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Diseases (Basel, Switzerland) Apr 2024This systematic review critically evaluates the impact of systemic treatments on outcomes and quality of life (QoL) in patients with RAS-positive stage IV colorectal... (Review)
Review
This systematic review critically evaluates the impact of systemic treatments on outcomes and quality of life (QoL) in patients with RAS-positive stage IV colorectal cancer, with studies published up to December 2023 across PubMed, Scopus, and Web of Science. From an initial pool of 1345 articles, 11 relevant studies were selected for inclusion, encompassing a diverse range of systemic treatments, including panitumumab combined with FOLFOX4 and FOLFIRI, irinotecan paired with panitumumab, regorafenib followed by cetuximab ± irinotecan and vice versa, and panitumumab as a maintenance therapy post-induction. Patient demographics predominantly included middle-aged to elderly individuals, with a slight male predominance. Racial composition, where reported, showed a majority of Caucasian participants, highlighting the need for broader demographic inclusivity in future research. Key findings revealed that the addition of panitumumab to chemotherapy (FOLFOX4 or FOLFIRI) did not significantly compromise QoL while notably improving disease-free survival, with baseline EQ-5D HSI mean scores ranging from 0.76 to 0.78 and VAS mean scores from 70.1 to 74.1. Improvements in FACT-C scores and EQ-5D Index scores particularly favored panitumumab plus best supportive care in KRAS wild-type mCRC, with early dropout rates of 38-42% for panitumumab + BSC. Notably, cetuximab + FOLFIRI was associated with a median survival of 25.7 months versus 16.4 months for FOLFIRI alone, emphasizing the potential benefits of integrating targeted therapies with chemotherapy. In conclusion, the review underscores the significant impact of systemic treatments, particularly targeted therapies and their combinations with chemotherapy, on survival outcomes and QoL in patients with RAS-positive stage IV colorectal cancer, and the need for personalized treatment.
PubMed: 38667537
DOI: 10.3390/diseases12040079 -
Acta Oto-laryngologica Mar 2024Larynx transplantation has been successfully performed four times, in 1998, 2010, 2015 and 2023 remained the ultimate goal of voice, feeding and breathing rehabilitation. (Review)
Review
BACKGROUNDS
Larynx transplantation has been successfully performed four times, in 1998, 2010, 2015 and 2023 remained the ultimate goal of voice, feeding and breathing rehabilitation.
OBJECTIVE
Immunosuppressive protocols used during the previous successful larynx allotransplantation are detailed.
MATERIAL AND METHODS
A systematic review of the literature on PUBMED/Medline, Cochrane and Embase was conducted. Articles relating to actual human larynx transplantations were included.
RESULTS
Bibliography search gathered = 10 publications related to the performance and follow-up of human laryngeal transplantations. = 8 publications were included corresponding to = 3 actual human larynx transplantations performed in 1998 and 2010 in the USA and in 2015 in Poland. Immunosuppression protocols, induction and maintenance strategies, rejection monitoring and history of all the three previous laryngeal grafts were detailed.
CONCLUSIONS
Beyond the surgical prowess, larynx transplantation is feasible and associated with a reasonably successful outcome when compared to other solid organ transplants. Immunosuppressive regimen protocols and technologies for the monitoring of the organ viability have evolved.
SIGNIFICANCE
The reevaluation of this surgical option serves as the reminder of the critical necessity to implement a meticulous immunosuppression protocol when transplanting this inherently immunogenic composite organ, the larynx.
Topics: Humans; Larynx; Immunosuppressive Agents; Immunosuppression Therapy; Graft Rejection
PubMed: 38662869
DOI: 10.1080/00016489.2024.2339341 -
Cancer Medicine Apr 2024Sleep disorders are often complained by cancer patients and can last years after the end of therapies, leading to different negative consequences. Non-pharmacological... (Meta-Analysis)
Meta-Analysis Review
Effects of resistance training on sleep quality and disorders among individuals diagnosed with cancer: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Sleep disorders are often complained by cancer patients and can last years after the end of therapies, leading to different negative consequences. Non-pharmacological strategies such as exercise interventions may be considered to counteract this phenomenon. The literature supports the beneficial effects of aerobic training (AT), while evidence on resistance training (RT) is scarce. Accordingly, our systematic review aims to investigate the potential novel effect of RT on sleep outcomes in cancer survivors.
METHODS
The literature search was conducted on MEDLINE (Pubmed), Web of Science, Scopus, and Cochrane Central Register of Controlled Trials databases, including only randomized controlled trials (RCTs). The screening procedure was conducted using the web-based software COVIDENCE. Sleep outcomes assessed through self-reported questionnaires or objective sleep measurements were extracted from RCTs recruiting cancer survivors of any age and gender, on or off treatment. The risk of bias (RoB) for each study was assessed using the Cochrane RoB 2 tool for RCTs. Meta-analytic syntheses were performed on sleep quality and insomnia.
RESULTS
A total of 21 studies were included in the review. Considering the mean percentage differences of all studies combined, promising positive results were found after combined aerobic and resistance exercise program (COMB) for sleep quality (-19%) and sleep disturbance (-17.3%). The meta-analysis results showed significant improvement for both sleep quality and insomnia (d = 0.28, SE: 0.11, Z = 2.51, p < 0.01, 95% CI: 0.07-0.49 and d = 0.43, SE: 0.20, Z = 2.18, p = 0.029, 95% CI: 0.07-0.49, respectively).
CONCLUSION
RT interventions of 60 minutes per session, performed 2-3 times a week for 12 weeks, with exercise intensity ranging from 60% to 80% of one-repetition maximum can be administered to cancer survivors, aiming to improve sleep outcomes.
Topics: Humans; Resistance Training; Neoplasms; Randomized Controlled Trials as Topic; Cancer Survivors; Sleep Quality; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders; Male; Female
PubMed: 38650577
DOI: 10.1002/cam4.7179 -
Seizure May 2024To compare the efficacy, safety, and tolerability of cenobamate with other newer anti-seizure medications (ASMs) including brivaracetam, eslicarbazepine, lacosamide,... (Meta-Analysis)
Meta-Analysis Comparative Study Review
PURPOSE
To compare the efficacy, safety, and tolerability of cenobamate with other newer anti-seizure medications (ASMs) including brivaracetam, eslicarbazepine, lacosamide, perampanel, and zonisamide, approved for adjunctive treatment of drug-resistant focal-onset seizures (FOS) in adults with epilepsy.
METHODS
A systematic literature review (SLR) was conducted to obtain relevant efficacy, safety, and tolerability data for ASMs for the treatment of drug-resistant FOS. All studies were thoroughly assessed for potential sources of heterogeneity and analysed via Bayesian network meta-analyses (NMAs). Efficacy outcomes were ≥50 % responder rate and seizure freedom during the maintenance period, which were modelled simultaneously using a multinomial Bayesian NMA. Safety and tolerability outcomes were the proportion of patients who experienced at least one treatment-emergent adverse event (TEAE) and the proportion who experienced at least one TEAE leading to discontinuation.
RESULTS
The SLR identified 76 studies, of which 23 were included in the Bayesian NMAs. Cenobamate was associated with statistically significant higher rates for the ≥50 % responder rate and seizure freedom outcomes compared with all ASMs analysed. The point estimates indicated that cenobamate was associated with higher rates of experiencing at least one TEAE and at least one TEAE leading to discontinuation compared with brivaracetam, lacosamide, and zonisamide; however, no results were statistically significant.
CONCLUSION
Cenobamate was associated with increased efficacy compared with all ASMs analysed. There were no statistically significant differences in the safety and tolerability outcomes. The results presented corroborate the conclusions drawn from previous published NMAs, which also highlight the notable efficacy of cenobamate in comparison with other ASMs.
Topics: Humans; Anticonvulsants; Network Meta-Analysis; Seizures; Carbamates; Epilepsies, Partial; Chlorophenols; Tetrazoles
PubMed: 38643679
DOI: 10.1016/j.seizure.2024.04.004 -
European Neuropsychopharmacology : the... Jul 2024Binge eating disorder (BED) is the most prevalent eating disorder. Treatment options include pharmacotherapy as well as psychotherapy, with the latter recommended as a... (Meta-Analysis)
Meta-Analysis
Binge eating disorder (BED) is the most prevalent eating disorder. Treatment options include pharmacotherapy as well as psychotherapy, with the latter recommended as a first-line option. However, the use of psychotherapeutic interventions poses several challenges. Antidepressants are easily accessible, but they lack robust evidence-base. This systematic review aims to comprehensively examine the efficacy and safety of antidepressants for the treatment of BED. Five databases were searched for randomized controlled trials (RCTs) comparing antidepressants vs. placebo in BED until 23/11/2023. Pairwise meta-analytic evaluations were performed. The primary outcomes were remission and binge eating frequency. Secondary outcomes were response to treatment, eating psychopathology, depression, anxiety, body weight, Body Mass Index (BMI), all-cause discontinuation, discontinuation due to adverse effects and total adverse events. Sixteen RCTs with a total of 984 participants were meta-analysed. Antidepressants were more effective than placebo in achieving remission (RR: 1.39, 95 % CI: 1.04 to 1.86) and in reducing binge eating episodes (SMD: -0.29, 95 % CI: -0.51 to -0.06). Similarly, in the secondary outcomes of response and depression, antidepressants demonstrated superiority over placebo. Antidepressants appear to be effective in reducing symptoms of BED. Small samples and effect sizes hinder the generalizability and clinical utility of these results. There is a lack of follow-up findings regarding the maintenance of effects. There is a pressing need for more RCTs examining antidepressants and other types of pharmacotherapy. Future research should include larger number of participants and increase the duration of follow-up.
Topics: Humans; Antidepressive Agents; Binge-Eating Disorder; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 38642437
DOI: 10.1016/j.euroneuro.2024.03.006 -
Hand Surgery & Rehabilitation Jun 2024The most common symptom and reason patients seek treatment for carpal tunnel syndrome is lack of sleep. Our purpose was to determine how much sleep-related symptoms of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The most common symptom and reason patients seek treatment for carpal tunnel syndrome is lack of sleep. Our purpose was to determine how much sleep-related symptoms of carpal tunnel syndrome improve after carpal tunnel release using validated patient-reported outcome measures (PROMs) and objective sleep data as primary measures of interest.
METHODS
A PRISMA-guided literature search was conducted using Ovid MEDLINE, PubMed, Cochrane, and ClinicalTrials.gov. Only interventional clinical trials that examined primary outcome measures of interest were included. Patient-reported outcome measures underwent meta-analysis to determine how much scores improved following carpal tunnel release.
RESULTS
The Pittsburgh Sleep Quality Index improved significantly after carpal tunnel release, by 4.43 points and 6.02 points at 1-3 and 6-12 months postoperatively, respectively, and continued to improve up to 2 years. Improvement on the Insomnia Severity Index after carpal tunnel release was also significant, with improvement up to 1 year postoperatively, by 8.54 points and 9.05 points at 1-3 and 6-12 months, respectively. Insomnia Severity Index scores improved significantly after splinting as well.
CONCLUSIONS
The present meta-analysis determined to what extent patients can expect their sleep to improve after operative and non-operative intervention, as measured by various patient-reported outcome measures that assess sleep. The Pittsburgh Sleep Quality Index and Insomnia Severity Index correlated very well between studies and across hundreds of patients with carpal tunnel syndrome. Data are lacking to define the minimal clinically important difference and assess whether patients achieve a minimal clinically important difference for sleep questionnaires; more information on this topic is needed.
LEVEL OF EVIDENCE
III.
Topics: Carpal Tunnel Syndrome; Humans; Patient Reported Outcome Measures; Sleep Quality; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders; Decompression, Surgical
PubMed: 38641062
DOI: 10.1016/j.hansur.2024.101698 -
International Endodontic Journal Aug 2024Microorganisms colonizing the apical root canal system are conceivably the ones directly involved with the causation and maintenance of apical periodontitis. (Review)
Review
BACKGROUND
Microorganisms colonizing the apical root canal system are conceivably the ones directly involved with the causation and maintenance of apical periodontitis.
OBJECTIVES
This article systematically reviews the reports on the microbiome occurring exclusively at the apical root canal of teeth with primary and posttreatment apical periodontitis.
METHODS
The electronic databases PubMed, Embase, Web of Science, Science Direct, and Proquest were searched up to August 2023. Clinical studies using culture and molecular microbiology methods to identify the microbial taxa present exclusively in the apical root canal segment of infected teeth with apical periodontitis were included. Studies were critically assessed using the Joanna Briggs Institute Critical Prevalence Assessment Checklist.
RESULTS
From 2277 articles initially detected, 52 were selected for full reading and 21 were eventually included in this review. Of these, molecular methods were used in 19 and culture in 2 studies. Ten studies evaluated primary infections, 8 evaluated posttreatment infections, and 3 included both. Cryopulverization of the apical root specimens was conducted in 11 studies. All studies evaluated the prevalence and diversity of bacteria, and only one also reported on fungi. Overall, the most frequent/abundant bacterial taxa found in the apical canal of primary infections were Pseudoramibacter alactolyticus, Olsenella uli, Fusobacterium species, Streptococcus species, Porphyromonas endodontalis, Prevotella species, Actinomyces species, Parvimonas micra, Treponema denticola, Synergistetes species, and an as-yet uncharacterized taxon. In posttreatment infections, the most prevalent/abundant bacterial taxa included species of Streptococcus, Enterococcus, Fusobacterium, Actinomyces, Pseudoramibacter, Pseudomonas, and Propionibacterium. At the phylum level, Firmicutes was the most represented. The average apical bacterial load ranged from 10 to 10 in primary infections and from 10 to 10 in posttreatment infections.
DISCUSSION
Microbial diversity in the apical part of the root canal system was examined encompassing data from both primary and posttreatment infections. Heterogeneity amongst the studies, especially in sample collection and microbial identification methods, is an important limitation that prevented a meta-analysis.
CONCLUSIONS
There is a pronounced bacterial diversity in the infected apical canal, with a high interindividual variability. Different microbiome compositions at the species/genus level are observed according to the infection type.
REGISTRATION
PROSPERO CRD42021275886.
Topics: Periapical Periodontitis; Humans; Microbiota; Dental Pulp Cavity; Bacteria
PubMed: 38634795
DOI: 10.1111/iej.14071 -
Frontiers in Neurology 2024Immune checkpoint inhibitors (ICI)-induced myasthenia gravis (MG) is an uncommon but potentially fatal neurotoxicity. We aim to help physicians familiarize themselves...
BACKGROUND
Immune checkpoint inhibitors (ICI)-induced myasthenia gravis (MG) is an uncommon but potentially fatal neurotoxicity. We aim to help physicians familiarize themselves with the clinical characteristics of ICI-induced MG, facilitating early diagnosis and prompt intervention.
METHODS
We searched the Chinese People's Liberation Army General Hospital medical record system from January 2017 to August 2023 for patients diagnosed with ICI-induced MG. We systematically reviewed the literature until August 2023 to identify all similar patients. We collected clinical information on these patients.
RESULTS
110 patients were identified, 9 from our institution and 101 from case reports. In our institution, Median age was 66 years (range: 49-79 years). 6 were males. The most common was lung cancer ( = 4). All patients had no previous history of MG and received PD-1 or PD-L1 inhibitors. The median time from ICI initiation to first MG symptoms was 4 weeks (range: 2-15 weeks). ICIs were discontinued in all patients. Most patients initially received high-dose corticosteroids, and their symptoms improved. Some patients are discharged with corticosteroids maintenance therapy. In addition, 55 patients (50%) with concomitant myositis and/or myocarditis and MG-induced mortality were more common in the myositis and/or myocarditis group (10.9% vs. 34.5%, = 0.016). Overlap of myositis with MG (OR = 3.148, = 0.009) and anti-AChR antibody positivity (OR = 3.364, = 0.005) were both significantly associated with poor outcomes.
CONCLUSION
Our study reveals the prognosis of ICI-induced MG and suggests that myositis and/or myocarditis are severe comorbidities of ICI-induced MG, emphasizing the importance of early diagnosis and clinical intervention.
PubMed: 38633537
DOI: 10.3389/fneur.2024.1372861 -
Diabetologia Jul 2024We conducted a systematic review and network meta-analysis to compare the efficacy and safety of s.c. administered tirzepatide vs s.c. administered semaglutide for... (Meta-Analysis)
Meta-Analysis Review
AIMS/HYPOTHESIS
We conducted a systematic review and network meta-analysis to compare the efficacy and safety of s.c. administered tirzepatide vs s.c. administered semaglutide for adults of both sexes with type 2 diabetes mellitus.
METHODS
We searched PubMed and Cochrane up to 11 November 2023 for RCTs with an intervention duration of at least 12 weeks assessing s.c. tirzepatide at maintenance doses of 5 mg, 10 mg or 15 mg once weekly, or s.c. semaglutide at maintenance doses of 0.5 mg, 1.0 mg or 2.0 mg once weekly, in adults with type 2 diabetes, regardless of background glucose-lowering treatment. Eligible trials compared any of the specified doses of tirzepatide and semaglutide against each other, placebo or other glucose-lowering drugs. Primary outcomes were changes in HbA and body weight from baseline. Secondary outcomes were achievement of HbA target of ≤48 mmol/mol (≤6.5%) or <53 mmol/mol (<7.0%), body weight loss of at least 10%, and safety outcomes including gastrointestinal adverse events and severe hypoglycaemia. We used version 2 of the Cochrane risk-of-bias tool (ROB 2) to assess the risk of bias, conducted frequentist random-effects network meta-analyses and evaluated confidence in effect estimates utilising the Confidence In Network Meta-Analysis (CINeMA) framework.
RESULTS
A total of 28 trials with 23,622 participants (44.2% female) were included. Compared with placebo, tirzepatide 15 mg was the most efficacious treatment in reducing HbA (mean difference -21.61 mmol/mol [-1.96%]) followed by tirzepatide 10 mg (-20.19 mmol/mol [-1.84%]), semaglutide 2.0 mg (-17.74 mmol/mol [-1.59%]), tirzepatide 5 mg (-17.60 mmol/mol [-1.60%]), semaglutide 1.0 mg (-15.25 mmol/mol [-1.39%]) and semaglutide 0.5 mg (-12.00 mmol/mol [-1.09%]). In between-drug comparisons, all tirzepatide doses were comparable with semaglutide 2.0 mg and superior to semaglutide 1.0 mg and 0.5 mg. Compared with placebo, tirzepatide was more efficacious than semaglutide for reducing body weight, with reductions ranging from 9.57 kg (tirzepatide 15 mg) to 5.27 kg (tirzepatide 5 mg). Semaglutide had a less pronounced effect, with reductions ranging from 4.97 kg (semaglutide 2.0 mg) to 2.52 kg (semaglutide 0.5 mg). In between-drug comparisons, tirzepatide 15 mg, 10 mg and 5 mg demonstrated greater efficacy than semaglutide 2.0 mg, 1.0 mg and 0.5 mg, respectively. Both drugs increased incidence of gastrointestinal adverse events compared with placebo, while neither tirzepatide nor semaglutide increased the risk of serious adverse events or severe hypoglycaemia.
CONCLUSIONS/INTERPRETATION
Our data show that s.c. tirzepatide had a more pronounced effect on HbA and weight reduction compared with s.c. semaglutide in people with type 2 diabetes. Both drugs, particularly higher doses of tirzepatide, increased gastrointestinal adverse events.
REGISTRATION
PROSPERO registration no. CRD42022382594.
Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Glucagon-Like Peptides; Randomized Controlled Trials as Topic; Network Meta-Analysis; Glycated Hemoglobin; Adult; Blood Glucose; Female; Male; Injections, Subcutaneous; Glucagon-Like Peptide-2 Receptor; Gastric Inhibitory Polypeptide
PubMed: 38613667
DOI: 10.1007/s00125-024-06144-1 -
Zeitschrift Fur Gastroenterologie Apr 2024Phytotherapeutics are gaining influence in the treatment of gastroenterological diseases. Their popularity and growing evidence of efficacy contribute to their...
Phytotherapeutics are gaining influence in the treatment of gastroenterological diseases. Their popularity and growing evidence of efficacy contribute to their integration into medical guidelines. A systematic screening identified recommended phytotherapeutic approaches. Based on current scientific data, some recommendations for the use of phytotherapeutic agents are given. For the use of is "strongly recommended", especially for pain and flatulence. Other phytotherapeutics such as , Tibetan or warm pads have proven effective in alleviating symptoms. It is "recommended" to integrate them into the treatment concept. For , 30g of fiber per day is recommended. Best data exists for with moderate evidence and . In case of , as well as the combination of , and can be used as a complementary treatment in maintaining remission. There is also an "open recommendation" for for both, remission induction and maintenance. Some phytotherapeutic treatments (e.g., , ) show evidence of effectiveness for the treatment of , but data are not yet sufficient for recommendations. Cannabis-based medicines can be considered for abdominal pain and clinically relevant appetite loss if standard therapy is ineffective or contraindicated, but they should not be used for acute inflammation in active Crohn's disease. Further recommendations for other gastroenterological diseases are discussed. The safety and tolerability of the phytotherapeutics were rated as predominantly "very good" to "acceptable". Some clear recommendations for the use of phytotherapeutics to treat gastroenterological diseases show their great potential. Due to their wide range of effects, phytotherapeutics can be used very well as a complement to conventional medicines in case of complex regulatory disorders. However, further methodologically well-conducted impact studies would be helpful in order to be able to make further recommendations.
PubMed: 38604221
DOI: 10.1055/a-2279-5045