Are non-steroidal anti-inflammatory drugs effective for the management of neck pain and associated disorders, whiplash-associated disorders, or non-specific low back pain? A systematic review of systematic reviews by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

PURPOSE: To evaluate the effectiveness of non-steroidal anti-inflammatory drugs (NSAIDs) for the management of neck pain and associated disorders (NAD), whiplash-associated disorders, and non-specific low back pain (LBP) with or without radiculopathy. METHODS: We systematically searched six databases from 2000 to 2014. Random pairs of independent reviewers critically appraised eligible systematic reviews using the Scottish Intercollegiate Guidelines Network criteria. We included systematic reviews with a low risk of bias in our best evidence synthesis. RESULTS: We screened 706 citations and 14 systematic reviews were eligible for critical appraisal. Eight systematic reviews had a low risk of bias. For recent-onset NAD, evidence suggests that intramuscular NSAIDs lead to similar outcomes as combined manipulation and soft tissue therapy. For NAD (duration not specified), oral NSAIDs may be more effective than placebo. For recent-onset LBP, evidence suggests that: (1) oral NSAIDs lead to similar outcomes to placebo or a muscle relaxant; and (2) oral NSAIDs with bed rest lead to similar outcomes as placebo with bed rest. For persistent LBP, evidence suggests that: (1) oral NSAIDs are more effective than placebo; and (2) oral NSAIDs may be more effective than acetaminophen. For recent-onset LBP with radiculopathy, there is inconsistent evidence on the effectiveness of oral NSAIDs versus placebo. Finally, different oral NSAIDs lead to similar outcomes for neck and LBP with or without radiculopathy. CONCLUSIONS: For NAD, oral NSAIDs may be more effective than placebo. Oral NSAIDs are more effective than placebo for persistent LBP, but not for recent-onset LBP. Different oral NSAIDs lead to similar outcomes for neck pain and LBP.

The Effectiveness of Multimodal Care for Soft Tissue Injuries of the Lower Extremity: A Systematic Review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

OBJECTIVE: The purpose of this systematic review was to evaluate the effectiveness of multimodal care for the management of soft tissue injuries of the lower extremity. METHODS: We systematically searched MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from 1990 to 2015. Random pairs of independent reviewers screened studies for relevance and critically appraised eligible studies using the Scottish Intercollegiate Guidelines Network criteria. We included studies with a low risk of bias in our best evidence synthesis. RESULTS: We screened 6794 articles. Six studies had a low risk of bias and addressed the following: plantar heel pain (n = 2), adductor-related groin pain (n = 1), and patellofemoral pain (n = 3). The evidence suggests that multimodal care for the management of persistent plantar heel pain may include mobilization and stretching exercise. An intensive, clinic-based, group exercise program (strengthening, stretching, balance, agility) is more effective than multimodal care for the management of adductor-related groin pain in male athletes. There is inconclusive evidence to support the use of multimodal care for the management of persistent patellofemoral pain. Our search did not identify any low risk of bias studies examining multimodal care for the management of other soft tissue injuries of the lower extremity. CONCLUSION: A multimodal program of care for the management of persistent plantar heel pain may include mobilization and stretching exercise. Multimodal care for adductor-related groin pain is not recommended based on the current evidence. There is inconclusive evidence to support the use of multimodal care for the management of persistent patellofemoral pain.

The Effectiveness of Exercise on Recovery and Clinical Outcomes in Patients With Soft Tissue Injuries of the Hip, Thigh, or Knee: A Systematic Review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

OBJECTIVE: The purpose of this systematic review was to determine the effectiveness of exercise for the management of soft tissue injuries of the hip, thigh, and knee. METHODS: We conducted a systematic review and searched MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials, and CINAHL Plus with Full Text from January 1, 1990, to April 8, 2015, for randomized controlled trials (RCTs), cohort studies, and case-control studies evaluating the effect of exercise on pain intensity, self-rated recovery, functional recovery, health-related quality of life, psychological outcomes, and adverse events. Random pairs of independent reviewers screened titles and abstracts and assessed risk of bias using the Scottish Intercollegiate Guidelines Network criteria. Best evidence synthesis methodology was used. RESULTS: We screened 9494 citations. Eight RCTs were critically appraised, and 3 had low risk of bias and were included in our synthesis. One RCT found statistically significant improvements in pain and function favoring clinic-based progressive combined exercises over a "wait and see" approach for patellofemoral pain syndrome. A second RCT suggests that supervised closed kinetic chain exercises may lead to greater symptom improvement than open chain exercises for patellofemoral pain syndrome. One RCT suggests that clinic-based group exercises may be more effective than multimodal physiotherapy in male athletes with persistent groin pain. CONCLUSION: We found limited high-quality evidence to support the use of exercise for the management of soft tissue injuries of the lower extremity. The evidence suggests that clinic-based exercise programs may benefit patients with patellofemoral pain syndrome and persistent groin pain. Further high-quality research is needed.

The Effectiveness of Multimodal Care for the Management of Soft Tissue Injuries of the Shoulder: A Systematic Review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

OBJECTIVE: The purpose of this systematic review was to evaluate the effectiveness of multimodal care for the management of soft tissue injuries of the shoulder. METHODS: We conducted a systematic review and searched MEDLINE, EMBASE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials from 1990 to 2015. Two independent reviewers critically appraised studies using the Scottish Intercollegiate Guidelines Network criteria. We used best evidence synthesis to synthesize evidence from studies with low risk of bias. RESULTS: We screened 5885 articles, and 19 were eligible for critical appraisal. Ten randomized controlled trials had low risk of bias. For persistent subacromial impingement syndrome, multimodal care leads to similar outcomes as sham therapy, radial extracorporeal shock-wave therapy, or surgery. For subacromial impingement syndrome, multimodal care may be associated with small and nonclinically important improvement in pain and function compared with corticosteroid injections. For rotator cuff tendinitis, dietary-based multimodal care may be more effective than conventional multimodal care (exercise, soft tissue and manual therapy, and placebo tablets). For nonspecific shoulder pain, multimodal care may be more effective than wait list or usual care by a general practitioner, but it leads to similar outcomes as exercise or corticosteroid injections. CONCLUSIONS: The current evidence suggests that combining multiple interventions into 1 program of care does not lead to superior outcomes for patients with subacromial impingement syndrome or nonspecific shoulder pain. One randomized controlled trial suggested that dietary-based multimodal care (dietary advice, acupuncture, and enzyme tablets) may provide better outcomes over conventional multimodal care. However, these results need to be replicated.

The effectiveness of noninvasive interventions for musculoskeletal thoracic spine and chest wall pain: a systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) collaboration.

OBJECTIVE: The purpose of this study was to critically appraise and synthesize evidence on the effectiveness of noninvasive interventions, excluding pharmacological treatments, for musculoskeletal thoracic pain. METHODS: Randomized controlled trials (RCTs), cohort studies, and case-control studies evaluating the effectiveness of noninvasive interventions were eligible. We searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials accessed through Ovid Technologies, Inc, and CINAHL Plus with Full Text accessed through EBSCOhost from 1990 to 2015. Our search strategies combined controlled vocabulary relevant to each database (eg, MeSH for MEDLINE) and text words relevant to our research question and the inclusion criteria. Random pairs of independent reviewers screened studies for relevance and critically appraised relevant studies using the Scottish Intercollegiate Guidelines Network criteria. Studies with a low risk of bias were synthesized following best evidence synthesis principles. RESULTS: We screened 6988 articles and critically appraised 2 studies. Both studies had a low risk of bias and were included in our synthesis. One RCT compared thoracic spinal manipulation, needle acupuncture, and placebo electrotherapy for recent thoracic spine pain. There were statistically significant but clinically nonimportant short-term reductions in pain favoring manipulation. There were no differences between acupuncture and placebo electrotherapy. Another RCT compared a multimodal program of care and a session of education for recent musculoskeletal chest wall pain. The multimodal care resulted in statistically significant but clinically nonimportant short-term reductions in pain over education. However, participants receiving multimodal care were more likely to report important improvements in chest pain. CONCLUSIONS: Quality evidence on the management of musculoskeletal thoracic pain is sparse. The current evidence suggests that compared to placebo, spinal manipulation is associated with a small and clinically nonimportant reduction in pain intensity and that acupuncture leads to similar outcomes as placebo. Furthermore, a multimodal program of care (ie, manual therapy, soft tissue therapy, exercises, heat/ice, and advice) and a single education session lead to similar pain reduction for recent-onset musculoskeletal chest wall pain. However, patients who receive multimodal care are more likely to report pain improvements.

A clinical systematic literature review of treatments among patients with advanced and/or metastatic human epidermal growth factor receptor 2 positive breast cancer.

Aim: This systematic literature review aims to summarize the efficacy/effectiveness of treatments, including eribulin (ERI)-based and anti-human epidermal growth factor receptor 2 (HER2) treatments in advanced/metastatic HER2+ breast cancer. Methods: Three databases from 2016 to September 2021 were searched for clinical trials and observational studies in patients receiving first-line (1L) standard of care (SOC), second-line (2L) SOC or third-line or subsequent lines (3L+). Results: 2692 citations were screened, and 38 studies were included. Eleven studies were randomized-controlled trials (RCTs; 5 in 1L, 6 in 3L+), 6 were single-arm trials (5 in 1L, 1 in 3L+) and 21 were observational studies (13 in 1L, 6 in 2L, 4 in 3L+ [note that studies with subgroups for 1L, 2L, 3L+ are double-counted]). Longer overall survival (OS) was associated with 1L and 2L treatment, and for 3L+ studies that included ERI, ERI or trastuzumab (Tmab) + ERI led to longer OS than treatments of physician's choice (median OS of 11, 10 and 8.9 months, respectively). Progression-free survival was 9 months in Tmab + pertuzumab (Pmab) + ERI, 4 months in Tmab + ERI and 3.3 months in ERI. Conclusion: Available treatments provide a wide range of efficacy. However, later lines lack standardization and conclusions on comparative effectiveness are limited by differing trial designs. Thus, the chance of prolonged survival with new agents warrants further research.

Agalsidase beta treatment slows estimated glomerular filtration rate loss in classic Fabry disease patients: results from an individual patient data meta-analysis.

BACKGROUND: Fabry disease is a rare, X-linked genetic disorder that, if untreated in patients with the Classic phenotype, often progresses to end-stage kidney disease. This meta-analysis determined the effect of agalsidase beta on loss of estimated glomerular filtration rate (eGFR) in the Classic phenotype using an expansive evidence base of individual patient-level data. METHODS: The evidence base included four Sanofi-Genzyme studies and six studies from a systematic literature review. These were restricted to Classic Fabry patients meeting the eligibility criteria from Phases III and IV agalsidase beta trials, including 315 patients (161 treated). Linear regression was first used to model annual change in eGFR for each patient and the resulting annualized eGFR slopes were modelled with treatment and covariates using quantile regression. These results were then used to estimate median annualized eGFR change in agalsidase beta treated versus untreated groups. RESULTS: Imbalances across treatment groups were found in baseline age, sex and proteinuria, but not in the use of renin-angiotensin system blockers. The adjusted model suggests that treated (agalsidase beta) patients experienced a slower median eGFR decrease [2.46 mL/min/1.73 m2/year slower; 95% confidence interval (CI) 0.63-4.29; P = 0.0087] than comparable untreated patients. The median eGFR decrease was 2.64 mL/min/1.73 m2/year slower (95% CI 0.53-4.78; P = 0.0141) in treated Classic males. CONCLUSIONS: Using an expansive evidence base and robust modelling approach, these data indicate that agalsidase beta-treated patients with the Classic phenotype conserve their renal function better than untreated patients.

Indirect comparison of nivolumab ± ipilimumab (CheckMate 032) versus other treatments for recurrent small-cell lung cancer.

Aim: To estimate the comparative efficacy of nivolumab ± ipilimumab versus alternative treatments for small-cell lung cancer after at least one prior line of chemotherapy. Materials & methods: A systematic literature review identified six randomized controlled trials (RCTs) that could be connected in a network. The Kaplan-Meier survival curves from these RCTs were synthesized using network meta-analysis models. Aggregate-level matching was used to connect CheckMate 032 to the RCTs. Results: CheckMate 032 was connected to the network by Amrubicin Clinical Trial-1. Nivolumab ± ipilimumab had a more durable tumor response and more favorable long-term survival versus topotecan via intravenous and versus amrubicin. Conclusion: Compared with chemotherapies for recurrent small-cell lung cancer, nivolumab ± ipilimumab improves response duration, which may translate to long-term survival benefits.

Network meta-analysis of liraglutide versus dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes in Japanese patients.

AIMS: To determine the comparative efficacy and safety of liraglutide and dipeptidyl peptidase-4 (DPP-4) inhibitors as antidiabetics for Japanese patients with uncontrolled type 2 diabetes (T2DM). METHODS AND MATERIALS: We searched for randomized controlled trials (RCTs) evaluating outcomes among Japanese adults with uncontrolled T2DM and including liraglutide or DPP-4 inhibitors up to August 2016. We extracted data on trial and patient characteristics, and the following outcomes: HbA1c, weight, patients meeting HbA1c <7%, patients experiencing hypoglycemic events, microalbuminuria, estimated glomerular filtration rate (eGFR) and creatinine. We synthesized data using network meta-analyses (NMA) using a Bayesian framework. Continuous outcomes were modeled using normal likelihoods and an identity link, while dichotomous outcomes were modeled using a binomial likelihood and a logit link. RESULTS: The systematic literature review yielded 39 publications pertaining to 38 trials. A total of 27 trials (5032 patients) reported change in HbA1c at 12 weeks and at 24 weeks 9 trials (2091 patients). All treatments showed statistically significant reductions in HbA1c relative to placebo at 12 and 24 weeks. Liraglutide 0.9 mg was statistically superior to all DPP-4 interventions (vildagliptin, sitagliptin, linagliptin, alogliptin, teneligliptin, trelagliptin and omarigliptin) at 12 weeks and 24 weeks among those reporting. Treatments were not statistically differentiable with respect to weight change and risk of hypoglycemia. Finally, no comparisons of eGFR and microalbuminuria were conducted, as this data was reported in too few trials to conduct analyses. LIMITATIONS: Some important outcomes were limited by poor reporting (eGFR and microalbuminuria) or low event rates (hypoglycemia). The follow-up time was relatively short. Clinically, the 24 week time point is more important as it demonstrates more sustained results. CONCLUSIONS: Our research suggests that liraglutide 0.9 mg offers a more efficacious treatment option for T2DM than the DPP-4 inhibitors among adult Japanese patients and that it is a viable option for this population.

Multimodal care for the management of musculoskeletal disorders of the elbow, forearm, wrist and hand: a systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

BACKGROUND: Musculoskeletal disorders of the elbow, forearm, wrist and hand are associated with pain, functional impairment and decreased productivity in the general population. Combining several interventions in a multimodal program of care is reflective of current clinical practice; however there is limited evidence to support its effectiveness. The purpose of our review was to investigate the effectiveness of multimodal care for the management of musculoskeletal disorders of the elbow, forearm, wrist and hand on self-rated recovery, functional recovery, or clinical outcomes in adults or children. METHODS: We conducted a systematic review of the literature and best evidence synthesis. We searched MEDLINE, EMBASE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials from January 1990 to March 2015. Randomized controlled trials, cohort studies, and case-control studies were eligible. Random pairs of independent reviewers screened studies for relevance and critically appraised relevant studies using the Scottish Intercollegiate Guidelines Network criteria. Studies with a low risk of bias were synthesized following best evidence synthesis principles. RESULTS: We screened 5989 articles, and critically appraised eleven articles. Of those, seven had a low risk of bias; one addressed carpal tunnel syndrome and six addressed lateral epicondylitis. Our search did not identify any low risk of bias studies examining the effectiveness of multimodal care for the management of other musculoskeletal disorders of the elbow, forearm, wrist or hand. The evidence suggests that multimodal care for the management of lateral epicondylitis may include education, exercise (strengthening, stretching, occupational exercise), manual therapy (manipulation) and soft tissue therapy (massage). The evidence does not support the use of multimodal care for the management of carpal tunnel syndrome. CONCLUSIONS: The current evidence on the effectiveness of multimodal care for musculoskeletal disorders of the elbow, forearm, wrist and hand is limited. The available evidence suggests that there may be a role for multimodal care in the management of patients with persistent lateral epicondylitis. Future research is needed to examine the effectiveness of multimodal care and guide clinical practice. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42014009093.

The effectiveness of manual therapy for the management of musculoskeletal disorders of the upper and lower extremities: a systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

BACKGROUND: Musculoskeletal disorders (MSDs) of the upper and lower extremities are common in the general population and place a significant burden on the health care system. Manual therapy is recommended by clinical practice guidelines for the management of these injuries; however, there is limited evidence to support its effectiveness. The purpose of our review was to investigate the effectiveness of manual therapy in adults or children with MSDs of the upper or lower extremity. METHODS: Randomized controlled trials (RCTs), cohort studies, and case-control studies evaluating the effectiveness of manual therapy were eligible. We searched MEDLINE, EMBASE, PsycINFO, CINAHL, and the Cochrane Central Register of Controlled Trials from 1990 to 2015. Paired reviewers screened studies for relevance and critically appraised relevant studies using the Scottish Intercollegiate Guidelines Network criteria. Studies with low risk of bias were synthesized following best-evidence synthesis principles. Where available, we computed mean changes between groups, relative risks and 95 % CI. RESULTS: We screened 6047 articles. Seven RCTs were critically appraised and three had low risk of bias. For adults with nonspecific shoulder pain of variable duration, cervicothoracic spinal manipulation and mobilization in addition to usual care may improve self-perceived recovery compared to usual care alone. For adults with subacromial impingement syndrome of variable duration, neck mobilization in addition to a multimodal shoulder program of care provides no added benefit. Finally, for adults with grade I-II ankle sprains of variable duration, lower extremity mobilization in addition to home exercise and advice provides greater short-term improvements in activities and function over home exercise and advice alone. No studies were included that evaluated the effectiveness of manual therapy in children or for the management of other extremity injuries in adults. CONCLUSIONS: The current evidence on the effectiveness of manual therapy for MSDs of the upper and lower extremities is limited. The available evidence supports the use of manual therapy for non-specific shoulder pain and ankle sprains, but not for subacromial impingement syndrome in adults. Future research is needed to determine the effectiveness of manual therapy and guide clinical practice. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42014009899.