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Pain Jan 2022Pragmatic randomised clinical trials aim to directly inform clinical or health policy decision making. Here, we systematically review methods and design of pragmatic...
Pragmatic randomised clinical trials aim to directly inform clinical or health policy decision making. Here, we systematically review methods and design of pragmatic trials of pain therapies to examine methods, identify common challenges, and areas for improvement. Seven databases were searched for pragmatic randomised controlled clinical trials that assessed pain treatment in a clinical population of adults reporting pain. All screening steps and data extractions were performed twice. Data were synthesised descriptively, and correlation analyses between prespecified trial features and PRECIS-2 (PRagmatic-Explanatory Continuum Indicator Summary 2) ratings and attrition were performed. Protocol registration: PROSPERO-ID CRD42020178954. Of 57 included trials, only 21% assessed pharmacological interventions, the remainder physical, surgical, psychological, or self-management pain therapies. Three-quarters of the trials were comparative effectiveness designs, often conducted in multiple centres (median: 5; Q1/3: 1, 9.25) and with a median sample size of 234 patients at randomization (Q1/3: 135.5; 363.5). Although most trials recruited patients with chronic pain, reporting of pain duration was poor and not well described. Reporting was comprehensive for most general items, while often deficient for specific pragmatic aspects. Average ratings for pragmatism were highest for treatment adherence flexibility and clinical relevance of outcome measures. They were lowest for patient recruitment methods and extent of follow-up measurements and appointments. Current practice in pragmatic trials of pain treatments can be improved in areas such as patient recruitment and reporting of methods, analysis, and interpretation of data. These improvements will facilitate translatability to other real-world settings-the purpose of pragmatic trials.
Topics: Adult; Humans; Pain; Research Design
PubMed: 34490854
DOI: 10.1097/j.pain.0000000000002317 -
The Cochrane Database of Systematic... Jul 2016Pseudomonas aeruginosa is the most common bacterial pathogen causing lung infections in people with cystic fibrosis and appropriate antibiotic therapy is vital.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pseudomonas aeruginosa is the most common bacterial pathogen causing lung infections in people with cystic fibrosis and appropriate antibiotic therapy is vital. Antibiotics for pulmonary exacerbations are usually given intravenously, and for long-term treatment, via a nebuliser. Oral anti-pseudomonal antibiotics with the same efficacy and safety as intravenous or nebulised antibiotics would benefit people with cystic fibrosis due to ease of treatment and avoidance of hospitalisation. This is an update of a previous review.
OBJECTIVES
To determine the benefit or harm of oral anti-pseudomonal antibiotic therapy for people with cystic fibrosis, colonised with Pseudomonas aeruginosa, in the:1. treatment of a pulmonary exacerbation; and2. long-term treatment of chronic infection.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.We contacted pharmaceutical companies and checked reference lists of identified trials.Date of last search: 08 July 2016.
SELECTION CRITERIA
Randomised or quasi-randomised controlled trials comparing any dose of oral anti-pseudomonal antibiotics, to other combinations of inhaled, oral or intravenous antibiotics, or to placebo or usual treatment for pulmonary exacerbations and long-term treatment.
DATA COLLECTION AND ANALYSIS
Two authors independently selected the trials, extracted data and assessed quality. We contacted trial authors to obtain missing information.
MAIN RESULTS
We included three trials examining pulmonary exacerbations (171 participants) and two trials examining long-term therapy (85 participants). We regarded the most important outcomes as quality of life and lung function. The analysis did not identify any statistically significant difference between oral anti-pseudomonal antibiotics and other treatments for these outcome measures for either pulmonary exacerbations or long-term treatment. One of the included trials reported significantly better lung function when treating a pulmonary exacerbation with ciprofloxacin when compared with intravenous treatment; however, our analysis did not confirm this finding. We found no evidence of difference between oral anti-pseudomonal antibiotics and other treatments regarding adverse events or development of antibiotic resistance, but trials were not adequately powered to detect this. None of the studies had a low risk of bias from blinding which may have an impact particularly on subjective outcomes such as quality of life. The risk of bias for other criteria could not be clearly stated across the studies.
AUTHORS' CONCLUSIONS
We found no conclusive evidence that an oral anti-pseudomonal antibiotic regimen is more or less effective than an alternative treatment for either pulmonary exacerbations or long-term treatment of chronic infection with P. aeruginosa. Until results of adequately-powered future trials are available, treatment needs to be selected on a pragmatic basis, based upon any available non-randomised evidence, the clinical circumstances of the individual, the known effectiveness of drugs against local strains and upon individual preference.
Topics: Administration, Oral; Adult; Anti-Bacterial Agents; Child; Chronic Disease; Cystic Fibrosis; Humans; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Respiratory Tract Infections; Treatment Outcome
PubMed: 27412131
DOI: 10.1002/14651858.CD005405.pub4 -
The Cochrane Database of Systematic... Feb 2018Systemic therapies for metastatic cutaneous melanoma, the most aggressive of all skin cancers, remain disappointing. Few lasting remissions are achieved and the... (Review)
Review
BACKGROUND
Systemic therapies for metastatic cutaneous melanoma, the most aggressive of all skin cancers, remain disappointing. Few lasting remissions are achieved and the therapeutic aim remains one of palliation.Many agents are used alone or in combination with varying degrees of toxicity and cost. It is unclear whether evidence exists to support these complex regimens over best supportive care / placebo.
OBJECTIVES
To review the benefits from the use of systemic therapies in metastatic cutaneous melanoma compared to best supportive care/placebo, and to establish whether a 'standard' therapy exists which is superior to other treatments.
SEARCH METHODS
Randomised controlled trials were identified from the MEDLINE, EMBASE and CCTR/CENTRAL databases. References, conference proceedings, and Science Citation Index/Scisearch were also used to locate trials. Cancer registries and trialists were also contacted.
SELECTION CRITERIA
Randomised controlled trials of adults with histologically proven metastatic cutaneous melanoma in which systemic anti-cancer therapy was compared with placebo or supportive care.
DATA COLLECTION AND ANALYSIS
Study selection was performed by two independent reviewers. Data extraction forms were used for studies which appeared to meet the selection criteria and, where appropriate, full text articles were retrieved and reviewed independently.
MAIN RESULTS
No randomised controlled trials were found comparing a systemic therapy with placebo or best supportive care in metastatic cutaneous melanoma.
AUTHORS' CONCLUSIONS
There is no evidence from randomised controlled clinical trials to show superiority of systemic therapy over best supportive care / placebo in the treatment of malignant cutaneous melanoma.Given that patients with metastatic melanoma frequently receive systemic therapy, it is our pragmatic view that a future systematic review could compare any systemic treatment, or combination of treatments, to single agent dacarbazine.
Topics: Antineoplastic Agents; Humans; Melanoma; Skin Neoplasms
PubMed: 29411867
DOI: 10.1002/14651858.CD001215.pub2 -
PloS One 2023Children with neurodevelopmental disorders such as attention-deficit hyperactivity disorder (ADHD), autism, developmental language disorder (DLD), intellectual... (Meta-Analysis)
Meta-Analysis
RATIONALE
Children with neurodevelopmental disorders such as attention-deficit hyperactivity disorder (ADHD), autism, developmental language disorder (DLD), intellectual disability (ID), and social (pragmatic) communication disorder (SPCD) experience difficulties with social functioning due to differences in their social, emotional and cognitive skills. Previous systematic reviews have focussed on specific aspects of social functioning rather than broader peer functioning and friendships.
OBJECTIVE
To systematically review and methodologically appraise the quality and effectiveness of existing intervention studies that measured friendship outcomes for children with ADHD, autism, DLD, ID, and SPCD.
METHOD
Following PRISMA guidelines, we searched five electronic databases: CINAHL, Embase, Eric, PsycINFO, and PubMed. Two independent researchers screened all abstracts and disagreements were discussed with a third researcher to reach consensus. The methodological quality of studies was assessed using the Cochrane Risk of Bias Tool for Randomised Trials.
RESULTS
Twelve studies involving 15 interventions were included. Studies included 683 children with a neurodevelopmental disorder and 190 typically-developing children and diagnosed with either autism or ADHD. Within-group meta-analysis showed that the pooled intervention effects for friendship across all interventions were small to moderate (z = 2.761, p = 0.006, g = 0.485). The pooled intervention effect between intervention and comparison groups was not significant (z = 1.206, p = 0.400, g = 0.215).
CONCLUSION
Findings provide evidence that some individual interventions are effective in improving social functioning and fostering more meaningful friendships between children with neurodevelopmental disorders and their peers. Effective interventions involved educators, targeted child characteristics known to moderate peer functioning, actively involved peers, and incorporated techniques to facilitate positive peer perceptions and strategies to support peers. Future research should evaluate the effectiveness of friendship interventions for children with DLD, ID and SPCD, more comprehensively assess peer functioning, include child self-report measures of friendship, and longitudinally evaluate downstream effects on friendship.
Topics: Child; Humans; Friends; Attention Deficit Disorder with Hyperactivity; Peer Group; Social Adjustment; Neurodevelopmental Disorders
PubMed: 38096327
DOI: 10.1371/journal.pone.0295917 -
Journal of the Neurological Sciences Oct 2016The aim of the present systematic review is to critically evaluate the effectiveness of OMT as an adjuvant therapy in the management of patients with neurological... (Review)
Review
OBJECTIVE
The aim of the present systematic review is to critically evaluate the effectiveness of OMT as an adjuvant therapy in the management of patients with neurological diseases.
METHODS
A systematic review was conducted and the findings were reported following the PRISMA statement. Twelve databases were searched for articles reporting the use of osteopathic manipulative treatment in neurological disorders. Each article was assessed using the Cochrane risk of bias tool and the Jadad score.
RESULTS
10 articles were included. OMT was used to test its efficacy and/or effectiveness in treating tension-type headache, migraine, cerebral palsy and gait analysis in patients affected by Parkinson's Disease. The general quality of the included trials ranged from very low, to low and moderate according to Cochrane standards. High heterogeneity between studies was found for the type of intervention, control and outcome measures used.
CONCLUSION
Results showed that studies on the efficacy and/or effectiveness of OMT treatments are scarce, heterogeneous, and of low methodological quality. Further studies should be conducted including a more pragmatic methodology, an exhaustive description of all investigated and concurrent interventions, and a systematic report of adverse events, so as to obtain robust and generalizable results.
Topics: Animals; Databases, Bibliographic; Humans; Manipulation, Osteopathic; Nervous System Diseases
PubMed: 27653920
DOI: 10.1016/j.jns.2016.08.062 -
Journal of Medical Internet Research Apr 2022Digital health refers to the proper use of technology for improving the health and well-being of people and enhancing the care of patients through the intelligent... (Review)
Review
BACKGROUND
Digital health refers to the proper use of technology for improving the health and well-being of people and enhancing the care of patients through the intelligent processing of clinical and genetic data. Despite increasing interest in well-being in both health care and technology, there is no clear understanding of what constitutes well-being, which leads to uncertainty in how to create well-being through digital health. In an effort to clarify this uncertainty, Brey developed a framework to define problems in technology for well-being using the following four categories: epistemological problem, scope problem, specification problem, and aggregation problem.
OBJECTIVE
This systematic scoping review aims to gain insights into how to define and address well-being in digital health.
METHODS
We followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist. Papers were identified from 6 databases and included if they addressed the design or evaluation of digital health and reported the enhancement of patient well-being as their purpose. These papers were divided into design and evaluation papers. We studied how the 4 problems in technology for well-being are considered per paper.
RESULTS
A total of 117 studies were eligible for analysis (n=46, 39.3% design papers and n=71, 60.7% evaluation papers). For the epistemological problem, the thematic analysis resulted in various definitions of well-being, which were grouped into the following seven values: healthy body, functional me, healthy mind, happy me, social me, self-managing me, and external conditions. Design papers mostly considered well-being as healthy body and self-managing me, whereas evaluation papers considered the values of healthy mind and happy me. Users were rarely involved in defining well-being. For the scope problem, patients with chronic care needs were commonly considered as the main users. Design papers also regularly involved other users, such as caregivers and relatives. These users were often not involved in evaluation papers. For the specification problem, most design and evaluation papers focused on the provision of care support through a digital platform. Design papers used numerous design methods, whereas evaluation papers mostly considered pre-post measurements and randomized controlled trials. For the aggregation problem, value conflicts were rarely described.
CONCLUSIONS
Current practice has found pragmatic ways of circumventing or dealing with the problems of digital health for well-being. Major differences exist between the design and evaluation of digital health, particularly regarding their conceptualization of well-being and the types of users studied. In addition, we found that current methodologies for designing and evaluating digital health can be improved. For optimal digital health for well-being, multidisciplinary collaborations that move beyond the common dichotomy of design and evaluation are needed.
Topics: Caregivers; Delivery of Health Care; Humans
PubMed: 35377328
DOI: 10.2196/33787 -
Cancer Treatment Reviews Jun 2022Research on therapeutic strategies for patients with unknown primary cancer (CUP) has been underwhelming. This paper summarized and evaluated the CUP therapeutic... (Review)
Review
BACKGROUND
Research on therapeutic strategies for patients with unknown primary cancer (CUP) has been underwhelming. This paper summarized and evaluated the CUP therapeutic research over the previous five years. Based on this evaluation, recommendations for clinical trial designs are made to improve the impact of CUP research on patients.
METHODS
Published and ongoing research were evaluated. PubMed was searched from January 1, 2015, to November 1, 2021. The start date of 2015 was chosen to identify research published after ESMO issued new diagnostic and therapeutic guidelines. The US National Library of Medicine indexed ongoing clinical trials.
FINDINGS
Of the 244 CUP studies indexed in PubMed, 11.9% were prospective studies, and 4.9% were clinical trials. The review protocol deemed 65 publications eligible for full-text review. Eleven studies evaluating therapeutic regimens were retained. The two prospective studies and non-randomized trials showed promising outcomes for site-specific treatments. Randomized clinical trials were less promising; however, the trials had recruitment challenges resulting in biased accrual and the inability to keep pace with advancing diagnostics and therapeutics. Most of the 35 ongoing studies were phase II single-arm trials assessing immune checkpoint inhibitors (ICI) or site-specific therapies among CUP patients with suspected favorable prognoses.
CONCLUSION
Our evaluation suggests two prospective clinical trial designs that addressed recent study design and recruitment challenges. A visionary approach uses a multi-arm, multistage randomized trial to address rapid advancements in diagnosis and therapy. A pragmatic approach utilizes a single-arm trial with historical controls to overcome comparison group and recruitment challenges.
Topics: Humans; Immune Checkpoint Inhibitors; Prospective Studies; Research Design
PubMed: 35569387
DOI: 10.1016/j.ctrv.2022.102407 -
Sports Medicine (Auckland, N.Z.) Sep 2016The physiological impairments most strongly associated with functional performance in older people are logically the most efficient therapeutic targets for exercise... (Review)
Review
BACKGROUND
The physiological impairments most strongly associated with functional performance in older people are logically the most efficient therapeutic targets for exercise training interventions aimed at improving function and maintaining independence in later life.
OBJECTIVES
The objectives of this review were to (1) systematically review the relationship between muscle power and functional performance in older people; (2) systematically review the effect of power training (PT) interventions on functional performance in older people; and (3) identify components of successful PT interventions relevant to pragmatic trials by scoping the literature.
METHODS
Our approach involved three stages. First, we systematically reviewed evidence on the relationship between muscle power, muscle strength and functional performance and, second, we systematically reviewed PT intervention studies that included both muscle power and at least one index of functional performance as outcome measures. Finally, taking a strong pragmatic perspective, we conducted a scoping review of the PT evidence to identify the successful components of training interventions needed to provide a minimally effective training dose to improve physical function.
RESULTS
Evidence from 44 studies revealed a positive association between muscle power and indices of physical function, and that muscle power is a marginally superior predictor of functional performance than muscle strength. Nine studies revealed maximal angular velocity of movement, an important component of muscle power, to be positively associated with functional performance and a better predictor of functional performance than muscle strength. We identified 31 PT studies, characterised by small sample sizes and incomplete reporting of interventions, resulting in less than one-in-five studies judged as having a low risk of bias. Thirteen studies compared traditional resistance training with PT, with ten studies reporting the superiority of PT for either muscle power or functional performance. Further studies demonstrated the efficacy of various methods of resistance and functional task PT on muscle power and functional performance, including low-load PT and low-volume interventions.
CONCLUSIONS
Maximal intended movement velocity, low training load, simple training methods, low-volume training and low-frequency training were revealed as components offering potential for the development of a pragmatic intervention. Additionally, the research area is dominated by short-term interventions producing short-term gains with little consideration of the long-term maintenance of functional performance. We believe the area would benefit from larger and higher-quality studies and consideration of optimal long-term strategies to develop and maintain muscle power and physical function over years rather than weeks.
Topics: Aged; Aging; Humans; Muscle Strength; Resistance Training
PubMed: 26893098
DOI: 10.1007/s40279-016-0489-x -
Journal of Medical Internet Research Sep 2023eHealth is increasingly considered an important tool for supporting pharmacotherapy management. (Review)
Review
BACKGROUND
eHealth is increasingly considered an important tool for supporting pharmacotherapy management.
OBJECTIVE
We aimed to assess the (1) use of eHealth in pharmacotherapy management with patients with asthma or chronic obstructive pulmonary disease (COPD), diabetes, or cardiovascular disease (CVD); (2) effectiveness of these interventions on pharmacotherapy management and clinical outcomes; and (3) key factors contributing to the success of eHealth interventions for pharmacotherapy management.
METHODS
We conducted a scoping review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping review) statement. Databases searched included Embase, MEDLINE (PubMed), and Cochrane Library. Screening was conducted by 2 independent researchers. Eligible articles were randomized controlled trials and cohort studies assessing the effect of an eHealth intervention for pharmacotherapy management compared with usual care on pharmacotherapy management or clinical outcomes in patients with asthma or COPD, CVD, or diabetes. The interventions were categorized by the type of device, pharmacotherapy management, mode of delivery, features, and domains described in the conceptual model for eHealth by Shaw at al (Health in our Hands, Interacting for Health, Data Enabling Health). The effectiveness on pharmacotherapy management outcomes and patient- and clinician-reported clinical outcomes was analyzed per type of intervention categorized by number of domains and features to identify trends.
RESULTS
Of 63 studies, 16 (25%), 31 (49%), 13 (21%), and 3 (5%) included patients with asthma or COPD, CVD, diabetes, or CVD and diabetes, respectively. Most (38/63, 60%) interventions targeted improving medication adherence, often combined for treatment plan optimization. Of the 16 asthma or COPD interventions, 6 aimed to improve inhaled medication use. The majority (48/63, 76%) of the studies provided an option for patient feedback. Most (20/63, 32%) eHealth interventions combined all 3 domains by Shaw et al, while 25% (16/63) combined Interacting for Health with Data Enabling Health. Two-thirds (42/63, 67%) of the studies showed a positive overall effect. Respectively, 48% (23/48), 57% (28/49), and 39% (12/31) reported a positive effect on pharmacotherapy management and clinician- and patient-reported clinical outcomes. Pharmacotherapy management and patient-reported clinical outcomes, but not clinician-reported clinical outcomes, were more often positive in interventions with ≥3 features. There was a trend toward more studies reporting a positive effect on all 3 outcomes with more domains by Shaw et al. Of the studies with interventions providing patient feedback, more showed a positive clinical outcome, compared with studies with interventions without feedback. This effect was not seen for pharmacotherapy management outcomes.
CONCLUSIONS
There is a wide variety of eHealth interventions combining various domains and features to target pharmacotherapy management in asthma or COPD, CVD, and diabetes. Results suggest feedback is key for a positive effect on clinician-reported clinical outcomes. eHealth interventions become more impactful when combining domains.
Topics: Humans; Cardiovascular Diseases; Asthma; Pulmonary Disease, Chronic Obstructive; Diabetes Mellitus; Databases, Factual; Randomized Controlled Trials as Topic
PubMed: 37751232
DOI: 10.2196/42474 -
International Journal of Colorectal... Oct 2023A watch-and-wait (WW) strategy or surgery for low to intermediate rectal cancer that has reached clinical complete remission (cCR) after neoadjuvant chemotherapy (nCRT)... (Meta-Analysis)
Meta-Analysis Review
Oncologic outcomes of watch-and-wait strategy or surgery for low to intermediate rectal cancer in clinical complete remission after adjuvant chemotherapy: a systematic review and meta-analysis.
BACKGROUND
A watch-and-wait (WW) strategy or surgery for low to intermediate rectal cancer that has reached clinical complete remission (cCR) after neoadjuvant chemotherapy (nCRT) or total neoadjuvant therapy (TNT) has been widely used in the clinic, but both treatment strategies are controversial.
OBJECTIVE
The aim of this study was to compare the oncologic outcomes of a watch-and-wait strategy or a surgical approach to treat rectal cancer in complete remission and to report the evidence-based clinical advantages of the two treatment strategies.
METHODS
Seven national and international databases were searched for clinical trials comparing the watch-and-wait strategy with surgical treatment for oncological outcomes in patients with rectal cancer in clinical complete remission.
RESULTS
In terms of oncological outcomes, there was no significant difference between the watch-and-wait strategy and surgical treatment in terms of overall survival (OS) (HR = 0.92, 95% CI (0.52, 1.64), P = 0.777), and subgroup analysis showed no significant difference in 5-year disease-free survival (5-year DFS) between WW and both local excision (LE) and radical surgery (RS) (HR = 1.76, 95% CI (0.97, 3.19), P = 0.279; HR = 1.98, 95% CI (0.95, 4.13), P = 0.164), in distant metastasis rate (RR = 1.12, 95% CI (0.73, 1.72), P = 0.593), mortality rate (RR = 1.62, 95% CI (0.93, 2.84), P = 0.09), and organ preservation rate (RR = 1.05, 95% CI (0.94, 1.17), P = 0.394) which were not statistically significant and on the outcome indicators of local recurrence rate (RR = 2.09, 95% CI (1.44, 3.03), P < 0.001) and stoma rate (RR = 0.35, 95% CI (0.20, 0.61), P < 0.001). There were significant differences between the WW group and the surgical treatment group.
CONCLUSION
There were no differences in OS, 5-year DFS, distant metastasis, and mortality between the WW strategy group and the surgical treatment group. The WW strategy did not increase the risk of local recurrence compared with local resection but may be at greater risk of local recurrence compared with radical surgery, and the WW group was significantly better than the surgical group in terms of stoma rate; the WW strategy was evidently superior in preserving organ integrity compared to radical excision. Consequently, for patients who exhibit a profound inclination towards organ preservation and the evasion of stoma formation in the scenario of clinically complete remission of rectal cancer, the WW strategy can be contemplated as a pragmatic alternative to surgical interventions. It is, however, paramount to emphasize that the deployment of such a strategy should be meticulously undertaken within the ambit of a multidisciplinary team's management and within specialized centers dedicated to rectal cancer management.
Topics: Humans; Rectal Neoplasms; Remission Induction; Disease-Free Survival; Chemoradiotherapy; Digestive System Surgical Procedures; Neoadjuvant Therapy; Watchful Waiting; Neoplasm Recurrence, Local; Treatment Outcome
PubMed: 37787779
DOI: 10.1007/s00384-023-04534-2