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Acta Oncologica (Stockholm, Sweden) Oct 2021For patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) for acute myeloid leukemia (AML), disease relapse remains the most common reason for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
For patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) for acute myeloid leukemia (AML), disease relapse remains the most common reason for transplant failure and patient death. Recent randomized controlled trials (RCTs) have aimed to reduce the risk of relapse by means of post-transplant maintenance therapy.
METHODS
We performed a systematic review and meta-analysis of RCTs comparing the efficacy and safety of maintenance with observation or placebo in patients with AML after allogeneic HSCT. We searched Cochrane Library, PubMed and conference proceedings up to Febuary 2021.
RESULTS
Our search yielded five trials including 736 patients. Maintenance therapy consisted of tyrosine kinase inhibitors (TKIs) in 3 studies (sorafenib 2 studies; midostaurin 1 study) and hypomethylating agents (HMAs) in 2 studies (decitabine and azacytidine 1 study each). Maintenance therapy was associated with an improved overall survival (OS), HR = 0.61 (95% CI 0.47-0.80). Subgroup analysis revealed advantage in OS with either TKI or HMA maintenance. Relapse free survival (RFS) was also improved in the maintenance arm compared with the control arm HR = 0.51(95% CI 0.40 - 0.66). There was no difference between the two arms in overall grade 3/4 adverse events or overall infections, in grade 3/4 infections, or in acute and chronic graft versus host disease.
CONCLUSIONS
Our meta-analysis shows that post-transplant maintenance therapy in AML patients is effective in improving RFS and OS, with a satisfactory safety profile.
Topics: Hematopoietic Stem Cell Transplantation; Humans; Leukemia, Myeloid, Acute; Recurrence; Sorafenib
PubMed: 34325602
DOI: 10.1080/0284186X.2021.1955969 -
Seminars in Oncology Oct 2022We performed an updated meta-analysis to explore the role of maintenance therapy in SCLC. Clinical trials with randomization to maintenance/consolidation (V) placebo or... (Meta-Analysis)
Meta-Analysis
We performed an updated meta-analysis to explore the role of maintenance therapy in SCLC. Clinical trials with randomization to maintenance/consolidation (V) placebo or observation or best supportive care in SCLC, both extended and limited disease were searched from January 2009 to March 2022. The hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) with the relative 95% confidence interval (CI) were extracted from each study. Summary HR was calculated using random- or fixed-effects models, depending on the heterogeneity of the included studies. A total of 9 studies were identified. Neither PFS nor OS were improved with maintenance/consolidation (PFS: random-effect; HR 0.93; 95% CI 0.71-1.21; P=0.10; OS: fixed-effect; HR 0.98; 95% CI 0.89-1.08; P=0.14). Among the different strategies, immunotherapy maintenance showed a significantly decreased risk of progression (V)standard of care (random-effect; HR 0.80; 95% CI 0.66-0.97; P=0.03). The current updated meta-analysis did not demonstrate a benefit of maintenance/consolidation therapy in SCLC, with only a PFS benefit for immunotherapy approach.
Topics: Humans; Lung Neoplasms; Consolidation Chemotherapy; Immunotherapy; Progression-Free Survival
PubMed: 36184311
DOI: 10.1053/j.seminoncol.2022.09.001 -
Sleep Medicine Reviews Apr 2024Diabetic retinopathy (DR) is one of the most prevalent microvascular diabetic complications. Poor sleep health and obstructive sleep apnea (OSA) are risk factors for... (Meta-Analysis)
Meta-Analysis Review
Diabetic retinopathy (DR) is one of the most prevalent microvascular diabetic complications. Poor sleep health and obstructive sleep apnea (OSA) are risk factors for diabetes and poor glycemic control. Recent studies have suggested associations between poor sleep health/OSA and DR. Furthermore, there have been suggestions of melatonin dysregulation in the context of DR. We conducted a systematic review and meta-analysis exploring the associations between multidimensional sleep health (duration, satisfaction, efficiency, timing/regularity and alertness), OSA and melatonin with DR. Forty-two studies were included. Long, but not short sleep, was significantly associated with DR, OR 1.41 (95%CI 1.21, 1.64). Poor sleep satisfaction was also significantly associated with DR, OR 2.04 (1.41, 2.94). Sleep efficiency and alertness were not associated with DR, while the evidence on timing/regularity was scant. Having OSA was significantly associated with having DR, OR 1.34 (1.07, 1.69). Further, those with DR had significantly lower melatonin/melatonin metabolite levels than those without DR, standardized mean difference -0.94 (-1.44, -0.44). We explored whether treating OSA with continuous positive airway pressure (CPAP) led to improvement in DR (five studies). The results were mixed among studies, but potential benefits were observed in some. This review highlights the association between poor multidimensional sleep health and DR.
Topics: Humans; Diabetic Retinopathy; Melatonin; Sleep; Risk Factors; Sleep Apnea, Obstructive; Sleep Initiation and Maintenance Disorders; Continuous Positive Airway Pressure; Diabetes Mellitus
PubMed: 38118339
DOI: 10.1016/j.smrv.2023.101891 -
International Journal of Colorectal... Mar 2023There is not enough information to position medications for the treatment of Crohn's disease (CD). Therefore, using a network meta-analysis and systematic review, we... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
There is not enough information to position medications for the treatment of Crohn's disease (CD). Therefore, using a network meta-analysis and systematic review, we evaluated the efficacy and safety of combination therapy and infliximab (IFX) monotherapy in CD patients.
METHODS
We identified randomized controlled trials (RCTs) in CD patients who were given IFX-containing combination therapy versus IFX monotherapy. Induction and maintenance of clinical remission were the efficacy outcomes, while adverse events were the safety outcomes. The surface under cumulative ranking (SUCRA) probabilities was used to assess ranking in the network meta-analysis.
RESULTS
In total, 15 RCTs with 1586 CD patients were included in this study. There was no statistical difference between different combination therapies in induction and maintenance of remission. In terms of inducing clinical remission, IFX + EN (SUCRA: 0.91) ranked highest; in terms of maintaining clinical remission, IFX + AZA (SUCRA: 0.85) ranked highest. There was no treatment that was significantly safer than the others. In terms of any adverse events, serious adverse events, serious infections, and infusion/injection-site reactions, IFX + AZA (SUCRA: 0.36, 0.12, 0.19, and 0.24) was ranked lowest for all risks; while IFX + MTX (SUCRA: 0.34, 0.06, 0.13, 0.08, 0.34, and 0.08) was rated lowest for risk of abdominal pain, arthralgia, headache, nausea, pyrexia, and upper respiratory tract infection.
CONCLUSION
Indirect comparisons suggested that efficacy and safety of different combination treatments are comparable in CD patients. For maintenance therapies, IFX + AZA was ranked highest for clinical remission and lowest for adverse events. Further head-to-head trials are required.
Topics: Humans; Infliximab; Crohn Disease; Immunosuppressive Agents; Network Meta-Analysis; Remission Induction
PubMed: 36971914
DOI: 10.1007/s00384-023-04378-w -
Archives of Physical Medicine and... Jul 2022To determine if improvements in cardiorespiratory fitness are maintained in the short-, medium- and long-term after a cardiorespiratory fitness intervention in people... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To determine if improvements in cardiorespiratory fitness are maintained in the short-, medium- and long-term after a cardiorespiratory fitness intervention in people with stroke.
DATA SOURCES
MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Embase, (CENTRAL) Cochrane, Web of Science, Sports Discus, and Physiotherapy Evidence Database were searched from inception.
STUDY SELECTION
Randomized controlled trials and cohort studies including (1) people with stroke; (2) cardiorespiratory fitness interventions; (3) a direct measure of cardiorespiratory fitness; and (4) short- (0 to <3 months), medium- (3-6 months), or long-term (>6 months) follow-up data.
DATA EXTRACTION
Two reviewers independently screened full texts and extracted data, including study methods, participant demographic information, stroke type and severity, outcome measures, intervention information, follow-up time points, and results, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A lower limit of -1.0 mL•kg•min was used to determine maintenance (ie, no change) of cardiorespiratory fitness.
DATA SYNTHESIS
Fourteen studies (N=324 participants) were included. Participants completed cardiorespiratory fitness training 2-5 days per week over 4-13 weeks at moderate to high intensity (40%-70% heart rate reserve [HRR]; n=4 studies), high intensity (60% to <90% HRR; n=7 studies), and intervals of high intensity (85%-95% peak heart rate or maximal heart rate; n=3 studies). Most people with stroke did maintain cardiorespiratory fitness in the short- (-0.19 mL•kg•min [95% CI, -1.66 to 1.28]), medium- (-0.61 mL•kg•min [95% CI, -3.95 to 2.74]), and long-term (0.00 mL•kg•min [95% CI, -2.23 to 2.23]) after completion of cardiorespiratory fitness interventions.
CONCLUSIONS
People with stroke maintain cardiorespiratory fitness after a cardiorespiratory fitness intervention in the short-, medium-, and longer-term. However, little is known about the impact of participant and intervention characteristics on the long-term maintenance of cardiorespiratory fitness.
Topics: Cardiorespiratory Fitness; Exercise Therapy; Humans; Stroke; Stroke Rehabilitation
PubMed: 35172177
DOI: 10.1016/j.apmr.2022.01.151 -
Efficacy and safety of biologic therapy in microscopic colitis: systematic review and meta-analysis.European Journal of Gastroenterology &... Oct 2022This systematic review and meta-analysis sought to evaluate the effectiveness and safety of biologic therapy in the treatment of steroid-refractory microscopic colitis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis sought to evaluate the effectiveness and safety of biologic therapy in the treatment of steroid-refractory microscopic colitis (MC).
METHODS
We searched MEDLINE, Embase, Web of Science, and Cochrane Central to identify articles and abstracts reporting efficacy or safety data on biologic use (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) for induction and maintenance of remission in MC. We assessed clinical remission and response rates and all reported adverse events (AEs).
RESULTS
A total of 376 studies were screened yielding 13 articles (including four abstracts) with a combined information on 78 patients for efficacy and safety outcomes. Most studies were case series. Vedolizumab was used in five studies, adalimumab in three, and a combination of infliximab and adalimumab in five studies. The rates of remission were 66.08% (95% CI, 36.79-95.37%; I2 , 71%) at weeks 3-6 and 54.20% (95% CI, 39.39-69.01%; I2 , 0%) at weeks 12-16. Clinical response rates were 100% (95% CI, 88.04-100%; I2 , 0%) at weeks 3-6 and 67.20% (95% CI, 47.72-86.69%; I2 , 52%) at weeks 12-16. Most frequent AE was medication discontinuation with a pooled incidence of 16.1% (95% CI, 5.9-37.5%). No deaths attributable to biologic use were reported. The overall quality of evidence was very low due to the high risk of biases.
CONCLUSION
Low-quality evidence supports the short-term efficacy of biologics in budesonide refractory MC. While our findings represent the most comprehensive evaluation of biologic therapy in severe MC, further research including randomized clinical trials is needed to better define the role of specific agents and long-term therapy.
Topics: Adalimumab; Biological Therapy; Colitis, Microscopic; Humans; Infliximab; Ustekinumab
PubMed: 36052677
DOI: 10.1097/MEG.0000000000002409 -
Sleep Medicine Apr 2023Despite improvements in survival rates, risk of recurrent events following stroke remains high. Identifying intervention targets to reduce secondary cardiovascular risk... (Meta-Analysis)
Meta-Analysis Review
Despite improvements in survival rates, risk of recurrent events following stroke remains high. Identifying intervention targets to reduce secondary cardiovascular risk in stroke survivors is a priority. The relationship between sleep and stroke is complex: sleep disturbances are likely both a contributor to, and consequence of, stroke. The current aim was to examine the association between sleep disturbance and recurrent major acute coronary events or all-cause mortality in the post-stroke population. Thirty-two studies were identified, including 22 observational studies and 10 randomized clinical trials (RCTs). Identified studies included the following as predictors of post-stroke recurrent events: obstructive sleep apnea (OSA, n = 15 studies), treatment of OSA with positive airway pressure (PAP, n = 13 studies), sleep quality and/or insomnia (n = 3 studies), sleep duration (n = 1 study), polysomnographic sleep/sleep architecture metrics (n = 1 study), and restless legs syndrome (n = 1 study). A positive relationship of OSA and/or OSA severity with recurrent events/mortality was seen. Findings on PAP treatment for OSA were mixed. Positive findings indicating a benefit of PAP for post-stroke risk came largely from observational studies (pooled RR [95% CI] for association between PAP and recurrent cardiovascular event: 0.37 [0.17-0.79], I = 0%). Negative findings came largely from RCTs (RR [95% CI] for association between PAP and recurrent cardiovascular event + death: 0.70 [0.43-1.13], I = 30%). From the limited number of studies conducted to date, insomnia symptoms/poor sleep quality and long sleep duration were associated with increased risk. Sleep, a modifiable behavior, may be a secondary prevention target to reduce the risk of recurrent event and death following stroke. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021266558.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Stroke; Sleep Apnea, Obstructive; Sleep; Continuous Positive Airway Pressure
PubMed: 36889030
DOI: 10.1016/j.sleep.2023.02.019 -
Arthritis Research & Therapy Nov 2023To determine the prevalence of sustained remission/low disease activity (LDA) in patients with rheumatoid arthritis (RA) after discontinuation of tumor necrosis factor...
Prevalence and predictors of sustained remission/low disease activity after discontinuation of induction or maintenance treatment with tumor necrosis factor inhibitors in rheumatoid arthritis: a systematic and scoping review.
BACKGROUND
To determine the prevalence of sustained remission/low disease activity (LDA) in patients with rheumatoid arthritis (RA) after discontinuation of tumor necrosis factor inhibitors (TNFi), separately in induction treatment and maintenance treatment studies, and to identify predictors of successful discontinuation.
METHODS
We performed a systematic literature review of studies published from 2005 to May 2022 that reported outcomes after TNFi discontinuation among patients in remission/LDA. We computed prevalences of successful discontinuation by induction or maintenance treatment, remission criterion, and follow-up time. We performed a scoping review of predictors of successful discontinuation.
RESULTS
Twenty-two induction-withdrawal studies were identified. In pooled analyses, 58% (95% confidence interval (CI) 45, 70) had DAS28 < 3.2 (9 studies), 52% (95% CI 35, 69) had DAS28 < 2.6 (9 studies), and 40% (95% CI 18, 64) had SDAI ≤ 3.3 (4 studies) at 37-52 weeks after discontinuation. Among patients who continued TNFi, 62 to 85% maintained remission. Twenty-two studies of maintenance treatment discontinuation were also identified. At 37-52 weeks after TNFi discontinuation, 48% (95% CI 38, 59) had DAS28 < 3.2 (10 studies), and 47% (95% CI 33, 62) had DAS28 < 2.6 (6 studies). Heterogeneity among studies was high. Data on predictors in induction-withdrawal studies were limited. In both treatment scenarios, longer duration of RA was most consistently associated with less successful discontinuation.
CONCLUSIONS
Approximately one-half of patients with RA remain in remission/LDA for up to 1 year after TNFi discontinuation, with slightly higher proportions in induction-withdrawal settings than with maintenance treatment discontinuation.
Topics: Humans; Antirheumatic Agents; Tumor Necrosis Factor Inhibitors; Prevalence; Tumor Necrosis Factor-alpha; Remission Induction; Arthritis, Rheumatoid; Treatment Outcome
PubMed: 37986101
DOI: 10.1186/s13075-023-03199-0 -
Alimentary Pharmacology & Therapeutics Aug 2021Loss of response to anti-TNF agents is a common clinical problem. Dose escalation may be effective for reestablishing clinical response in Crohn's disease (CD). (Review)
Review
BACKGROUND
Loss of response to anti-TNF agents is a common clinical problem. Dose escalation may be effective for reestablishing clinical response in Crohn's disease (CD).
AIMS
To perform a systematic review assessing the efficacy of escalated maintenance anti-TNF therapy in CD.
METHODS
EMBASE, MEDLINE, Web of Science, and CENTRAL databases were searched for English language publications through to April 25, 2021. Full-text articles evaluating escalated maintenance treatment (infliximab or adalimumab) in adult CD patients were included.
RESULTS
A total of 4733 records were identified, and 68 articles met eligibility criteria. Rates of clinical response (33%-100%) and remission (15%-83%) after empiric dose escalation for loss of response to standard anti-TNF therapy were high but varied across studies. Dose intensification strategies (doubling the dose versus shortening the therapeutic interval) were similarly efficacious. Dose-escalated patients tended to have higher serum drug levels compared to those on standard dosing. An exposure-response relationship following dose escalation was found in a number of observational studies. Randomised controlled trials comparing therapeutic drug monitoring (TDM) to empiric treatment intensification have failed to reach their primary end-points. Strategies including Bayesian dashboard-dosing and early treatment escalation targeting biomarker normalisation were found to be associated with improved long-term outcomes.
CONCLUSIONS
Empiric escalation of maintenance anti-TNF therapy can recapture clinical response in a majority of patients with secondary loss of response to standard maintenance doses. Proactive optimisation of maintenance dosing might prolong time to loss of response in some patients.
Topics: Adalimumab; Adult; Bayes Theorem; Crohn Disease; Humans; Infliximab; Remission Induction; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha
PubMed: 34153124
DOI: 10.1111/apt.16479 -
Scientific Reports Sep 2023To explore the efficacy and safety of fecal microbiota transplantation (FMT) as a treatment approach for ulcerative colitis (UC), a comprehensive systematic review and... (Meta-Analysis)
Meta-Analysis
To explore the efficacy and safety of fecal microbiota transplantation (FMT) as a treatment approach for ulcerative colitis (UC), a comprehensive systematic review and meta-analysis of randomized controlled trials was conducted. To collect and evaluate randomized controlled trials of high quality on FMT for UC, we searched a number of databases, including PubMed, Web of Science, Cochrane, Embase, and Medline, for studies published between the establishment of the databases and March 2023. We conducted a meta-analysis of the studies using Review Manager software (version 5.4.1) to determine the differences in rates of remission and adverse reactions between the FMT group and the control group, utilizing the risk ratio (RR) and 95% confidence interval (CI) to combine our findings. A total of 13 randomized controlled trials (RCTs) on the efficacy of FMT in patients with UC were included in the study, in which 580 patients participated, including 293 patients treated with FMT and 287 control subjects. Meta-analysis revealed that clinical remission was significantly better in the FMT group than in the control group [RR = 1.73; 95% CI = (1.41, 2.12); P < 0.00001]; endoscopic remission was significantly better in the FMT group than in the control group [RR = 1.74; 95% CI = (1.24, 2.44); P = 0.001]. Additionally, there were no significant differences in the incidence of adverse reactions between the two groups [RR = 1.00; 95% CI = (0.86, 1.15); P = 0.96]. Fecal microbiota transplantation has shown potential as a therapeutic intervention for inducing clinical remission in ulcerative colitis UC; nevertheless, the attainment of endoscopic remission and the maintenance of long-term remission continue to present challenges. Safety concerns persist throughout the treatment process, necessitating the implementation of measures to augment both safety and success rates.
Topics: Humans; Colitis, Ulcerative; Fecal Microbiota Transplantation; Databases, Factual; MEDLINE; Odds Ratio; Randomized Controlled Trials as Topic
PubMed: 37661203
DOI: 10.1038/s41598-023-41182-6