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Frontiers in Pharmacology 2023Metastatic castration-resistant prostate cancer (mCRPC) presents significant treatment selection challenges due to limited therapeutic options. This study aimed to...
Metastatic castration-resistant prostate cancer (mCRPC) presents significant treatment selection challenges due to limited therapeutic options. This study aimed to comprehensively assess the efficacy of multiple treatment regimens for mCRPC through a network meta-analysis (NMA) of randomized controlled trials (RCTs). A systematically comprehensive search for randomized controlled trials (RCTs) was performed in Pubmed, Cochrane Library, Embase, and Web of Science databases. The network meta-analysis was employed to compare the overall survival (OS), progression-free survival (PFS), and radiographic progression-free survival (rPFS) among different interventions at specific time points. This study was prospectively registered with PROSPERO (CRD42023422823). A total of 29 RCTs, involving 12,706 patients and investigating 16 interventions, were included in the analysis. Chempretarget ((capivasertib or cabozantinib) + docetaxel + prednisone)) and PARP (Olaparib or rucaparib) inhibitors emerged as interventions that significantly improved survival outcomes compared to first-line treatment in mCRPC patients. Chempretarget demonstrated superior overall survival starting from the 12th month, while PARP inhibitors showed a clear advantage in progression-free survival within the 3-18 months range. Notably, chempre ((Docetaxel or Cabazitaxel) + prednisone) exhibited favorable performance in radiographic progression-free survival during the 3-18 month period. Our findings underscore the efficacy of chempretarget, PARP inhibitors, and chempre in enhancing survival outcomes for mCRPC patients. Further head-to-head comparisons are warranted to validate these results. These findings carry important implications for treatment decision-making in mCRPC and may guide the development of more effective therapeutic strategies.
PubMed: 38074136
DOI: 10.3389/fphar.2023.1290990 -
The Journal of Clinical Endocrinology... May 2024Synthetic glucocorticoids are widely used to treat patients with a broad range of diseases. While efficacious, glucocorticoids can be accompanied by neuropsychiatric... (Meta-Analysis)
Meta-Analysis
CONTEXT
Synthetic glucocorticoids are widely used to treat patients with a broad range of diseases. While efficacious, glucocorticoids can be accompanied by neuropsychiatric adverse effects.
OBJECTIVE
This systematic review and meta-analysis assesses and quantifies the proportion of different neuropsychiatric adverse effects in patients using synthetic glucocorticoids.
METHODS
Six electronic databases were searched to identify potentially relevant studies. Randomized controlled trials, cohort studies, and cross-sectional studies assessing psychiatric side effects of glucocorticoids measured with validated questionnaires were eligible. Risk of bias was assessed with RoB 2, ROBINS-I, and AXIS appraisal tool. For proportions of neuropsychiatric outcomes, we pooled proportions, and when possible, differences in questionnaire scores between glucocorticoid users and nonusers were expressed as standardized mean differences (SMD). Data were pooled in a random-effects logistic regression model.
RESULTS
We included 49 studies with heterogeneity in study populations, type, dose, and duration of glucocorticoids. For glucocorticoid users, meta-analysis showed a proportion of 22% for depression (95% CI, 14%-33%), 11% for mania (2%-46%), 8% for anxiety (2%-25%), 16% for delirium (6%-36%), and 52% for behavioral changes (42%-61%). Questionnaire scores for depression (SMD of 0.80 [95% CI 0.35-1.26]), and mania (0.78 [0.14-1.42]) were higher than in controls, indicating more depressive and manic symptoms following glucocorticoid use.
CONCLUSION
The heterogeneity of glucocorticoid use is reflected in the available studies. Despite this heterogeneity, the proportion of neuropsychiatric adverse effects in glucocorticoid users is high. The most substantial associations with glucocorticoid use were found for depression and mania. Upon starting glucocorticoid treatment, awareness of possible psychiatric side effects is essential. More structured studies on incidence and potential pathways of neuropsychiatric side effects of prescribed glucocorticoids are clearly needed.
Topics: Humans; Glucocorticoids; Mental Disorders
PubMed: 38038629
DOI: 10.1210/clinem/dgad701 -
Journal of Personalized Medicine Nov 2023The nasal microbiome represents the main environmental factor of the inflammatory process in chronic rhinosinusitis (CRS). Antibiotics and steroids constitute the... (Review)
Review
BACKGROUND
The nasal microbiome represents the main environmental factor of the inflammatory process in chronic rhinosinusitis (CRS). Antibiotics and steroids constitute the mainstay of CRS therapies. However, their impact on microbial communities needs to be better understood. This systematic review summarizes the evidence about antibiotics' and steroids' impact on the nasal microbiota in patients with CRS.
METHODS
The search strategy was conducted in accordance with the PRISMA guidelines for systematic reviews. The authors searched all papers in the three major medical databases (PubMed, Scopus, and Cochrane Library) using the PICO tool (population, intervention, comparison, and outcomes). The search was carried out using a combination of the key terms "Microbiota" or "Microbiome" and "Chronic Rhinosinusitis".
RESULTS
Overall, 402 papers were identified, and after duplicate removal (127 papers), excluding papers off-topic (154) and for other structural reasons (110), papers were assessed for eligibility; finally, only 11 papers were included and summarized in the present systematic review. Some authors used only steroids, other researchers used only antibiotics, and others used both antibiotics and steroids. With regard to the use of steroids as exclusive medical treatment, topical mometasone and budesonide were investigated. With regard to the use of antibiotics as exclusive medical treatments, clarithromycin, doxycycline, roxithromycin, and amoxicillin clavulanate were investigated. Regarding the use of both antibiotics and steroids, two associations were investigated: systemic prednisone combined with amoxicillin clavulanate and topical budesonide combined with azithromycin.
CONCLUSIONS
The impact that therapies can have on the nasal microbiome of CRS patients is very varied. Further studies are needed to understand the role of the nasal microbiome, prevent CRS, and improve therapeutic tools for personalized medicine tailored to the individual patient.
PubMed: 38003898
DOI: 10.3390/jpm13111583 -
Biomedicines Sep 2023The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence... (Review)
Review
The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others.
PubMed: 37761003
DOI: 10.3390/biomedicines11092562 -
Cancers Aug 2023Patients with diffuse large B-cell lymphoma (DLBCL) are treated with rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).... (Review)
Review
Consolidative Radiotherapy after Complete Remission following R-CHOP Immunochemotherapy in Stage III-IV Diffuse Large B-Cell Lymphoma Patients: A Systematic Review and Meta-Analysis.
Patients with diffuse large B-cell lymphoma (DLBCL) are treated with rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). The role of consolidative radiation therapy (RT) remains unclear among patients with advanced DLBCL who achieved complete remission (CR) after R-CHOP immunochemotherapy. The current systematic review and meta-analysis aimed to clarify the role of consolidative RT among these patients. The MEDLINE, Embase, and Cochrane Library databases were searched for studies comparing RT to no RT following CR after R-CHOP immunochemotherapy in Ann Arbor stage III-IV DLBCL patients. Overall survival (OS) was the primary endpoint, and disease-free survival (DFS) was the secondary endpoint. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the primary and secondary outcomes. Review Manager (version 5.4) was used to analyze the data. Six retrospective studies involving 813 patients who received R-CHOP ± consolidative RT were identified. OS was higher in the consolidative RT group, with an HR of 2.01 and a 95% CI of 1.30 to 3.12 ( = 0.002). DFS was also higher in the RT group, with an HR of 2.18 and a 95% CI of 1.47 to 3.24 ( < 0.0001). The results suggested that consolidative RT improved OS and DFS compared to no RT among advanced-stage DLBCL patients. Further research is needed to determine the optimal radiation fields and the appropriate indications for consolidative RT for advanced-stage DLBCL patients in the rituximab era.
PubMed: 37568756
DOI: 10.3390/cancers15153940 -
Frontiers in Oncology 2023The best choice of first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. We aimed to compare the effectiveness and safety determined...
BACKGROUND
The best choice of first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. We aimed to compare the effectiveness and safety determined in randomized clinical trials of doublet and triplet treatments for mHSPC.
METHODS
Medline, Embase, Cochrane Central and ClinicalTrials.gov were searched from inception through July 01, 2022. Eligible studies were phase III randomized clinical trials evaluating androgen deprivation treatment (ADT) alone, doublet therapies [ADT combined with docetaxel (DOC), novel hormonal agents (NHAs), or radiotherapy (RT)], or triplet therapies (NHA+DOC+ADT) as first-line treatments for mHSPC. Outcomes of interest included overall survival (OS), progression-free survival (PFS) and grades 3-5 adverse events (AEs). Subgroup analyses were performed based on tumor burden. The effects of competing treatments were assessed by Bayesian network meta-analysis using R software.
RESULTS
Ten trials with 12,298 patients comparing nine treatments were included. Darolutamide (DARO) +DOC+ADT ranked best in terms of OS benefits (OR 0·52 [95% CI 0·39-0·70]), but its advantages were all statistically insignificant compared with other therapy options except for DOC+ADT (OR 0·68 [95% CI 0·53-0·88]) and RT+ADT (OR 0·57 [95% CI 0·40-0·80]). In terms of PFS, enzalutamide(ENZA)+DOC+ADT (OR 0·32 [95% CI 0·24-0·44]) and abiraterone and prednisone (AAP) +DOC+ADT (OR 0·33 [95% CI 0·25-0·45]) ranked best. For patients with high volume disease (HVD), low volume disease (LVD), and visceral metastases, the optimal therapies were AAP+DOC+ADT (OR 0·52 [95% CI 0·33-0·83]), apalutamide+ADT (OR 0·52 [95% CI 0·26-1·05]) and DARO+DOC+ADT (OR 0·42 [95% CI 0·13-1·34]), respectively. For safety, AAP+DOC+ADT (OR 3·56 [95% CI 1·51-8·43]) ranked worst with the highest risk of grade 3-5 AEs.
CONCLUSIONS
Triple therapies may further improve OS and PFS but may be associated with a decrease in safety. Triplet therapies could be suggested for HVD patients, while doublet combinations should still be preferred for LVD patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPEROFILES/303117_STRATEGY_20220202.pdf, identifier CRD4202303117.
PubMed: 36959793
DOI: 10.3389/fonc.2023.1104242 -
Journal of Medicine and Life Feb 2023A promising strategy for controlling repeated implantation failure (RIF) may be the use of hydroxychloroquine (HCQ). To the best of our knowledge, no systematic review... (Meta-Analysis)
Meta-Analysis Review
A promising strategy for controlling repeated implantation failure (RIF) may be the use of hydroxychloroquine (HCQ). To the best of our knowledge, no systematic review has been conducted on the effects of hydroxychloroquine on pregnancy outcomes. A systematic research of the following electronic databases was conducted: Cochrane, EMBASE-Ovid, PubMed, Web of Science, and Scopus from inception to December 2021, using the following keywords [hydroxychloroquine] AND [infertility]. Fertilization and rate of live birth were significantly higher in the HCQ+ prednisone (PDN) group than in the PDN alone group. However, the abortion rate was not different between the two groups. The meta-analysis of two studies revealed no statistical significance between the PDN group and HCQ+PDN group regarding clinical pregnancy rate (OR=.14 [95%CI: 0.4-4.370]; heterogeneity; P=0.13; I2=54%; random effect model) and implantation rate (OR=1.99 [95%CI: 0.94-4.2]; heterogeneity; P=0.37; I2=0%; fixed-effect model). While HCQ may help improve fertilization and live birth rates, adding it to prednisone did not improve overall pregnancy outcomes. This systematic review should be used with caution due to the small size, study design, and difference in the studies' population.
Topics: Pregnancy; Female; Humans; Pregnancy Outcome; Hydroxychloroquine; Infertility, Female; Prednisone; Live Birth
PubMed: 36937474
DOI: 10.25122/jml-2022-0095 -
The Cochrane Database of Systematic... Feb 2023IgA vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is the most common vasculitis of childhood but may also occur in adults. This small vessel... (Review)
Review
BACKGROUND
IgA vasculitis (IgAV), previously known as Henoch-Schönlein purpura, is the most common vasculitis of childhood but may also occur in adults. This small vessel vasculitis is characterised by palpable purpura, abdominal pain, arthritis or arthralgia and kidney involvement. This is an update of a review first published in 2009 and updated in 2015.
OBJECTIVES
To evaluate the benefits and harms of different agents (used singularly or in combination) compared with placebo, no treatment or any other agent for (1) the prevention of severe kidney disease in people with IgAV with or without kidney involvement at onset, (2) the treatment of established severe kidney disease (macroscopic haematuria, proteinuria, nephritic syndrome, nephrotic syndrome with or without acute kidney failure) in IgAV, and (3) the prevention of recurrent episodes of IgAV-associated kidney disease.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 2 February 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (RCTs) comparing interventions used to prevent or treat kidney disease in IgAV compared with placebo, no treatment or other agents were included.
DATA COLLECTION AND ANALYSIS
Two authors independently determined study eligibility, assessed the risk of bias and extracted data from each study. Statistical analyses were performed using the random-effects model, and the results were expressed as risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Twenty studies (1963 enrolled participants) were identified; one three-arm study has been assessed as two studies. Nine studies were at low risk of bias for sequence generation (selection bias), and nine studies were at low risk of bias for allocation concealment (selection bias). Blinding of participants and personnel (performance bias) and outcome assessment (detection bias) was at low risk of bias in four and seven studies, respectively. Nine studies reported complete outcome data (attrition bias), while 10 studies reported expected outcomes, so were at low risk of reporting bias. Five studies were at low risk of other bias. Eleven studies evaluated therapy to prevent persistent kidney disease in IgAV with or without kidney involvement at presentation. There was probably no difference in the risk of persistent kidney disease any time after treatment (5 studies, 746 children: RR 0.74, 95% CI 0.42 to 1.32) or at one, three, six and 12 months in children given prednisone for 14 to 28 days at presentation of IgAV compared with placebo or supportive treatment (moderate certainty evidence). There may be no differences in the risk of any persistent kidney disease with antiplatelet therapy (three studies) or heparin (two studies) in children with or without any kidney disease at study entry, although heparin may reduce the risk of proteinuria by three months compared with placebo or no specific treatment (2 studies, 317 children: RR 0.47, 95% CI 0.31 to 0.73). One study comparing montelukast with placebo found no differences in outcomes as assessed by severity scale scores. Nine studies examined the treatment of severe IgAV-associated kidney disease. In two studies (one involving 56 children and the other involving 54 adults), there may be no differences in efficacy outcomes or adverse effects with cyclophosphamide compared with placebo or supportive treatment. In two studies, there may be no differences in the numbers achieving remission of proteinuria with intravenous (IV) cyclophosphamide compared with mycophenolate mofetil (MMF) (65 children evaluated) or tacrolimus (142 children evaluated). In three small studies comparing cyclosporin with methylprednisolone (15 children), MMF with azathioprine (26 children), or MMF with leflunomide (19 children), it is unclear whether the treatment had any effect on the numbers in remission or the degree of proteinuria between treatment groups because of small numbers of included participants. In one study comparing plasmapheresis, cyclophosphamide and methylprednisolone with cyclophosphamide and methylprednisolone, there may be no difference in the numbers achieving remission. One study compared fosinopril with no specific therapy and reported fosinopril reduced the number of participants with proteinuria. No studies were identified that evaluated the efficacy of therapy on kidney disease in participants with recurrent episodes of IgAV.
AUTHORS' CONCLUSIONS
There are no substantial changes in conclusions from this update compared with the initial review or the previous update despite the addition of five studies. From generally low to moderate certainty evidence, we found that there may be little or no benefit in the use of corticosteroids or antiplatelet agents to prevent persistent kidney disease in children with IgAV in participants with no or minimal kidney involvement at presentation. We did not find any studies which evaluated corticosteroids in children presenting with IgAV and nephritic and/or nephrotic syndrome, although corticosteroids are recommended in such children in guidelines. Though heparin may be effective in reducing proteinuria, this potentially dangerous therapy is not justified to prevent serious kidney disease when few children with IgAV develop severe kidney disease. There may be no benefit of cyclophosphamide compared with no specific treatment or corticosteroids. While there may be no benefit in the efficacy of MMF or tacrolimus compared with IV cyclophosphamide in children or adults with IgAV and severe kidney disease, adverse effects, particularly infections, may be lower in MMF or tacrolimus-treated children. Because of small patient numbers and events leading to imprecision in results, it remains unclear whether cyclosporin, MMF or leflunomide have any role in the treatment of children with IgAV and severe kidney disease. We did not identify any studies which evaluated corticosteroids.
Topics: Adult; Child; Humans; Fosinopril; IgA Vasculitis; Kidney Diseases; Leflunomide; Proteinuria; Tacrolimus; Vasculitis
PubMed: 36853224
DOI: 10.1002/14651858.CD005128.pub4 -
Journal of Clinical and Experimental... Jan 2023Sjogren's Syndrome (SS) is characterized by xeropthalmia and/or xerostomia. Treating the associated salivary gland hypofunction has been challenging to the clinicians. A... (Review)
Review
BACKGROUND
Sjogren's Syndrome (SS) is characterized by xeropthalmia and/or xerostomia. Treating the associated salivary gland hypofunction has been challenging to the clinicians. A variety of topical and systemic therapies have been tried to restore/stimulate the gland function or replace saliva reducing the symptoms of xerostomia and to avoid the problems of diminished salivary flow.
MATERIAL AND METHODS
Four search engines (PUBMED/Medline, EMBASE, Google Scholar and The Cochrane) were used in conducting a systematic review using the terms "Sjogren's syndrome" with the combination of other terms. To define these study acceptability criteria, we used PICO model (Population, Intervention, Control and Outcome) and study design technique.
RESULTS
Out of 47 articles initially screened, 28 studies met our selection criteria. Included studies showed positive results with interventions such as pilocarpine, rituximab, and interferon-alpha (IFN-α) for enhancing salivary flow and lacrimal secretion in SS condition. One study showed promising results for combination of prednisone and hydroxychloroquine in SS, however dose of prednisone is recommended to be tapered. Another study demonstrated comparable effects of dehydroepiandrosterone and the placebo in alleviation of dry mouth symptoms (=0.006). Therapeutic effects have been reported with LASER therapy.
CONCLUSIONS
Pilocarpine was found to be highly beneficial whereas, rituximab and IFN-α were moderately effective in the reduction of hyposalivation in SS patient. Adverse events were common. Use of any alternative modalities for the management cannot be supported based on the current evidence; this demands more studies in future to be conducted staking into account adverse effects which might occur particularly with the pharmacological therapies. Sjogren's Syndrome, Xerostomia, Hyposalivation, Pilocarpine, Rituximab, Sialagogue.
PubMed: 36755678
DOI: 10.4317/jced.59891 -
Indian Journal of Otolaryngology and... Dec 2022There is limited knowledge in the literature and lack of clear protocols among practitioners regarding preoperative steroids administration for patients undergoing...
There is limited knowledge in the literature and lack of clear protocols among practitioners regarding preoperative steroids administration for patients undergoing endoscopic sinus surgery (ESS). This study aimed to identify the practice patterns of rhinologists in Saudi Arabia as well as systematically review all health-related evidence regarding the use of preoperative steroids for ESS. A previously used questionnaire was modified and distributed in Saudi Arabia among rhinologists who finished their residency training. It entailed questions about their qualifications and preoperative steroids use, preferred regimen, and possible benefits. Also, a systematic literature review using four major databases was conducted to build a scoping view of the current evidence. A total of 94 subjects responded to the mailed survey. Of them, 72(76.6%) used preoperative steroids; 40 subjects believed that there is a strong supporting evidence while 32 reported that there is no solid evidence. The commonest indication was chronic rhinosinusitis with nasal polyp followed by allergic fungal rhinosinusitis. More than half of subjects (54.2%) preferred medium-dose prednisone (30-40 mg/day). A considerable number believed that steroids decreased surgical bleeding (n = 57, 79.2%), improved surgical field visualization (77.8%), decreased surgical time (77.8%), and decreased mucosal inflammation (61.1%). Thirteen studies including 1028 patients were eligible for the systematic review. Only three studies reported a statistically significant effect of steroids in reducing intraoperative hemorrhage, while only two studies revealed that steroids significantly improved surgical field quality. In two studies, steroids showed a significant effect in reducing eosinophil infiltration. There is a major number of rhinology experts using preoperative steroids for patients undergoing ESS but there is a wide variation among their practice patterns. The current potential advantages of steroids need to be supported by further large randomized clinical trials to establish clear guidelines.
PubMed: 36742850
DOI: 10.1007/s12070-021-02888-z