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Journal of Cachexia, Sarcopenia and... Jun 2024Regulatory agencies require evidence that endpoints correlate with clinical benefit before they can be used to approve drugs. Biomarkers are often considered surrogate... (Review)
Review
Regulatory agencies require evidence that endpoints correlate with clinical benefit before they can be used to approve drugs. Biomarkers are often considered surrogate endpoints. In cancer cachexia trials, the measurement of biomarkers features frequently. The aim of this systematic review was to assess the frequency and diversity of biomarker endpoints in cancer cachexia trials. A comprehensive electronic literature search of MEDLINE, Embase and Cochrane (1990-2023) was completed. Eligible trials met the following criteria: adults (≥18 years), prospective design, more than 40 participants, use of a cachexia intervention for more than 14 days and use of a biomarker(s) as an endpoint. Biomarkers were defined as any objective measure that was assayed from a body fluid, including scoring systems based on these assays. Routine haematology and biochemistry to monitor intervention toxicity were not considered. Data extraction was performed using Covidence, and reporting followed PRISMA guidance (PROSPERO: CRD42022276710). A total of 5975 studies were assessed, of which 52 trials (total participants = 6522) included biomarkers as endpoints. Most studies (n = 29, 55.7%) included a variety of cancer types. Pharmacological interventions (n = 27, 51.9%) were most evaluated, followed by nutritional interventions (n = 20, 38.4%). Ninety-nine different biomarkers were used across the trials, and of these, 96 were assayed from blood. Albumin (n = 29, 55.8%) was assessed most often, followed by C-reactive protein (n = 22, 42.3%), interleukin-6 (n = 16, 30.8%) and tumour necrosis factor-α (n = 14, 26.9%), the latter being the only biomarker that was used to guide sample size calculations. Biomarkers were explicitly listed as a primary outcome in six trials. In total, 12 biomarkers (12.1% of 99) were used in six trials or more. Insulin-like growth factor binding protein 3 (IGFBP-3) and insulin-like growth factor 1 (IGF-1) levels both increased significantly in all three trials in which they were both used. This corresponded with a primary outcome, lean body mass, and was related to the pharmacological mechanism. Biomarkers were predominately used as exploratory rather than primary endpoints. The most commonly used biomarker, albumin, was limited by its lack of responsiveness to nutritional intervention. For a biomarker to be responsive to change, it must be related to the mechanism of action of the intervention and/or the underlying cachexia process that is modified by the intervention, as seen with IGFBP-3, IGF-1 and anamorelin. To reach regulatory approval as an endpoint, the relationship between the biomarker and clinical benefit must be clarified.
Topics: Cachexia; Humans; Neoplasms; Biomarkers; Clinical Trials as Topic
PubMed: 38783477
DOI: 10.1002/jcsm.13491 -
Clinical and Experimental Medicine Oct 2023Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies that mostly affect the elderly and have poor prognoses. Mutations in... (Meta-Analysis)
Meta-Analysis
Efficacy of epigenetic agents for older patients with acute myeloid leukemia and myelodysplastic syndrome in randomized controlled trials: a systematic review and network meta-analysis.
Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies that mostly affect the elderly and have poor prognoses. Mutations in epigenetic regulatory genes cause AML/MDS through changes in DNA methylation and histone modifications. Some epigenetic agents are used in patients with AML and MDS. However, most studies have focused on azacitidine (AZA) or decitabine (DEC), and few studies have been conducted on combination therapies or other epigenetic therapies. This network meta-analysis (NMA) aimed to compare the efficacy of epigenetic agents overall in patients with AML and MDS. A systematic review and NMA of all available II-III phase randomized controlled trials (RCTs) comparing epigenetic agents were performed. The Embase and PubMed databases were searched for relevant studies. The Bayesian model was used in the NMA, and the surface under the cumulative ranking curve (SUCRA) was used to rank comparisons. The primary endpoint was overall survival (OS), and the secondary endpoints were complete response (CR) and partial response (PR). OS was extended by AZA + venetoclax (SUCRA 0.94) in patients with AML and MDS. DEC (SUCRA 0.78) relatively improved CR and PR. In this study, AZA-related treatment was relatively effective in improving the OS of patients with AML and MDS, and DEC-related treatment showed a relatively high effect on CR and PR. The protocol for this systematic review was registered with the International Prospective Register of Systematic Reviews (CRD42022303601).
Topics: Aged; Humans; Azacitidine; Epigenesis, Genetic; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Network Meta-Analysis; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Treatment Outcome
PubMed: 36964818
DOI: 10.1007/s10238-023-01041-0 -
BJA Open Dec 2022The use of high-flow nasal oxygen (HFNO) has the potential to improve patient safety by limiting hypoxaemia during gastrointestinal endoscopy. The degree of benefit is... (Review)
Review
BACKGROUND
The use of high-flow nasal oxygen (HFNO) has the potential to improve patient safety by limiting hypoxaemia during gastrointestinal endoscopy. The degree of benefit is not adequately established.
METHODS
English language literature searches of PubMed, Scopus, Web of Science, and Cochrane Library electronic databases were performed to identify randomised controlled trials comparing HFNO and conventional oxygen therapy (COT) for patients undergoing gastrointestinal endoscopy under deep sedation. The primary endpoint was the incidence of hypoxic events observed during endoscopic procedures. The secondary endpoints were the incidence of recourse to rescue manoeuvres, procedure interruption, and adverse events. A meta-analysis and a trial sequence analysis were performed.
RESULTS
A total of 2867 patients from six randomised controlled trials were considered. Desaturation was observed in 5.2% and 27.2% of patients receiving HFNO and COT, respectively. Desaturation <90% was observed in 1.8% and 12.6% of the patients receiving HFNO and COT, respectively. In the subgroup analysis, desaturation occurrence was lower during HFNO than during COT in non-obese patients (2.2% 25.2%) and obese patients (22.9% 43.3%). Desaturation occurrence was lower during maximum (3.6% 26.9%) and minimum (15.9% 29.8%) HFNO therapy than during COT. HFNO showed a lower recurrence to rescue manoeuvres rate (4.7% 34.3%), a lower procedure interruption rate (0.4% 6.7%), and a lower adverse events rate (18.7% 21%) than COT. A high level of heterogeneity between the studies precluded confidence in drawing inference from the meta-analysis.
CONCLUSIONS
The evidence reviewed suggests that compared with COT, HFNO has fewer hypoxaemic events during gastrointestinal endoscopy, but this may not apply to all patients and clinical scenarios.
PubMed: 37588780
DOI: 10.1016/j.bjao.2022.100098 -
Dermatology and Therapy Oct 2020To investigate the associations of alopecia areata (AA) with serum vitamin D and calcium levels. (Review)
Review
INTRODUCTION
To investigate the associations of alopecia areata (AA) with serum vitamin D and calcium levels.
METHODS
A systematic review of all relevant articles published up to February 2020 in PubMed, Embase, and Cochrane Library databases was conducted. Primary endpoints were serum 25-hydroxyvitamin D [25(OH)D] levels and vitamin D deficiency, and the secondary endpoint was serum calcium level. Odds ratio (OR) and standardized mean difference (SMD) with 95% CI across studies were analyzed.
RESULTS
Data on 1585 patients with AA and 1114 controls from 16 case-control studies and three cross-sectional studies were included in this meta-analysis. A pooled meta-analysis was conducted using the random-effects model because of inter-study heterogeneity (vitamin D level, I = 87.90%; vitamin D deficiency, I = 81.10%; serum calcium level, I = 83.80%). A combined analysis revealed that patients with AA had significantly lower mean serum 25(OH)D level compared with control (WMD - 9.08, 95% CI - 11.65, - 6.50, p < 0.001), and were more likely to have vitamin D deficiency (OR 4.14, 95% CI 2.34, 7.35, p < 0.001). However, the pooled analysis revealed that patients with AA did not have significantly lower serum calcium levels compared with control (WMD - 0.17, 95% CI - 0.40, 0.06, p = 0.143). Subgroup analysis suggested that matched control, mean age, and country might contribute to the heterogeneity of serum vitamin D level, while study design, matched control, and country might contribute to the heterogeneity of vitamin D deficiency.
CONCLUSION
Deficiency of serum 25(OH)D level, rather than calcium level, was present in patients with AA. Screening for vitamin D deficiency and vitamin D supplementation may be beneficial in the treatment of patients with AA.
PubMed: 32772238
DOI: 10.1007/s13555-020-00433-4 -
Cancers Feb 2024Stereotactic body radiotherapy (SBRT) is increasingly used to treat disease in the oligometastatic (OM) setting due to mounting evidence demonstrating its efficacy and... (Review)
Review
INTRODUCTION
Stereotactic body radiotherapy (SBRT) is increasingly used to treat disease in the oligometastatic (OM) setting due to mounting evidence demonstrating its efficacy and safety. Given the low population representation in prospective studies, we performed a systematic review and meta-analysis of outcomes of HNC patients with extracranial OM disease treated with SBRT.
METHODS
A systematic review was conducted with Cochrane, Medline, and Embase databases queried from inception to August 2022 for studies with extracranial OM HNC treated with stereotactic radiotherapy. Polymetastatic patients (>five lesions), mixed-primary cohorts failing to report HNC separately, lack of treatment to all lesions, nonquantitative endpoints, and other definitive treatments (surgery, conventional radiotherapy, and radioablation) were excluded. The meta-analysis examined the pooled effects of 12- and 24-month local control (LC) per lesion, progression-free survival (PFS), and overall survival (OS). Weighted random-effects were assessed using the DerSimonian and Laird method, with heterogeneity evaluated using the statistic and Cochran Qtest. Forest plots were generated for each endpoint.
RESULTS
Fifteen studies met the inclusion criteria (639 patients, 831 lesions), with twelve eligible for quantitative synthesis with common endpoints and sufficient reporting. Fourteen studies were retrospective, with a single prospective trial. Studies were small, with a median of 32 patients (range: 6-81) and 63 lesions (range: 6-126). The OM definition varied, with a maximum of two to five metastases, mixed synchronous and metachronous lesions, and a few studies including oligoprogressive lesions. The most common site of metastasis was the lung. Radiation was delivered in 1-10 fractions (20-70 Gy). The one-year LC (LC1), reported in 12 studies, was 86.9% (95% confidence interval [CI]: 79.3-91.9%). LC2 was 77.9% (95% CI: 66.4-86.3%), with heterogeneity across studies. PFS was reported in five studies, with a PFS1 of 43.0% (95% CI: 35.0-51.4%) and PFS2 of 23.9% (95% CI: 17.8-31.2%), with homogeneity across studies. OS was analyzed in nine studies, demonstrating an OS1 of 80.1% (95% CI: 74.2-85.0%) and OS2 of 60.7% (95% CI: 51.3-69.4%). Treatment was well tolerated with no reported grade 4 or 5 toxicities. Grade 3 toxicity rates were uniformly below 5% when reported.
CONCLUSIONS
SBRT offers excellent LC and promising OS, with acceptable toxicities in OM HNC. Durable PFS remains rare, highlighting the need for effective local or systemic therapies in this population. Further investigations on concurrent and adjuvant therapies are warranted.
PubMed: 38473213
DOI: 10.3390/cancers16050851 -
BMC Anesthesiology Apr 2019Airway management is crucial and, probably, even the most important key competence in anaesthesiology, which directly influences patient safety and outcome. However,...
Outcomes in video laryngoscopy studies from 2007 to 2017: systematic review and analysis of primary and secondary endpoints for a core set of outcomes in video laryngoscopy research.
BACKGROUND
Airway management is crucial and, probably, even the most important key competence in anaesthesiology, which directly influences patient safety and outcome. However, high-quality research is rarely published and studies usually have different primary or secondary endpoints which impedes clear unbiased comparisons between studies. The aim of the present study was to gather and analyse primary and secondary endpoints in video laryngoscopy studies being published over the last ten years and to create a core set of uniform or homogeneous outcomes (COS).
METHODS
Retrospective analysis. Data were identified by using MEDLINE® database and the terms "video laryngoscopy" and "video laryngoscope" limited to the years 2007 to 2017. A total of 3351 studies were identified by the applied search strategy in PubMed. Papers were screened by two anaesthesiologists independently to identify study endpoints. The DELPHI method was used for consensus finding.
RESULTS
In the 372 studies analysed and included, 49 different outcome categories/columns were reported. The items "time to intubation" (65.86%), "laryngeal view grade" (44.89%), "successful intubation rate" (36.56%), "number of intubation attempts" (23.39%), "complications" (21.24%), and "successful first-pass intubation rate" (19.09%) were reported most frequently. A total of 19 specific parameters is recommended.
CONCLUSIONS
In recent video laryngoscopy studies, many different and inhomogeneous parameters were used as outcome descriptors/endpoints. Based on these findings, we recommend that 19 specific parameters (e.g., "time to intubation" (inserting the laryngoscope to first ventilation), "laryngeal view grade" (C&L and POGO), "successful intubation rate", etc.) should be used in coming research to facilitate future comparisons of video laryngoscopy studies.
Topics: Clinical Trials as Topic; Endpoint Determination; Humans; Laryngoscopes; Laryngoscopy; Treatment Outcome; Video-Assisted Surgery
PubMed: 30947694
DOI: 10.1186/s12871-019-0716-8 -
Journal of Clinical Anesthesia May 2024In labor, programmed intermittent epidural bolus (PIEB) can be defined as the bolus administration of epidural solution at scheduled time intervals. Compared to... (Meta-Analysis)
Meta-Analysis Review
Influence of different volumes and frequency of programmed intermittent epidural bolus in labor on maternal and neonatal outcomes: A systematic review and network meta-analysis.
STUDY OBJECTIVE
In labor, programmed intermittent epidural bolus (PIEB) can be defined as the bolus administration of epidural solution at scheduled time intervals. Compared to continuous epidural infusion (CEI) with or without patient controlled epidural analgesia (PCEA), PIEB has been associated with decreased pain scores and need for rescue analgesia and increased maternal satisfaction. The optimal volume and dosing interval of PIEB, however, has still not been determined.
DESIGN
Systematic review and network meta-analysis registered with PROSPERO (CRD42022362708).
SETTINGS
Labor.
PATIENTS
Pregnant patients.
INTERVENTIONS
Central, CINAHL, Global Health, Ovid Embase, Ovid Medline and Web of Science were searched for randomized controlled trials that examined pregnant patients in labor who received CEI or PIEB with or without a PCEA component. Network meta-analysis was performed with a frequentist method, facilitating the indirect comparison of PIEB with different volumes and dosing intervals through the common comparator of CEI and substituting or supplementing direct comparisons with these indirect ones. Continuous and dichotomous outcomes were presented as mean differences and odds ratios, respectively, with 95% confidence intervals. The risk of bias was evaluated using the Cochrane risk of bias 2 tool.
MAIN RESULTS
Overall, 30 trials were included. For the first primary endpoint, need for rescue analgesia, PIEB delivered at a volume of 4 ml and frequency of 45 min (4/45) was inferior to PIEB 8/45 (OR 3.55; 95% CI 1.12-11.33), PIEB 10/60 was superior to PIEB 2.5/15 (OR 0.36; 95% CI 0.16-0.82), PIEB 4/45 (OR 0.14; 95% CI 0.03-0.71) and PIEB 5/60 (OR 0.23; 95% CI 0.08-0.70), and PIEB 5/30 was not inferior to PIEB 10/60 (OR 0.61; 95% CI 0.31-1.19). For the second primary endpoint, maternal satisfaction, no differences were present between the various PIEB regimens. The quality of evidence for these multiple primary endpoints was low owing to the presence of serious limitations and imprecision. Importantly, PIEB 5/30 decreased the pain score at 4 h compared to PIEB 2.5/15 (MD 2.45; 95% CI 0.13-4.76), PIEB 5/60 (MD -2.28; 95% CI -4.18--0.38) and PIEB 10/60 (MD 1.73; 95% CI 0.31-3.16). Mean ranking of interventions demonstrated PIEB 10/60 followed by PIEB 5/30 to be best placed to reduce the cumulative dose of local anesthetic, and this resulted in an improved incidence of lower limb motor blockade for PIEB 10/60 in comparison to CEI (OR 0.30; 95% CI 0.14-0.67). No differences in neonatal outcomes were found. Some concerns were present for the risk of bias in two thirds of trials and the risk of bias was shown to be high in the remaining one third of trials.
CONCLUSIONS
Future research should focus on PIEB 5/30 and PIEB 10/60 and how the method of analgesia initiation, nature and concentration of local anesthetic, design of epidural catheter and rate of administration might influence outcomes related to the mother and neonate.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Anesthetics, Local; Network Meta-Analysis; Labor, Obstetric; Analgesia, Epidural; Analgesia, Patient-Controlled; Pain; Analgesia, Obstetrical
PubMed: 38176084
DOI: 10.1016/j.jclinane.2023.111364 -
Journal of Robotic Surgery Oct 2023The number of robotic hiatal hernia repairs (RHHR) is increasing. However, the superiority of this minimally invasive approach remains controversial. The aim of this... (Meta-Analysis)
Meta-Analysis Review
The number of robotic hiatal hernia repairs (RHHR) is increasing. However, the superiority of this minimally invasive approach remains controversial. The aim of this study was to evaluate the available literature reporting on outcomes of RHHR compared with laparoscopic hiatal hernia repair (LHHR) in adult patients. The design of this systematic review was developed using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Web of Science, PubMed, the Cochrane Library, and ClinicalTrials.gov databases were searched. Identified publications were reviewed independently by two authors. High heterogeneity was further explored through sensitivity analysis. The primary endpoint was the development of postoperative complications. Secondary endpoints included operation time, intraoperative complications, 30 day readmission rates and length of stay. The analysis was performed using Stata 17.0 software. A total of 7 studies totaling 10078 patients met the inclusion criteria. Five studies included postoperative complications. The postoperative complications rate was 4.25% (302/7111) in the LHHR group, and 3.49% (38/1088) in the RHHR group. Postoperative complications significantly decreased after RHHR compared with LHHR (OR 0.52; 95% CI 0.36 to 0.75, P = 0.000). Three studies involving 2176 patients reported length of hospital stay. In the three studies, the mean Length of hospital stay was 3.2 days in the RHHR group, and 4.2 days in the LHHR group. Length of hospital stay was decreased by a mean of 0.68 days for RHHR compared with LHHR (WMD, - 0.68 days; 95% CI - 1.32 to - 0.03, P = 0.02). There was no significant difference between the RHHR group and the LHHR group regarding operative time, intraoperative complications, and 30 day readmission (P > 0.05). Our research shows that RHHR may be the better option, as the approach decreases postoperative complications and length of hospital stay.
Topics: Adult; Humans; Herniorrhaphy; Robotic Surgical Procedures; Laparoscopy; Intraoperative Complications; Postoperative Complications; Length of Stay; Hernia, Hiatal
PubMed: 37247119
DOI: 10.1007/s11701-023-01636-5 -
Transplantation May 2009The risk of graft failure is the pivotal measure of effectiveness when evaluating immunosuppressive regimens for renal transplantation. However, to date most randomized... (Review)
Review
BACKGROUND
The risk of graft failure is the pivotal measure of effectiveness when evaluating immunosuppressive regimens for renal transplantation. However, to date most randomized trials of immunosuppressive therapy have had acute rejection as the primary endpoint for treatment comparisons. The objective here was to review the evidence relating acute rejection to renal graft function and graft survival.
METHODS
A systematic review of the published literature was undertaken. Studies were reviewed if they included the following: study populations of adults undergoing renal transplantation, endpoints of graft loss or survival, and quantitative data on the associations between acute rejection and graft function and survival.
RESULTS
Overall, 31 observational studies were included. The definition of acute rejection varied, and there was substantial heterogeneity in study design and methodology. In all but two studies, acute rejection was associated with an increased risk of graft loss-risk ratios ranged from 1.2 (no definition reported) to 10.5 (confirmed by biopsy and grade I Banff criteria). In addition, there was fairly strong evidence linking timing of acute rejection and graft survival and weaker evidence linking the number of episodes and graft survival. The heterogeneity between studies invalidated pooling of quantitative studies.
CONCLUSIONS
The weight of the evidence indicates that occurrence, timing, and number of acute rejection episodes are associated with increased risk of graft loss. Less is known about the severity of rejection, which is important because many immunosuppressive regimens lessen severity. Quantifying these relationships is a priority if acute rejection continues to be a surrogate trial endpoint.
Topics: Graft Rejection; Graft Survival; Humans; Immunosuppression Therapy; Kidney Diseases; Kidney Transplantation; Postoperative Complications; Risk Factors
PubMed: 19424033
DOI: 10.1097/TP.0b013e3181a236e0 -
Wideochirurgia I Inne Techniki... Dec 2022Imaging-guided percutaneous ablation (PA) is commonly employed for the treatment of patients diagnosed with adrenal metastasis (AM), but comprehensive analyses are...
INTRODUCTION
Imaging-guided percutaneous ablation (PA) is commonly employed for the treatment of patients diagnosed with adrenal metastasis (AM), but comprehensive analyses are essential to validate the efficacy and safety of this approach.
AIM
The present meta-analysis was designed to evaluate the safety, efficacy, and long-term outcomes associated with the imaging-guided PA treatment of AM.
MATERIAL AND METHODS
Relevant studies in the PubMed, Embase, and Wanfang databases published as of June 2022 were identified, and pooled endpoint analyses were performed with Stata 12.0.
RESULTS
This meta-analysis included 15 studies. Overall, the respective pooled primary technical success, secondary technical success, local hemorrhage, pneumothorax, hypertension crisis, local recurrence, 1-year overall survival (OS), and 3-year OS rates in study participants were 88%, 93%, 3%, 6%, 6%, 19%, 80%, and 46%. High levels of heterogeneity were evident for the 1-year OS (I = 79.6%) and 3-year OS endpoints (I = 67.1%), but meta-regression analyses failed to identify predictors of these OS rates. Low heterogeneity was observed for subgroups of patients who had undergone cryoablation (I = 0%) or patients with multiple primary cancers (I = 0%) with respect to 1-year OS. Similarly, low heterogeneity for the 3-year OS endpoint was detected in subgroups of patients who had undergone cryoablation (I = 0%), ultrasound-guided PA (I = 0%), individuals with AMs secondary to hepatocellular carcinoma (I = 0%), and patients with multiple primary cancers (I = 0%).
CONCLUSIONS
These results suggest imaging-guided PA to be a safe and effective treatment for AM associated with satisfactory long-term patient outcomes.
PubMed: 36818506
DOI: 10.5114/wiitm.2022.119585