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BMC Public Health Jun 2024Owing to the introduction of highly active antiretroviral therapy (HAART), the trajectory of mortality and morbidity associated with human immunodeficiency virus (HIV)... (Meta-Analysis)
Meta-Analysis
Highly active antiretroviral therapy is necessary but not sufficient. A systematic review and meta-analysis of mortality incidence rates and predictors among HIV-infected adults receiving treatment in Ethiopia, a surrogate study for resource-poor settings.
BACKGROUND
Owing to the introduction of highly active antiretroviral therapy (HAART), the trajectory of mortality and morbidity associated with human immunodeficiency virus (HIV) infection has significantly decreased in developed countries. However, this remains a formidable public health challenge for people living with HIV in resource-poor settings. This study was undertaken to determine the pooled person-time incidence rate of mortality, analyze the trend, and identify predictors of survival among HIV-infected adults receiving HAART.
METHODS
Quantitative studies were searched in PubMed, Embase, Scopus, Google Scholar, African Journals Online, and Web of Science. The Joana Briggs Institute critical appraisal tool was used to assess the quality of the included articles. The data were analyzed using the random-effects Dersimonian-Laird model.
RESULTS
Data abstracted from 35 articles involving 39,988 subjects were analyzed. The pooled person-time incidence rate of mortality (all-cause) was 4.25 ([95% uncertainty interval (UI), 3.65 to 4.85]) per 100 person-years of observations. Predictors of mortality were patients aged ≥ 45 years (hazard ratio (HR), 1.70 [95% UI,1.10 to 2.63]), being female (HR, 0.82 [95% UI, 0.70 to 0.96]), history of substance use (HR, 3.10 [95% UI, 1.31 to 7.32]), HIV positive status non disclosure (HR, 3.10 [95% UI,1.31 to 7.32]), cluster of differentiation 4 + T cell - count < 200 cells/mm3 (HR, 3.23 [95% UI, [2.29 to 4.75]), anemia (HR, 2.63 [95% UI, 1.32 to 5.22]), World Health Organisation classified HIV clinical stages III and IV (HR, 3.02 [95% UI, 2.29 to 3.99]), undernutrition (HR, 2.24 [95% UI, 1.61 to 3.12]), opportunistic infections (HR, 1.89 [95% UI, 1.23 to 2.91]), tuberculosis coinfection (HR, 3.34 [95% UI, 2.33 to 4.81]),bedridden or ambulatory (HR,3.30 [95% UI, 2.29 to 4.75]), poor treatment adherence (HR, 3.37 [95% UI,1.83 to 6.22]), and antiretroviral drug toxicity (HR, 2.60 [95% UI, 1.82 to 3.71]).
CONCLUSION
Despite the early introduction of HAART in Ethiopia, since 2003, the mortality rate has remained high. Therefore, guideline-directed intervention of identified risk factors should be in place to improve overall prognosis and increase quality-adjusted life years.
Topics: Humans; HIV Infections; Antiretroviral Therapy, Highly Active; Ethiopia; Incidence; Adult; Female; Male
PubMed: 38943123
DOI: 10.1186/s12889-024-19268-1 -
The Oncologist Jun 2024There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due...
BACKGROUNDS
There is little evidence on the safety, efficacy, and survival benefit of restarting immune checkpoint inhibitors (ICI) in patients with cancer after discontinuation due to immune-related adverse events (irAEs) or progressive disease (PD). Here, we performed a meta-analysis to elucidate the possible benefits of ICI rechallenge in patients with cancer.
METHODS
Systematic searches were conducted using PubMed, Embase, and Cochrane Library databases. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and incidence of irAEs were the outcomes of interest.
RESULTS
Thirty-six studies involving 2026 patients were analyzed. ICI rechallenge was associated with a lower incidence of all-grade (OR, 0.05; 95%CI, 0.02-0.13, P < .05) and high-grade irAEs (OR, 0.37; 95%CI, 0.21-0.64, P < .05) when compared with initial ICI treatment. Though no significant difference was observed between rechallenge and initial treatment regarding ORR (OR, 0.69; 95%CI, 0.39-1.20, P = .29) and DCR (OR, 0.85; 95%CI, 0.51-1.40, P = 0.52), patients receiving rechallenge had improved PFS (HR, 0.56; 95%CI, 0.43-0.73, P < .05) and OS (HR, 0.55; 95%CI, 0.43-0.72, P < .05) than those who discontinued ICI therapy permanently. Subgroup analysis revealed that for patients who stopped initial ICI treatment because of irAEs, rechallenge showed similar safety and efficacy with initial treatment, while for patients who discontinued ICI treatment due to PD, rechallenge caused a significant increase in the incidence of high-grade irAEs (OR, 4.97; 95%CI, 1.98-12.5, P < .05) and a decrease in ORR (OR, 0.48; 95%CI, 0.24-0.95, P < .05).
CONCLUSION
ICI rechallenge is generally an active and feasible strategy that is associated with relative safety, similar efficacy, and improved survival outcomes. Rechallenge should be considered individually with circumspection, and randomized controlled trials are required to confirm these findings.
PubMed: 38940446
DOI: 10.1093/oncolo/oyae134 -
Frontiers in Oncology 2024To assess the efficacy and safety of nimotuzumab in combination with radiotherapy or chemoradiotherapy for locally advanced head and neck squamous cell carcinoma.
Nimotuzumab combined with radiotherapy+/- chemotherapy for definitive treatment of locally advanced squamous cell carcinoma of head and neck: a metanalysis of randomized controlled trials.
OBJECTIVES
To assess the efficacy and safety of nimotuzumab in combination with radiotherapy or chemoradiotherapy for locally advanced head and neck squamous cell carcinoma.
METHODS
Systematic searches were performed on PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biomedical Medicine, Wanfang, VIP databases. Seven eligible randomized controlled trials (n = 1012) were selected through rigorous inclusion and exclusion criteria.
RESULTS
A total of 1012 cases were included. including 508 (50.2%) in the nimotuzumab combination treatment group; There were 504 cases (49.8%) in the control group. The results of meta-analysis showed that the overall survival (Hazard Ratio [HR]=0.75, 95% Confidence Interval [CI]: 0.62-0.90, P<0.05), progression-free survival (HR=0.69, 95% CI: 0.54-0.87, P<0.05), complete response rate (Risk Ratio [RR]=1.52, 95% CI: 1.24-1.86, P<0.05), and objective response rate (RR=1.32, 95% CI: 1.17-1.48, P<0.05) were significantly improved in the nimotuzumab combination treatment group compared with the control group. In terms of the incidence of adverse effects, only the incidence of rash was the nimotuzumab combination group higher than in the treatment alone group, and there was no significant difference between the remaining adverse reactions (neutropenia, anemia, nausea/vomiting, mucositis, dermatitis, dysphagia).
CONCLUSION
Nimotuzumab combined with radiotherapy or chemoradiotherapy is more effective than radiotherapy alone or chemoradiotherapy in locally advanced squamous cell carcinoma of the head and neck, and the safety profile is controllable. Therefore, the addition of nimotuzumab to treatment is expected to be an effective treatment option for this disease. However, more prospective randomized controlled trials are needed to fully explore the effectiveness of this treatment in patients with locally advanced head and neck squamous cell carcinoma.
SYSTEMATIC REVIEW REGISTRATION
identifier PROSPERO (CRD: 42022383313).
PubMed: 38939342
DOI: 10.3389/fonc.2024.1380428 -
International Journal of Surgery... Jun 2024The aim was to explore the optimal neoadjuvant therapy strategy for resectable, borderline resectable, and locally advanced pancreatic cancer, in order to provide a... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparing upfront surgery with neoadjuvant treatments in patients with resectable, borderline resectable or locally advanced pancreatic cancer: a systematic review and network meta-analysis of randomized clinical trials.
BACKGROUND
The aim was to explore the optimal neoadjuvant therapy strategy for resectable, borderline resectable, and locally advanced pancreatic cancer, in order to provide a theoretical basis for the development of new neoadjuvant treatment protocols for clinical use.
PATIENTS AND METHODS
The authors reviewed literature titles and abstracts comparing three treatment strategies (neoadjuvant chemoradiotherapy, neoadjuvant chemotherapy, and upfront surgery) in PubMed, Embase, The Cochrane Library, Web of Science from 2009 to 2023 to estimate relative odds ratios for resection rate and hazard ratios (HRs) for overall survival (OS) in all include trials.
RESULTS
A total of nine studies involving 889 patients were included in the analysis. The treatment methods included upfront surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy followed by surgery. The network meta-analysis results demonstrated that neoadjuvant chemoradiotherapy followed by surgery was an effective approach in improving OS for resectable and borderline resectable pancreatic cancer (RPC) patients compared to upfront surgery (HR: 0.79, 95% CI: 0.64-0.98) and neoadjuvant chemotherapy (HR: 0.79, 95% CI: 0.64-0.98). Additionally, neoadjuvant chemoradiotherapy significantly increased the margin negative resection (R0) rate and pathological negative lymph node (pN0) rate in patients with resectable and borderline RPC. However, it is worth noting that neoadjuvant chemoradiotherapy increased the risk of grade 3 or higher treatment-related adverse events, including in patients with locally advanced pancreatic cancer.
CONCLUSIONS
The current evidence suggests that neoadjuvant chemoradiotherapy followed by surgery is the optimal choice for treating patients with resectable and borderline RPC. Future research should focus on optimizing neoadjuvant chemoradiotherapy regimens to effectively improve OS while reducing the occurrence of adverse events.
Topics: Humans; Pancreatic Neoplasms; Neoadjuvant Therapy; Network Meta-Analysis; Randomized Controlled Trials as Topic; Pancreatectomy
PubMed: 38935819
DOI: 10.1097/JS9.0000000000001313 -
Frontiers in Pharmacology 2024Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug...
Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.
PubMed: 38933670
DOI: 10.3389/fphar.2024.1377924 -
Human Vaccines & Immunotherapeutics Dec 2024Treating non-small-cell lung cancer (NSCLC) has gained increased importance in recent years due to the high mortality rate and dismal five-year survival rate. Immune... (Review)
Review
Treating non-small-cell lung cancer (NSCLC) has gained increased importance in recent years due to the high mortality rate and dismal five-year survival rate. Immune checkpoint inhibitors (ICI) are a promising approach with exceptional outcomes in NSCLC thanks to the antigenic nature of cells. Conversely, immune system over-stimulation with ICI is a double-edged sword that can lead to various negative effects ranging from mild to life-threatening. This review explores current breakthroughs in nanoparticle-based ICI and their limitations. The PubMed, Scopus and Web of Science were examined for relevant publications. Thirty-eight trials ( = 16,781) were included in the analyses. The mixed effects analyses on quantifying the treatment effect contributed significantly to the subgroups within studies for ICI treatment effect. Models confirmed ICI's higher impact on treatment effectivity and the decrease in respondents' mortality compared to conventional treatment regiments. ICI might be used as first-line therapy due to their proven effectiveness and safety profile.
Topics: Humans; Immune Checkpoint Inhibitors; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Immunotherapy; Nanoparticles; Treatment Outcome
PubMed: 38932682
DOI: 10.1080/21645515.2024.2365771 -
Journal of Clinical Medicine Jun 2024Mandibular defects resulting from oncological treatment pose significant aesthetic and functional challenges due to the involvement of bone and soft tissues. Immediate... (Review)
Review
Mandibular defects resulting from oncological treatment pose significant aesthetic and functional challenges due to the involvement of bone and soft tissues. Immediate reconstruction is crucial to address complications such as malocclusion, mandibular deviation, temporomandibular joint (TMJ) changes, and soft tissue retraction. These issues can lead to functional impairments, including difficulties in chewing, swallowing, and speech. The fibula flap is widely used for mandibular reconstruction due to its long bone segment and robust vascular supply, though it may not always provide adequate bone height for optimal dental rehabilitation. This systematic review aims to determine if the double-barreled fibula flap (DBFF) configuration is a viable alternative for mandibular reconstruction and to evaluate the outcomes of dental implants placed in this type of flap. This study adhered to the Cochrane Collaboration criteria and PRISMA guidelines and was registered on the International Platform of Registered Systematic Review and Meta-Analysis Protocols Database (INPLASY2023120026). We included clinical studies published in English, Spanish, or French that focused on adult patients undergoing segmental mandibulectomy followed by DBFF reconstruction and dental rehabilitation. Data sources included Medline/PubMed, the Cochrane Library, EMBASE, Scopus, and manual searches. Two reviewers independently screened and selected studies, with discrepancies resolved by a third reviewer. Data extraction captured variables such as publication year, patient demographics, number of implants, follow-up duration, flap survival, implant failure, and aesthetic outcomes. The risk of bias was assessed using the JBI appraisal tool, and the certainty of evidence was evaluated using the GRADE approach. A total of 17 clinical studies were included, evaluating 245 patients and 402 dental implants. The average patient age was 43.7 years, with a mean follow-up period of 34.3 months. Flap survival was high, with a 98.3% success rate and only four flap losses. The implant failure rate was low at 1.74%. Esthetic outcomes were varied, with only three studies using standardized protocols for evaluation. The overall certainty of evidence for flap survival was moderate, low for implant failure, and very low for aesthetics due to the subjective nature of assessments and variability in reporting. The primary limitations of the evidence included in this review are the observational design of the studies, leading to an inherent risk of bias, inconsistency in reporting methods, and imprecision in outcome measures. Additionally, the subjective nature of aesthetic evaluations and the variability in assessment tools further limit the reliability of the findings. The DBFF technique demonstrates excellent outcomes for mandibular reconstruction, with high flap survival and low implant failure rates, making it a viable option for dental rehabilitation. However, the evidence for aesthetic outcomes is less certain, highlighting the need for more rigorous and standardized research. This review supports the DBFF as a good alternative for mandibular reconstruction with successful dental implant integration, although further studies are needed to enhance the reliability of aesthetic evaluations.
PubMed: 38930078
DOI: 10.3390/jcm13123547 -
Children (Basel, Switzerland) Jun 2024Prior guidelines recommended maintaining normothermia following traumatic brain injury (TBI), but recent studies suggest therapeutic hypothermia as a viable option in... (Review)
Review
BACKGROUND
Prior guidelines recommended maintaining normothermia following traumatic brain injury (TBI), but recent studies suggest therapeutic hypothermia as a viable option in pediatric cases. However, some others demonstrated a higher mortality rate. Hence, the impact of hypothermia on neurological symptoms and overall survival remains contentious.
METHODS
We conducted a systematic review and meta-analysis to evaluate the effects of hypothermia on neurological outcomes in pediatric TBI patients. The PubMed/Medline, Scopus, and Web of Science databases were searched until 1 January 2024 and data were analyzed using appropriate statistical methods.
RESULTS
A total of eight studies, comprising nine reports, were included in this analysis. Our meta-analysis did not reveal significant differences in mortality (RR = 1.58; 95% CI = 0.89-2.82, = 0.055), infection (RR = 0.95: 95% CI = 0.79-1.1, = 0.6), arrhythmia (RR = 2.85: 95% CI = 0.88-9.2, = 0.08), hypotension (RR = 1.54: 95% CI = 0.91-2.6, = 0.10), intracranial pressure (SMD = 5.07: 95% CI = -4.6-14.8, = 0.30), hospital length of stay (SMD = 0.10; 95% CI = -0.13-0.3, = 0.39), pediatric intensive care unit length of stay (SMD = 0.04; 95% CI = -0.19-0.28, = 0.71), hemorrhage (RR = 0.86; 95% CI = 0.34-2.13, = 0.75), cerebral perfusion pressure (SMD = 0.158: 95% CI = 0.11-0.13, = 0.172), prothrombin time (SMD = 0.425; 95% CI = -0.037-0.886, = 0.07), and partial thromboplastin time (SMD = 0.386; 95% CI = -0.074-0.847, = 0.10) between the hypothermic and non-hypothermic groups. However, the heart rate was significantly lower in the hypothermic group (-1.523 SMD = -1.523: 95% CI = -1.81--1.22 < 0.001).
CONCLUSIONS
Our findings challenge the effectiveness of therapeutic hypothermia in pediatric TBI cases. Despite expectations, it did not significantly improve key clinical outcomes. This prompts a critical re-evaluation of hypothermia's role as a standard intervention in pediatric TBI treatment.
PubMed: 38929280
DOI: 10.3390/children11060701 -
Clinical & Translational Oncology :... Jun 2024This meta-analysis aims to evaluate the safety and efficacy of restarting immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC) after... (Review)
Review
Safety and efficacy of restarting immune checkpoint inhibitors in non-small cell lung cancer patients following immune-related adverse events: a systematic review and meta-analysis.
OBJECTIVE
This meta-analysis aims to evaluate the safety and efficacy of restarting immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC) after experiencing immune-related adverse events (irAEs).
METHODS
A comprehensive search of PubMed, Web of Science, Embase, and the Cochrane Library was conducted to identify studies investigating the safety and efficacy of restarting ICIs in NSCLC patients after irAEs. Outcome measures, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) after ICI restarting, were extracted. Meta-analysis was performed using the R meta-package.
RESULTS
Four studies involving a total of 326 subjects were included, comprising 137 patients who restarted ICI treatment after irAEs and 189 patients who did not restart ICI treatment. The results revealed that ICI restarting was associated with an increased ORR (OR = 2.36, 95% CI 1.49-3.84), prolonged PFS (HR = 0.60, 95% CI 0.42-0.86), and prolonged OS (HR = 0.65, 95% CI 0.43-0.99) compared to non-restarting. The incidence of irAEs after ICI restarting was 45% (95% CI 0.27-0.63).
CONCLUSION
Restarting ICI treatment after discontinuation due to previous irAEs appears to be a reasonable option for NSCLC patients. However, a comprehensive assessment of the potential benefits and risks to individual patients is crucial, and close monitoring of irAEs is warranted.
PubMed: 38922538
DOI: 10.1007/s12094-024-03529-x -
Dentistry Journal Jun 2024Short dental implants have been proposed as an alternative treatment option to bone regeneration procedures for the rehabilitation of resorbed alveolar ridges. The aim... (Review)
Review
Survival Rates of Short Dental Implants (≤6 mm) Used as an Alternative to Longer (>6 mm) Implants for the Rehabilitation of Posterior Partial Edentulism: A Systematic Review of RCTs.
Short dental implants have been proposed as an alternative treatment option to bone regeneration procedures for the rehabilitation of resorbed alveolar ridges. The aim of this paper was to systematically review randomized controlled trials (RCTs) comparing short implants (≤6 mm) and longer implants (>6 mm) in atrophic alveolar ridges in terms of implant survival rates, peri-implant marginal bone loss (MBL), prevalence of peri-implantitis and technical complications. A thorough electronic search was performed until September 2023. RCTs with follow-up of at least 1-year post-loading comparing short implants with rough surfaces to longer implants in the posterior jaws of systemically and periodontally healthy, partially edentulous adults were considered. Studies with incomplete information on the number of patients, follow-up or definition of "short implants" were excluded. The revised Cochrane risk-of-bias tool for randomized trials was used for Risk of bias assessment. Fixed-effects meta-analysis of the selected studies was applied to compare the outcome variables. Random-effect meta-analysis was performed, on the basis of within-study comparisons. In total, 16 articles were selected for meta-analysis and incorporated 408 short implants and 475 longer implants inserted in 317 and 388 patients, respectively. The survival rates of longer implants in pristine or augmented bone were significantly increased compared to short implants (95%CI: 2-5%, < 0.001). Standard-length implants displayed increased, although non-statistically significant MBL (95%CI: -0.17-0.04, > 0.05), and prevalence of peri-implantitis (95%CI: 0-5%, > 0.05). No statistically significant differences were observed between short and long implants in terms of technical complications (implant-level 95%CI: -4-6%, > 0.05). Short implants represent a promising alternative treatment option for the rehabilitation of posterior jaws to avoid additional bone augmentation procedures. Nonetheless, they should be selected cautiously due to a potentially limited survival rate compared to longer implants. A major limitation of this study is the variability in the included studies regarding sample size, patient profile, type of bone, loading protocol, definition of peri-implantitis, among others. This study received no external funding. The study protocol was registered in PROSPERO (CRD42023485514).
PubMed: 38920886
DOI: 10.3390/dj12060185