anurajms/meta_analysis huggingface dataset:
primary outcome:
Corticosteroids for the treatment of Duchenne muscular dystrophy
Prolongation of time to loss of ambulation (independent walking without long leg calipers) (Heckmatt 1985; Spencer 1962).Only Angelini 1994 (n = 28), a two‐year study, used prolongation of time to loss of ambulation as an outcome measure. The other studies were of short duration (six months or one year), and not designed to demonstrate prolongation of walking.Angelini 1994 reported that deflazacort (2 mg/kg on alternate days) prolonged ambulation by 13 months, but the statistical technique used to infer this result was not appropriate. Four of the 17 participants in the deflazacort group became wheelchair dependent, at a mean interval of 33.2 months after randomisation, versus six of 11 placebo participants, at a mean interval of 20.5 months. The trial authors reported the difference of 13 months between these two sets of participants who lost walking ability as "mean prolongation of walking", ignoring the 13 participants in the deflazacort group and five in the placebo group who were still walking at the end of the study. The trialists did not report the age of boys who remained ambulant at the end of the study and this information was not available on contacting the lead investigator. We therefore were not able to construct Kaplan‐Meier survival curves for evaluating prolongation of walking as an outcome measure.Not reported.Not measured.Loss of ambulation is the key milestone in the natural history of DMD, and is of maximal functional significance. Prevention or postponement of this event is the key aim of therapeutic interventions in the first decade of life, and a desired outcome measure. Prolongation of time to loss of ambulation was not the stated primary outcome measure of most RCTs, probably because to achieve sufficient power to demonstrate this effect, studies would require a large sample size and long duration (Muntoni 2002). As progressive muscle weakness is the major contributor to loss of walking, trialists have used measurements of muscle strength as a surrogate marker, enabling clinical trials to be completed in as little as six months. These short‐term studies do not demonstrate prolongation of time to loss of ambulation or allow evaluation of adverse effects that develop after long‐term use of corticosteroids (Griggs 1991; Mendell 1989; Rahman 2001).Although Angelini 1994 assessed our primary outcome measure, the data available did not allow us to create survival curves for prolongation of walking. Some disparities that cannot be readily explained further highlight the need for appropriate statistical analysis. Deflazacort and placebo groups were evenly matched at randomisation, and among participants who lost ambulation during the study, the mean age at which boys became wheelchair‐dependent was very similar in the two groups (deflazacort group, 108 months; and placebo group, 104 months). Comparing these groups, the significance of the difference of 13 months in duration of walking between randomisation and becoming wheelchair‐dependent cannot be ascertained without knowing the ages of the ambulant children at the end of the study.
primary outcome:
Antiepileptic drugs for the primary and secondary prevention of seizures after intracranial venous thrombosis
The primary outcome was the proportion of participants who experienced clinical seizures in the scheduled follow‐up period. In cases where seizures had occurred, their nature (generalised or focal), timing (early or late), and whether an electroencephalography had been performed were noted. The investigators were contacted if the outcome data were not readily available in the published report. As described in the Background, seizures occurring within the first week of ICVT were defined as early seizures, and those occurring after the first week were defined as late seizures (ILAE 1981). The occurrence of recurrent late seizures was defined as post‐ICVT epilepsy.
primary outcome:
Sumatriptan plus naproxen for the treatment of acute migraine attacks in adults
pain‐free at two hours, without the use of rescue medication;reduction in headache pain ('headache relief') at two hours (pain reduced from moderate or severe to none or mild without the use of rescue medication).
primary outcome:
Drugs for the acute treatment of migraine in children and adolescents
The primary outcome measure for efficacy was the percentage of pain‐free participants at two hours; we defined pain freedom as the absence of pain at two hours before the use of additional or rescue medication (see Differences between protocol and review). Headache relief is a frequently used primary outcome measure that is variably defined based on the scale used to assess pain. For example, if using the four level scale of none, mild, moderate, or severe pain, investigators or physicians may define headache relief as a decrease in pain from moderate or severe to mild or none. Some in the migraine research community have challenged the use of headache relief as a primary outcome measure; for example, migraine sufferers generally do not consider headache relief a success and expect pain freedom from an intervention (Davies 2000; Lipton 2002). Given these considerations, we classified headache relief as a secondary outcome measure (see Differences between protocol and review).We used the percentage of participants with any adverse event(s) as the primary safety outcome measure, and this was required for inclusion in the analysis (see Differences between protocol and review). We defined adverse events as any unwanted effect that occurred during treatment. We also documented the proportion of participants reporting any serious adverse events when possible. Serious adverse events included death, any life‐threatening condition, hospitalization, disability or permanent damage, required intervention to prevent permanent damage, or any other important medical event that could jeopardize the participant or require medical or surgical intervention.Some aspects of the original protocol were not necessary to implement given the way studies reported outcome data. We document these considerations in the Differences between protocol and review section.
primary outcome:
Fingolimod for relapsing‐remitting multiple sclerosis
1. Number of participants relapse‐free at six,12 and 24 months after randomisation and at the end of follow‐up.2. Number of participants free from disability worsening at 12, 24 and 36 months after randomisation and at the end of follow‐up. Disability worsening is defined as at least one point Expanded Disability Status Scale (EDSS) (Kurtzke 1983) increase, or a 0.5 point increase if the baseline EDSS was > 5.5, confirmed during two subsequent neurological examinations separated by at least 6 months' interval free of relapses. We considered separately studies that reported disability worsening defined using different criteria.3. Number of participants who withdrew from the study due toa) adverse events;b) serious adverse events, i.e. death, life‐threatening, hospitalisation, disability or permanent damage, congenital anomaly/birth defect (FDA 2013).
primary outcome:
Posture and fluids for preventing post‐dural puncture headache
We assessed the presence of PDPH defined as each headache occurring within five days of a lumbar puncture, caused by CSF leakage through the dural puncture (IHS 2013). We used the PDPH diagnosis criteria specified by the International Headache Society (IHS) (IHS 2004; IHS 2013), as well as the definition used in each study.
primary outcome:
Interventions for psychotic symptoms concomitant with epilepsy
The outcomes of interest were:
primary outcome:
Alprazolam for essential tremor
Tremor severity, as measured by the Fahn‐Tolosa‐Marin Tremor Rating Scale (TRS) (Fahn 1993), at the end of follow‐up.The TRS assesses rest and postural and action tremor. The TRS score is derived from three TRS subscales.Examiner‐reported upper limb postural and action tremor severity (amplitude), four elements.Examiner‐reported ability to perform specific motor tasks (writing, drawing and pouring with dominant and non‐dominant hands), nine elements.Patient‐reported functional disabilities due to tremor (eating, speaking, drinking, performing hygiene, dressing, writing, working and social activities), eight elements.Withdrawals due to adverse events (AEs) as defined in a standard manner in studies, and the number of participants with any AE associated with treatment.
primary outcome:
Vigabatrin versus carbamazepine monotherapy for epilepsy
Time to treatment withdrawal (retention time) for any reason.This global effectiveness outcome includes both efficacy and tolerability and is recommended as a primary outcome by the Commission on Antiepileptic Drugs of the International League Against Epilepsy (ILAE) (Commission 1998).
primary outcome:
Routine intracranial pressure monitoring in acute coma
All‐cause mortality at the end of the follow‐up periodSevere disability at the end of the follow‐up period. If the trial presented Glasgow Outcome Score (GOS), we defined severe disability as a GOS outcome of 'severe disability' or 'persistent vegetative state'. If trials presented other outcome scoring systems, we mapped these to the GOS (Jennett 1975).
primary outcome:
Psychological therapies for the management of chronic neuropathic pain in adults
Pain experience, as measured by a self‐rating of pain intensity or pain distress according to VAS or NRS.Mood, as measured by a standard anxiety scale such as Spielberger State/Trait Anxiety Inventory (STAI; Spielberger 1983), standard depression scale such as Beck Depression Inventory (BDI; Beck 1961), or a standard distress scale such as the Hospital Anxiety and Depression Scale (HADS; Zigmond 1983).Disability or quality of life, as measured by the Brief Pain Inventory (BPI; Cleeland 1994) or the 36‐ or 12‐item Short Form Health Survey (SF‐36 or SF‐12; Medical Outcomes Study).Adverse events and dropouts.
primary outcome:
Sodium channel blockers for neuroprotection in multiple sclerosis
The number of participants who experienced disability progression. Disability progression was defined as a one‐point increase in the Expanded Disability Status Score (EDSS) score (or a half‐point increase for participants with a baseline score ≥ 5.5) that was confirmed three or six months later, in the absence of relapse (Freedman 2011; Gold 2012; Jacobs 1996; Johnson 1995; PRISMS 1998; Polman 2006). In addition, other definitions of disability progression reported in the trials (such as the Multiple Sclerosis Functional Composite) were accepted (Cohen 2012).The number of participants experiencing at least one relapse. Definitions of relapse given in the original studies were accepted.Adverse events (AEs) as reported in the trial:the number of participants experiencing at least one AE, irrespective of whether it was mild or severe (no period restriction);the number of participants experiencing treatment discontinuation caused by an AE.
primary outcome:
Milnacipran for pain in fibromyalgia in adults
Participant reported pain relief of 30% or greaterParticipant reported pain relief of 50% or greaterPGIC much or very much improvedPGIC very much improved
primary outcome:
Interventions for fatigue in Parkinson's disease
The primary outcomes for this systematic review were subjective fatigue, subjective physical fatigue and subjective mental fatigue as measured by self‐report questionnaires. If possible, we categorised the theoretical construct of fatigue as 'impact of fatigue on activities in daily life (ADL)' or 'fatigue severity' (Elbers 2012a).We examined the numbers of adverse effects (i.e. anxiety, falls, headache, hypertension, impulse control disorders, life‐threatening skin conditions, nausea, orthostatic hypotension, psychosis, suicidal ideation and tachycardia).
primary outcome:
Oral nonsteroidal anti‐inflammatory drugs for neuropathic pain
Patient‐reported pain relief of 30% or greaterPatient‐reported pain relief of 50% or greaterPGIC much or very much improvedPGIC very much improved
primary outcome:
Surgery for scoliosis in Duchenne muscular dystrophy
Survival: to allow for studies using different follow‐up periods, we planned to use hazard ratios from survival data regression analysis.
primary outcome:
Buprenorphine for neuropathic pain in adults
Participant‐reported pain relief of 30% or greater.Participant‐reported pain relief of 50% or greater.PGIC much or very much improved.PGIC very much improved.
primary outcome:
Exercise therapy for fatigue in multiple sclerosis
questionnaires that primarily assessed fatigue, such as: Fatigue Severity Scale (FSS; Krupp 1989), Modified Fatigue Impact Scale (MFIS; Fisk 1994), Multidimensional Fatigue Index (MFI; Smets 1995), Visual Analogue Scale for fatigue;sub‐scales of questionnaires that measured fatigue or sub‐scales not primarily designed for the assessment of fatigue but used in such, for example: Short Form‐36 sub‐scale (SF‐36; e.g. vitality sub‐scale; Ware 1992), and Multiple Sclerosis Quality of Life 54 (MSQoL‐54; e.g. physical functioning sub‐scale; Vickrey 1995). We only used these sub‐scales if it was specifically noted that these were included to assess fatigue.
primary outcome:
Plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy
The primary outcome measure was the change in disability measured by a validated scale at least four weeks after treatment onset. We intended to convert the scale used by the authors to the Modified Rankin Scale (van Swieten 1988).
primary outcome:
Venlafaxine for neuropathic pain in adults
Participant‐reported pain relief of 30% or greater.Participant‐reported pain relief of 50% or greater.Participant‐reported global impression of change (PGIC) much or very much improved.Participant‐reported global impression of change (PGIC) very much improved.
primary outcome:
Pharmacological treatments for preventing epilepsy following traumatic head injury
Proportion of participants who experience an early seizure post‐trauma, defined as occurring within one week of trauma.Proportion of participants who experience a late seizure post‐trauma, defined as occurring later than one week post‐trauma.
primary outcome:
Ibuprofen for acute treatment of episodic tension‐type headache in adults
The primary outcome was the pain‐free rate at the end of two hours using any standard method of pain assessment and without the use of rescue medication.
primary outcome:
Neuropsychological and psychological interventions for people with newly diagnosed epilepsy
Improved quality of life: any overall significant improvements in validated self reported quality‐of‐life measures;Description of risk factors: whether there are any associated risks with the interventions.
primary outcome:
Drug therapy for treating post‐dural puncture headache
PDPH persistence of any severity at follow‐up. We considered the rate of persistent PDPH at short (< 12 hours), medium (< 24 hours) or long‐term (≥ 24 hours) follow‐up.
primary outcome:
Amitriptyline for neuropathic pain in adults
Patient reported pain relief of 30% or greater.Patient reported pain relief of 50% or greater.Patient Global Impression of Change (PGIC) much or very much improved.Patient Global Impression of Change (PGIC) very much improved.
primary outcome:
Milnacipran for neuropathic pain in adults
Patient reported pain relief of 30% or greater.Patient reported pain relief of 50% or greater.Patient reported global impression of clinical change (PGIC) much or very much improved.Patient reported global impression of clinical change (PGIC) very much improved.
primary outcome:
Selective serotonin reuptake inhibitors for fibromyalgia syndrome
Number of patients with at least 30% pain reduction rates: If not reported, we calculated responder rates by a validated imputation method (Furukawa 2005) based on means and standard deviations (SDs) of average pain scores. We preferred single item pain scales (e.g. Visual Analogue Scale (VAS) or numeric rating scales) over composite pain scales, (e.g. McGill Pain Questionnaire).Global improvement: Number of patients with a clinically important global improvement: We preferred proportion of patients who reported to be much or very much improved over investigator‐defined composite responder scores. If these outcomes were not available, we used the proportion of patients with a >= 25% reduction of the Fibromyalgia Impact Questionnaire (FIQ)FIQ total score. We calculated responder rates by a validated imputation method (Furukawa 2005) based on means and SDs of average FIQ total scores.Fatigue: We preferred total scores of validated fatigue instruments (e.g. Fatigue Impact Scale) over single item scales (e.g. VAS 0‐10).Sleep problems: We preferred total scores of validated sleep problem instruments (e.g. Medical Outcomes Study (MOS) sleep scale) over single item scales (e.g. VAS 0‐10).Depression: We preferred total scores of validated depression instruments (e.g. Beck Depression Inventory (BDI)) over single item scales (e.g. VAS 0‐10).Tolerability: Discontinuation rates due to adverse events.Safety: Proprotion of patients with any serious adverse event.
primary outcome:
Selective serotonin reuptake inhibitors (SSRIs) and serotonin‐norepinephrine reuptake inhibitors (SNRIs) for the prevention of tension‐type headache in adults
Headache frequency.number of attacks per evaluation period;number of days with tension‐type headache; andresponders, i.e. patients with ≥ 50% reduction in headache frequency.
primary outcome:
Dimethyl fumarate for multiple sclerosis
We assessed the following primary outcomes.
primary outcome:
Telerehabilitation for persons with multiple sclerosis
improvement in functional activity; such as activities of daily living (ADL), mobility, continence, etc.;improvement in symptoms or impairments, e.g. pain, spasm frequency, joint range of movement, involuntary movements, spasticity, etc.;improvement in participation and environmental or personal context, or both; e.g. quality of life (QoL), psychosocial function, employment, education, social and vocational activities, patient and carer mood, relationships, social integration, etc.
primary outcome:
Selective serotonin reuptake inhibitors (SSRIs) and serotonin‐norepinephrine reuptake inhibitors (SNRIs) for the prevention of migraine in adults
Migraine frequency.number of migraine attacks per evaluation period;number of days with migraine per evaluation period;responders, i.e. patients with ≥ 50% reduction in headache frequency.
primary outcome:
Treatment for IgG and IgA paraproteinaemic neuropathy
The predefined primary outcome measure was: change in disability at six months after randomisation, measured by a validated scale such as the Overall Disability Scale (ODS) (Merkies 2003a).We selected a disability score for the primary outcome, as such scores are considered to be the most relevant measures in immune‐mediated neuropathies (Merkies 2003b). They are also potentially easy to derive retrospectively from collected data. We predefined six months as a favoured time point for re‐evaluation, on the basis that IgG or IgA paraproteinaemic peripheral neuropathy is a chronic and slowly progressive or relapsing‐remitting disorder. However, to avoid limiting the scope of the review we considered trials using other trial periods and follow‐up intervals, and made appropriate adjustments in our analysis.In the randomised controlled phase of the trial, the trial did not report our predefined primary outcome measure, although it did measure disability at three weeks. Comparing the overall NDS, the treatment group improved by a mean of 20 points (95% CI 3.4 to 36.6) compared to 2 points (95% CI ‐9.2 to 13.2) for the control group (MD 18.00; 95% CI ‐2.03 to 38.03; Analysis 1.1). This was not statistically significant.
primary outcome:
Immunosuppressant and immunomodulatory treatments for multifocal motor neuropathy
Significant improvement at least six months after randomisation. We considered significant improvement to have occurred if a participant improved by one or more points on the modified Rankin disability scale (van Swieten 1988). This scale has the following grades:
0: asymptomatic;
1: non‐disabling symptoms not interfering with lifestyle;
2: minor disability symptoms leading to some restriction of lifestyle but not interfering with the person's capacity to look after themselves;
3: moderate disability symptoms significantly interfering with lifestyle or preventing fully independent existence;
4: moderately severe disability symptoms preventing independent existence although people do not need constant attention day and night;
5: totally dependent, requiring constant attention day and night.
We would have converted any other similar disability scales (for example a functional scale for upper and lower limbs (Nobile‐Orazio 1993)) so that a one point change would have been similar to the modified Rankin scale.
primary outcome:
Physical rehabilitation for critical illness myopathy and neuropathy
Our primary outcome measure was activities of daily living (for example, mobility, walking, transfers and self care), as measured by validated outcome tools.Measurement tools were the Functional Independence Measure (FIM) (Dodds 1993), the Barthel Index (Mahoney 1965), and other validated scales for the ICU such as the Functional Status Score for ICU (FSS‐ICU) (Zanni 2010), the Acute Care Index of Function (ACIF) (Roach 1988), the Physical Function Outcome Measure (PFIT) (Skinner 2009), or other validated measures. Measures of walking ability were gait speed in metres per second and six‐minute walking distance and other validated measures (Nordon‐Craft 2012).If studies used multiple scales to measure our primary outcome, we planned, in the absence of our preferred measures, to report all scales and measures used.
primary outcome:
Early versus late antiepileptic drug withdrawal for people with epilepsy in remission
The primary outcome is the risk ratio of seizure relapse as a consequence of early AED discontinuation in contrast to late withdrawal.
primary outcome:
Interventions for fatigue in peripheral neuropathy
Our primary outcome was fatigue severity and symptoms as measured by any validated scale evaluated at least four weeks and less than 12 weeks after commencement of the intervention. Where studies used more than one scale, we used the preferred ranking of commonly‐used scales shown below to identify the scale to be used in the primary outcome analysis. Instruments that we considered appropriate included: Fatigue Severity Scale (FSS) (Krupp 1989), Chalder Fatigue Scale (Chalder 1993), Fatigue Impact Scale or daily‐FIS (D‐FIS) (Fisk 1994; Fisk 2002), Visual Analogue Scale of Fatigue (VAS‐F) (Lee 1991), and Piper Fatigue Scale (PFS) (Piper 1998).
primary outcome:
Non‐pharmacological interventions for chronic pain in people with spinal cord injury
Primary outcome measures consisted of any measure of pain on scales for pain intensity or pain relief. Included studies used various pain measures and measurement schemes during follow‐up, including numerical rating scales (NRSs), visual analogue scales (VASs) and pain questionnaires (e.g. McGill Pain Questionnaire, Wheelchair User's Shoulder Pain Index (WUSPI), Short Form (SF)‐36). Details on the observation period were extracted from the original reports. From studies that reported several outcome measures of pain, we extracted data for all measures and selected the most frequently reported measure across included studies for use in meta‐analysis. However, if we found a serious imbalance among baseline pain scores between intervention and control groups for the most common measure, we chose a pain measure without imbalance for further analysis.
primary outcome:
Pharmacotherapy for sleep bruxism
Indexes of bruxism motor activity demonstrated by EMG of the masseter muscle associated with PSG audio‐video recordings: frequency of sleep bruxism episodes per hour of sleep (at least four episodes) and number of episodes with grinding noise (minimum of two).
primary outcome:
Acetylcholinesterase inhibitor treatment for myasthenia gravis
Improvement in the presenting symptoms within one to 14 days of the start of treatment.
primary outcome:
Intravenous immunoglobulin for Guillain‐Barré syndrome
healthy;minor symptoms or signs of neuropathy but capable of manual work;able to walk without support of a stick but incapable of manual work;able to walk with a stick, appliance or support;confined to bed or chair bound;requiring assisted ventilation; anddead.
primary outcome:
Anticonvulsant therapy for status epilepticus
The outcomes considered depended on the stage of status epilepticus at which the treatment was tested. For the purpose of this review, our intention was to analyse treatment failure as the primary outcome. We intended to define treatment failure for the various stages as any of the following.
primary outcome:
Comparison of antiepileptic drugs, no treatment, or placebo for children with benign epilepsy with centro temporal spikes
The outcome measures included:Resolution of EEG abnormalities was not included as an outcome as the clinical manifestation of seizures is probably not related to persisting EEG abnormality, though cognitive functioning may be.
primary outcome:
Zolmitriptan for acute migraine attacks in adults
Pain‐free at two hours, without the use of rescue medication.Reduction in headache pain ('headache relief') at two hours (pain reduced from moderate or severe to none or mild without the use of rescue medication).
primary outcome:
Carbamazepine for chronic neuropathic pain and fibromyalgia in adults
Participant‐reported pain intensity reduction of 30% or greater.Participant‐reported pain intensity reduction of 50% or greater.Participant‐reported global impression of clinical change (PGIC) much or very much improved.Participant‐reported global impression of clinical change (PGIC) very much improved.
primary outcome:
Mycophenolate mofetil for relapsing‐remitting multiple sclerosis
Proportions of participants who had relapses at 12 and 24 months after randomization.Proportions of participants who experienced disease progression, as measured by the Expanded Disability Status Scale (EDSS) (Kurtzke 1983), at 12 and 24 months after randomization. Progression is defined as an increase of 0.5 point of disability for participants with baseline EDSS greater than or equal to 5.5, and 1.0 point of disability for those with basal EDSS less than or equal to 5.0, sustained for six months.
primary outcome:
Antiviral treatment for preventing postherpetic neuralgia
The primary outcome was the presence of PHN six months after the onset of the acute herpetic rash.We defined PHN according to clinical diagnostic criteria as pain persisting or recurring at the site of shingles and lasting at least 120 days from rash onset (Desmond 2002). Where pain severity was described, we categorised pain as mild (less than a score of 4 on a scale of 0 to 10) or moderate (4 out of 10 or higher).
primary outcome:
Immunotherapy for idiopathic lumbosacral plexopathy
Our primary outcome was change in disability from baseline as measured by an appropriate, validated scale such as the lower limb scale of the Overall Disability Sum Score (ODSS) (Merkies 2002), at 12 months. We planned to scale results from publications using different follow‐up periods to the same follow‐up period before pooling in a meta‐analysis and to investigate the implications of the necessary assumptions.
primary outcome:
Mechanical insufflation‐exsufflation for people with neuromuscular disorders
The primary outcomes were the pooled mortality hazard ratio (HR) calculated using deaths throughout follow‐up, or the pooled mortality risk ratio (RR) at a single follow‐up time (at six months).
primary outcome:
Passive movements for the treatment and prevention of contractures
joint mobility, including measures of active or passive range of motion with or without standardised torques. Units of measure were expressed in degrees (degree per unit of torque) or centimetre. Unidirectional and bidirectional range of motion measurements were included; andadverse events, grouped in the following ways: joint subluxations or dislocations, heterotopic ossification, autonomic dysreflexia (an exaggerated response of the sympathetic nervous system typically seen in people with spinal cord injury), fractures and muscle tears.
primary outcome:
Daclizumab for relapsing remitting multiple sclerosis
We assessed the following primary outcomes measured at two years of follow‐up.
primary outcome:
Pharmacological treatment for memory disorder in multiple sclerosis
CVLT‐II (Delis 2000);SRT (Buschke 1974);BVMTR (Benedict 1997);Wechsler Memory Scale ‐ Third Edition (WMS‐III) (Wechsler 1997a);10/36 SRT (Rao 1990b);7/24 Spatial Recall Test (7/24 SRT) (Rao 1991c);Backward Digit Span (Wechsler 1997b);Logical Memory (LM) subset of the Wechsler Memory Scale‐Revised (WMS‐R) (Wechsler 1987);Rey Auditory Verbal Learning Test (RAVLT) (Lezak 2004);PASAT (Rao 1990a);SDMT (Smith 1982).
primary outcome:
Rituximab for relapsing‐remitting multiple sclerosis
We assessed the following primary outcomes measured in the treatment phase and at the completion of follow‐up versus baseline.
primary outcome:
Non‐antiepileptic drugs for trigeminal neuralgia
The primary outcome was immediate improvement in pain relief evaluated as decreased pain intensity or trigeminal neuralgia score, that is number of attacks per day and their intensity.A visual analogue scale (VAS) was used to evaluate pain but the report does not include the results. The investigators reported overall efficacy assessed by participants and investigators on a four‐point scale (no efficacy, slight, moderate, good or very good) but provide no other details of the measure. At the end of treatment, one of five participants improved with tizanidine and four of six with carbamazepine (RR 0.30, 95% CI 0.05 to 1.89) (Analysis 1.1). The difference was not statistically significant.A verbal pain rating scale (VRS) was used to assess the effect. There was no significant reduction of pain after 3, 10 or 30 days. At 30 days, six of 25 participants improved (i.e. had a 2 or more level decrease in pain on 10‐point scale, or pain was gone or rare) with proparacaine hydrochloride 0.5%, and five of 22 improved with placebo (RR 1.06, 95% CI 0.37 to 2.99) (Analysis 2.1). Eleven participants in the treatment group and 14 participants in the control group underwent surgery during follow‐up. Two participants in the control group required medication.A trigeminal neuralgia score ranging from 0 to 100 was used to assess the effect. However, the authors did not state how they defined 'improvement', other than stating that all of the 48 participants on pimozide and 27 out of 48 participants on carbamazepine "showed improvement". They do give a percentage improvement score for each group after six weeks' treatment (when the authors state that there was "maximal improvement"); they also report that "similar differences were obtained" at weeks seven and eight, week eight being the end of the first treatment period. Week seven and eight results are provided in graph form in the study report as are second period results. In the first period, the reduction in total trigeminal neuralgia score was 78.4% with pimozide and 49.7% with carbamazepine, six weeks after starting treatment (MD 28.70%, 95% CI 20.88% to 36.52%) (see Analysis 3.1).
primary outcome:
Lamotrigine for chronic neuropathic pain and fibromyalgia in adults
Participant‐reported pain intensity reduction of 30% or greater.Participant‐reported pain intensity reduction of 50% or greater.Participant‐reported global impression of clinical change (Patient Global Impression of Change, PGIC) much or very much improved.Participant‐reported global impression of clinical change (PGIC) very much improved.
primary outcome:
Naproxen with or without an antiemetic for acute migraine headaches in adults
Pain‐free at two hours, without the use of rescue medication.Reduction in headache pain ('headache relief') at two hours (pain reduced from moderate or severe to none or mild without the use of rescue medication).
primary outcome:
Thymectomy for non‐thymomatous myasthenia gravis
Improvement in myasthenic weakness within 12 months of thymectomy. We had planned to rely on each individual study's method for evaluating improvement of myasthenic weakness.
primary outcome:
Physiotherapy versus placebo or no intervention in Parkinson's disease
Gait outcomes such as:Functional mobility and balance outcomes such as:Data on falls such as:Clinician‐rated impairment and disability measures such as:Patient‐rated quality of life such as:Adverse events (e.g. fractures, pain).Compliance (e.g. participant adherence, treatment fidelity).Economic analysis.
primary outcome:
Botulinum toxin for masseter hypertrophy
Self‐assessed improvement in facial appearance and patient satisfaction using any validated scale or questionnaire.Patient‐assessed improvement in pain or discomfort associated with the temporo‐mandibular joints or jaw muscles using any recognised validated pain scale.
primary outcome:
Topiramate for neuropathic pain and fibromyalgia in adults
Patient‐reported pain relief of 30% or greater.Patient‐reported pain relief of 50% or greater.PGIC much or very much improved.PGIC very much improved.
primary outcome:
Nonoperative treatment for lumbar spinal stenosis with neurogenic claudication
Studies were included if they measured at least one of the following outcomes: walking ability, pain intensity, function, quality of life, and global improvement. Common outcome measures used in this patient population included the following.The Zurich Claudication Questionnaire (ZCQ), also known as the Swiss Spinal Stenosis questionnaire, is a validated self report, condition specific questionnaire for patients with neurogenic claudication (Comer 2011). It measures symptom intensity, function, and satisfaction with treatment. Walking ability is often measured using subscales of the Oswestry Disability Index (Fairbank 1980) or the Zurich Claudication Questionnaire (Stucki 1996), or objectively using the Self Paced Walking Test, Treadmill Walking Test, and distance walked. Pain intensity is usually measured using a visual analog scale (VAS), verbal response scale (VRS), McGill pain questionnaire (Melzack 2005), or numerical pain rating scale (NPRS). Function in patients with neurogenic claudication can be measured using the Oswestry Disability Index or the Roland Morris Disability Questionnaire (Brouwer 2004). Quality of life can be measured using the Short Form‐36 (SF‐36) questionnaire (Ware 1995). A subjective global rating of change or improvement can also be employed, typically in the form of a Likert scale.Outcomes were categorized according to these follow‐up periods: immediate (up to one week), short‐term (between one week and three months), intermediate (between three months and one year), and long‐term (one year or longer).
primary outcome:
Triptans for acute cluster headache
headache relief (assessed on the 5‐point pain relief scale described above, or defined as a reduction in pain intensity from moderate or severe or very severe to none or mild) at 15, 30, or 60 minutes, without use of rescue medication;pain‐free at 15, 30, or 60 minutes, without use of rescue medication.
primary outcome:
Antiepileptic drugs for the primary and secondary prevention of seizures after subarachnoid haemorrhage
Proportion of patients who experienced clinical seizures in the scheduled follow‐up period. In cases where seizures occurred, we noted their nature (generalised or focal), timing and whether an EEG was performed to aid the diagnosis and seizure classification.Proportion of patients with a previous seizure who achieved remission for a predefined period of time (e.g. 12 or 24 months).Proportion of patients who withdrew from the allocated treatment within the scheduled follow‐up period. This was a composite outcome that took into account several factors, including adverse events, compliance and effectiveness of treatment. We were particularly interested in the occurrence of side effects for the different AEDs, which might be physical or neurobehavioural (e.g. problems with memory, attention and performance skills).Proportion of patients who had either died or were dependent at the end of the scheduled follow‐up period. 'Independent' individuals were defined as those who did not require regular physical assistance from another person for activities of daily living such as mobility, dressing, transfers and feeding. 'Dependent' individuals were those who failed to meet one or more of these criteria.
primary outcome:
Therapeutic exercise for people with amyotrophic lateral sclerosis or motor neuron disease
Improvement in functional ability, decrease in disability or reduction in rate of decline as measured by a validated outcome tool at three months; for example ALS Functional Rating Scale (ALSFRS) (CNTF 1996), ALSFRS‐Revised (Cedarbaum 1999), Schwab & England Rating Scale (Schwab 1969), the Appel ALS Scale (Appel 1987), the ALS Severity Scale (Hillel 1989), the Norris Scale (Norris 1974).
primary outcome:
Mitoxantrone for multiple sclerosis
The primary outcome measures were as follows.
1) Number of participants who had confirmed disability progression at one year and after, from the inclusion into the trial. Disability progression was defined as an increase of at least 1 point above the entry score if baseline score < 5.5, and of at least a half‐point if baseline score > 5.5, of the Kurtzke Expanded Disability Status Scale (EDSS) (Kurtzke 1983), assessed in two different and subsequent neurological examinations separated by at least a six month interval free of relapses.*
2) Number of participants who withdrew from the study because of major side effects of the drug, considered as those side effects causing death or hospitalisation of the participant.* Please note: at the time we assessed the data for this review, we realised that the definitions and measures of disability progression varied between the included trials. Therefore, we decided to perform, in addition to the originally planned analyses, additional analyses accepting the definitions of disability given in the original papers and to include this outcome here, with due allowance for its post hoc nature.
primary outcome:
Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults
Pain‐free at two hours, without the use of rescue medication (PF2).Reduction in headache pain ('headache relief') at two hours (HR2) ‐ pain reduced from moderate or severe to none or mild without the use of rescue medication.
primary outcome:
Aspirin with or without an antiemetic for acute migraine headaches in adults
Pain‐free at two hours, without the use of rescue medication (PF2).Reduction in headache pain ('headache relief') at wo hours (HR2) ‐ pain reduced from moderate or severe to none or mild without the use of rescue medication.
primary outcome:
Diclofenac with or without an antiemetic for acute migraine headaches in adults
Pain‐free at two hours, without the use of rescue medication (PF2).Reduction in headache pain ('headache relief') at two hours (HR2) ‐ (pain reduced from moderate or severe to none or mild without the use of rescue medication).
primary outcome:
Ibuprofen with or without an antiemetic for acute migraine headaches in adults
Pain‐free at two hours, without the use of rescue medication (PF2).Reduction in headache pain ('headache relief') at two hours (HR2) ‐ (pain reduced from moderate or severe to none or mild without the use of rescue medication).
primary outcome:
Drug therapy for preventing post‐dural puncture headache
Number of participants affected by PDPH of any severity after a lumbar puncture.
primary outcome:
Intravenous immunoglobulin for myasthenia gravis
In participants treated for exacerbation, the primary end point was a change in a specific score between the day before and days seven to fifteen after start of treatment (or day of randomisation). This score was a unified strength/fatigue measurement obtained from the various scores reported. If a unified score could not be obtained, the specific score reported in each individual study was used.In participants treated for chronic (severe but stable) MG, the primary end point was an improvement by at least one grade in a functional scale (as described below) between the day before and at least six months after start of treatment (or day of randomisation).
primary outcome:
Cognitive behavioural therapy (CBT) with and without exercise to reduce fear of falling in older people living in the community
FoF. As an umbrella term, FoF is documented by different assessment methods focusing on concepts related to emotional (fear) as well as cognitive appraisal (concerns). FoF can be measured through single‐item questionnaires, or through multi‐item measures, such as those for falls efficacy, and balance confidence. Relevant measurement tools to identify FoF are summarised by Kendrick 2014 and Moore 2008. These are:ABC and its associated versions (e.g. its UK version ABC‐UK) (Powell 1995)Falls Efficacy Scale (FES) (Tinetti 1990) and its associated versions (e.g. modified FES (mFES) (Hill 1996), or FES‐I) (Yardley 2005)Geriatric Fear of Falling Measure (GFFM) (Huang 2006)Single‐item Instruments (Tinetti 1990; Howland 1993)Mobility Efficacy Scale (MES) (Lusardi 1997)University of Illinois at Chicago Fear of Falling Measure (UICFFM) (Velozo 2001)
primary outcome:
Hypothermia for neuroprotection in adults after cardiac arrest
Neurological recovery. We expected the ideal time point of outcome to be reported as the best neurological outcome during the hospital stay and in cerebral performance categories (CPCs) (Stiell 2009). CPC categories are defined as follows.CPC 1: good cerebral performance: conscious, alert and capable of normal life. Normal cerebral function. May have minor psychological or neurological deficits that do not significantly compromise cerebral or physical function.CPC 2: moderate cerebral disability: conscious, alert, sufficient cerebral function for activities of daily life (e.g. able to dress, travel by public transportation, food preparation). May have hemiplegia, seizures, ataxia, dysarthria, dysphasia, or permanent memory or mental changes.CPC 3: severe cerebral disability: conscious, with at least limited cognition. Dependent on others for daily life support (i.e. institutionalised or at home with exceptional family effort) because of impaired brain function. Includes individuals with a wide range of cerebral abnormalities, from ambulatory participants with severe memory disturbance or dementia precluding independent existence to paralysed participants who can communicate only with their eyes (e.g. the locked‐in syndrome).CPC 4: coma or vegetative state: not conscious, unaware of surroundings, no cognition. No verbal or psychological interaction with the environment. May appear awake because of spontaneous eye‐opening or sleep–wake cycle. Includes individuals showing all degrees of unresponsiveness that are neither CPC three (conscious) nor CPC five (coma, which satisfies brain death criteria).CPC 5: certified brain death.
primary outcome:
Environmental interventions for preventing falls in older people living in the community
Rate of falls (number of falls; falls per person‐year).
primary outcome:
Systemic corticosteroids for radicular and non‐radicular low back pain
We focused on participant‐centered clinical outcomes. We did not evaluate physiologic, biomechanical (e.g. range of motion, measures of muscular strength), and laboratory parameters.
primary outcome:
Peripheral nerve blocks for hip fractures in adults
Pain on movement 30 minutes after block placement (study author's scale; Thong 2018)Acute confusional state (study author's definition), 0 to 30 daysMyocardial infarction (study author's definition), 0 to 30 days
primary outcome:
Shoulder replacement surgery for osteoarthritis and rotator cuff tear arthropathy
Based on the preliminary core domain set described by the OMERACT (Outcome Measures in Rheumatology) Special Interest Group (Buchbinder 2017), we measured the following major outcomes.
primary outcome:
Shock wave therapy for rotator cuff disease with or without calcification
There is considerable variation in the outcome measures reported in clinical trials of interventions for pain. For the purpose of this systematic review, we aimed to include clinically important changes in pain, as recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). Reductions in pain intensity of 30% or greater reflect moderate clinically important differences and 50% or greater reflect substantial clinically important differences, and it is recommended that the proportion of patients who respond with these degrees of pain relief be reported (Dworkin 2008).Continuous outcome measures in pain trials (such as mean change on a 100 mm Visual Analogue Scale (VAS)) may not follow a Gaussian distribution. Often, a bimodal distribution is seen instead, where patients tend to report either very good or very poor pain relief (Moore 2010). This creates difficulty in interpreting mean changes in continuous pain measures. For this reason, a dichotomous outcome measure (the proportion of participants reporting 30% or greater pain relief) is likely to be more clinically relevant and was the main outcome measure of benefit in this review. However, it is recognised that it has been the practice in most trials of interventions for chronic pain to report continuous measures and, therefore, the mean pain score or mean change in pain score were also included as major outcomes.The pain state at the end of a clinical trial of an analgesic intervention, in contrast to measures of pain improvement, has also been recommended as a clinically relevant dichotomous outcome measure and was included as a secondary efficacy measure in this review (Moore 2010). A global rating of treatment satisfaction, such as the Patient Global Impression of Change scale (PGIC), which provides an outcome measure that integrates pain relief, changes in function and adverse effects, into a single, interpretable measure, is also recommended by IMMPACT, and was included as a major outcome (Dworkin 2008).
primary outcome:
Prophylactic antibiotics for penetrating abdominal trauma
Septic complications, including intra‐abdominal abscesses and wound infections.
primary outcome:
Pregabalin for neuropathic pain in adults
Participant‐reported pain intensity reduction of 30% or greaterParticipant‐reported pain intensity reduction of 50% or greaterPatient‐reported global impression of clinical change (PGIC) much or very much improvedPatient‐reported global impression of clinical change (PGIC) very much improved
primary outcome:
Multifactorial and multiple component interventions for preventing falls in older people living in the community
Rate of falls (falls per person‐years).Number of people who have sustained one or more falls (risk of falling).Number of people who have sustained recurrent falls (defined as two or more falls in a specified time period) (risk of recurrent falls).
primary outcome:
One‐incision versus two‐incision techniques for arthroscopically assisted anterior cruciate ligament reconstruction in adults
Functional assessments based on subjectively assessed, preferably validated questionnaires of knee function, e.g. the International Knee Documentation Committee (IKDC) subjective part for knee ligament injuries and the Lysholm score (Irrgang 2001; Lysholm 1982).Quality of life assessments based on subjective and preferably validated questionnaires, e.g. the ACL Quality of Life outcome measure (Mohtadi 1998), the Knee Injury and Osteoarthritis Outcome Score (KOOS) for the knee in general (Roos 1998), and the Medical Outcomes Study 36‐item short‐form health survey (SF‐36) for general measures (Ware 1992).Adverse events including treatment failure (implant breakage, screw migration, graft loss, residual instability, infection, knee stiffness).
primary outcome:
Neuromuscular electrical stimulation (NMES) for patellofemoral pain syndrome
Knee pain (measured by validated pain scores, such as visual analogue scales (VAS)) (Revill 1976).Knee function measured by validated knee questionnaires (such as Kujala Patellofemoral Score and Lysholm score) (Kujala 1993; Lysholm 1982).Adverse events (e.g. skin injuries, excessive discomfort, excessive fatigue, bradycardia or other cardiac arrhythmia, or substantially increased pain as a direct effect of treatment).