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A total of seven relevant publications were included in this report: five systematic reviews (two with meta-analysis), one cluster randomized controlled trial and one evidence-based guideline. Two of the five systematic reviews were aimed at postoperative pain; the remaining three were aimed at subacute low back pain (7–12 weeks), subacute neck pain (≤ 3 months), and all types of musculoskeletal pain. The randomized controlled trial was aimed at subacute low back pain (2–12 weeks), and the guideline provided recommendations on all forms of low back pain. Overall, cognitive-behavioral therapy and low back pain were the most studied psychological intervention and musculoskeletal condition, respectively.

Cognitive-behavioral therapy combined with physiotherapy appeared to provide functional improvements following back-surgery, without any impact on pain resolution. Psychotherapies based on relaxation or mindfulness techniques showed mixed results on pain following knee surgery; a firm conclusion could not be drawn due to widely variable intervention scheme.

With respect to musculoskeletal pain, psychotherapy combined with physiotherapy was shown to improve pain and disability resulting from musculoskeletal pain overall; however, these benefits were not found when low back pain, neck and whiplash-associated pain, and osteoarthritis-related pain were investigated separately. Cognitive-behavioral therapy was found to be beneficial in subacute neck pain, although the evidence was of low quality. There was some evidence that cognitive-behavioral therapies may reduce disability and improve body functions in patients with subacute low back pain, particularly when integrated with physiotherapy and personalized to patients’ context; however, the effects on pain resolution was less pronounced. The clinical guideline made no reference to psychotherapies for the management of short-term low back pain, and instead recommended other forms of non-pharmacologic therapies since most patients achieve resolution naturally.

Overall, the included studies showed substantial heterogeneity in psychotherapies used and outcomes measures, making it difficult to compare findings across studies and to obtain an overall picture of the various psychotherapies for different types of musculoskeletal pain. Nevertheless, psychological therapies, most notably cognitive-behavioral therapy, has some clinical benefits in improving short-term pain and body functions resulting from surgery or musculoskeletal conditions when combined with other interventions aimed at improving body functions e.g. physiotherapy.

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One systematic review pooled estimates for diagnostic accuracy and found that semi-rigid thoracoscopy had high sensitivity and specificity for diagnosing pleural effusions of unknown etiology. One non-randomized retrospective study observed a high sensitivity and specificity for rigid thoracoscopy for the diagnosis of tuberculous pleural effusion.  Similarly, non-randomized retrospective and prospective studies found a high sensitivity and specificity for rigid or semi-rigid thoracoscopy for the diagnosis of malignant pleural effusion or malignancy. One non-randomized retrospective study reported no statistical difference in diagnostic accuracy between semi-rigid thoracoscopy compared with video-assisted thoracoscopic surgery in the assessment of pleural effusions that were malignant, suspicious for malignancy, or granulomatous inflammation combined.

An economic evaluation reported the mean procedure-related cost of semi-rigid thoracoscopy as $2,815 Canadian dollars (95% Confidence Interval $2,010 to $3,620) compared to video-assisted thoracoscopic surgery of $7,962 Canadian dollars (95% Confidence Interval $7,134 to $8,790) in patients with undiagnosed pleural effusions. Since all video-assisted thoracoscopic surgery was conducted in the hospital whereas 68% of semi-rigid thoracoscopy was performed as outpatient procedures, the longer hospital stay associated with video-assisted thoracoscopic surgery may have contributed to some of the difference in procedure cost.

Among the systematic reviews, randomized, and non-randomized retrospective and prospective studies, few significant procedural complications occurred among patients with undiagnosed pleural effusions that received medical thoracoscopy (pleuroscopy).

One evidence-based guideline suggests that medical thoracoscopy is well tolerated among patients with undiagnosed pleural effusions and exhibits a higher likelihood of diagnosis and pleurodesis in comparison to video-assisted thoracoscopic surgery as patients may have comorbidities and not tolerate general anesthesia.

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​There were inconsistencies regarding the effectiveness of foot orthoses compared with control (standard insole, placebo, or none) in alleviating pain in adult patients with foot pain based on findings from three systematic reviews and two randomized controlled trials (RCTs); reported results from these studies included statistically significant improvements in pain with foot orthoses compared to control (one systematic review, and two RCTs), no statistically significant between group difference (one systematic review) and inconsistent findings for between group differences (one systematic review describing studies individually).

There were inconsistencies regarding the effectiveness of foot orthoses compared with control (standard insole, placebo, or none) in improving function in adult patients with foot pain based on findings from two systematic reviews and one RCT; reported results from these studies included a statistically significant improvement with foot orthoses compared to control (one RCT) and no statistically significant between group differences (two systematic reviews and one RCT).

Limited evidence (one RCT) showed improvement in pain and function with foot orthoses compared to no foot orthoses, in adult patients with chronic low back pain.

Findings need to be interpreted with caution considering the limitations (such as unclear or variable quality of included studies, small sample size and overlap of studies included in the systematic reviews). 

No studies were identified that compared treatments with foot orthoses with pharmacological treatments for non-cancer pain in adults. 

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One relevant randomized controlled trial was identified regarding the effectiveness of skin preparation prior to vaccinations in children. The study found that there was no statistically significant difference in local skin reactions and infection rates when comparing alcohol skin cleansing to no cleansing prior to vaccinations. The duration of pain was statically significantly higher in the alcohol swab group compared to the control group. There were no identified cases of cellulitis, pus leaking and infectious abscess. However, the study was insufficiently powered to detect a difference in the primary outcome of skin infection. Due to the limitations of the study it is difficult to draw sound conclusions of whether alcohol swabbing reduces infection rates compared to no swabbing. No cost-effectiveness studies or evidence-based guidelines were identified regarding skin preparation prior to injection.

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This review included two systematic reviews and two randomized controlled trials regarding the clinical effectiveness of exercise for the treatment of individuals with ankle sprain, and one guideline regarding the use of non-pharmacological interventions in this population.

Based on the findings of the systematic reviews that compared structured exercise-based rehabilitation plus usual care versus usual care alone, or supervised rehabilitation versus home exercise, there were no significant differences between treatment groups in terms of foot and ankle function, pain, subjective ankle instability, or subjective recovery. The results for ankle sprain recurrence were mixed. Specifically, one systematic review showed significant reduction in ankle sprain recurrence in those who received exercise-based rehabilitation plus usual care compared with usual care alone at 7 to 12 months, but not at 3 to 6 months of follow-up. In the other systematic review, one study showed that there was a significantly lower proportion of patients with recurrent ankle sprain in the supervised rehabilitation versus home exercise group, while the other study found no significant difference between groups. 

One randomized controlled trial found that compared with the traditional PRICE (protection, rest, ice, compression, and elevation) treatment, early mobilization using a stretch band ankle traction technique resulted in no significant differences in ankle strength, ankle function, pain and number of days to returning to sport in children and adolescents.

Another randomized controlled trial compared Wii Fit™ exercise therapy with conventional physical therapy and with no therapy, and found no significant differences between treatment groups for ankle function, pain, time to returning to sport, and self-reported satisfaction and effectiveness. 

The included guideline recommends the use exercise therapy in combination with functional support (i.e., ankle brace) or manual mobilization in the treatment of acute lateral ankle sprain (level 2 evidence). The guideline does not recommend the use of RICE (rest, ice, compression, and elevation) alone (level 2 evidence), or other therapies such as acupuncture, vibration therapy, laser therapy, ultrasound, electrotherapy, short wave therapy and Bioptron light therapy (level 3 evidence) in the treatment of acute lateral ankle sprain. The strength of the recommendation statements were not indicated.

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One health technology assessment, three systematic reviews of primary studies, and two non-randomized studies were identified regarding the clinical effectiveness of the BCG vaccine for the prevention of TB. One systematic review of guidelines and four evidence-based guidelines were identified regarding the use of the BCG vaccine in populations at risk of exposure to TB.

The evidence included in this report was mostly low- to moderate-quality with considerable heterogeneity and may be considered outdated. However, in people who are immunocompetent, the BCG vaccine consistently demonstrated a lower risk of TB compared those unvaccinated with BCG, however, the duration of the vaccine effectiveness was less certain. The BCG vaccine was also associated with a lower risk of morality compared to the unvaccinated population. Insufficient evidence was found on the adverse effects of the BCG vaccine. The BCG vaccine is recommended for people who are immunocompetent who have a high risk of exposure to TB, including: those who live in countries or settings with a high incidence of TB; those who have a family history of TB; those with potential occupational exposure to TB; and those travelling to countries with a high incidence of TB. Revaccination with BCG is not recommended.

The evidence identified in this report suggests that the BCG vaccine is not effective in people with HIV, and the BCG vaccine is not recommended in adults with HIV. Recommendations concerning BCG vaccination of newborns with confirmed or suspected HIV is less certain, and may depend on the risk of exposure to TB.

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Three systematic reviews (that included 13 unique relevant primary studies) and two non-randomized studies were identified regarding the clinical effectiveness of body weight modification interventions (e.g., diet-only, exercise-only, combination diet and exercise) for the treatment of chronic non-cancer pain in adults with excess body weight (body mass index ≥ 25 kg/m²). No evidence regarding the clinical effectiveness of body weight modification interventions in adults with body mass index < 18.5 kg/m² was identified.

The three systematic reviews were generally well-conducted, but there were methodological limitations in their included primary studies which provided low to moderate strength evidence. The identified literature revealed mixed conclusions regarding the clinical effectiveness of body weight modification interventions for chronic non-cancer pain for overweight adults. Specifically, in most studies, body weight modification interventions (i.e., diet or exercise) resulted in statistically significant weight reductions, and improvements in pain and physical function compared to no diet or exercise. However, in some studies, no statistically significant differences were detected in weight, pain, and physical function between diet and/or exercise groups and control groups (i.e., no diet and exercise). There were numerically more nonserious gastrointestinal issues associated with diet interventions compared to non-diet groups; however, specific numbers were not reported. Furthermore, no serious adverse events were reported for any intervention or control groups.

The limitations of the included studies (e.g., heterogeneity of interventions and outcome measures, variation in treatment durations, risk of performance bias due to unblinded participants, inconsistencies in study findings) should be taken into consideration when interpreting the findings of this report.

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Three randomized controlled trials (RCTs), one economic evaluation report and two guideline documents are included in this review. The findings observed in two RCTs indicated that one intravitreal dexamethasone implant (IDI) dose appeared to be a safe and effective option in preventing the complications of uveitic cataract surgery. One RCT suggested that IDI was superior to periocular triamcinolone injection for treating uveitic macular edema with minimal risk of intraocular pressure elevation. However, the findings reported in the three RCTs should be interpreted with caution due to various limitations of the study design. The UK economic report indicated that IDI was cost-effective compared with the limited current practice in the treatment of non-infectious uveitis (NIU). Nevertheless, uncertainty remains due to scarcity of evidence. American Academy of Ophthalmology (AAO) guidance provided the recommendations on the use of non-corticosteroid systemic immunomodulatory treatment in NIU. NICE guideline recommended adalimumab and IDI be options for the treatment of NIU. No recommendation on the IDI dose regimen (i.e., the number of implants and frequency of reinjections) was specified in NICE guideline. Further research needed to address uncertainty on the clinical efficacy and safety, cost-effective as well as the clinical guidelines regarding the use of different dose regimens of IDI in the treatment of NIU.​

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