Four systematic reviews (SRs) and 1 economic evaluation were identified regarding the clinical effectiveness (including safety) and cost-effectiveness of adalimumab in adults with non-infectious uveitis. In adults with active non-infectious uveitis (VISUAL I), adalimumab significantly lowered the risk of treatment failure and significantly improved changes in best-corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Additionally, the number and rate of adverse events and serious adverse events were greater in the adalimumab group compared to the placebo group. Clinical effectiveness and safety findings from the Japanese sub study (VISUAL I Japan) and data from a randomized controlled trial of a younger adult population (ADUR) demonstrated that adalimumab may have no treatment effect. In adults with inactive non-infectious uveitis (VISUAL II), adalimumab significantly lowered risk of treatment failure; however, adalimumab may have no treatment effect on changes in best-corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Additionally, the number and rate of adverse events and serious adverse events were variable in the adalimumab versus placebo groups (e.g., number of adverse events was greater in the adalimumab group but the rate of adverse events was higher in the placebo groups). Clinical effectiveness and safety findings from the Japanese substudy (VISUAL II Japan) demonstrated that adalimumab may have no treatment effect. Considering both active and inactive non-infectious uveitis (VISUAL I, VISUAL I [Japan], VISUAL II, VISUAL II [Japan], and ADUR), change in vitreous haze grade improved significantly more in the adalimumab group than the control group. In the perspective of the health care system in the UK, adalimumab (plus systemic corticosteroid and immunosuppressant therapy) is not more cost-effective than systemic corticosteroid and immunosuppressant use alone (modelled by placebo data) in adults with active and inactive non-infectious uveitis influencing the posterior segment (i.e., back of the eye). No evidence-based guidelines regarding the use of adalimumab for the treatment of adults with non-infectious uveitis were identified.

Vertical current steering (vCS) divides current between multiple contacts, which reduces radial spread to fine-tune the electric field shape and improves neuroanatomical targeting. vCS may improve the variable responsiveness of Parkinsonian gait to conventional deep brain stimulation. We hypothesized that vCS elicits greater improvement in ambulation in Parkinson's disease patients compared to conventional, single-contact stimulation. vCS was implemented with divisions of 70%/30% and 50%/50% and compared to single-contact stimulation with four therapeutic window amplitudes in current-controlled systems. Walking at a self-selected pace was evaluated in seven levodopa-responsive patients. Integrative measures of gait and stimulation parameters were assessed with the functional ambulation performance (FAP) score and total electrical energy delivered (TEED), respectively. A twotailed Wilcoxon matched-pairs signed rank test assessed the effect of each stimulation condition on FAP and TEED and compared regression slopes; further, a two-tailed Spearman test identified correlations. vCS significantly lowered the TEED (P < 0.0001); however, FAP scores were not different between conditions (P = 0.786). Compared to single-contact stimulation, vCS elicited higher FAP scores with lower TEED (P = 0.031). FAP and TEED were positively correlated in vCS (P = 2.000 × 10-5 , r = 0.397) and single-contact stimulation (P = 0.034, r = 0.205). Therefore, vCS and single-contact stimulation improved ambulation similarly but vCS reduced the TEED and side-effects at higher amplitudes. Parkinson's disease and deep brain stimulation Deep brain stimulation (DBS) consistently relieves appendicular symptoms in Parkinson's disease (PD) but its effect on Parkinsonian gait deficits remains more elusive and variable 1. Thus, in present clinical practice, PD patients with severe postural and gait instabilities or levodopa (L-DOPA) resistant postural and gait instabilities are often excluded from receiving DBS 2-4. DBS chronically transmits electrical pulses from a sub-dermally implanted impulse generator (IPG) in the upper chest to neural tissue through implanted electrodes to address disabling dyskinesia and motor fluctuations from long-term use of L-DOPA 5. The varying response of Parkinsonian gait deficits to DBS may be attributed to extensive physiological integration of various networks necessary for gait facilitation, the influence of bradykinesia and rigidity on Parkinsonian gait deficits, and the bias of upper limb symptom improvement during contact localization and selection 6,7. Gait deficits attributed to rigidity and bradykinesia such as reduced step length and gait velocity tend to respond to L-DOPA and subthalamic nucleus (STN)-DBS. However, L-DOPA responsive gait deficits still exhibit a more variable responsiveness to STN-DBS as compared to appendicular symptoms such as tremor and rigidity. For instance, stimulation spread into the zona incerta and/or fields of forel from STN targeted electrodes has been reported to induce gait akine...

Evidence-based clinical practice guidelines recommend the use of botulinum toxin (which includes onabotulinum toxin A [Botox]) to treat spasticity caused by multiple sclerosis. There is a lack of recent evidence regarding the clinical and cost-effectiveness of Botox as a treatment for spasticity caused by multiple sclerosis; thus, there is a need for well-designed studies on this topic.

Two systematic reviews, 1 economic evaluation, and 2 evidence-based guidelines were identified regarding the clinical effectiveness (including safety), cost-effectiveness, and use of adalimumab in pediatric populations with non-infectious uveitis. Pooled data of the SYCAMORE and ADJUVITE randomized controlled trials comparing adalimumab to placebo demonstrated that adalimumab significantly increased the likelihood of reducing or interrupting corticosteroid use (which is beneficial as long-term corticosteroid use can result in cataracts and glaucoma). Adalimumab significantly increased the event of a satisfactory response rate, but there was no difference in safety assessed as systemic adverse events and local adverse effects. Specific to the ADJUVITE trial, visual acuity slightly worsened before and after treatment with adalimumab and it was unclear if adalimumab increased control of intraocular inflammation. Specific to the SYCAMORE trial, adalimumab significantly lowered the risk of treatment failure and the rate and number of adverse events and serious adverse events were higher in the adalimumab group compared to the placebo group. For the adalimumab group, the most common adverse event type was infections and infestations and the most common serious adverse events were glaucoma, cataracts, injection site reactions, arthritis, and arthralgia. In the perspective of the health care system in the UK, adalimumab plus methotrexate was not found to be cost-effective compared to methotrexate alone (modelled by placebo data) in uveitis associated with juvenile idiopathic arthritis. Cost-effectiveness analyses of adalimumab at a discounted price lowered the incremental cost-effectiveness ratio, which supports the potential use of biosimilars in the future due to cost savings. Both guidelines recommended the use of treatment that blocks proteins that cause inflammation (tumour necrosis factor-alpha inhibitors) such as adalimumab in combination with an immunosuppressive agent such as methotrexate (i.e., adalimumab plus methotrexate) in patients with uveitis associated with juvenile idiopathic arthritis who are not responsive to initial treatment (e.g., topical corticosteroids) and are at risk for severe uveitis or vision threatening complications. The American College of Rheumatology/ Arthritis Foundation recommended the use of adalimumab and infliximab over etanercept with no preference between adalimumab and infliximab. Conversely, the guideline from multiple interdisciplinary German groups recommended that adalimumab and infliximab are the first- and second-choice tumour necrosis factor-alpha inhibiting drugs, respectively. They recommended a treatment switch to infliximab then golimumab when adalimumab is not effective or there is treatment failure with adalimumab.

This report provides an overview of evidence regarding evidence-based risk factors and pre-surgical screening tools or assessments that may help identify individuals at risk for developing chronic post-surgical pain. This is not a systematic review and a formal critical appraisal was not performed. Our review identified 19 evidence-based risk factors for chronic post-surgical pain from published systematic reviews. The most commonly reported chronic post-surgical pain risk factors were anxiety (7 studies), catastrophizing (pain or general) (catastrophizing is the tendency to exaggerate a situation in a negative manner [e.g., imagine the worst possible outcome]) (6 studies); depression (5 studies); and psychological distress (non-specific symptoms of depression, anxiety, and stress), kinesiophobia (fear of movement), and age (3 studies each). These risk factors were reported among various surgical procedures (e.g., mixed surgery types, total knee and hip replacements, spine surgery) and age populations (adult, pediatric, adult plus pediatric). Definitive conclusions cannot be made regarding particular risk factors and their association with chronic post-surgical pain. The evidence was either mixed and/or associated with limitations in the methodology of the study and unclear whether the results may apply in groups other than those included in the studies. Our review identified 11 pre-surgical screening tools or assessments that were studied for their ability to predict chronic post-surgical pain. These included various quantitative sensory testing measures (e.g., mechanical, heat or cold, electrical), validated scales of other conditions, and screening tools. Four of the identified screening tools or assessments were found to predict chronic post-surgical pain but their it is unknown whether they can be applied to broader clinical practice (i.e., various surgery types among different age groups). These were only investigated in 1 study among specific populations. These 4 tools or assessments included a pain threshold evaluation performed with a sphygmomanometer (blood pressure monitor comprised of an inflatable cuff) in adults who underwent total knee replacement; the modified Tampa Scale of Kinesiophobia with 13-items (i.e., only the positively scored items) in pediatric patients who underwent orthopedic or general surgery; the Presurgical Psychological Screening algorithm in adults who underwent spine surgery; and the Pediatric Pain Screening tool in pediatric patients who underwent major musculoskeletal surgery. The remaining screening tools or assessments that were identified reported either mixed findings or no association with chronic post-surgical pain in various surgical populations. Definitive conclusions cannot be made for the use of pre-surgical screening tools or assessments to identify risk of developing chronic post-surgical pain.