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Psychiatrike = Psychiatriki 2020Clozapine is an atypical antipsychotic used for the treatment of resistant schizophrenia, exhibiting significant advantages over other antipsychotic agents. Clozapine...
Clozapine is an atypical antipsychotic used for the treatment of resistant schizophrenia, exhibiting significant advantages over other antipsychotic agents. Clozapine efficacy is well established in people diagnosed with schizophrenia via reducing both positive and negative symptoms. Also, is associated with a low risk of extrapyramidal side effects compared to other antipsychotics. Despite the above, clozapine is an unpopular therapeutic option for patients not previously responded to other antipsychotics, because of adverse side effects, such as hyper-salivation and weight gain or critical side effects, i.e., risk for developing neutropenia and agranulocytosis and the need for a systematic and vigilant patients' monitoring, causing discomfort to them and increased expenses to the healthcare system. The aim of the present article is to describe (a) the development of a "clozapine treatment monitoring protocol", and (b) the monitoring process applied at the Department of Psychiatry of Aghioi Anargyroi Cancer Hospital in patients under clozapine treatment. For the protocol development a systematic review of the existing literature was conducted. An advanced search in Medline, CINAHL, Scopus and Google Scholar was conducted, as well as at the National Organization of Greece for Medicines database, with the following key- words: "clozapine", "clozapine protocol", "clozapine monitoring", "clozapine guidelines". Based on this procedure, the Victorian Consensus View protocol applied in Australia was evaluated as the most appropriate since it encompasses: (a) monitoring of multiple systems based on a holistic healthcare approach towards patients, and (b) Intense cardiovascular functioning monitoring, highly relevant to the Greek population due to increased incidence of myocarditis. Overall, the necessary interventions prior and after clozapine treatment initiation are, monitoring of heamatological and cardiovascular function and related side effects, metabolic monitoring and related side effects, monitoring of metabolic adverse effects, gastrointestinal and neurological adverse effects, hepatic function monitoring and related side effects. Clozapine treatment monitoring protocol applied at special settings, e.g., Clozapine Clinics, is highly beneficial, since the risk of neutropenia, agronulocytosis is minimized, while suicidal behavior and substance use are reduced along with risky health behaviors, i.e., nicotine use and sedentary lifestyle. The current protocol may be applied by mental healthcare professionals aiming to empower individuals with schizophrenia through promoting their independency and quality of life.
Topics: Clozapine; Greece; Humans; Schizophrenia; Schizophrenic Psychology
PubMed: 32544078
DOI: 10.22365/jpsych.2020.311.70 -
American Journal of Hematology Jul 2022Bruton tyrosine kinase inhibitors (BTKi) are important treatment options in Waldenström's macroglobulinemia (WM). Whether second-generation BTKi are associated with... (Meta-Analysis)
Meta-Analysis
Bruton tyrosine kinase inhibitors (BTKi) are important treatment options in Waldenström's macroglobulinemia (WM). Whether second-generation BTKi are associated with improved outcomes and/or better safety profile remains unclear. We did a systematic review and meta-analysis of clinical trials that reported data on the outcomes of patients with WM who received either first- or second-generation BTKi in the period between January 2010 and August 2021. Studies with twenty or fewer patients were excluded. The primary outcomes were efficacy measured by response and survival data. Eleven studies met the eligibility criteria and were included in the final analysis (n = 730 patients). A total of 298 patients received 1st-generation BTKi and 432 received a 2nd-generation BTKi. Pooled overall response rate (ORR) and major response rate (MRR) for both generations were similar (94.2% and 78.5% in 1st vs. 88.9% and 75.1% in 2nd, respectively). MRR for both generations was higher in MYD88 Mut/CXCR4 WT patients compared to MYD88 Mut/CXCR4 Mut patients (odds ratio [OR]: 3.9, 95% CI: 2.2 to 5.5). Pooled 18-mo progression-free survival (PFS) was similar for both generations (88.5% vs. 87.3%). Grade 3/4 atrial fibrillation was higher in 1st-generation BTKi (3.1% vs. 0.4%); however, grade-3/-4 infections and neutropenia were more frequent in 2nd-generarion BTKi (20.9% vs. 13.2%, 17.7% vs. 12%, respectively). The efficacy of 1st- and 2nd-generation BTKis is comparable. The 1st-generation BTKi were associated with a higher risk of atrial fibrillation, whereas infections and neutropenia occurred more frequently in 2nd-generation BTKi.
Topics: Atrial Fibrillation; Humans; Lymphoma, B-Cell; Mutation; Myeloid Differentiation Factor 88; Neutropenia; Protein Kinase Inhibitors; Pyrimidines; Waldenstrom Macroglobulinemia
PubMed: 35358350
DOI: 10.1002/ajh.26552 -
The Cochrane Database of Systematic... May 2020Glioblastoma is an uncommon but highly aggressive type of brain tumour. Significant gains have been achieved in the molecular understanding and the pathogenesis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Glioblastoma is an uncommon but highly aggressive type of brain tumour. Significant gains have been achieved in the molecular understanding and the pathogenesis of glioblastomas, however clinical improvements are difficult to obtain for many reasons. The current standard of care involves maximal safe surgical resection followed by chemoradiation and then adjuvant chemotherapy European Organisation for Research and Treatment of Cancer and the NCIC Clinical Trials Group (EORTC-NCIC) protocol with a median survival of 14.6 months. Successive phase III international randomised controlled studies have failed to significantly demonstrate survival advantage with newer drugs. Epidermal growth factor receptor (EGFR) is observed to be aberrant in 30% to 60% of glioblastomas. The receptor aberrancy is driven by abnormal gene amplification, receptor mutation, or both, in particular the extracellular vIII domain. EGFR abnormalities are common in solid tumours, and the advent of anti-EGFR therapies in non-small cell lung cancer and colorectal adenocarcinomas have greatly improved clinical outcomes. Anti-EGFR therapies have been investigated amongst glioblastomas, however questions remain about its ongoing role in glioblastoma management. This review aimed to report on the available evidence to date and perform a systematic analysis on the risks and benefits of use of anti-EGFR therapies in glioblastomas.
OBJECTIVES
To evaluate the efficacy and harms of anti-EGFR therapies for glioblastoma in adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, EBM Reviews databases, with supplementary handsearches to identify all available and relevant studies to 20 April 2020.
SELECTION CRITERIA
All randomised controlled trials (RCTs) using anti-EGFR therapies in adults with glioblastoma were eligible for inclusion. Anti-EGFR therapies included tyrosine kinase inhibitors, monoclonal antibodies, or vaccines. The comparison included investigational product added to standard of care versus standard of care or placebo, or investigational product against standard of care or placebo.
DATA COLLECTION AND ANALYSIS
The authorship team screened the search results and recorded the extracted data for analysis. We used standard Cochrane methodology to performed quantitative meta-analysis if two or more studies had appropriate and available data. Otherwise, we conducted a qualitative and descriptive analysis. We used the GRADE system to rate the certainty of the evidence. The analysis was performed along the two clinical settings: first-line (after surgery) and recurrent disease (after failure of first line treatment). Where information was available, we documented overall survival, progression-free survival, adverse events, and quality of life data from eligible studies.
MAIN RESULTS
The combined searches initially identified 912 records (after removal of duplicates), and further screening resulted in 19 records for full consideration. We identified nine eligible studies for inclusion in the review. There were three first-line studies and six recurrent studies. Five studies used tyrosine kinase inhibitors (TKIs); two studies used monoclonal antibodies; and two studies used targeted vaccines. More recent studies presented greater detail in the conduct of their studies and thus had a lower risk of bias. We observed no evidence benefit in overall survival with the use of anti-EGFR therapy in the first-line or recurrent setting (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.76 to 1.04; 3 RCTs, 1000 participants, moderate-certainty evidence; and HR 0.79, 95% CI 0.51 to 1.21, 4 RCTs, 489 participants, low-certainty evidence, respectively). All the interventions were generally well tolerated with low-certainty evidence for lymphopenia (odds ratio (OR) 0.97, 95% CI 0.19 to 4.81; 4 RCTs, 1146 participants), neutropenia (OR 1.29, 95% CI 0.82 to 2.03; 4 RCTs, 1146 participants), and thrombocytopenia (OR 3.69, 95% CI 0.51 to 26.51; 4 RCTs, 1146 participants). A notable toxicity relates to ABT-414, where significant ocular issues were detected. The addition of anti-EGFR therapy showed no evidence of an increase in progression-free survival (PFS) in the first-line setting (HR 0.94, 95% CI 0.81 to 1.10; 2 RCTs, 894 participants, low-certainty evidence). In the recurrent setting, there was an increase in PFS with the use of anti-EGFR therapy (HR 0.75, 95% CI 0.58 to 0.96, 3 RCTs, 275 participants, low-certainty evidence). The available quality of life assessment data showed that anti-EGFR therapies were neither detrimental or beneficial when compared to standard care (not estimable).
AUTHORS' CONCLUSIONS
In summary, there is no evidence of a demonstrable overall survival benefit with the addition of anti-EGFR therapy in first-line and recurrent glioblastomas. Newer drugs that are specially designed for glioblastoma targets may raise the possibility of success in this population, but data are lacking at present. Future studies should be more selective in pursuing people displaying specific EGFR targets.
Topics: Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Agents, Immunological; Brain Neoplasms; Cancer Vaccines; Disease Progression; ErbB Receptors; Glioblastoma; Humans; Lymphopenia; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Randomized Controlled Trials as Topic; Thrombocytopenia
PubMed: 32395825
DOI: 10.1002/14651858.CD013238.pub2 -
Medicine Dec 2021Antipseudomonal β-lactams have been used for the treatment of febrile neutropenia (FN); however, the efficacy and safety of antipseudomonal β-lactams in pediatric...
BACKGROUND
Antipseudomonal β-lactams have been used for the treatment of febrile neutropenia (FN); however, the efficacy and safety of antipseudomonal β-lactams in pediatric patients remain unclear. The aim of this study was to comprehensively compare the efficacy and side effects of optional antipseudomonal β-lactams for pediatric FN.
METHODS
PubMed, Embase, Medline, and Cochrane Library were systematically searched from their inception to December 18, 2020. Eligible randomized controlled trials in which pediatric FN patients were treated with an empiric monotherapy of antipseudomonal β-lactams were selected. Data synthesis was performed using WinBUGS 14.0 software and meta packages implemented in R 3.6.2. Random-effects network meta-analysis was performed, and dichotomous data were pooled as odds ratios with 95% confidence intervals. The primary outcome was treatment success without modification; the secondary outcomes were adverse events (AEs), all-cause mortality, and new infections. The GRADE tool was used to assess the quality of the evidence. The protocol was registered with PROSPERO ID CRD42021226763.
RESULTS
Eighteen studies with 2517 patients were included. The results showed no statistically significant difference between the optional antipseudomonal β-lactams in the outcomes of treatment success without modification, all AEs, all-cause mortality, and new infections for pediatric FN. Based on the results of Bayesian rank probability, meropenem was ranked highest among all the treatment options with regard to treatment success without modification benefit; ceftazidime and meropenem were associated with a lower risk of AEs; cefoperazone/sulbactam and piperacillin/tazobactam were associated with a lower risk of mortality, and piperacillin/tazobactam and meropenem were associated with a lower risk of new infections. The quality of evidence was moderate.
CONCLUSIONS
Meropenem and piperacillin/tazobactam were found to be better with regard to treatment success without modification, with a comparable safety profile. Therefore, our findings support the use of meropenem and piperacillin/tazobactam as a treatment option for pediatric FN patients.
Topics: Anti-Bacterial Agents; Ceftazidime; Child; Drug Therapy, Combination; Febrile Neutropenia; Female; Humans; Imipenem; Male; Meropenem; Network Meta-Analysis; Piperacillin, Tazobactam Drug Combination; Pseudomonas Infections; Pseudomonas aeruginosa; Randomized Controlled Trials as Topic; Treatment Outcome; beta-Lactams
PubMed: 34918626
DOI: 10.1097/MD.0000000000027266 -
Cancer Medicine Jan 2023This meta-analysis was conducted to evaluate the efficacy and safety of the addition of Traditional Chinese Medicine (TCMs) to capecitabine-based regimens for colorectal... (Meta-Analysis)
Meta-Analysis
This meta-analysis was conducted to evaluate the efficacy and safety of the addition of Traditional Chinese Medicine (TCMs) to capecitabine-based regimens for colorectal cancer (CRC) in term of tumor. The eight electronic databases including Cochrane Library, PubMed, Web of Science (WOS), Excerpt Medica Database (Embase), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journals (CQVIP), and Wanfang Database were systematically searched for eligible studies from their inception to March 2021. Thirty-nine randomized controlled trials were involved in this study, and all the data were analyzed by Review Manager 5.3 (Nordic Cochran Centre, Copenhagen, Denmark) and R 4.0.5 software. The meta-analyses suggested that TCMs in combination with capecitabine-based regimens increased objective response rate (ORR) in the palliative treatment of CRC (risk ratio [RR], 1.35 [1.17, 1.55], I = 0%), disease control rate (DCR) (RR, 1.22 [1.12, 1.32], I = 3%), and quality of life (QOL) (RR, 1.71 [1.44, 2.03], I = 0%), with decreased risks of myelosuppression, anemia, thrombocytopenia, liver/renal dysfunction, neurotoxicity, nausea/vomiting, neutropenia, diarrhea, leukopenia, improved the peripheral lymphocyte, reduced the expression of tumor markers, and related factors. Further sensitivity analysis of specific plant-based TCMs found that dangshen, fuling, and gancao had significantly higher contributions to the results of the RR. The results show that capecitabine-based chemotherapy combined with TCM in the treatment of CRC increases the efficiency of ORR and DCR, reduces chemotherapeutic agents-associated adverse reactions, and improves their life quality as compared with chemotherapy alone, but further randomized and large sample of studies are needed.
Topics: Humans; Medicine, Chinese Traditional; Capecitabine; Quality of Life; Drugs, Chinese Herbal; Neutropenia; Colorectal Neoplasms; Randomized Controlled Trials as Topic
PubMed: 35650714
DOI: 10.1002/cam4.4896 -
Frontiers in Endocrinology 2019Granulocyte-colony-stimulating factor (G-CSF) is highly beneficial as a general treatment for anti-thyroid drug (ATD)-induced agranulocytosis. This meta-analysis aimed...
Granulocyte-colony-stimulating factor (G-CSF) is highly beneficial as a general treatment for anti-thyroid drug (ATD)-induced agranulocytosis. This meta-analysis aimed to assess the clinical effects of G-CSF and non-G-CSF on recovery duration in patients with ATD-induced agranulocytosis by analyzing the overall clinical outcomes. The PubMed, Embase, Ovid, Cochrane, Google Scholar, China National Knowledge Infrastructure (CNKI) databases were searched for published studies from 1900 to 2018. No language restriction was implemented. This meta-analysis included 10 published retrospective studies and one prospective study. Data were obtained from 11 trials (474 patients: 247 with G-CSF and 227 with non-G-CSF treatment). Compared with the non-G-CSF group, the G-CSF group presented shorter recovery duration [weighted mean difference (WMD) = -3.04 days, 95% confidence interval (95% CI): -4.38 to -1.69 ( = 4.43 = 0.000)]. However, the recovery duration varied across regions and recovery criteria. Asian patients achieved significant clinical outcomes [WMD = -3.16 days (95% CI: -4.58 to -1.74, = 0.000)] compared with European and South American patients [WMD = -2.19 days (95% CI: -7.38 to 3.01, = 0.409)]. Also, according to various recovery criteria, a duration of granulocyte count increase of more than 1.5 or 1.0 × 10/L [WMD = -3.50 days (95% CI: -4.82 to -2.18 = 0.000)] revealed a better treatment effect. G-CSF can significantly shorten the recovery duration in patients with ATD-induced agranulocytosis.
PubMed: 31824417
DOI: 10.3389/fendo.2019.00789 -
Cerebellum (London, England) Jun 2021Superficial siderosis describes haemosiderin deposition on the surface of the brain. When present on infratentorial structures, it can cause ataxia, sensorineural...
Superficial siderosis describes haemosiderin deposition on the surface of the brain. When present on infratentorial structures, it can cause ataxia, sensorineural hearing loss and pyramidal signs. There is no proven treatment and patients experience slow progression of symptoms. Iron-chelating agents have been suggested as a therapeutic option and deferiprone is suited as it crosses the blood-brain barrier. However, deferiprone is reported to have a 1-2% risk of agranulocytosis. We performed a systematic review on treatment of infratentorial superficial siderosis with deferiprone based on PRISMA guidelines. Studies were included if in English or an English language translation was available, were about human subjects and referred to patients with ataxia. Studies were excluded if they did not possess an English translation, included animal studies or did not have ataxia. Studies were excluded if they discussed cerebral amyloid angiopathy or siderosis of other regions. Eleven papers were included. We identified 69 patients. Seventeen patients (25%) discontinued the drug. The most encountered adverse effect was anaemia (21.7%). Neutropaenia was observed in 8.7% and agranulocytosis in 5.8% of patients. Clinically, response varied, and stability or improvement was seen across neurological domains in 6 studies while 5 showed a mixed response. On imaging, 13 (28.9%) patients improved, 24 (53.3%) stabilised and 8 (17.8%) deteriorated. A prospective international centralised register of patients should be developed to inform the design and conduct of a multicentre, placebo-controlled, randomised clinical trial to evaluate the efficacy of deferiprone. The evidence from this systematic review is that deferiprone is a promising intervention.
Topics: Animals; Deferiprone; Hemosiderin; Humans; Iron Chelating Agents; Randomized Controlled Trials as Topic; Siderosis
PubMed: 33409768
DOI: 10.1007/s12311-020-01222-7 -
The Journal of International Medical... Jul 2019We investigated the risk of acute and late toxicities of concurrent chemoradiotherapy (CCRT) and radiotherapy alone in patients with nasopharynx carcinoma (NPC). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We investigated the risk of acute and late toxicities of concurrent chemoradiotherapy (CCRT) and radiotherapy alone in patients with nasopharynx carcinoma (NPC).
METHODS
In this meta-analysis, we searched the PubMed, Embase, Cochrane Library, and Web of Science databases for eligible randomized clinical trials (RCTs). In addition to the incidence of specific toxicities, risk ratios (RRs) or odd ratios (ORs) and 95% confidence intervals (CIs) were obtained using fixed-effect or random-effects models.
RESULTS
In total, 11 RCTs involving 2801 patients with NPC were included in this analysis. For grade ≥3 adverse events, patients who received CCRT treatment had a higher proportion of acute mucositis (39.9% vs. 30.5%, RR=1.30, 95%CI, 1.16–1.46) acute nausea and vomiting (RR=6.26, 95% CI: 2.01–19.45), and neutropenia (RR=30.86, 95% CI: 7.36 to 129.35). For late severe toxicities, CCRT treatment was significantly associated with higher incidence of hearing loss (116.56% vs. 411.43%, RR=1.461, 95%CI, 1.043–21.095). The incidence of acute nausea and vomiting was more frequent in patients receiving CCRT.
CONCLUSION
Compared with radiotherapy alone, CCRT increases the risk of severe acute toxicities (mucositis, nausea/vomiting, and neutropenia) and severe late toxicity (hearing loss) in patients with NPC. However, larger studies are needed to confirm this finding.
Topics: Chemoradiotherapy; Humans; Mucositis; Nasopharyngeal Neoplasms; Nausea; Neutropenia; Prognosis; Radiation Injuries; Radiotherapy; Vomiting
PubMed: 31272262
DOI: 10.1177/0300060519858031 -
Pediatric Blood & Cancer Oct 2019Routinely measurable biomarkers as predictors for adverse outcomes in febrile neutropenia could improve management through risk stratification. This systematic review... (Meta-Analysis)
Meta-Analysis
Updated systematic review and meta-analysis of the predictive value of serum biomarkers in the assessment and management of fever during neutropenia in children with cancer.
Routinely measurable biomarkers as predictors for adverse outcomes in febrile neutropenia could improve management through risk stratification. This systematic review assesses the predictive role of biomarkers in identifying events such as bacteraemia, clinically documented infections, microbiologically documented infection, severe sepsis requiring intensive care or high dependency care and death. This review collates 8319 episodes from 4843 patients. C-reactive protein (CRP), interleukin (IL)-6, IL-8 and procalcitonin (PCT) consistently predict bacteraemia and severe sepsis; other outcomes have highly heterogeneous results. Performance of the biomarkers at admission using different thresholds demonstrates that PCT > 0.5 ng/mL offers the best compromise between sensitivity and specificity: sensitivity 0.67 (confidence interval [CI] 0.53-0.79) specificity 0.73 (CI 0.66-0.77). Seventeen studies describe the use of serial biomarkers, with PCT having the greatest discriminatory role. Biomarkers, potentially with serial measurements, may predict adverse outcomes in paediatric febrile neutropenia and their role in risk stratification is promising.
Topics: Adolescent; Biomarkers; Child; Child, Preschool; Febrile Neutropenia; Female; Humans; Infant; Male; Neoplasms; Predictive Value of Tests; Young Adult
PubMed: 31250539
DOI: 10.1002/pbc.27887 -
Haematologica Apr 20246-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene... (Meta-Analysis)
Meta-Analysis
Association of gene polymorphism with adverse reaction, treatment efficacy, and dose of 6-mercaptopurine in patients with acute lymphoblastic leukemia: a systematic review and meta-analysis.
6-mercaptopurine (6-MP) serves as the backbone in the maintenance regimens of acute lymphoblastic leukemia (ALL). We aimed to evaluate the influence of NUDT15 gene polymorphism on the risk of myelosupression, hepatotoxicity and interruption of 6-MP, as well as treatment efficacy and dose of 6-MP in ALL patients. A total of 24 studies with 3,374 patients were included in this meta-analysis. We found 9-fold higher risk of 6-MP induced leukopenia (odds ratio [OR] =9.00, 95% confidence interval [CI]: 3.73-21.74) and 2.5-fold higher risk of 6-MP-induced neutropenia (OR=2.52, 95% CI: 1.72-3.69) for NUDT15 c.415C>T variant carriers in the dominant model. Moreover, we found that the dose intensity of 6-MP in ALL patients with one NUDT15 c.415C>T variant alleles (CT) was 19% less than that in wild-type patients (CC) (mean differences: 19.43%, 95% CI: -25.36 to -13.51). The tolerable dose intensity of 6-MP in NUDT15 c.415C>T homozygote variant (TT) and heterozygote variant (CT) carriers was 49% and 15% less than that in wild-type patients, respectively. The NUDT15 c.415C>T variant group (CT+TT) had seven times (OR=6.98, 95% CI: 2.83-17.22) higher risk of developing 6-MP intolerance than the CC group. However, NUDT15 c.415C>T polymorphism did not appear significantly associated with hepatotoxicity, treatment interruption or relapse incidence. We concluded that NUDT15 c.415C>T was a good predictor for 6-MP-induced myelosuppression in ALL patients. The dose intensity of 6-MP in ALL patients with NUDT15 c.415C>T variants was significantly lower than that in wild-type patients. This research provided a basis for further investigation into relations between NUDT15 gene and adverse reaction, treatment efficacy and dose intensity of 6-MP.
Topics: Humans; Mercaptopurine; Pyrophosphatases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Polymorphism, Genetic; Neutropenia; Treatment Outcome; Chemical and Drug Induced Liver Injury
PubMed: 37794799
DOI: 10.3324/haematol.2023.282761