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Current Neuropharmacology Oct 2021Both prescription and over-the-counter (OTC) drugs recently emerged among novel psychoactive substances (NPS) being reported as ingested for recreational purposes. Among...
BACKGROUND
Both prescription and over-the-counter (OTC) drugs recently emerged among novel psychoactive substances (NPS) being reported as ingested for recreational purposes. Among them, benzydamine (BZY), normally prescribed as an OTC anti-inflammatory drug, is reportedly being diverted and recreationally used.
OBJECTIVE
The aim of this study was to investigate how the misuse of BZY has been reported, illustrating its psychotropic molecular mechanism, and studying its psychopathological effects.
METHODS
We firstly conducted a systematic review of the literature concerning the abuse of BZY and its effects. For data gathering purposes, both PRISMA and PROSPERO guidelines were followed. All research methods were approved by PROSPERO (identification code CRD42020187266). Second, we analysed BZY-related data from the European Monitoring Agency (EMA) Adverse Drug Reactions (ADRs) database recorded during 2005-2020 regarding its abuse.
RESULTS
Eleven articles, published during 1997-2019, were included in our systematic review, including five case reports, four surveys, and two retrospective case series analyses. While nine articles dealt with the recreational use of BZY, two described an oral overdose of the drug. When specified, dosages of BZY consumed ranged from 500 to 1500mg. The EMA dataset contained three cases of BZY abuse.
CONCLUSION
Results from the systematic review showed BZY might be diverted for typical hallucinogenic properties occurring at high dosages. Healthcare professionals should be warned about a possible misuse/abuse of a commonly prescribed anti-inflammatory drug and be vigilant when prescribing it. Physicians working in emergency units should know that psychotic symptoms may be related to BZY abuse.
Topics: Anti-Inflammatory Agents; Benzydamine; Humans; Psychotic Disorders; Retrospective Studies
PubMed: 33441070
DOI: 10.2174/1570159X19666210113151136 -
Current Oncology (Toronto, Ont.) Jan 2022Patients with epithelial ovarian cancer (EOC), treated with niraparib maintenance, present with haematological and gastrointestinal toxicities. Limited data exist on... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with epithelial ovarian cancer (EOC), treated with niraparib maintenance, present with haematological and gastrointestinal toxicities. Limited data exist on niraparib safety assessment.
OBJECTIVE
To evaluate niraparib safety profile, as maintenance therapy, in women with platinum-sensitive EOC.
METHODS
PubMed and Cochrane searches were carried out up to April 2021 for randomised controlled trials (RCTs) evaluating niraparib versus placebo in EOC patients with a response to platinum-based chemotherapy. Regarding the meta-analysis, for dichotomous data, the pooled risk ratio (RR) was calculated.
RESULTS
A total of 1539 patients from three RCTs revealed that niraparib-treated patients are associated with a significantly higher risk of any grade of nausea (RR, 2.15; 95% CI, 1.86 to 2.48), fatigue (RR, 1.26; 95% CI, 1.05 to 1.52, < 0.00001), anemia (RR, 6.86; 95% CI, 2.54 to 18.52, = 0.0001), thrombocytopenia (RR, 7.02; 95% CI, 1.68 to 29.38, < 0.00001), vomiting (RR, 2.51; 95% CI, 1.50 to 4.19, = 0.0005), neutropenia (RR, 2.96; 95% CI, 1.13 to 7.73, < 0.00001), headache (RR, 2.08; 95% CI, 1.57 to 2.74, < 0.00001), constipation (RR, 2.10; 95% CI, 1.72 to 2.57, < 0.00001) and insomnia (RR, 2.48; 95% CI, 1.52 to 2.89, = 0.0003) when compared with placebo. For grade 3 or 4 adverse effects, significantly higher risk was only noted for fatigue (RR,6.25; 95% CI, 1.70 to 23.05, = 0.006), anemia (RR, 16.23; 95% CI, 4.86 to 54.17, < 0.00001), thrombocytopenia (RR, 35.12; 95% CI, 12.23 to 100.82, < 0.00001) and neutropenia episodes (RR, 6.35; 95% CI, 2.08 to 19.39, = 0.001) for those taking niraparib. Notably, incidents of adverse effects and discontinuation rates were substantially lower among patients treated with an individualised niraparib dose than those treated with the standard one. Efficacy was not reduced, and no treatment-related deaths occurred during the included trials.
CONCLUSION
Niraparib is considered an effective and well-tolerated choice, with an improved safety profile, for the maintenance treatment of EOC patients.
Topics: Carcinoma, Ovarian Epithelial; Female; Humans; Indazoles; Neoplasm Recurrence, Local; Ovarian Neoplasms; Piperidines
PubMed: 35049703
DOI: 10.3390/curroncol29010029 -
JBRA Assisted Reproduction Jun 2024To verify, based on a systematic literature review, the effects of the main analgesics on male fertility. (Review)
Review
OBJECTIVE
To verify, based on a systematic literature review, the effects of the main analgesics on male fertility.
DATA SOURCES
The studies were analyzed from the PubMed, SciELO and LILACS databases.
STUDY SELECTION
The articles selected for the present review included: cohort studies; cross-sectional studies, clinical trials; complete studies; studies with animal models that addressed the proposed theme and that were published within the stipulated period from March 1, 2013, to March 31, 2023, in English, Portuguese and Spanish. These would later have to go through inclusion stages such as framing the type of study and exclusion criteria.
DATA COLLECTION
Author's name, year of publication, study population, number of patients, analgesic, administration time, dose, and effect.
CONCLUSIONS
There are in vitro and in vivo studies that link paracetamol and ibuprofen to endocrine and seminal changes that are harmful to male fertility. However, more clinical research is needed to determine the doses and timing of administration that affect fertility. The effects of aspirin on male fertility are still unclear due to the lack of studies and consistent methodologies. There is not enough research on dipyrone and its relationship with male fertility, requiring more studies in this area.
Topics: Humans; Male; Analgesics; Fertility; Infertility, Male; Ibuprofen; Acetaminophen; Animals; Dipyrone; Aspirin
PubMed: 38546117
DOI: 10.5935/1518-0557.20240020 -
Blood Advances Aug 2019Both apixaban and rivaroxaban have been approved for use in acute venous thromboembolism (VTE). Although indirect comparison through network meta-analyses of randomized... (Meta-Analysis)
Meta-Analysis
Both apixaban and rivaroxaban have been approved for use in acute venous thromboembolism (VTE). Although indirect comparison through network meta-analyses of randomized trials have been performed to compare the efficacy and safety of these agents, further comparison between these agents was lacking until recently. We sought to systematically review and carry out a meta-analysis of studies to further compare apixaban with rivaroxaban from multiple studies done in the real-world settings. Studies comparing rivaroxaban with apixaban in patients with acute VTE were identified through electronic literature searches of MEDLINE, EMBASE, Scopus, and the Cochrane library up to May 2019. Study-specific risk ratios (RRs) were calculated and combined using a random-effects model meta-analysis. In an analysis involving 24 041 patients, recurrent VTE within 6 months occurred in 56 of 4897 patients (1.14%) in the apixaban group and 258 of 19 144 patients (1.35%) in the rivaroxaban group (RR, 0.89; 95% confidence interval [CI], 0.67-1.19; = .45). Clinically relevant major bleeding occurred in 85 of 11 559 patients (0.74%) in the apixaban group and 350 of 33 909 patients (1.03%) in the rivaroxaban group (RR, 0.73; 95% CI, 0.58-0.93; = .01). Clinically relevant nonmajor bleeding occurred in 169 of 3417 patients (4.95%) in the apixaban group and 1094 of 12 475 patients (8.77%) in the rivaroxaban group (RR, 0.59; 95% CI, 0.50-0.70; < .01). Apixaban shows equivalent efficacy in prevention of recurrent VTE but decreased risk of major and minor bleeding events compared with rivaroxaban.
Topics: Blood Coagulation; Hemorrhage; Humans; Odds Ratio; Pyrazoles; Pyridones; Rivaroxaban; Treatment Outcome; Venous Thromboembolism
PubMed: 31405948
DOI: 10.1182/bloodadvances.2019000572 -
Aging Sep 2021Many recent studies have investigated the role of drug interventions for coronavirus disease 2019 (COVID-19) infection. However, an important question has been raised... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many recent studies have investigated the role of drug interventions for coronavirus disease 2019 (COVID-19) infection. However, an important question has been raised about how to select the effective and secure medications for COVID-19 patients. The aim of this analysis was to assess the efficacy and safety of the various medications available for severe and non-severe COVID-19 patients based on randomized placebo-controlled trials (RPCTs).
METHODS
We did an updated network meta-analysis. We searched the databases from inception until July 31, 2021, with no language restrictions. We included RPCTs comparing 49 medications and placebo in the treatment of severe and non-severe patients (aged 18 years or older) with COVID-19 infection. We extracted data on the trial and patient characteristics, and the following primary outcomes: all-cause mortality, the ratios of virological cure, and treatment-emergent adverse events. Odds ratio (OR) and their 95% confidence interval (CI) were used as effect estimates.
RESULTS
From 3,869 publications, we included 61 articles related to 73 RPCTs (57 in non-severe COVID-19 patients and 16 in severe COVID-19 patients), comprising 20,680 patients. The mean sample size was 160 (interquartile range 96-393) in this study. The median duration of follow-up drugs intervention was 28 days (interquartile range 21-30). For increase in virological cure, we only found that proxalutamide (OR 9.16, 95% CI 3.15-18.30), ivermectin (OR 6.33, 95% CI 1.22-32.86), and low dosage bamlanivimab (OR 5.29, 95% CI 1.12-24.99) seemed to be associated with non-severe COVID-19 patients when compared with placebo, in which proxalutamide seemed to be better than low dosage bamlanivimab (OR 5.69, 95% CI 2.43-17.65). For decrease in all-cause mortality, we found that proxalutamide (OR 0.13, 95% CI 0.09-0.19), imatinib (OR 0.49, 95% CI 0.25-0.96), and baricitinib (OR 0.58, 95% CI 0.42-0.82) seemed to be associated with non-severe COVID-19 patients; however, we only found that immunoglobulin gamma (OR 0.27, 95% CI 0.08-0.89) was related to severe COVID-19 patients when compared with placebo. For change in treatment-emergent adverse events, we only found that sotrovimab (OR 0.21, 95% CI 0.13-0.34) was associated with non-severe COVID-19 patients; however, we did not find any medications that presented a statistical difference when compared with placebo among severe COVID-19 patients.
CONCLUSION
We conclude that marked variations exist in the efficacy and safety of medications between severe and non-severe patients with COVID-19. It seems that monoclonal antibodies (e.g., low dosage bamlanivimab, baricitinib, imatinib, and sotrovimab) are a better choice for treating severe or non-severe COVID-19 patients. Clinical decisions to use preferentially medications should carefully consider the risk-benefit profile based on efficacy and safety of all active interventions in patients with COVID-19 at different levels of infection.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Azetidines; COVID-19; Humans; Imatinib Mesylate; Immunologic Factors; Network Meta-Analysis; Oxazoles; Purines; Pyrazoles; SARS-CoV-2; Severity of Illness Index; Sulfonamides; Thiohydantoins; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34531332
DOI: 10.18632/aging.203522 -
British Journal of Haematology Feb 2020Persistent immune thrombocytopenia (ITP) patients require second-line treatments, for which information on clinical outcomes are lacking. A systematic review and network... (Meta-Analysis)
Meta-Analysis
Persistent immune thrombocytopenia (ITP) patients require second-line treatments, for which information on clinical outcomes are lacking. A systematic review and network meta-analysis (NMA) were conducted. Only randomised controlled trials (RCT) of second-line drugs in adult persistent ITP patients with platelet response, platelet count, any bleeding or serious adverse events (SAE) outcome were eligible. Twelve RCTs (n = 1313) were included in NMA. For platelet response outcome, eltrombopag and romiplostin were the best relative to placebo; the former had a non-significant advantage [risk ratio (RR) = 1·10 (95% confidence interval: 0·46, 2·67)]. Both treatments were superior to rituximab and recombinant human thrombopoietin (rhTPO)+rituximab, with corresponding RRs of 4·56 (1·89, 10·96) and 4·18 (1·21, 14·49) for eltrombopag; 4·13 (1·56, 10·94) and 3·79 (1·02, 14·09) for romiplostim. For platelet count, romiplostim ranked highest, followed by eltrombopag, rhTPO+rituximab, and rituximab. For bleeding, rituximab had lowest risk, followed by eltrombopag and romiplostim. For SAEs, rhTPO+rituximab had highest risk, followed by rituximab, eltrombopag and romiplostim. From clustered ranking, romiplostim had the best balance between short-term efficacy and SAEs, followed by eltrombopag. In conclusion, romiplostim and eltrombopag may yield high efficacy and safety. Rituximab may not be beneficial due to lower efficacy and higher complications compared with the thrombopoietin receptor agonists. RCTs with long-term clinical outcomes are required.
Topics: Adult; Benzoates; Drug Therapy, Combination; Female; Humans; Hydrazines; Male; Platelet Count; Prospective Studies; Purpura, Thrombocytopenic, Idiopathic; Pyrazoles; Randomized Controlled Trials as Topic; Receptors, Fc; Recombinant Fusion Proteins; Rituximab; Thrombopoietin
PubMed: 31423574
DOI: 10.1111/bjh.16161 -
BMC Gastroenterology Aug 2023The effectiveness of selective COX-2 inhibitors in preventing colorectal cancer recurrence has been demonstrated, however it is unknown how safe and successful they will... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effectiveness of selective COX-2 inhibitors in preventing colorectal cancer recurrence has been demonstrated, however it is unknown how safe and successful they will be over the long term. As a result, we looked at the efficacy, safety, and consequences of adding COX-2 inhibitors to the treatment plan afterward.
METHODS
In patients with advanced colorectal cancer, we compared the efficacy of celecoxib at two different doses (200 mg twice day and 400 mg twice daily) with placebo. To evaluate the impacts of post-treatment, several datasets from inception to June 2022 were searched. Response rate, illness control rate, and 3-year survival were the main results. And evaluated several safety outcomes, particularly those that were susceptible to adverse events.
RESULTS
The study comprised a total of 9 randomized controlled trials (3206 participants). Celecoxib and rofecoxib doidn't significantly improved the 1-3 year remission rate (OR, 1.57 [95% CI: 0.95-2.57]) and disease control rate (OR, 1.08 [95% CI: 0.99-1.17]). Subgroup analysis of different doses showed that 400 mg of celecoxib significantly improved the response rate (OR, 2.82 [95%CI: 1.20-6.61]). 200 mg celecoxib was not significant (OR, 1.28 [95% CI: 0.66-2.49]). Rofecoxib also did not fully improve disease response rates. Celecoxib at any dose improved 3-year survival (OR, 1.21 [95% CI: 1.02-1.45]). It is important to note that COX-2 inhibitors did not significantly enhance the likelihood of adverse events including gastrointestinal or cardiovascular side effects at any dose.
CONCLUSIONS
For patients with advanced colorectal cancer, a reasonable chemoprevention regimen can include celecoxib 400 mg twice daily.
Topics: Humans; Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Colorectal Neoplasms; Cyclooxygenase 2 Inhibitors; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Sulfones
PubMed: 37580670
DOI: 10.1186/s12876-023-02918-w -
Annals of Palliative Medicine Sep 2022To study and review the effectiveness of oral care interventions for palliative patients for amelioration of clinical conditions affecting oral cavity.
BACKGROUND
To study and review the effectiveness of oral care interventions for palliative patients for amelioration of clinical conditions affecting oral cavity.
METHODS
Following PRISMA standard, a systematic evaluation of articles published between 2000 and 2021 was undertaken utilising five databases on interventions studies. This comprehensive review consists of randomised controlled trials (RCTs) and specific types of non-randomised studies (NRS) examining oral care interventions for palliative patients. Three independent authors screened search records, identified related studies, extracted data and evaluated risk of bias. The key findings of each study were summarised according to the research questions and data that generated during the data extraction procedure.
RESULTS
Out of the 67 identified studies, seven were included in this review (five RCTs and two NRSs) involving head-and-neck cancer, oral cancer, oral mucositis, xerostomia and individuals with malignant disease. Interventions studied were: Ziziphus honey, artificial saliva, CAM2028-Benzydamine, morphine mouthwash, ketamine mouthwash, bethanechol tablets and caphosol with regular oral-care. The durations of interventions in the included studies were largely short-term (six weeks or less). Overall, six studies revealed good results in support of the intervention, with magnitudes of effect ranging from 13.2-10,110.0%. However, just four researches found significant changes, with magnitudes of effect ranging from 50.0-10,110.0%. Although two of the trials have not revealed significant changes in the results, investigations have indicated a reduction in oral conditions in the group with interventions. Only one trial has not indicated an improvement in oral conditions in the groups which received the interventions.
DISCUSSION
By assessing the efficacy of available oral hygiene interventions for palliative patients, this systematic review can help palliative team finds the viable strategies to apply in controlling oral problems among hospice patients. Even though only four of the seven research found a statistically significant difference, most studies found great effectiveness in favour of intervention.
Topics: Benzydamine; Bethanechol; Head and Neck Neoplasms; Humans; Ketamine; Morphine Derivatives; Mouthwashes; Palliative Care; Saliva, Artificial
PubMed: 36096743
DOI: 10.21037/apm-22-215 -
Journal For Immunotherapy of Cancer May 2021COVID-19, the syndrome caused by the infection with SARS-CoV-2 coronavirus, is characterized, in its severe form, by interstitial diffuse pneumonitis and acute...
COVID-19, the syndrome caused by the infection with SARS-CoV-2 coronavirus, is characterized, in its severe form, by interstitial diffuse pneumonitis and acute respiratory distress syndrome (ARDS). ARDS and systemic manifestations of COVID-19 are mainly due to an exaggerated immune response triggered by the viral infection. Cytokine release syndrome (CRS), an inflammatory syndrome characterized by elevated levels of circulating cytokines, and endothelial dysfunction are systemic manifestations of COVID-19. CRS is also an adverse event of immunotherapy (IMTX), the treatment of diseases using drugs, cells, and antibodies to stimulate or suppress the immune system. Graft-versus-host disease complications after an allogeneic stem cell transplant, toxicity after the infusion of chimeric antigen receptor-T cell therapy and monoclonal antibodies can all lead to CRS. It is hypothesized that anti-inflammatory drugs used for treatment of CRS in IMTX may be useful in reducing the mortality in COVID-19, whereas IMTX itself may help in ameliorating effects of SARS-CoV-2 infection. In this paper, we focused on the potential shared mechanisms and differences between COVID-19 and IMTX-related toxicities. We performed a systematic review of the clinical trials testing anti-inflammatory therapies and of the data published from prospective trials. Preliminary evidence suggests there might be a benefit in targeting the cytokines involved in the pathogenesis of COVID-19, especially by inhibiting the interleukin-6 pathway. Many other approaches based on novel drugs and cell therapies are currently under investigation and may lead to a reduction in hospitalization and mortality due to COVID-19.
Topics: Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; COVID-19; Cytokine Release Syndrome; Humans; Immunization, Passive; Immunotherapy; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Interleukin-6; Nitriles; Pyrazoles; Pyrimidines; SARS-CoV-2; Tumor Necrosis Factor-alpha; COVID-19 Serotherapy; COVID-19 Drug Treatment
PubMed: 33986127
DOI: 10.1136/jitc-2021-002392 -
Journal of the American Heart... Jul 2019Background Several studies have investigated the effect of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer, but the... (Meta-Analysis)
Meta-Analysis
Background Several studies have investigated the effect of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer, but the results remain controversial. Therefore, we conducted a meta-analysis to compare the efficacy and safety of NOACs versus warfarin in this population. Methods and Results We systematically searched the PubMed and Embase databases until February 16, 2019 for studies comparing the effect of NOACs with warfarin in AF patients with cancer. Risk ratios (RRs) with 95% CIs were extracted and pooled by a random-effects model. Five studies involving 8908 NOACs and 12 440 warfarin users were included. There were no significant associations between cancer status and risks of stroke or systemic embolism, major bleeding, or death in AF patients. Compared with warfarin, NOACs were associated with decreased risks of stroke or systemic embolism (RR, 0.52; 95% CI, 0.28-0.99), venous thromboembolism (RR, 0.37, 95% CI, 0.22-0.63), and intracranial or gastrointestinal bleeding (RR, 0.65; 95% CI, 0.42-0.98) and with borderline significant reductions in ischemic stroke (RR, 0.63; 95% CI, 0.40-1.00) and major bleeding (RR, 0.73; 95% CI, 0.53-1.00). In addition, risks of efficacy and safety outcomes of NOACs versus warfarin were similar between AF patients with and without cancer. Conclusions In patients with AF and cancer, compared with warfarin, NOACs had lower or similar rates of thromboembolic and bleeding events and posed a reduced risk of venous thromboembolism.
Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Venous Thromboembolism; Warfarin
PubMed: 31310583
DOI: 10.1161/JAHA.119.012540