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Journal of Dentistry Nov 2022To systematically retrieve and assess studies regarding the effectiveness of basic behavioral management techniques (BMTs) in pediatric patients. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically retrieve and assess studies regarding the effectiveness of basic behavioral management techniques (BMTs) in pediatric patients.
DATA SOURCES
Electronic and hand searches were conducted to locate Randomized Controlled Trials (RCTs) reporting on objective and subjective evaluation of anxiety and behavior of children up to 12 years of age. Data extraction and risk of bias evaluation, using the Cochrane risk of bias tool (RoB 2.0 Tool), were performed independently and in duplicate for all included studies. Mean differences and standard deviations were used to summarize the data from each study and meta-analyses were conducted with studies of limited heterogeneity.
STUDY SELECTION
A total of 708 papers were identified and screened, 122 retrieved for full text appraisal and 62 finally included. Results suggested that all basic BMTs have acceptable effectiveness on pediatric patients' anxiety, fear and behavior during dental treatment. Meta-analysis showed a statistically significant difference in favor of distraction for subjective anxiety using Facial scale (Mean diff.: 2.78; 95% CI: -3.08, -0.53; p = 0.005) and Modified Child Dental Anxiety Scale (Mean diff.: 12.76; 95% CI: -6.09, -4.47; p = 0.001) and a non-significant difference for heart rate (Mean diff.: 1.70; 95% CI: -6.54, 0.46; p = 0.09). Music significantly reduced heart rate when compared to a control comparator, underlining the superiority of the BMT (Mean diff.: 2.71; 95% CI: -3.70, -0.59; p = 0.007).
CONCLUSIONS
Limited evidence about efficacy of one technique over another raises important issues on the topic for future research regarding the management of the child patient in the dental setting of the 21st century.
CLINICAL SIGNIFICANCE
Behavioral management comprises a challenge for clinicians, who need to be familiar with a range of techniques to meet patients' needs at individual level and be flexible in their implementation. Appropriate technique should incorporate patients' personality and parents' active involvement, within the contents of the changes in modern societies.
Topics: Child; Humans; Pediatric Dentistry; Anxiety; Anxiety Disorders
PubMed: 36152953
DOI: 10.1016/j.jdent.2022.104303 -
JAMA Surgery Sep 2022Appendectomy remains the standard of care for uncomplicated acute appendicitis despite several randomized clinical trials pointing to the safety and efficacy of... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Appendectomy remains the standard of care for uncomplicated acute appendicitis despite several randomized clinical trials pointing to the safety and efficacy of nonoperative management of this disease. A meta-analysis of randomized clinical trials may contribute to the body of evidence and help surgeons select which patients may benefit from surgical and nonsurgical treatment.
OBJECTIVE
To assess the efficacy and safety of nonoperative management vs appendectomy for acute uncomplicated appendicitis.
DATA SOURCES
A systematic review was conducted using indexed sources (Embase and PubMed) to search for published randomized clinical trials in English comparing nonoperative management with appendectomy in adult patients presenting with uncomplicated acute appendicitis. To increase sensitivity, no limits were set for outcomes reported, sex, or year of publication. All nonrandomized or quasi-randomized trials were excluded, and validated primers were used.
STUDY SELECTION
Among 1504 studies imported for screening, 805 were duplicates, and 595 were excluded for irrelevancy. A further 96 were excluded after full-text review, mainly owing to wrong study design or inclusion of pediatric populations. Eight studies met the inclusion criteria and were selected for the meta-analysis.
DATA EXTRACTION AND SYNTHESIS
Meta-extraction was conducted with independent extraction by multiple reviewers using the Covidence platform for systematic reviews and in accordance with PRISMA guidelines. Data were pooled by a random-effects model.
MAIN OUTCOMES AND MEASURES
Treatment success and major adverse effects at 30 days' follow-up.
RESULTS
The main outcome (treatment success proportion at 30 days of follow-up) was not significantly different in the operative and nonoperative management cohorts (risk ratio [RR], 0.85; 95% CI, 0.66-1.11). Likewise, the percentage of major adverse effects was similar in both cohorts (RR, 0.72; 95% CI, 0.29-1.79). However, in the nonoperative management group, length of stay was significantly longer (RR, 1.48; 95% CI, 1.26-1.70), and a median cumulative incidence of 18% of recurrent appendicitis was observed.
CONCLUSIONS AND RELEVANCE
These results point to the general safety and efficacy of nonoperative management of uncomplicated acute appendicitis. However, this strategy may be associated with an increase in duration of hospital stay and a higher rate of recurrent appendicitis. This meta-analysis may help inform decision-making in nonoperative management of uncomplicated acute appendicitis.
Topics: Acute Disease; Adult; Anti-Bacterial Agents; Appendectomy; Appendicitis; Child; Humans; Treatment Outcome
PubMed: 35895073
DOI: 10.1001/jamasurg.2022.2937 -
Journal of Medical Internet Research Jun 2021The influence of social media among adolescent peer groups can be a powerful change agent. (Review)
Review
BACKGROUND
The influence of social media among adolescent peer groups can be a powerful change agent.
OBJECTIVE
Our scoping review aimed to elucidate the ways in which social media use among adolescent peers influences eating behaviors.
METHODS
A scoping review of the literature of articles published from journal inception to 2019 was performed by searching PubMed (ie, MEDLINE), Embase, CINAHL, PsycINFO, Web of Science, and other databases. The review was conducted in three steps: (1) identification of the research question and clarification of criteria using the population, intervention, comparison, and outcome (PICO) framework; (2) selection of articles from the literature using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines; and (3) charting and summarizing information from selected articles. PubMed's Medical Subject Headings (MeSH) and Embase's Emtree subject headings were reviewed along with specific keywords to construct a comprehensive search strategy. Subject headings and keywords were based on adolescent age groups, social media platforms, and eating behaviors. After screening 1387 peer-reviewed articles, 37 articles were assessed for eligibility. Participant age, gender, study location, social media channels utilized, user volume, and content themes related to findings were extracted from the articles.
RESULTS
Six articles met the final inclusion criteria. A final sample size of 1225 adolescents (aged 10 to 19 years) from the United States, the United Kingdom, Sweden, Norway, Denmark, Portugal, Brazil, and Australia were included in controlled and qualitative studies. Instagram and Facebook were among the most popular social media platforms that influenced healthful eating behaviors (ie, fruit and vegetable intake) as well as unhealthful eating behaviors related to fast food advertising. Online forums served as accessible channels for eating disorder relapse prevention among youth. Social media influence converged around four central themes: (1) visual appeal, (2) content dissemination, (3) socialized digital connections, and (4) adolescent marketer influencers.
CONCLUSIONS
Adolescent peer influence in social media environments spans the spectrum of healthy eating (ie, pathological) to eating disorders (ie, nonpathological). Strategic network-driven approaches should be considered for engaging adolescents in the promotion of positive dietary behaviors.
Topics: Adolescent; Data Management; Diet, Healthy; Feeding Behavior; Humans; Peer Influence; Social Media; United States
PubMed: 34081018
DOI: 10.2196/19697 -
Journal of Medical Internet Research May 2021Machine learning systems are part of the field of artificial intelligence that automatically learn models from data to make better decisions. Natural language processing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Machine learning systems are part of the field of artificial intelligence that automatically learn models from data to make better decisions. Natural language processing (NLP), by using corpora and learning approaches, provides good performance in statistical tasks, such as text classification or sentiment mining.
OBJECTIVE
The primary aim of this systematic review was to summarize and characterize, in methodological and technical terms, studies that used machine learning and NLP techniques for mental health. The secondary aim was to consider the potential use of these methods in mental health clinical practice.
METHODS
This systematic review follows the PRISMA (Preferred Reporting Items for Systematic Review and Meta-analysis) guidelines and is registered with PROSPERO (Prospective Register of Systematic Reviews; number CRD42019107376). The search was conducted using 4 medical databases (PubMed, Scopus, ScienceDirect, and PsycINFO) with the following keywords: machine learning, data mining, psychiatry, mental health, and mental disorder. The exclusion criteria were as follows: languages other than English, anonymization process, case studies, conference papers, and reviews. No limitations on publication dates were imposed.
RESULTS
A total of 327 articles were identified, of which 269 (82.3%) were excluded and 58 (17.7%) were included in the review. The results were organized through a qualitative perspective. Although studies had heterogeneous topics and methods, some themes emerged. Population studies could be grouped into 3 categories: patients included in medical databases, patients who came to the emergency room, and social media users. The main objectives were to extract symptoms, classify severity of illness, compare therapy effectiveness, provide psychopathological clues, and challenge the current nosography. Medical records and social media were the 2 major data sources. With regard to the methods used, preprocessing used the standard methods of NLP and unique identifier extraction dedicated to medical texts. Efficient classifiers were preferred rather than transparent functioning classifiers. Python was the most frequently used platform.
CONCLUSIONS
Machine learning and NLP models have been highly topical issues in medicine in recent years and may be considered a new paradigm in medical research. However, these processes tend to confirm clinical hypotheses rather than developing entirely new information, and only one major category of the population (ie, social media users) is an imprecise cohort. Moreover, some language-specific features can improve the performance of NLP methods, and their extension to other languages should be more closely investigated. However, machine learning and NLP techniques provide useful information from unexplored data (ie, patients' daily habits that are usually inaccessible to care providers). Before considering It as an additional tool of mental health care, ethical issues remain and should be discussed in a timely manner. Machine learning and NLP methods may offer multiple perspectives in mental health research but should also be considered as tools to support clinical practice.
Topics: Artificial Intelligence; Data Management; Humans; Machine Learning; Mental Health; Natural Language Processing
PubMed: 33944788
DOI: 10.2196/15708 -
Journal of Orthopaedic Surgery and... Nov 2022To assess the time required to return to sport (RTS) after conservative versus surgical treatment in athletes for pubalgia. (Review)
Review
BACKGROUND
To assess the time required to return to sport (RTS) after conservative versus surgical treatment in athletes for pubalgia.
METHODS
The PRISMA guidelines were followed. Pubmed, SportDiscus and Web of Science were last accessed on September 2022. All the studies investigating the time to RTS after conservative versus surgical treatment in athletes for pubalgia.
RESULTS
In total, 33 studies were selected for full text assessment, and 10 studies were included in the qualitative analysis. Seven studies reported data on conservative management, two on surgical management and one compared both. A total of 468 subjects were included for analysis. 58.7% (275 of 468) were soccer players, 5.9% (28 of 468) runners, and 3.8% (18 of 468) hockey players. Two studies did not specify the type of sport. The quality of the studies detailing the results of conservative management was higher than surgical procedures.
CONCLUSION
This review highlights that individuals undergoing surgery for pubalgia may return to sport earlier than those receiving conservative treatment. However, conservative management should be considered before surgical treatment is indicated.
Topics: Humans; Athletes; Athletic Injuries; Conservative Treatment; Return to Sport; Sports; Groin
PubMed: 36369155
DOI: 10.1186/s13018-022-03376-y -
Brain and Behavior Aug 2022To synthesize recent empirical evidence for the prevention and management of falls and fear of falling in patients with Parkinson's disease (PD). (Review)
Review
OBJECTIVE
To synthesize recent empirical evidence for the prevention and management of falls and fear of falling in patients with Parkinson's disease (PD).
DATA SOURCE
Database from PubMed, Cochrane Library, and EMBASE.
STUDY DESIGN
Systematic review.
DATA COLLECTION
We searched the PubMed, Cochrane Library, and EMBASE databases for studies published from inception to February 27, 2021. Inclusion criteria were nonreview articles on prevention and management measures related to falls and fall prevention in Parkinson's disease patients.
PRINCIPAL FINDINGS
We selected 45 articles and conducted in-depth research and discussion. According to the causes of falls in PD patients, they were divided into five directions, namely physical status, pre-existing conditions, environment, medical care, and cognition. In the cognitive domain, we focused on the fear of falling. On the above basis, we constructed a fall prevention model, which is a tertiary prevention health care network, based on The Johns Hopkins Fall Risk Assessment Tool to provide ideas for the prevention and management of falling and fear of falling in PD patients in clinical practice CONCLUSIONS: Falls and fear of falls in patients with Parkinson's disease can be reduced by effective clinical prevention and management. Future studies are needed to explore the efficacy of treatment and prevention of falls and fear of falls.
Topics: Fear; Humans; Parkinson Disease
PubMed: 35837986
DOI: 10.1002/brb3.2690 -
Journal of Medical Systems Sep 2018Electronic health records (EHRs) have emerged among health information technology as "meaningful use" to improve the quality and efficiency of healthcare, and health... (Review)
Review
Electronic health records (EHRs) have emerged among health information technology as "meaningful use" to improve the quality and efficiency of healthcare, and health disparities in population health. In other instances, they have also shown lack of interoperability, functionality and many medical errors. With proper implementation and training, are electronic health records a viable source in managing population health? The primary objective of this systematic review is to assess the relationship of electronic health records' use on population health through the identification and analysis of facilitators and barriers to its adoption for this purpose. Authors searched Cumulative Index of Nursing and Allied Health Literature (CINAHL) and MEDLINE (PubMed), 10/02/2012-10/02/2017, core clinical/academic journals, MEDLINE full text, English only, human species and evaluated the articles that were germane to our research objective. Each article was analyzed by multiple reviewers. Group members recognized common facilitators and barriers associated with EHRs effect on population health. A final list of articles was selected by the group after three consensus meetings (n = 55). Among a total of 26 factors identified, 63% (147/232) of those were facilitators and 37% (85/232) barriers. About 70% of the facilitators consisted of productivity/efficiency in EHRs occurring 33 times, increased quality and data management each occurring 19 times, surveillance occurring 17 times, and preventative care occurring 15 times. About 70% of the barriers consisted of missing data occurring 24 times, no standards (interoperability) occurring 13 times, productivity loss occurring 12 times, and technology too complex occurring 10 times. The analysis identified more facilitators than barriers to the use of the EHR to support public health. Wider adoption of the EHR and more comprehensive standards for interoperability will only enhance the ability for the EHR to support this important area of surveillance and disease prevention. This review identifies more facilitators than barriers to using the EHR to support public health, which implies a certain level of usability and acceptance to use the EHR in this manner. The public-health industry should combine their efforts with the interoperability projects to make the EHR both fully adopted and fully interoperable. This will greatly increase the availability, accuracy, and comprehensiveness of data across the country, which will enhance benchmarking and disease surveillance/prevention capabilities.
Topics: Electronic Health Records; Humans; Meaningful Use; Population Health
PubMed: 30269237
DOI: 10.1007/s10916-018-1075-6 -
The Cochrane Database of Systematic... Jan 2022Self-management interventions help people with chronic obstructive pulmonary disease (COPD) to acquire and practise the skills they need to carry out disease-specific... (Review)
Review
BACKGROUND
Self-management interventions help people with chronic obstructive pulmonary disease (COPD) to acquire and practise the skills they need to carry out disease-specific medical regimens, guide changes in health behaviour and provide emotional support to enable them to control their disease. Since the 2014 update of this review, several studies have been published.
OBJECTIVES
Primary objectives To evaluate the effectiveness of COPD self-management interventions compared to usual care in terms of health-related quality of life (HRQoL) and respiratory-related hospital admissions. To evaluate the safety of COPD self-management interventions compared to usual care in terms of respiratory-related mortality and all-cause mortality. Secondary objectives To evaluate the effectiveness of COPD self-management interventions compared to usual care in terms of other health outcomes and healthcare utilisation. To evaluate effective characteristics of COPD self-management interventions.
SEARCH METHODS
We searched the Cochrane Airways Trials Register, CENTRAL, MEDLINE, EMBASE, trials registries and the reference lists of included studies up until January 2020.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and cluster-randomised trials (CRTs) published since 1995. To be eligible for inclusion, self-management interventions had to include at least two intervention components and include an iterative process between participant and healthcare provider(s) in which goals were formulated and feedback was given on self-management actions by the participant.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion, assessed trial quality and extracted data. We resolved disagreements by reaching consensus or by involving a third review author. We contacted study authors to obtain additional information and missing outcome data where possible. Primary outcomes were health-related quality of life (HRQoL), number of respiratory-related hospital admissions, respiratory-related mortality, and all-cause mortality. When appropriate, we pooled study results using random-effects modelling meta-analyses.
MAIN RESULTS
We included 27 studies involving 6008 participants with COPD. The follow-up time ranged from two-and-a-half to 24 months and the content of the interventions was diverse. Participants' mean age ranged from 57 to 74 years, and the proportion of male participants ranged from 33% to 98%. The post-bronchodilator forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio of participants ranged from 33.6% to 57.0%. The FEV1/FVC ratio is a measure used to diagnose COPD and to determine the severity of the disease. Studies were conducted on four different continents (Europe (n = 15), North America (n = 8), Asia (n = 1), and Oceania (n = 4); with one study conducted in both Europe and Oceania). Self-management interventions likely improve HRQoL, as measured by the St. George's Respiratory Questionnaire (SGRQ) total score (lower score represents better HRQoL) with a mean difference (MD) from usual care of -2.86 points (95% confidence interval (CI) -4.87 to -0.85; 14 studies, 2778 participants; low-quality evidence). The pooled MD of -2.86 did not reach the SGRQ minimal clinically important difference (MCID) of four points. Self-management intervention participants were also at a slightly lower risk for at least one respiratory-related hospital admission (odds ratio (OR) 0.75, 95% CI 0.57 to 0.98; 15 studies, 3263 participants; very low-quality evidence). The number needed to treat to prevent one respiratory-related hospital admission over a mean of 9.75 months' follow-up was 15 (95% CI 8 to 399) for participants with high baseline risk and 26 (95% CI 15 to 677) for participants with low baseline risk. No differences were observed in respiratory-related mortality (risk difference (RD) 0.01, 95% CI -0.02 to 0.04; 8 studies, 1572 participants ; low-quality evidence) and all-cause mortality (RD -0.01, 95% CI -0.03 to 0.01; 24 studies, 5719 participants; low-quality evidence). We graded the evidence to be of 'moderate' to 'very low' quality according to GRADE. All studies had a substantial risk of bias, because of lack of blinding of participants and personnel to the interventions, which is inherently impossible in a self-management intervention. In addition, risk of bias was noticeably increased because of insufficient information regarding a) non-protocol interventions, and b) analyses to estimate the effect of adhering to interventions. Consequently, the highest GRADE evidence score that could be obtained by studies was 'moderate'.
AUTHORS' CONCLUSIONS
Self-management interventions for people with COPD are associated with improvements in HRQoL, as measured with the SGRQ, and a lower probability of respiratory-related hospital admissions. No excess respiratory-related and all-cause mortality risks were observed, which strengthens the view that COPD self-management interventions are unlikely to cause harm. By using stricter inclusion criteria, we decreased heterogeneity in studies, but also reduced the number of included studies and therefore our capacity to conduct subgroup analyses. Data were therefore still insufficient to reach clear conclusions about effective (intervention) characteristics of COPD self-management interventions. As tailoring of COPD self-management interventions to individuals is desirable, heterogeneity is and will likely remain present in self-management interventions. For future studies, we would urge using only COPD self-management interventions that include iterative interactions between participants and healthcare professionals who are competent using behavioural change techniques (BCTs) to elicit participants' motivation, confidence and competence to positively adapt their health behaviour(s) and develop skills to better manage their disease. In addition, to inform further subgroup and meta-regression analyses and to provide stronger conclusions regarding effective COPD self-management interventions, there is a need for more homogeneity in outcome measures. More attention should be paid to behavioural outcome measures and to providing more detailed, uniform and transparently reported data on self-management intervention components and BCTs. Assessment of outcomes over the long term is also recommended to capture changes in people's behaviour. Finally, information regarding non-protocol interventions as well as analyses to estimate the effect of adhering to interventions should be included to increase the quality of evidence.
Topics: Aged; Hospitalization; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Pulmonary Disease, Chronic Obstructive; Quality of Life; Self-Management
PubMed: 35001366
DOI: 10.1002/14651858.CD002990.pub4 -
Journal of Medical Internet Research Feb 2015Adherence to chronic disease management is critical to achieving improved health outcomes, quality of life, and cost-effective health care. As the burden of chronic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Adherence to chronic disease management is critical to achieving improved health outcomes, quality of life, and cost-effective health care. As the burden of chronic diseases continues to grow globally, so does the impact of non-adherence. Mobile technologies are increasingly being used in health care and public health practice (mHealth) for patient communication, monitoring, and education, and to facilitate adherence to chronic diseases management.
OBJECTIVE
We conducted a systematic review of the literature to evaluate the effectiveness of mHealth in supporting the adherence of patients to chronic diseases management ("mAdherence"), and the usability, feasibility, and acceptability of mAdherence tools and platforms in chronic disease management among patients and health care providers.
METHODS
We searched PubMed, Embase, and EBSCO databases for studies that assessed the role of mAdherence in chronic disease management of diabetes mellitus, cardiovascular disease, and chronic lung diseases from 1980 through May 2014. Outcomes of interest included effect of mHealth on patient adherence to chronic diseases management, disease-specific clinical outcomes after intervention, and the usability, feasibility, and acceptability of mAdherence tools and platforms in chronic disease management among target end-users.
RESULTS
In all, 107 articles met all inclusion criteria. Short message service was the most commonly used mAdherence tool in 40.2% (43/107) of studies. Usability, feasibility, and acceptability or patient preferences for mAdherence interventions were assessed in 57.9% (62/107) of studies and found to be generally high. A total of 27 studies employed randomized controlled trial (RCT) methods to assess impact on adherence behaviors, and significant improvements were observed in 15 of those studies (56%). Of the 41 RCTs that measured effects on disease-specific clinical outcomes, significant improvements between groups were reported in 16 studies (39%).
CONCLUSIONS
There is potential for mHealth tools to better facilitate adherence to chronic disease management, but the evidence supporting its current effectiveness is mixed. Further research should focus on understanding and improving how mHealth tools can overcome specific barriers to adherence.
Topics: Cardiovascular Diseases; Chronic Disease; Diabetes Mellitus; Disease Management; Humans; Lung Diseases; Patient Compliance; Randomized Controlled Trials as Topic; Telemedicine; Text Messaging; Treatment Outcome
PubMed: 25803266
DOI: 10.2196/jmir.3951 -
The Cochrane Database of Systematic... Jan 2024Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Different therapeutic strategies are available for the treatment of people with relapsing-remitting multiple sclerosis (RRMS), including immunomodulators, immunosuppressants and biological agents. Although each one of these therapies reduces relapse frequency and slows disability accumulation compared to no treatment, their relative benefit remains unclear. This is an update of a Cochrane review published in 2015.
OBJECTIVES
To compare the efficacy and safety, through network meta-analysis, of interferon beta-1b, interferon beta-1a, glatiramer acetate, natalizumab, mitoxantrone, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, pegylated interferon beta-1a, daclizumab, laquinimod, azathioprine, immunoglobulins, cladribine, cyclophosphamide, diroximel fumarate, fludarabine, interferon beta 1-a and beta 1-b, leflunomide, methotrexate, minocycline, mycophenolate mofetil, ofatumumab, ozanimod, ponesimod, rituximab, siponimod and steroids for the treatment of people with RRMS.
SEARCH METHODS
CENTRAL, MEDLINE, Embase, and two trials registers were searched on 21 September 2021 together with reference checking, citation searching and contact with study authors to identify additional studies. A top-up search was conducted on 8 August 2022.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that studied one or more of the available immunomodulators and immunosuppressants as monotherapy in comparison to placebo or to another active agent, in adults with RRMS.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies and extracted data. We considered both direct and indirect evidence and performed data synthesis by pairwise and network meta-analysis. Certainty of the evidence was assessed by the GRADE approach.
MAIN RESULTS
We included 50 studies involving 36,541 participants (68.6% female and 31.4% male). Median treatment duration was 24 months, and 25 (50%) studies were placebo-controlled. Considering the risk of bias, the most frequent concern was related to the role of the sponsor in the authorship of the study report or in data management and analysis, for which we judged 68% of the studies were at high risk of other bias. The other frequent concerns were performance bias (34% judged as having high risk) and attrition bias (32% judged as having high risk). Placebo was used as the common comparator for network analysis. Relapses over 12 months: data were provided in 18 studies (9310 participants). Natalizumab results in a large reduction of people with relapses at 12 months (RR 0.52, 95% CI 0.43 to 0.63; high-certainty evidence). Fingolimod (RR 0.48, 95% CI 0.39 to 0.57; moderate-certainty evidence), daclizumab (RR 0.55, 95% CI 0.42 to 0.73; moderate-certainty evidence), and immunoglobulins (RR 0.60, 95% CI 0.47 to 0.79; moderate-certainty evidence) probably result in a large reduction of people with relapses at 12 months. Relapses over 24 months: data were reported in 28 studies (19,869 participants). Cladribine (RR 0.53, 95% CI 0.44 to 0.64; high-certainty evidence), alemtuzumab (RR 0.57, 95% CI 0.47 to 0.68; high-certainty evidence) and natalizumab (RR 0.56, 95% CI 0.48 to 0.65; high-certainty evidence) result in a large decrease of people with relapses at 24 months. Fingolimod (RR 0.54, 95% CI 0.48 to 0.60; moderate-certainty evidence), dimethyl fumarate (RR 0.62, 95% CI 0.55 to 0.70; moderate-certainty evidence), and ponesimod (RR 0.58, 95% CI 0.48 to 0.70; moderate-certainty evidence) probably result in a large decrease of people with relapses at 24 months. Glatiramer acetate (RR 0.84, 95%, CI 0.76 to 0.93; moderate-certainty evidence) and interferon beta-1a (Avonex, Rebif) (RR 0.84, 95% CI 0.78 to 0.91; moderate-certainty evidence) probably moderately decrease people with relapses at 24 months. Relapses over 36 months findings were available from five studies (3087 participants). None of the treatments assessed showed moderate- or high-certainty evidence compared to placebo. Disability worsening over 24 months was assessed in 31 studies (24,303 participants). Natalizumab probably results in a large reduction of disability worsening (RR 0.59, 95% CI 0.46 to 0.75; moderate-certainty evidence) at 24 months. Disability worsening over 36 months was assessed in three studies (2684 participants) but none of the studies used placebo as the comparator. Treatment discontinuation due to adverse events data were available from 43 studies (35,410 participants). Alemtuzumab probably results in a slight reduction of treatment discontinuation due to adverse events (OR 0.39, 95% CI 0.19 to 0.79; moderate-certainty evidence). Daclizumab (OR 2.55, 95% CI 1.40 to 4.63; moderate-certainty evidence), fingolimod (OR 1.84, 95% CI 1.31 to 2.57; moderate-certainty evidence), teriflunomide (OR 1.82, 95% CI 1.19 to 2.79; moderate-certainty evidence), interferon beta-1a (OR 1.48, 95% CI 0.99 to 2.20; moderate-certainty evidence), laquinimod (OR 1.49, 95 % CI 1.00 to 2.15; moderate-certainty evidence), natalizumab (OR 1.57, 95% CI 0.81 to 3.05), and glatiramer acetate (OR 1.48, 95% CI 1.01 to 2.14; moderate-certainty evidence) probably result in a slight increase in the number of people who discontinue treatment due to adverse events. Serious adverse events (SAEs) were reported in 35 studies (33,998 participants). There was probably a trivial reduction in SAEs amongst people with RRMS treated with interferon beta-1b as compared to placebo (OR 0.92, 95% CI 0.55 to 1.54; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
We are highly confident that, compared to placebo, two-year treatment with natalizumab, cladribine, or alemtuzumab decreases relapses more than with other DMTs. We are moderately confident that a two-year treatment with natalizumab may slow disability progression. Compared to those on placebo, people with RRMS treated with most of the assessed DMTs showed a higher frequency of treatment discontinuation due to AEs: we are moderately confident that this could happen with fingolimod, teriflunomide, interferon beta-1a, laquinimod, natalizumab and daclizumab, while our certainty with other DMTs is lower. We are also moderately certain that treatment with alemtuzumab is associated with fewer discontinuations due to adverse events than placebo, and moderately certain that interferon beta-1b probably results in a slight reduction in people who experience serious adverse events, but our certainty with regard to other DMTs is lower. Insufficient evidence is available to evaluate the efficacy and safety of DMTs in a longer term than two years, and this is a relevant issue for a chronic condition like MS that develops over decades. More than half of the included studies were sponsored by pharmaceutical companies and this may have influenced their results. Further studies should focus on direct comparison between active agents, with follow-up of at least three years, and assess other patient-relevant outcomes, such as quality of life and cognitive status, with particular focus on the impact of sex/gender on treatment effects.
Topics: Adult; Humans; Immunosuppressive Agents; Multiple Sclerosis, Relapsing-Remitting; Glatiramer Acetate; Interferon beta-1a; Fingolimod Hydrochloride; Natalizumab; Interferon beta-1b; Cladribine; Alemtuzumab; Dimethyl Fumarate; Daclizumab; Network Meta-Analysis; Immunologic Factors; Recurrence
PubMed: 38174776
DOI: 10.1002/14651858.CD011381.pub3