return than electronic searching within a particular subject area (Hopewell et al. 2002).

Aging: aging

Autonomic Dysreflexia: AD, autonomic, dysreflexia, hyperreflexia, midodrine, fludrocortisone, beta-blockers, Viagra, nifedipine, phenazopyridine

Bladder Management: bladder, bladder functioning, catheter, catheterization, neurogenic bladder, incontinence, oxybuytnin, valsalva, crede, suprapubic catheterization, intermittent catheterization, stimulation, bladder stimulation, electrical stimulation, sphincterotomy, ileoreterostomy, anticholergics, tolterodine, intervention, bladder management, UTI, Mitrofanoff, MESH – SCI & neurogenic (plus catheter) (plus treatment) (plus intervention)

Bowel Management: bowel management, cisapride, colonic, colostomy, constipation, dietary fibre, hemorrhoids, incontinence, irregular, laxative, neurogenic bowel, suppositories

Bone Health: alendronate, Amino-bisphosphonates, bone + fracture, bone health, cyclic etidonate, exercise therapy, FES, heterotopic ossification, incidence + fracture, osteoporosis, pamidronate, skeletal + fracture, vibration

Cardiovascular Health: aerobic fitness, blood pressure, cardiac output, cardiovascular disease, cardiovascular fitness, coronary heart disease, endothelium, endurance performance, epoetin alfa, exercise, FES + blood pressure, fludrocortisone, glucose intolerance, glucose sensitivity, hydralazine, lipid, lipid + metabolism, maximal aerobic power (VO₂max), neuromuscular + blood, nifedipine, orthostatic hypotension, oxygen consumption (VO₂), phenazopyridine, physiotherapy + blood, stroke volume, thromboembolism, ventilation, ventilatory threshold

Depression: addiction, aging, alcohol abuse, antidepressants, anxiety, depression, drug abuse, drug therapy, gabaoentin, gender, gender differences, Iraq, intervention therapy, male and female, MDD, medication, military, military personnel, modafinal, pharmacological treatment, pharmacotherapy, psychosocial, PTSD, serotonin, service members, sexual health, sexual issues, sexuality, [specific researches: Krause, Noreau…], SSRI, substance abuse, veteran war, vocational issues, war effects, Zoloft.

Economic Costs: quality-adjusted life years, cost-benefit analysis, costs and cost analysis, economics, technology assessment, life expectancy, models, risk assessment, risk equation simulation model, spinal cord injuries.

Epidemiology: epidemiology, incidence, prevalence, etiology.

Heterotopic Ossification: heterotopic ossification, HO, excision surgery, etidronate, pharmacological, non-pharmacological, medication, radiation, treatment, intervention

Housing and Attendant Care: housing, public housing, independent living, independent living programs, housing for the elderly, homes for the aged, wheelchair accessible housing, disabled housing, social housing, visitability, non-profit housing, attendant care, personal care, personal support, home health aides, community heath nursing, community health services, health maintenance.

Lower Limb: 4-AP, 4-AP + ambulation, assisted walking device, walking, assisted rehabilitation device, biofeedback, body weight support, body weight supported treadmill training (BWSTT), brace, bracing, Clonidine, Cyproheptadine, EMG + feedback, epidural stimulation / epidural lumbar stimulation, FES + muscle, flexibility, gait, gait + bracing, gait + orthotics, gait devices, GM-1 ganglioside, knee-ankle-foot, leg + bracing, leg + FES, locomotion, locomotor training, lower extremity spasticity, orthotics, orthotics + lower limb, parawalker, robotics, salbutamol, scott-craig knee ankle foot orthosis, spasticity management, stepping, stretching, treadmill, trendelenburg gait, Vannini-rizzoli stabilizing orthosis, virtual reality, walking, weakness

Nutrition: nutrition, diabetes, insulin, vitamin A, vitamin C, vitamin B6, vitamin B12, energy, energy requirements, energy expenditure, calories, caloric intake, weight, weight gain, obesity, overweight, prevention, body composition, nutrient, cardiovascular disease, cardiovascular, supplements, supplementation, dietary, diet, nutrition intervention, folate, fatty acids, pressure ulcers/sores, vitamin supplement, mineral, mineral supplement, zinc, iron, protein, hydration, cranberry, neurogenic bowel, bowel, fibre (dietary, soluble, insoluble), peristalsis, osteoporosis, osteopenia, creatine, anemia, hemoglobin, vitamin D, calcium, magnesium, renal stone, kidney stone, urinary tract, hyperclacima, treatment, intervention, program, omega 3 fatty acids, fatty acids, bone density

Orthostatic Hypotension: orthostatic hypotension, dysreflexia, autonomic, hyperreflexia, midodrine, postural hypotension, orthostatic intolerance, orthostatic tolerance, orthostatic stress, blood flow, blood flow + exercise, blood pressure, blood vessel health

Pain Management: pain, pain treatment, pharmacology, surgery, surgical treatment, pain management, secondary complications, massage, heat, exercise, hypnotic, hypnosis, cannabinoids, acupuncture, TENS, antidepressants, medications,, FES, anaesthetic, antispastic, clindine, spinal cordotomy, neurosurgical, DREZotomy, dorsal rhizotomy, symapathectomy, spinaothalamic tractotomy.

Physical Activity: physical activity, exercise, spinal cord injury, tetraplegia, paraplegia, cardiovascular, secondary complications, UTI, bladder, spasticity, pain, pressure ulcers/sores, gait, motivation, participation, support, exercise tools, exercise aids, exercise instruments, exercise equipment, exercise assistive technology, endurance, function recovery, daily activity, psychological, well being, depression, anxiety, training program, FES, QOL, health, fitness, strength, atrophy, wheeling, hydrotherapy, treadmill, ergometry.

Pressure Sores: pressure sores, ulcers

Primary Care: primary health care, patient care team, multidisciplinary care team, community health services, general practice, physicians, family physicians, general practitioner, family doctor, case management, patient outreach, delivery of health care, integrated, transmural care, home care services, nurse liason, continuity of patient care, transitional rehabilitation, clinical practice guidelines, practice guidelines, outpatient clinic, ambulatory care facilities, health management, health education, outreach, telemedicine.

Rehabilitation Practice: ("rehabilitation"[Subheading] OR "Rehabilitation"[MeSH]) AND "Spinal Cord Injuries"[MeSH] AND "Treatment Outcome"[MeSH]

Respiratory Management: abdominal binder, acapello, assisted cough, asthma – incidence, prevalence, atelectasis, autogenic drainage, barotraumas, BiPAP, breathing exercises, bronchial lavage, bronchitis, bronchoscopy, cardiopulmonary function, chest physiotherapy, COPD – incidence, prevalence, CPAP, diaphragmatic pacemaker, dysphagia, exsufflation, flutter, flutter device, flutter valve, forced expiratory technique, Garshick, glossopharyngeal breathing, incentive spirometry, insufflation, intermittent positive pressure breathing, intrapulmonary percussive ventilation, IPPB stretch, manual percussion, manual vibration, mechanical vibration, paripep , PEP  /  PEEP, percussion, phrenic pacemaker, pneumonia  - incidence, prevalence, positive pressure breathing, postural drainage, progressive ventilatory free breathing, pulmonary capacity, pulmonary complications – incidence, prevalence, pulmonary embolism, pulmonary health, pulmonary secretions, respiratory complications – incidence, prevalence, secretion removal, sleep apnea, smoking – incidence, prevalence, spirometry, synchronous intermittent mandatory ventilation, TheraPep, tidal volume, tracheostomy, ventilator weaning, ventilatory capacity, ventilatory failure – incidence, prevalence

Sexual Health: autonomic dysreflexia, birth control, birthing, bladder + sex, bladder management + body image, bladder management + mitrofanoff, bladder management + sexual life, bladder management + suprapubic, body image, bowel + sex, Cesarean section, contraception, dysparunia, dyspareunia + infertility, ejaculation, ejaculatory disorder, electroejaculation, erection, female fertility, hypogonadism, ICSI, infertility + pregnancy, intercavernosal injection, intraurethral palette, intraurethro palette, urethra palette, IVF, labour, labour + delivery, marital, marital status + sexuality, menopause, menstruation, penile injection, post-partum, pregnancy, premature labour, semen quality, seminal emissions, sex, sex + depression, sex/sexual + foley catheter, sex/sexual + intermittent catheter, sexual adjustment, sexual changes, sexual function + medications, sexual functioning + foley catheter, sexual position, sexual relationships, sexual self-esteem, sexual self-views, sexuality, sexuality + depression, sperm/semen quality, sperm/semen retrieval, vacuum device, vaginal lubrication, Viagra, vibrator, vibrostimulation

Spasticity: botox, baclofen, spasticity, stimulation, movements, surgery

Syringomyelia: syringomyelia, syrinx, cystic myelopathy, shunt, untethering, spinal cord injury

Upper Limb: upper limb, FES and upper limb, exercise programs, upper limb injuries, splinting, specific researchers [Popovic…]

Venous Thromboembolism: deep venous thrombosis, vein thrombosis, DVT, VT, emboli, heparin, thromboembolism, vena cava filtration, venous ultrasound, venography, D-Dimer assay, pulmonary embolus, ventilation, spinal CT, anticoagulant.

Wheelchair and seating equipment: wheelchair, seating equipment, pressure mapping

Work and Employment: employment, supported employment, unemployment, employment status, employability, employment disabled, gainful employment, self employment, part time employment, temporary employment, employee assistance, employee assistance program, vocation, vocation assistance, vocational rehabilitation, vocational education, work resumption, workplace, return to work, work force, labor force, career assistance, career, job.

Appendix 2: The PEDro Scale

1. “Subjects were randomly allocated to groups.” (in a crossover study, subjects were randomly allocated an order in which treatments were received). A point for random allocation was awarded if random allocation of patients was stated in its methods. The precise method of randomization need not be specified. Procedures such as coin-tossing and dice-rolling were considered random. Quasi-randomization allocation procedures such as allocation by bed availability did not satisfy this criterion.
2. “Allocation was concealed.” A point was awarded for concealed allocation if this was explicitly stated in the methods section or if there was reference that allocation was by sealed opaque envelopes or that allocation involved contacting the holder of the allocation schedule who was "off-site."
3. “The groups were similar at baseline regarding the most important prognostic indicators.” A trial was awarded a point for baseline comparability if at least one key outcome measure at baseline was reported for the study and control groups. This criterion was satisfied even if only baseline data of study completed-only subjects were presented.
4. “There was blinding of all subjects.” The person in question (subject, therapist or assessor) was considered blinded if he/she did not know which group the subject had been allocated to. In addition, subjects and therapists were only considered to be "blind" if it could be expected that they would have been unable to distinguish between the treatments applied to different groups. In drug therapy trials, the administrator of the drug was considered the therapist and was considered blinded if he/she did not prepare the drug and was unaware of the drug being administered.
5. “There was blinding of all therapists who administered the therapy.” (criteria 4.)
6. “There was blinding of all assessors who measured at least one key outcome” (criteria 4).
7. “Adequacy of follow-up.” For the purposes of this review, follow-up was considered adequate if all of the subjects that had been originally randomized could be accounted for at the end of the study. The interpretation of this criterion differs from that described by PEDro, where adequacy is defined as the measurement of the main outcome in more than 85% of subjects.
8. “Intention to treat.” All subjects for whom outcome measures were available received the treatment or control condition as allocated or, where this was not the case, data for at least one key outcome was analyzed by "intention to treat". For purpose of the present evidence-based review, a trial was awarded a point for intention-to-treat if the trial explicitly stated that an intention-to-treat analysis was performed.
9. “The results of between-group statistical comparisons are reported for at least one key outcome.” Scoring of this criterion was design dependent. As such, between groups comparison may have involved comparison of two or more treatments, or comparison of treatment with a control condition. The analysis was considered a between-group analysis if either a simple comparison of outcomes measured after the treatment was administered was made, or a comparison of the change in one group with the change in another was made. The comparison may be in the form of hypothesis testing (e.g. p-value) or in the form of an estimate (e.g. the mean, median difference, difference in proportion, number needed to treat, relative risk or hazard ratio) and its confidence interval. A trial was awarded a point for this criterion if between group comparison on at least one outcome measure was made and its analysis of comparison was provided.
10. “The study provides both point measures and measures of variability for at least one key outcome.” A point measure was referred as to the measure of the size of the treatment effect. The treatment effect was described as being either a difference in group outcomes, or as the outcome in (each of) all groups. Measures of variability included standard deviations, standard errors, confidence intervals, interquartile ranges (or other quartile ranges), and ranges. Point measures and/or measures of variability that were provided graphically (for example, SDs may be given as error bars in a Figure) were awarded a point as long as it was clear what was being graphed (e.g. whether error bars represent SDs or SEs). For those outcomes that were categorical, this criterion was considered to have been met if the number of subjects in each category was given for each group.

Appendix 3: Downs and Black tool (Downs and Black 1998)

Reporting

1)   Is the hypothesis/aim/objective of the study clearly described?

2)   Are the main outcomes to be measured clearly described in the Introduction or Methods section? 

3)   Are the characteristics of the patients included in the study clearly described ?  I4)  Are the interventions of interest clearly described? 

4)   Are the interventions of interest clearly described?

5)   Are the distributions of principal confounders in each group of subjects to be compared clearly described? 

6)   Are the main findings of the study clearly described? 

7)   Does the study provide estimates of the random variability in the data for the main outcomes? 

8)   Have all important adverse events that may be a consequence of the intervention been reported? 

9)   Have the characteristics of patients lost to follow-up been described?

10) Have actual probability values been reported (e.g. 0.035 rather than <0.05) for the main outcomes except where the probability value is less than 0.001?

External validity

11)   Were the subjects asked to participate in the study representative of the entire population from which they were recruited?

12)   Were those subjects who were prepared to participate representative of the entire population from which they were recruited?

13)   Were the staff, places, and facilities where the patients were treated, representative of the treatment the majority of patients receive?

Internal validity - bias

14)   Was an attempt made to blind study subjects to the intervention they have received?

15)   Was an attempt made to blind those measuring the main outcomes of the intervention?

16)   If any of the results of the study were based on “data dredging”, was this made clear?

17)   In trials and cohort studies, do the analyses adjust for different lengths of follow-up of patients, or in case-control studies, is the time period between the intervention and outcome the same for cases and controls ?

18)   Were the statistical tests used to assess the main outcomes appropriate?

19)   Was compliance with the intervention/s reliable?

20)   Were the main outcome measures used accurate (valid and reliable)?

Internal validity – confounding (selection bias)

21)   Were the patients in different intervention groups (trials and cohort studies) or were the cases and controls (case-control studies) recruited from the same population? 

22)   Were study subjects in different intervention groups (trials and cohort studies) or were the cases and controls (case-control studies) recruited over the same period of time?

23)   Were study subjects randomised to intervention groups?

24)   Was the randomised intervention assignment concealed from both patients and health care staff until recruitment was complete and irrevocable?

25)   Was there adequate adjustment for confounding in the analyses from which the main findings were drawn?

26)   Were losses of patients to follow-up taken into account?

27)   Did the study have sufficient power to detect a clinically important effect where the probability value for a difference being due to chance is less than 5%?