Key Message

Seven relevant publications were identified, these comprised two systematic reviews of guidelines, and two individual guideline reports on osteoarthritis (OA); and three individual guideline reports on neuropathic pain (NP). There appears to be some variability in the recommendations for use of capsaicin for the management of pain in patients with OA. The two systematic reviews found that capsaicin was recommended for OA (two guidelines), hand OA (two guidelines), knee OA (three guidelines), and hip OA (one guideline); and capsaicin was not recommended for OA (one guideline). According to one guideline report, capsaicin is recommended for knee OA but not for hand OA (conditional recommendation); and the other guideline report does not recommend for or against use of capsaicin for treating glenohumeral joint OA (due to absence of reliable evidence). For treatment of patients with NP, one guideline recommends high concentration capsaicin patch (weak recommendation); and two guidelines recommend capsaicin (8%) patch as second-line treatment (strength of recommendation: weak according to one guideline and based on high level evidence according to another guideline).Findings need to be interpreted in the light of limitations (such as limited available evidence, and variability in the reported recommendations).

Key Message

Evidence from five systematic reviews (four with network meta-analysis and one with traditional meta-analysis) and one randomized controlled trial suggested that adalimumab was less effective than infliximab, ixekizumab, risankizumab, and secukinumab in achieving skin clearance and improvements in health-related quality of life in patients diagnosed with moderate-to-severe plaque psoriasis. Apart from the randomized controlled trial comparing adalimumab to risankizumab, separate data from direct comparison were not available for effectiveness and safety. There was not enough evidence to draw a firm conclusion about the comparative safety of adalimumab versus the other biologics of interest. Substantial overlap of primary studies across the systematic reviews showed that the pooled estimates from the separate reviews contain some data from the same primary studies. An assessment of the methodological quality of the included studies did not find issues that present significant uncertainty about the findings in four systematic reviews and the randomized controlled trial. The quality of one systematic review was limited due to inadequate reporting. However, the results from that study were consistent with the others. Thus, they did not appear likely to impact the overall evidence reported here. The consistency could be due to the overlap of the primary studies included in the systematic reviews.

Key Message

People with heart valve disease struggled with breathlessness, fatigue and pain that limited their ability to live independent and full lives, and left some feeling depressed, lonely and worthless. They saw surgery (either minimally invasive or open heart) as offering hope to live longer and fuller lives. The burden of their symptoms and the trust they placed in their doctors and the procedure were key factors in deciding whether to undergo heart valve surgery, whether either minimally invasive or open heart. Some viewed minimally invasive procedures specifically as being preventative, or pre-empting future health problems, while heart valve surgery in general was seen as potentially opening the door to other treatment options for other health problems or comorbidities.People who were not eligible for minimally invasive surgery felt they were left managing their heart failure symptoms as best as they could, but confronted the inevitable worsening of their symptoms and death. Others decided against minimally invasive surgery, for example due to comorbidities or religious beliefs. Some who decided against the procedure did so because they felt coping with heart failure symptoms was better than living longer with their comorbidities or the potential complications of surgery.Waiting for surgery was hard, involving fear over a potentially worsening condition and requiring coping skills and support. People with heart valve disease had to deal with travel and logistical challenges, including out of pocket expenses, while being assessed and undergoing minimally invasive surgery.People undergoing heart valve surgery expressed appreciating being offered minimally invasive surgery because of the anticipated shorter recovery time. People’s recovery after heart valve surgery varied, however. For some who underwent minimally invasive procedures, it was an immediate and dramatic change; for others, it was a slower struggle to return to normal. Family caregivers were seen by people who had heart valve surgery as playing a vital role in their recovery. Those who noticed an improvement in their symptoms following surgery reported appreciating a return of their breathing the most, describing once again being able to walk and engage in activities they had missed, leading to increased independence.One study was identified that described health care providers’ perspectives on heart valve surgery (i.e., TAVI). Cardiologists and cardiac surgeons expressed that they appreciated the short recovery time of minimally invasive procedures, but described their uncertainty around using the procedure in younger patients because of the lack of long-term data on valve durability. They described TAVI as a highly complex procedure with a steep learning curve, needing a dedicated heart team as a key success factor for implementation in a hospital.

Key Message

Five relevant systematic reviews (four with meta-analysis and one with network meta-analysis), two randomized controlled trials, and six non-randomized studies were identified regarding the safety of pioglitazone for patients with pre-diabetes or type 2 diabetes.In patients with pre-diabetes, evidence from one non-randomized study suggested that pioglitazone was associated with an increased likelihood of weight gain and edema when compared to placebo, while studies evaluating other safety outcomes generally found no significant differences between pioglitazone and comparators. Results in patients with type 2 diabetes were mixed, though there were often no significant differences from systematic reviews regarding several safety outcomes when comparing pioglitazone to other treatments for type 2 diabetes. However, the body of evidence was largely of low to moderate quality. As such, there remains some uncertainty around the overall safety profile of pioglitazone.The limitations of the included studies (e.g., heterogeneity of the literature, and lack of blinding to treatment), should be considered when interpreting the results.

Key Message

This report included one single-arm study regarding the clinical effectiveness of the transcatheter mitral valve repair device (MitraClip) for the treatment of tricuspid regurgitation, and four single-arm studies regarding the effectiveness of the device for tricuspid or both tricuspid and mitral regurgitation. No evidence regarding the cost-effectiveness of the transcatheter mitral valve repair device for this indication was identified.

Overall, compared to pre-procedure, patients MitraClip for the treatment of tricuspid regurgitation or both tricuspid and mitral regurgitation had significantly improved tricuspid regurgitation grade, New York Heart Association functional class, edema, and ascites at follow-up. Across four studies that reported on procedural success, the percentage of patients with procedural success ranged from 92% to 97%. There was no statistically significant difference in quality of life between baseline and follow-up in the three studies that measured this outcome. Four of the studies showed statistically significant improvement in the six-minute walking distance at one month or six months, in patients who received tricuspid valve (TV) repair or both TV and mitral valve (MV) repair. One study observed a numerical (but not significant) improvement in the six-minute walking distance from baseline to one-year follow up.  For heart failure severity when comparing baseline and follow up, two studies found significant improvement; two studies found no statistically significant difference; and one study demonstrated a statistically significant improvement in patients who received TV-only repair but no significant difference in patients who received both TV and MV repair. The mortality incidence after the procedure was 4.7% to 7% across the included studies.

The findings summarized in this report have a high degree of uncertainty due to the limitations of the included studies (e.g., a total of 209 patients in single-arm studies, longest follow-up duration of one year).

Key Message

​This review included two systematic reviews and two randomized controlled trials regarding the clinical effectiveness of ketamine for treating of patients with chronic non-cancer pain, and two guidelines regarding the use of ketamine for this population. No studies regarding the cost-effectiveness of ketamine were identified.

Based on findings of one systematic review compared to placebo, intravenous ketamine infusions significantly reduced pain scores, and had significantly higher positive response rates within two weeks of follow-up, but with significantly higher incidence of nausea, vomiting and psychomimetic effects, including delusion, hallucination and dysphoria. The positive short-term effect of ketamine was independent to dose, types of chronic pain or adjunct medication.

Another systematic review found that topical ketamine and oral ketamine were not efficacious for treatment of neuropathic pain, while IV ketamine was more effective in pain improvement for various conditions of chronic neuropathic pain when compared to placebo.

One included randomized controlled trial found that intravenous ketamine significantly reduced pain compared to placebo in chronic pain patients who experienced acute exacerbation within 60 minutes of treatment, but the ketamine analgesic effect was not observed at 24 to 48 hours of follow-up. Incidence of adverse events was significantly higher in the ketamine group than that in the placebo group.

Another included randomized controlled trial found that intraoperative ketamine infusion significantly reduced immediate postoperative intravenous morphine consumption after spinal fusion surgery in chronic pain patients compared to placebo, with no significant differences between treatment groups regarding acute pain (two to 24 hours postoperative), persistent pain (six months postoperative), and adverse events.

One included guideline does not recommend intravenous ketamine infusion for various chronic pain conditions such as chronic persistent pain, complex regional pain syndrome, fibromyalgia and neuropathic pain due to insufficient evidence. The other guideline also did not find any strong evidence for intravenous ketamine infusion for immediate pain improvement in those pain conditions. 

Evidence in this review suggests that intravenous ketamine could only provide short-term pain relief in patients with chronic non-cancer pain, with increased risks of some adverse events such as nausea, vomiting and psychotomimetic effects.

Key Message

Five relevant reports were identified. These comprised one systematic review, two randomized controlled trials (RCT), and two economic evaluations.

One systematic review found that compared to patients treated with other treatments (i.e., methadone, or any other treatment program) those treated with injectable diacetylmorphine (DAM) (with or without the addition of methadone) had statistically significantly greater retention in treatment, reduction in illicit drug use, reduction in criminal activities, and fewer convictions and imprisonments, but no statistically significant difference in mortality and greater occurrence of adverse events.

One RCT showed that injectable hydromorphone (HDM) was not inferior to injectable DAM with respect to days of street opioid use, and proportions of urinalysis positives for street heroin metabolites in urine samples. There were no statistically significant between-group differences with respect to retention to treatment, criminal activity, and physical health and psychological health, however there was statistically significantly higher risk of adverse events related to the intervention in the DAM group compared to the HDM group.

One crossover RCT with 28 patients showed that there was statistically significant improvement after injectable DAM treatment compared to before treatment with respect to anxiety, anger, emotional excitement and well-being, and statistically significantly less heroin craving with injectable DAM compared to injectable placebo.

The results of the economic evaluations, considering a lifetime time horizon and societal perspective, indicated that DAM and HDM treatments each provided more benefits than methadone treatment, and at lower cost for individuals who had previously used other treatment options. Based on incremental cost-effectiveness ratios, it was found that both DAM and HDM dominated methadone. One evaluation reported that the probability of DAM being cost-effective was 76% at a willingness-to-pay (WTP) threshold of $0 per QALY gained, and 95% at a WTP threshold of $100,000 per QALY gained. The second evaluation did not report the WTP threshold.

Findings need to be interpreted with caution, considering the overall limited quantity of evidence, and that the economic evaluations were based on several assumptions.

Key Message

Eight systematic reviews (SRs) provided direct and indirect comparative evidence of the clinical effectiveness of adalimumab compared to other biological Disease modifying Anti Rheumatic Drugs (DMARDs) and tofacitinib in adults with rheumatological disorders. Among them, four SRs considered patients with rheumatoid arthritis, three SRs considered patients with ankylosing spondylitis (AS) and one SR considered patients with psoriatic arthritis (PsA). No primary randomized controlled studies directly comparing adalimumab with other bDMARDs were identified.

In patients with RA, who were intolerant or inadequately responding to conventional DMARDS, the direct comparative evidence suggested that adalimumab was not superior to tocilizumab and sarilumab. The indirect comparison evidence suggested that adalimumab was no different in clinical efficacy when compared to etanercept, certolizumab pegol, and tofacitinib, but was less favoured when compared to tocilizumab and sarilumab. No evidence was found comparing the clinical efficacy of adalimumab compared to infliximab, golimumab and abatacept. Adalimumab was also found to have a similar safety profile compared to the other biological DMARDs.

In patients with PsA, no direct comparative evidence was found. Evidence from indirect comparisons suggested that adalimumab was superior to ixekizumab in achieving clinical response measured using American College of Rheumatology response, but no differences were found in Psoriatic Area severity index between the two drugs. No differences in clinical effectiveness were found between adalimumab and infliximab, etanercept, certolizumab pegol, secukinumab and golimumab. Adalimumab was also found to have fewer adverse events, but similar serious adverse events compared to the other bDMARDs.

In patients with AS, no direct comparative evidence was found between adalimumab and bDMARDs. Evidence from the indirect comparisons suggested that secukinumab was favoured over adalimumab in achieving clinical response. No differences in clinical effectiveness were found between adalimumab and infliximab, etanercept, certolizumab pegol and golimumab. Adalimumab was also found to have no differences in serious adverse events compared to infliximab, etanercept, certolizumab pegol and golimumab.

Key Message

One relevant evidence-based guideline on the management of chronic pain in children and young people was identified. The level of evidence going from the highest to the lowest was scored as 1++, 1+, 1-, 2++, 2+, 2-, 3, or 4 for the evidence presented in the guideline. Recommendations on various pharmacological treatments were presented but the strengths of recommendations were not provided and were based mainly on expert opinion (evidence level: 4). Lidocaine (5%) patches should be considered in the management of children and young people with localized neuropathic pain, particularly when improving compliance with physiotherapy interventions (evidence level: 3). Low dose amitriptyline should be considered for treating children and young people with functional gastrointestinal disorders (evidence level: 1-), chronic daily headache, chronic widespread pain or mixed nociceptive/neuropathic back pain (evidence level: 3).Recommendations for use of acetaminophen, NSAIDs, gabapentin, pregabalin, bisphosphonate, baclofen, pizotifen, and famotidine for management of chronic pain varied depending on the types of chronic pain and were based on expert opinion.Based on expert opinion, opioids are rarely recommended for chronic pain because of their adverse effect profile, and if used should be used as short a duration as possible.The recommendations need to be considered in the light of the limitations (such as evidence available was of limited amount and limited quality, and recommendations were based on expert opinion; and it was unclear if generalizable to the Canadian context).