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Journal of the American Geriatrics... Jul 2021Poor sleep quality is a common issue among older adults; it can lead to a poor quality of life and impairments in cognitive function and physical health. This study... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Poor sleep quality is a common issue among older adults; it can lead to a poor quality of life and impairments in cognitive function and physical health. This study aimed to conduct a systematic review and meta-analysis of the effect of listening to music on sleep quality in older adults.
DESIGN
Systematic review and meta-analyses.
SETTING
Five databases, including Embase, Ovid Medline, Cochrane Library, Scopus, and the Index to Taiwan Periodical Literature System, were searched to identify studies assessing the efficacy of music therapy in older adults aged 60 years and older published through February 20, 2021.
PARTICIPANTS
Adults aged 60 years and older.
MEASUREMENTS
We searched English- and Chinese-language studies of randomized control trials. All studies were reviewed by two independent investigators. The primary sleep outcome was the Pittsburgh sleep quality index. The Cochrane Collaboration tool was used to assess the risk of bias, and Review Manager 5.3 software was used to conduct the meta-analysis.
RESULTS
Five randomized control trials were included in the meta-analysis. Older adults who listened to music experienced significantly better sleep quality than those who did not listen to music [mean difference (MD): -1.96, 95% CI -2.23 to -1.73, P = 0.003]. The subgroup analysis revealed that older adults who listened to sedative music obtained a more effective improvement in sleep quality than those who listened to rhythm-centered music (MD: -2.35, 95% CI -3.59 to -1.10, P = 0.0002). Furthermore, listening to music for longer than 4 weeks (MD: -2.61, 95% CI -4.72 to -0.50, P = 0.02) was to be effective at improving sleep quality.
CONCLUSIONS
Music therapy is safe and easy to administer and can effectively improve sleep quality among older adults, particularly those listening to more sedative music for at least a four-week duration.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Music; Music Therapy; Quality of Life; Randomized Controlled Trials as Topic; Sleep; Sleep Initiation and Maintenance Disorders; Treatment Outcome
PubMed: 33880759
DOI: 10.1111/jgs.17149 -
Clinical Journal of the American... Apr 2021Hemodialysis is associated with a high symptom burden that impairs health-related quality of life and functional status. Effective symptom management is a priority for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Hemodialysis is associated with a high symptom burden that impairs health-related quality of life and functional status. Effective symptom management is a priority for individuals receiving hemodialysis. Aerobic exercise may be an effective, nonpharmacologic treatment for specific hemodialysis-related symptoms. This systematic review investigated the effect of aerobic exercise on hemodialysis-related symptoms in adults with kidney failure undergoing maintenance hemodialysis.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We searched MEDLINE, PubMed, Cochrane CENTRAL, CINAHL, PsycINFO, SPORTDiscus, EMBASE, PEDro, and Scopus databases from 1960 or inception until April 15, 2020 for randomized controlled trials investigating the effect of aerobic exercise on hemodialysis-related symptoms, identified as prespecified primary or secondary outcomes, as compared with controls in adults on maintenance hemodialysis. We identified restless legs syndrome as the primary outcome.
RESULTS
Of 3048 studies identified, 15 randomized controlled trials met the eligibility criteria. These studies investigated the effect of aerobic exercise on restless legs syndrome (two studies), sleep disturbance (four studies), anxiety (four studies), depression (nine studies), muscle cramping (one study), and fatigue (one study). Exercise interventions were intradialytic in ten studies and outside of hemodialysis in five studies. Heterogenous interventions and outcomes and moderate to high risk of bias precluded meta-analysis for most symptoms. Aerobic exercise demonstrated improvement in symptoms of restless legs syndrome, muscle cramping, and fatigue, as compared with nonexercise controls. Meta-analysis of depressive symptoms in studies using the Beck Depression Inventory demonstrated a greater reduction in Beck Depression Inventory score with exercise as compared with control (mean difference -7.57; 95% confidence interval, -8.25 to -6.89).
CONCLUSIONS
Our review suggests that in adults on maintenance hemodialysis, aerobic exercise improves several hemodialysis-related symptoms, including restless legs syndrome, symptoms of depression, muscle cramping, and fatigue. However, the use of validated outcome measures with demonstrated reliability and responsiveness in more diverse hemodialysis populations is required to fully characterize the effect of this intervention.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
PROSPERO #CRD42017056658.
Topics: Exercise; Exercise Therapy; Humans; Kidney Failure, Chronic; Renal Dialysis
PubMed: 33766925
DOI: 10.2215/CJN.15080920 -
Digestive Diseases and Sciences Sep 2023Targeting interleukin-23 (IL-23) is an important therapeutic strategy for Crohn's disease (CD). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Targeting interleukin-23 (IL-23) is an important therapeutic strategy for Crohn's disease (CD).
AIMS
This systematic review and meta-analysis assessed the efficacy and safety of selective IL-23p19 and IL-12/23p40 inhibitors in patients with moderate-to-severe CD.
METHODS
MEDLINE, Embase, and the Cochrane library (CENTRAL) were searched from inception to May 24, 2023, for randomized, placebo- or active comparator-controlled induction and/or maintenance trials of selective IL-23p19 and IL-12/23p40 inhibitors in pediatric and adult patients with CD. The primary outcome was the proportion of patients in clinical remission. Secondary outcomes were clinical response, endoscopic remission, endoscopic response, and safety. Data were pooled using a random-effects model. Risk of bias and certainty of evidence were assessed using the Cochrane risk of bias tool and the GRADE criteria, respectively.
RESULTS
Eighteen trials (n = 5561) were included. Most studies were rated as low risk of bias. Targeting IL-23 was significantly superior to placebo for inducing clinical (risk ratio [RR] = 1.87, 95% confidence interval [CI] 1.58-2.21) and endoscopic (RR = 3.20, 95%CI 2.17-4.70) remission and maintaining clinical remission (RR = 1.39, 95%CI 1.10-1.77) (GRADE high certainty evidence for all outcomes). Subgroup analysis showed that targeting IL-23 was superior to placebo for inducing clinical remission in biologic-naïve (RR = 2.20, 95%CI 1.46-3.32, I = 0%, p = 0.39) and biologic-experienced patients (RR = 1.82, 95%CI 1.27-2.60, I = 56.5%, p = 0.01). Targeting IL-23 was associated with a decreased risk of serious adverse events in induction (RR = 0.55, 95%CI 0.44-0.73) and maintenance (RR = 0.72, 95%CI 0.53-0.98) trials compared to placebo (high certainty evidence).
CONCLUSION
Targeting IL-23 is effective and safe for inducing and maintaining clinical and endoscopic remission in patients with moderate-to-severe CD.
Topics: Adult; Humans; Child; Crohn Disease; Interleukin-12; Interleukin-23 Subunit p19; Interleukin Inhibitors; Remission Induction; Interleukin-23; Biological Products
PubMed: 37378711
DOI: 10.1007/s10620-023-08014-z -
Lancet (London, England) Jun 2019Oral immunotherapy is an emerging experimental treatment for peanut allergy, but its benefits and harms are unclear. We systematically reviewed the efficacy and safety... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral immunotherapy is an emerging experimental treatment for peanut allergy, but its benefits and harms are unclear. We systematically reviewed the efficacy and safety of oral immunotherapy versus allergen avoidance or placebo (no oral immunotherapy) for peanut allergy.
METHODS
In the Peanut Allergen immunotherapy, Clarifying the Evidence (PACE) systematic review and meta-analysis, we searched MEDLINE, EMBASE, Cochrane Controlled Register of Trials, Latin American & Caribbean Health Sciences Literature, China National Knowledge Infrastructure, WHO's Clinical Trials Registry Platform, US Food and Drug Administration, and European Medicines Agency databases from inception to Dec 6, 2018, for randomised controlled trials comparing oral immunotherapy versus no oral immunotherapy for peanut allergy, without language restrictions. We screened studies, extracted data, and assessed risk of bias independently in duplicate. Main outcomes included anaphylaxis, allergic or adverse reactions, epinephrine use, and quality of life, meta-analysed by random effects. We assessed certainty (quality) of evidence by the GRADE approach. This study is registered with PROSPERO, number CRD42019117930.
RESULTS
12 trials (n=1041; median age across trials 8·7 years [IQR 5·9-11·2]) showed that oral immunotherapy versus no oral immunotherapy increased anaphylaxis risk (risk ratio [RR] 3·12 [95% CI 1·76-5·55], I=0%, risk difference [RD] 15·1%, high-certainty), anaphylaxis frequency (incidence rate ratio [IRR] 2·72 [1·57-4·72], I=0%, RD 12·2%, high-certainty), and epinephrine use (RR 2·21 [1·27-3·83], I=0%, RD 4·5%, high-certainty) similarly during build-up and maintenance (p=0·92). Oral immunotherapy increased serious adverse events (RR 1·92 [1·00-3·66], I=0%, RD 5·7%, moderate-certainty), and non-anaphylactic reactions (vomiting: RR 1·79 [95%CI 1·35-2·38], I=0%, high-certainty; angioedema: 2·25 [1·13-4·47], I=0%, high-certainty; upper tract respiratory reactions: 1·36 [1·02-1·81], I=0%, moderate-certainty; lower tract respiratory reactions: 1·55 [0·96-2·50], I=28%, moderate-certainty). Passing a supervised challenge, a surrogate for preventing out-of-clinic reactions, was more likely with oral immunotherapy (RR 12·42 [95% CI 6·82-22·61], I=0%, RD 36·5%, high-certainty). Quality of life was not different between groups (combined parents and self report RR 1·21 [0·87-1·69], I=0%, RD 0·03%, low-certainty). Findings were robust to IRR, trial sequential, subgroup, and sensitivity analyses.
INTERPRETATION
In patients with peanut allergy, high-certainty evidence shows that available peanut oral immunotherapy regimens considerably increase allergic and anaphylactic reactions over avoidance or placebo, despite effectively inducing desensitisation. Safer peanut allergy treatment approaches and rigorous randomised controlled trials that evaluate patient-important outcomes are needed.
FUNDING
None.
Topics: Administration, Oral; Child; Child, Preschool; Desensitization, Immunologic; Female; Humans; Male; Peanut Hypersensitivity; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 31030987
DOI: 10.1016/S0140-6736(19)30420-9 -
The Cochrane Database of Systematic... Apr 2023Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal (GI) tract that is thought to be associated with a complex interplay between the... (Review)
Review
BACKGROUND
Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal (GI) tract that is thought to be associated with a complex interplay between the immune system, the GI tract lining, the environment, and the gut microbiome, leading to an abnormal inflammatory response in genetically susceptible individuals. An altered composition of the gut's native microbiota, known as dysbiosis, may have a major role in the pathogenesis of ulcerative colitis (UC) and Crohn disease (CD), two subtypes of IBD. There is growing interest in the correction of this underlying dysbiosis using fecal microbiota transplantation (FMT).
OBJECTIVES
To evaluate the benefits and safety profile of FMT for treatment of IBD in adults and children versus autologous FMT, placebo, standard medication, or no intervention.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, two clinical trial registries, and the reference sections of published trials through 22 December 2022.
SELECTION CRITERIA
We included randomized controlled trials that studied adults and children with UC or CD. Eligible intervention arms used FMT, defined as the delivery of healthy donor stool containing gut microbiota to a recipient's GI tract, to treat UC or CD.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened studies for inclusion. Our primary outcomes were: 1. induction of clinical remission, 2. maintenance of clinical remission, and 3. serious adverse events. Our secondary outcomes were: 4. any adverse events, 5. endoscopic remission, 6. quality of life, 7. clinical response, 8. endoscopic response, 9. withdrawals, 10. inflammatory markers, and 11. microbiome outcomes. We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
We included 12 studies with 550 participants. Three studies were conducted in Australia; two in Canada; and one in each of the following: China, the Czech Republic, France, India, the Netherlands, and the USA. One study was conducted in both Israel and Italy. FMT was administered in the form of capsules or suspensions and delivered by mouth, nasoduodenal tube, enema, or colonoscopy. One study delivered FMT by both oral capsules and colonoscopy. Six studies were at overall low risk of bias, while the others had either unclear or high risk of bias. Ten studies with 468 participants, of which nine studies focused on adults and one focused on children, reported induction of clinical remission in people with UC at longest follow-up (range 6 to 12 weeks) and showed that FMT may increase rates of induction of clinical remission in UC compared to control (risk ratio (RR) 1.79, 95% confidence interval (CI) 1.13 to 2.84; low-certainty evidence). Five studies showed that FMT may increase rates of induction of endoscopic remission in UC at longest follow-up (range 8 to 12 weeks); however, the CIs around the summary estimate were wide and included a possible null effect (RR 1.45, 95% CI 0.64 to 3.29; low-certainty evidence). Nine studies with 417 participants showed that FMT may result in little to no difference in rates of any adverse events (RR 0.99, 95% CI 0.85 to 1.16; low-certainty evidence). The evidence was very uncertain about the risk of serious adverse events (RR 1.77, 95% CI 0.88 to 3.55; very low-certainty evidence) and improvement in quality of life (mean difference (MD) 15.34, 95% CI -3.84 to 34.52; very low-certainty evidence) when FMT was used to induce remission in UC. Two studies, of which one also contributed data for induction of remission in active UC, assessed maintenance of remission in people with controlled UC at longest follow-up (range 48 to 56 weeks). The evidence was very uncertain about the use of FMT for maintenance of clinical remission (RR 2.97, 95% CI 0.26 to 34.42; very low-certainty evidence) and endoscopic remission (RR 3.28, 95% CI 0.73 to 14.74; very low-certainty evidence). The evidence was also very uncertain about the risk of serious adverse events, risk of any adverse events, and improvement in quality of life when FMT was used to maintain remission in UC. None of the included studies assessed use of FMT for induction of remission in people with CD. One study with 21 participants reported data on FMT for maintenance of remission in people with CD. The evidence was very uncertain about the use of FMT for maintenance of clinical remission in CD at 24 weeks (RR 1.21, 95% CI 0.36 to 4.14; very low-certainty evidence). The evidence was also very uncertain about the risk of serious or any adverse events when FMT was used to maintain remission in CD. None of the studies reported data on use of FMT for maintenance of endoscopic remission or improvement in quality of life in people with CD.
AUTHORS' CONCLUSIONS
FMT may increase the proportion of people with active UC who achieve clinical and endoscopic remission. The evidence was very uncertain about whether use of FMT in people with active UC impacted the risk of serious adverse events or improvement in quality of life. The evidence was also very uncertain about the use of FMT for maintenance of remission in people with UC, as well as induction and maintenance of remission in people with CD, and no conclusive statements could be made in this regard. Further studies are needed to address the beneficial effects and safety profile of FMT in adults and children with active UC and CD, as well as its potential to promote longer-term maintenance of remission in UC and CD.
Topics: Adult; Child; Humans; Colitis, Ulcerative; Crohn Disease; Dysbiosis; Fecal Microbiota Transplantation; Inflammatory Bowel Diseases; Quality of Life; Remission Induction
PubMed: 37094824
DOI: 10.1002/14651858.CD012774.pub3 -
Critical Care Medicine Apr 2024Maintaining glycemic control of critically ill patients may impact outcomes such as survival, infection, and neuromuscular recovery, but there is equipoise on the target...
RATIONALE
Maintaining glycemic control of critically ill patients may impact outcomes such as survival, infection, and neuromuscular recovery, but there is equipoise on the target blood levels, monitoring frequency, and methods.
OBJECTIVES
The purpose was to update the 2012 Society of Critical Care Medicine and American College of Critical Care Medicine (ACCM) guidelines with a new systematic review of the literature and provide actionable guidance for clinicians.
PANEL DESIGN
The total multiprofessional task force of 22, consisting of clinicians and patient/family advocates, and a methodologist applied the processes described in the ACCM guidelines standard operating procedure manual to develop evidence-based recommendations in alignment with the Grading of Recommendations Assessment, Development, and Evaluation Approach (GRADE) methodology. Conflict of interest policies were strictly followed in all phases of the guidelines, including panel selection and voting.
METHODS
We conducted a systematic review for each Population, Intervention, Comparator, and Outcomes question related to glycemic management in critically ill children (≥ 42 wk old adjusted gestational age to 18 yr old) and adults, including triggers for initiation of insulin therapy, route of administration, monitoring frequency, role of an explicit decision support tool for protocol maintenance, and methodology for glucose testing. We identified the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the GRADE approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak or as a good practice statement. In addition, "In our practice" statements were included when the available evidence was insufficient to support a recommendation, but the panel felt that describing their practice patterns may be appropriate. Additional topics were identified for future research.
RESULTS
This guideline is an update of the guidelines for the use of an insulin infusion for the management of hyperglycemia in critically ill patients. It is intended for adult and pediatric practitioners to reassess current practices and direct research into areas with inadequate literature. The panel issued seven statements related to glycemic control in unselected adults (two good practice statements, four conditional recommendations, one research statement) and seven statements for pediatric patients (two good practice statements, one strong recommendation, one conditional recommendation, two "In our practice" statements, and one research statement), with additional detail on specific subset populations where available.
CONCLUSIONS
The guidelines panel achieved consensus for adults and children regarding a preference for an insulin infusion for the acute management of hyperglycemia with titration guided by an explicit clinical decision support tool and frequent (≤ 1 hr) monitoring intervals during glycemic instability to minimize hypoglycemia and against targeting intensive glucose levels. These recommendations are intended for consideration within the framework of the patient's existing clinical status. Further research is required to evaluate the role of individualized glycemic targets, continuous glucose monitoring systems, explicit decision support tools, and standardized glycemic control metrics.
Topics: Adolescent; Adult; Child; Humans; Blood Glucose; Blood Glucose Self-Monitoring; Critical Care; Critical Illness; Glycemic Control; Hyperglycemia; Insulin; Infant; Child, Preschool
PubMed: 38240484
DOI: 10.1097/CCM.0000000000006174 -
Advances in Therapy May 2023Dose escalation is one of the treatment approaches studied and suggested in advanced therapies for Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to... (Review)
Review
INTRODUCTION
Dose escalation is one of the treatment approaches studied and suggested in advanced therapies for Crohn's disease (CD) and ulcerative colitis (UC). This study aimed to identify and characterize the dosing escalation patterns of advanced therapies in CD and UC.
METHODS
Two systematic literature reviews (SLRs) were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE, Embase, and Cochrane Library were searched for articles published between January 2011 and October 2021 and limited to non-interventional studies in English language. Congress and bibliographic searches were also conducted. Articles were screened by two independent researchers. Dose escalation patterns were described and summarized considering the regional regulatory label recommendation (in North America [NA] or outside of North America [ONA]).
RESULTS
Among 3190 CD and 2116 UC articles identified in the Ovid searches, 100 CD and 54 UC studies were included in the SLR, with more studies conducted ONA. Most studies reported an initial maintenance dose pattern aligned with the lower starting dose per local regulatory label; however, several ONA studies (n = 13 out of 14) reported ustekinumab every 8 weeks as starting maintenance pattern in CD. In ONA studies, the median within-guideline escalation rates in CD and UC were 43% in ustekinumab (CD only), 33% and 32% for vedolizumab; 29% and 39% for adalimumab; and 14% and 10% for infliximab. Evidence regarding dose escalation patterns for tofacitinib, certolizumab pegol, and golimumab was limited. Some dose escalation patterns outside of label recommendations were observed including ustekinumab every 8 weeks to every 4 weeks and vedolizumab every 8 weeks to every 6 weeks.
CONCLUSION
Dose escalation strategies are widely documented in the literature. The reported dose escalation patterns and escalation rates vary by region and by CD and UC. Most escalation patterns reported were aligned with regulatory recommendations while some reported more diverse or aggressive dose escalation.
PROSPERO REGISTRATION
CRD42021289251.
Topics: Humans; Crohn Disease; Colitis, Ulcerative; Ustekinumab; Adalimumab; Infliximab
PubMed: 36930430
DOI: 10.1007/s12325-023-02457-6 -
Infection, Disease & Health Aug 2019Evidence-based bundles have reduced central line bloodstream infection rates in adult intensive care units. To tackle peripheral intravenous catheter (PIVC) bloodstream... (Meta-Analysis)
Meta-Analysis
Effectiveness of insertion and maintenance bundles in preventing peripheral intravenous catheter-related complications and bloodstream infection in hospital patients: A systematic review.
BACKGROUND
Evidence-based bundles have reduced central line bloodstream infection rates in adult intensive care units. To tackle peripheral intravenous catheter (PIVC) bloodstream infection, many hospitals have implemented PIVC insertion and maintenance bundles. However, the efficacy of PIVC bundles in preventing PIVC complications and infection in hospital patients is uncertain. The aim of this paper is to synthesize evidence on the effectiveness of PIVC insertion and maintenance bundles on preventing adverse events.
METHODS
In this systematic review, we searched multiple electronic databases, trial registries, and grey literature for eligible studies published in English (January 2000-December 2018) to identify intervention studies evaluating PIVC insertion or maintenance bundles with two or more components. Search terms: peripheral intravenous catheter/cannula, insertion, maintenance, bundle, infection, infiltration, extravasation, dislodgement, thrombosis, occlusion, and phlebitis. Two reviewers independently conducted data extraction and quality assessments using the Downs and Black checklist.
RESULTS
Of 14,456 records screened, 13 studies (6 interrupted time-series, 7 before-and-after) were included. Insertion and maintenance bundles included multiple components (2-7 items per bundle). Despite testing different bundles, 12 studies reported reductions in phlebitis and bloodstream infection, and one study reported no change in bloodstream infection and an increase in phlebitis rate. Methodological quality of all studies ranked between 'low' and 'fair'.
CONCLUSIONS
The effect of PIVC bundles on PIVC complications and bloodstream infection rates remains uncertain. Standardisation of bundle components and more rigorous studies are needed. PROSPERO registration number: CRD42017075142.
Topics: Bacteremia; Catheter-Related Infections; Catheterization, Peripheral; Evidence-Based Practice; Hospitalization; Humans; Phlebitis
PubMed: 31005606
DOI: 10.1016/j.idh.2019.03.001 -
Journal of Sleep Research Dec 2023Despite the success of cognitive behavioural therapy for insomnia and recent advances in pharmacotherapy, many patients with insomnia do not sufficiently respond to... (Review)
Review
Despite the success of cognitive behavioural therapy for insomnia and recent advances in pharmacotherapy, many patients with insomnia do not sufficiently respond to available treatments. This systematic review aims to present the state of science regarding the use of brain stimulation approaches in treating insomnia. To this end, we searched MEDLINE, Embase and PsycINFO from inception to 24 March 2023. We evaluated studies that compared conditions of active stimulation with a control condition or group. Outcome measures included standardized insomnia questionnaires and/or polysomnography in adults with a clinical diagnosis of insomnia. Our search identified 17 controlled trials that met inclusion criteria, and assessed a total of 967 participants using repetitive transcranial magnetic stimulation, transcranial electric stimulation, transcutaneous auricular vagus nerve stimulation or forehead cooling. No trials using other techniques such as deep brain stimulation, vestibular stimulation or auditory stimulation met the inclusion criteria. While several studies report improvements of subjective and objective sleep parameters for different repetitive transcranial magnetic stimulation and transcranial electric stimulation protocols, important methodological limitations and risk of bias limit their interpretability. A forehead cooling study found no significant group differences in the primary endpoints, but better sleep initiation in the active condition. Two transcutaneous auricular vagus nerve stimulation trials found no superiority of active stimulation for most outcome measures. Although modulating sleep through brain stimulation appears feasible, gaps in the prevailing models of sleep physiology and insomnia pathophysiology remain to be filled. Optimized stimulation protocols and proof of superiority over reliable sham conditions are indispensable before brain stimulation becomes a viable treatment option for insomnia.
Topics: Adult; Humans; Sleep Initiation and Maintenance Disorders; Transcranial Magnetic Stimulation; Sleep; Polysomnography; Brain; Treatment Outcome
PubMed: 37202368
DOI: 10.1111/jsr.13927 -
JAMA Oncology Mar 2020In metastatic colorectal cancer, induction combination chemotherapy with a targeted agent is considered the mainstay of treatment. Multiple randomized clinical trials... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
In metastatic colorectal cancer, induction combination chemotherapy with a targeted agent is considered the mainstay of treatment. Multiple randomized clinical trials have examined different strategies of continuing cytotoxic therapy until progression compared with a period of either observation or the use of various maintenance agents. However, those randomized clinical trials have shown inconsistent efficacy results that make it challenging to draw any conclusion on which strategy is preferred. Therefore, a network meta-analysis is helpful to compare different agents across randomized clinical trials.
OBJECTIVE
To evaluate the comparative effectiveness of different treatment strategies for patients with metastatic colorectal cancer.
EVIDENCE REVIEW
MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were searched for randomized clinical trials evaluating different strategies for patients with previously untreated metastatic colorectal cancer. Trials of interest included those including patients with metastatic colorectal cancer who were treated with an initial period of cytotoxic chemotherapy (with or without a biologic) and then switched to one of the following strategies: observation; maintenance with bevacizumab (Bev), fluoropyrimidine (FP), or both (FP + Bev); or continuing the induction regimen until progression. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the DerSimonian and Laird random-effects model. Network meta-analysis was conducted using a random-effects consistency model to pool evidence from direct and indirect comparisons. Agents were ranked using surface under the cumulative ranking (SUCRA) probabilities. Higher SUCRA scores correspond to greater efficacy. Initial analysis was performed on December 18, 2018. An updated search was performed in April 2019, and no additional studies were added.
FINDINGS
Twelve trials at low risk of bias (5540 patients; age range, 23-85 years; 64.4 % male) were included. Network meta-analysis showed no benefit of continuing full cytotoxic chemotherapy until progression vs observation in terms of PFS (hazard ratio, 0.71; 95% CI, 0.46-1.09) and OS (hazard ratio, 0.95; 95% CI, 0.85-1.07). Compared with observation, maintenance therapy showed a PFS benefit (hazard ratio, 0.58; 95% CI, 0.43-0.77) but not an OS benefit (hazard ratio, 0.91; 95% CI, 0.83-1.01). All maintenance strategies (FP, FP + Bev, and Bev) showed significant improvement in PFS vs observation. On SUCRA analysis, maintenance treatment (FP or FP + Bev) had the highest likelihood of achieving improved PFS (67.1% for FP, 99.8% for FP + Bev, and 36.5% for Bev) and OS (81.3% for FP, 73.2% for FP + Bev, and 32.6% for Bev).
CONCLUSIONS AND RELEVANCE
For patients with metastatic colorectal cancer, there is no benefit to continuing the full induction regimen until progression, without a period of either observation or maintenance treatment. A maintenance strategy with a fluoropyrimidine, with or without the addition of bevacizumab, is preferred. However, given the lack of a clear OS benefit, shared decision-making should include observation as an acceptable alternative.
Topics: Colorectal Neoplasms; Humans; Maintenance Chemotherapy; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 31855256
DOI: 10.1001/jamaoncol.2019.4489