Key Message

Evidence from two traditional systematic reviews and one systematic umbrella review suggested that in patients with knee osteoarthritis, physical activity significantly reduced pain and improved function, performance, and health-related quality of life compared with usual care (not consistently defined), no treatment, or sham interventions.

Limited evidence from one systematic review suggested higher temporary increases in minor pain with exercise than with sham interventions, and no difference in worsening pain, falls, or death between exercise and control groups. Also, limited evidence from a systematic review included in the systematic umbrella review indicated that three to 30 weeks of low-impact activity combining muscle-strengthening, stretching, and aerobic elements were not associated with serious adverse events in older adults, and the number of total knee replacement surgeries was not significantly different between patients who underwent physical activity compared to no-activity control groups over a two month to 24-month observation period.

Sources of uncertainty included the fact that the systematic reviews were based on studies of unclear or low methodological quality. Also, all three included systematic reviews reported significant heterogeneity of their included studies, lacked a standardized definition of "usual care", and had no information on symptom duration, clinical characteristics, comorbid conditions, and concomitant treatments. Therefore, it was difficult to determine if the findings were due entirely to the investigated interventions and controls or if other factors influenced the results.

There was no study identified that examined the comparative clinical effectiveness of physical activity versus pharmacological interventions in individuals with knee osteoarthritis.

Key Message

This review was comprised of one health technology assessment report, two systematic reviews with meta-analyses, one randomized controlled trial, and three economic evaluations regarding pharmacogenomic testing versus treatment as usual for treating all severities of diagnosed depression.

One health technology assessment report suggested that the evidence for pharmacogenomic testing for depressive disorders was limited and of low to very low quality for different outcomes measured. The authors concluded that the evidence was insufficient for forming conclusions regarding clinical use. One systematic review with meta-analysis suggested that pharmacogenetic-guided prescribing had a positive effect on the likelihood of achieving symptom remission which may be confined to individuals with moderate to severe depression and a history of inadequate response or intolerability to previous psychotropic medications. One systematic review with meta-analysis suggested that the evidence was limited in quality and quantity and that primary studies suggestive of a positive effect of pharmacogenomic testing in major depressive disorders were mostly of low quality. One randomized controlled trial reported no significant difference in the improvement of depressive symptoms or safety outcomes between pharmacogenomic testing guided and unguided groups.

The health technology assessment report stated that results in one cost-effectiveness study suggested moderate cost-effectiveness of pharmacogenomics testing given the probability of having an incremental cost-effectiveness ratio below the international $1,926 cost-effectiveness threshold was 90%, while another study suggested that based on the commonly used threshold of $50,000 per quality-adjusted life year, pharmacogenomics testing would not be cost-effective. One included systematic review reported the probability of pharmacogenomics testing being cost-effective at the willingness to pay threshold of $50,000 was 94.5%. One9 of the three included economic evaluations reported the lack of conclusion on cost-effectiveness of screening for CYP2D6 in primary care patients using antidepressants. Two economic evaluations reported that pharmacogenomics testing was dominant over treatment as usual.

One guideline within the health technology assessment report recommended that a combination of therapeutic drug monitoring and genotyping may be informative in potentially nonadherent patients.

Key Message

Two systematic reviews (one with meta-analysis), were identified regarding the effectiveness of pilocarpine for the treatment of dry mouth caused by radiotherapy of the head or neck. 

The identified literature was at high risk of bias and revealed conclusions that were based on studies of limited quality. One study found no difference between a pilocarpine mouthwash and saliva substitutes, while another study found more patients responded favourably to 5 mg pilocarpine lozenges over tablets, lozenges of a lower strength, and inactive lozenges.

One evidence-based guideline was identified regarding the use of pilocarpine for dry mouth caused by radiotherapy of the head or neck. It recommends that pilocarpine be offered, if available.

No evidence regarding the cost-effectiveness of pilocarpine for the treatment of dry mouth caused by radiotherapy of the head or neck was identified. Furthermore, no evidence regarding the clinical effectiveness and cost-effectiveness of pilocarpine for the treatment of dry eyes caused by radiotherapy of the head or neck was identified.

The limitations of the included studies, such as the high risk of bias of the primary studies included in the systematic review and the low-quality evidence upon which guideline recommendations were based, should be considered when interpreting the results.

Key Message

Three systematic reviews were identified regarding the clinical effectiveness of clozapine during the initiation phase, and three evidence-based guidelines were identified regarding monitoring of patients taking clozapine during the initiation phase.

The identified systematic reviews were of limited quality and focused primarily on cardiac complications during clozapine initiation. Side effects of clozapine included myocarditis, tachycardia, hypertension, hyperglycemia, and death. The average time until side effect onset ranged from 14 days to 7 weeks after clozapine initiation, with one study reporting heart rate changes after 2 to 3 days. There were no studies identified that reported on clozapine compared with other antipsychotics during the initiation phase.

The identified guidelines indicate and recommend monitoring of patients initiating clozapine, with recommendations varying in strength of evidence from randomized controlled trials to non-analytic studies and expert opinion. Non-graded evidence suggests assessments of patient history, weight, waist circumference, fasting plasma glucose, fasting lipid profile, prolactin, full blood count, electrocardiograms, electroencephalogram, pregnancy, and ophthalmological examinations for patients who have been prescribed antipsychotics. It was not clear what the strength of evidence for these specific assessments was.

Key Message

Seven diagnostic case-control studies were identified regarding the diagnostic accuracy of artificial intelligence for nodule classification in screening, incidental identification, or known or suspected malignancies for lung cancer. No evidence regarding the cost-effectiveness, clinical utility or evidence-based guidelines regarding artificial intelligence for nodule classification in screening, incidental identification, or known or suspected malignancies for lung cancer were identified.

Results from the case-control studies were mixed. Two studies reported that artificial intelligence models are significantly more accurate at nodule classification when compared to radiologists classifying lung nodules using the American College of Radiologists Lung CT [computed tomography] Screening Reporting and Data System. Two studies descriptively reported that artificial intelligence models are more accurate at nodule classification compared to human observation. However, three studies reported that artificial intelligence models were comparable or had a reduced accuracy when versus human observers (statistical testing performed for one study, descriptive results provided for two studies). Three studies descriptively reported on the sensitivity and specificity outcomes and found that artificial intelligence models had higher values for sensitivity and specificity outcomes than their respective comparators for the diagnosis of lung malignancy.

It may be premature to draw conclusions about artificial intelligence for lung nodule classification given the paucity of clinical utility, cost-effectiveness evidence and guidelines, and mixed results and inherent methodological flaws noted within the included diagnostic accuracy studies.

Key Message

​Three relevant systematic reviews, five randomized controlled trials, and five non-randomized studies were identified regarding the clinical effectiveness of elevated vacuum suspension systems for adults (≥18 years of age) with amputation. Evidence of limited quality suggested that elevated vacuum suspension systems may improve balance, physical capability, prosthetic pistoning, fear and risk of falling, residual limb volume, and skin health compared to non-vacuum suspension systems in adults with amputation; however, there was inconsistency in these results (i.e., in several instances there were no statistically significant differences between vacuum suspension systems and standard prosthetic systems). Two evidence-based guidelines regarding the use of elevated vacuum suspension systems were identified. One guideline suggests that vacuum assisted suspension sockets permit the least amount of pistoning, followed by suction suspension and pin-lock suspension systems. The guideline also recommends that vacuum suspension systems may decrease daily limb volume fluctuations and facilitate favourable pressure distribution during gait compared to other suspension systems. Despite these positive recommendations, the authors of the guideline noted that vacuum assisted suspension sockets are not universally indicated and that awareness and compliance are required from the user of the device. The strength of these recommendations was not assessed. The second guideline stated that there was insufficient evidence to recommend for or against any particular prosthetic suspension system for adults with lower limb amputation (weak recommendation). No evidence regarding the cost-effectiveness of elevated vacuum suspension systems versus standard prosthetic systems for adults with amputation was identified. The limitations of the included studies (e.g., high risk of performance bias due to a lack of blinding, lack of long-term follow-up data) should be considered when interpreting the findings of this report.