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Pain Reports 2022Pain is highly prevalent in patients with cancer-nearly 40% report moderate-severe pain, which is commonly treated with opioids. Increasing cancer survivorship, opioid... (Review)
Review
Pain is highly prevalent in patients with cancer-nearly 40% report moderate-severe pain, which is commonly treated with opioids. Increasing cancer survivorship, opioid epidemics in some regions of the world, and limited opioid access in other regions have focused attention on nonopioid treatments. Given the limitations of monotherapy, combining nonopioids-such as antiepileptics and antidepressants-have shown promise in noncancer pain. This review seeks to evaluate efficacy of nonopioid combinations for cancer-related pain. Systematic searches of PubMed, EMBASE, and Cochrane CENTRAL were conducted for double-blind, randomized, controlled trials comparing a nonopioid combination with at least one of its components and/or placebo. This search yielded 4 randomized controlled trials, published between 1998 and 2019 involving studies of (1) imipramine + diclofenac; (2) mitoxantrone + prednisone + clodronate; (3) pentoxifylline + tocopherol + clodronate; and (4) duloxetine + pregabalin + opioid. In the first 3 of these trials, trends favouring combination efficacy failed to reach statistical significance. However, in the fourth trial, duloxetine + pregabalin + opioid was superior to pregabalin + opioid. This review illustrates recognition for the need to evaluate nonopioid drug combinations in cancer pain, although few trials have been published to date. Given the growing practice of prescribing more than 1 nonopioid for cancer pain and the need to expand the evidence base for rational combination therapy, more high-quality trials in this area are needed.
PubMed: 35261931
DOI: 10.1097/PR9.0000000000000995 -
Cancers Jul 2021MYC/BCL2 protein co-expression (i.e., double expressor) has been shown to be a negative predictor of outcome in diffuse large B-cell lymphoma (DLBCL). We aimed to... (Review)
Review
MYC/BCL2 protein co-expression (i.e., double expressor) has been shown to be a negative predictor of outcome in diffuse large B-cell lymphoma (DLBCL). We aimed to establish the incidence of double expressor status in patients with de novo DLBCL and identify the predictive value of this biomarker on treatment response through systematic review and meta-analysis. PubMed and Embase were searched for studies published through December 2019 that reported proportions of double expressor DLBCL. The pooled proportions of MYC and BCL2 expression, both alone and in combination, were computed using the inverse variance method for calculating weights and by the DerSimonian-Laird method. The pooled odds ratios (ORs) of complete remission (CR) rate were calculated, and meta-regression analysis was conducted to explore heterogeneity. Forty-one studies (7054 patients) were included. The pooled incidence of double expressor status in DLBCL was 23% (95% confidence interval [CI], 20-26%), with an adjusted estimate of 31% (95% CI, 27-36%). Neither MYC/BCL2 protein cutoff values, race, mean, or median age of included patients, or overall study quality was a significant factor of heterogeneity ( ≥ 0.20). Cases without double expressor status demonstrated a higher probability of CR to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone treatment (OR, 2.69; 95% CI, 1.55-4.67). Our results reaffirm the predictive power of this important biomarker.
PubMed: 34282799
DOI: 10.3390/cancers13133369 -
Clinical Genitourinary Cancer Oct 2023While abiraterone acetate (AA) has demonstrated survival benefit in advanced prostate cancer (APC), meaningful cardiotoxicity is observed. It is unclear whether the... (Meta-Analysis)
Meta-Analysis Review
Association between RCT methodology and disease indication with mineralocorticoid-related toxicity for patients receiving abiraterone acetate for advanced prostate cancer: A meta-analysis of RCTs.
INTRODUCTION
While abiraterone acetate (AA) has demonstrated survival benefit in advanced prostate cancer (APC), meaningful cardiotoxicity is observed. It is unclear whether the magnitude differs based on disease indication and concurrent steroid administration.
METHODS
We performed a systematic review and meta-analysis of phase II/III RCTs of AA in APC published as of August 11, 2020. Primary outcomes examined were all- and high-grade (grade ≥ 3) hypokalemia and fluid retention, and secondary outcomes included hypertension and cardiac events. We performed random effects meta-analysis comparing intervention (AA + steroid) and control (placebo ± steroid), stratified by treatment indication and whether patients received steroids.
RESULTS
Among 2,739 abstracts, we included 6 relevant studies encompassing 5901 patients. Hypokalemia and fluid retention were observed more frequently among patients receiving AA (odds ratio [OR] 3.10 [95% CI 1.69-5.67] and 1.41 [95% CI 1.19-1.66]). This was modified by whether patients in the control received steroids: trials where control patients did not demonstrated a larger association between AA and hypokalemia (OR 6.88 [95% CI 1.48-2.36] versus OR 1.86 [95% CI 4.97-9.54], P < .0001) and hypertension (OR 2.53 [95% CI 1.91-3.36] vs. OR 1.55 [95% CI 1.17-2.04], P = .1) than those where steroids were administered. We observed heterogeneity due to indication: there were greater effects on hypokalemia (P < 0001), hypertension (P = .03), and cardiac disorders (P = .01) among patients treated for mHSPC than mCRPC.
CONCLUSIONS
The magnitude of cardiotoxicity with AA differs based on trial design and disease indication. These data are valuable in treatment decisions and highlight utilization of appropriate data for counseling.
Topics: Male; Humans; Abiraterone Acetate; Mineralocorticoids; Prednisone; Prostatic Neoplasms, Castration-Resistant; Hypokalemia; Cardiotoxicity; Antineoplastic Combined Chemotherapy Protocols; Hypertension; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37236862
DOI: 10.1016/j.clgc.2023.04.007 -
Frontiers in Medicine 2022Facial seborrheic dermatitis (FSD), also called facial seborrheic eczema, is a common disease affecting both male and female patients worldwide. Tanshinone is the main...
BACKGROUND
Facial seborrheic dermatitis (FSD), also called facial seborrheic eczema, is a common disease affecting both male and female patients worldwide. Tanshinone is the main bioactive component extracted from the Traditional Chinese Medicine , which is widely used in treating skin inflammatory diseases. It is necessary to evaluate the clinical evidence for tanshinone capsule treatment of FSD. This study aimed to evaluate the safety and effectiveness of tanshinone capsules combined with prednisone in the treatment of facial seborrheic dermatitis and to provide evidence for clinical practice.
METHODS
Studies were searched in PubMed, the Cochrane Library, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, the Chinese Scientific Journal Database, and WanFang Database before October 2021. We also searched for randomized controlled clinical trials (RCT) of tanshinone capsules combined with prednisone on facial seborrheic dermatitis. The meta-analysis was conducted according to the guidelines of the Cochrane Handbook. Two reviewers regulated the research selection, data extraction, and risk of bias assessment, respectively, and a third reviewer was used for consulting when necessary. Review Manager Software 5.3 was used for meta-analysis.
RESULTS
A total of 10 RCTs with 916 participants were included. Nine studies reported total effectiveness, five studies reported symptom score, seven studies reported adverse events, and four studies reported recurrence rate. The duration of treatment was 4 to 8 weeks. Combination therapy showed better clinical effects compared to the prednisone (OR: 5.82; 95% CI: 3.53, 9.59; < 0.00001). Combination therapy could repair skin lesions (MD: -0.40; 95% CI: -0.51, -0.30; < 0.00001), reduce skin erythema (MD: -0.58, 95% CI: -0.67, -0.49; < 0.00001), relieve skin itch (MD: -0.70; 95% CI -0.77, -0.63; < 0.00001), and desquamation score (MD: -0.64; 95% CI: -0.71, -0.56; < 0.00001). Furthermore, combination therapy could reduce adverse events (OR: 0.46; 95% CI: 0.26, 0.84; = 0.01) and control recurrence rate (OR: 0.22; 95% CI: 0.13, 0.36; < 0.00001).
CONCLUSIONS
Compared with prednisone, tanshinone capsules combined with prednisone may be effective in the treatment of facial seborrheic dermatitis. However, due to the high risk and ambiguity of bias in the included trials, the conclusion of this study must be interpreted carefully.
PubMed: 35572959
DOI: 10.3389/fmed.2022.816419 -
Clinical Genitourinary Cancer Dec 2022The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly modified by the availability of innovative but expensive... (Review)
Review
The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been significantly modified by the availability of innovative but expensive treatments, increasing the economic burden of prostate cancer. Here, we aimed to systematically identify and review published economic evaluations (EEs) related to the treatment of mHSPC and assess their quality. A systematic search was performed of the PubMed and Cochrane databases. Three reviewers independently selected EEs by defined inclusion and exclusion criteria. They extracted all data from each EE (general information, study population, data about the EE, interventions and comparators, and outcomes). They also assessed the quality of the selected EEs according to Drummond's checklist. Fourteen EEs published between 2016 and 2021 were eligible for the systematic review. The EEs found ADT + docetaxel to be the most cost-effective of all available treatments as a first-line strategy for mHSPC (abiraterone acetate plus prednisone, enzalutamide, and apalutamide). Five EEs showed that a simple price reduction of abiraterone acetate of 50% to 75% could change the results to render this treatment also cost-effective relative to that with docetaxel. Twelve EEs were of high quality, with a Drummond score ≥ 7. Analysis of the 14 EEs identified by our systematic review, amongst which 78.6% met high quality standards, showed that ADT + docetaxel tends to be the most cost-effective alternative for mHSPC. These results were assessed by sensitivity analysis. The data provided by this systematic review help to provide a better understanding of these treatments and the better use of healthcare resources.
Topics: Male; Humans; Docetaxel; Abiraterone Acetate; Cost-Benefit Analysis; Treatment Outcome; Prostatic Neoplasms; Hormones
PubMed: 35610112
DOI: 10.1016/j.clgc.2022.04.014 -
Arthritis & Rheumatology (Hoboken, N.J.) May 2024Our objective was to evaluate the effect of glucocorticoid regimens on renal response, infections, and mortality among patients with lupus nephritis (LN).
Impact of Glucocorticoid Dose on Complete Response, Serious Infections, and Mortality During the Initial Therapy of Lupus Nephritis: A Systematic Review and Meta-Analysis of the Control Arms of Randomized Controlled Trials.
OBJECTIVE
Our objective was to evaluate the effect of glucocorticoid regimens on renal response, infections, and mortality among patients with lupus nephritis (LN).
METHODS
We performed a systematic review and meta-analysis of the control arms of randomized clinical trials (RCTs). We included RCTs of biopsy-proven LN that used a protocolized regimen of glucocorticoids in combination with mycophenolic acid analogs or cyclophosphamide and reported the outcomes of complete response (CR), serious infections, and death. The starting dosage of glucocorticoids, tapering method, and administration of glucocorticoid pulses were abstracted. Meta-analysis of proportions, meta-regression, and subgroup meta-analysis were performed at 6 and 12 months for all outcomes.
RESULTS
Fifty RCT arms (3,231 patients with LN) were included. The predicted rates of CR, serious infections, and death when starting on oral prednisone at 25 mg/day without pulses were 19.5% (95% confidence interval [CI] 7.3-31.5), 3.2% (95% CI 2.4-4.0), and 0.2% (95% CI 0.0-0.4), respectively. Starting on prednisone at 60 mg/day (without pulses) increased the rates to 34.6% (95% CI 16.9-52.3), 12.1% (95% CI 9.3-14.9), and 2.7% (95% CI 0.0-5.3), respectively. Adding glucocorticoid pulses increased the rates of CR and death but not serious infections. We observed a dose-response gradient between the initial glucocorticoid dosage and all the outcomes at six months after accounting for the administration of glucocorticoid pulses, underlying immunosuppressant, and baseline proteinuria.
CONCLUSION
A higher exposure to glucocorticoids during the initial therapy of LN was associated with better renal outcomes at the cost of increased infections and death.
PubMed: 38766897
DOI: 10.1002/art.42920 -
Cureus Dec 2023Intravascular lymphoma (IVL) is an aggressive systemic large B-cell lymphoma that is a rare cause of stroke. The clinical characteristics of stroke associated with IVL... (Review)
Review
Intravascular lymphoma (IVL) is an aggressive systemic large B-cell lymphoma that is a rare cause of stroke. The clinical characteristics of stroke associated with IVL remain underexplored, contributing to diagnostic complexities and a high mortality rate. This study endeavors to elucidate the salient clinical and investigative features of stroke linked to this condition. A systematic review was performed using the PubMed database from the incident to August 2023 including search categories for IVL and stroke. All studies, excluding review articles, were included in this study. There were 58 cases with a confirmed diagnosis of IVL associated with stroke, with a mean age of 62.9 ± 9.6 years (female 50%). Classical lateralizing stroke symptoms were noted in only 69% of cases. Other clinical syndromes included altered sensorium (31%), rapidly progressive cognitive impairment (23%), seizures (22%), and gait disturbances (19%). Common hematological abnormalities included elevated lactate dehydrogenase (LDH, 97%), erythrocyte sedimentation rate (ESR, 79%), C-reactive protein (CRP, 61%), interleukin-2, microglobulins, and cerebrospinal fluid (CSF) protein. CSF flow cytometry was not diagnostic, and cytology was mostly negative. The dynamic pattern for DWI/T2 lesions was predominant and primarily located in the subcortical regions. Diffuse background slowing (64%) was a major finding in the electroencephalogram. Seventy-one percent of cases died (n=45) mostly due to delayed diagnosis. Only 31% were treated with first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, prednisone) chemotherapy, among whom 25% died. This study suggests that IVL-associated strokes carry a high mortality rate, largely due to challenges in timely diagnosis and therapy. Unlike classical stroke syndrome, key indicators to aid in early diagnosis include a clinical syndrome of multiple non-lateralizing neurological symptoms, dynamic MRI DWI/T2-lesions primarily located in subcortical regions, elevated serum LDH, ESR, CRP, interleukins, microglobulin, CSF protein, and CSF polymerase chain reaction analysis, apart from tissue examination. Larger studies should be performed to establish diagnostic and predictive scores.
PubMed: 38249220
DOI: 10.7759/cureus.50896 -
PloS One 2021Evidence on the use of non-steroidal anti-inflammatory drugs (NSAIDs) and corticoids for rheumatoid arthritis (RA) is inconclusive and is not up to date. This systematic...
Evidence on the use of non-steroidal anti-inflammatory drugs (NSAIDs) and corticoids for rheumatoid arthritis (RA) is inconclusive and is not up to date. This systematic review assessed the effectiveness and safety of these anti-inflammatories (AI) in the treatment of RA. COCHRANE (CENTRAL), MEDLINE, EMBASE, CINAHL, Web of Science and Virtual Health Library were searched to identify randomized controlled trials (RCT) with adults which used AI (dose represented in mg/day) compared with placebo or active controls and was carried out up to December of 2019. Reviewers, in pairs and independently, selected studies, performed the data extraction and assessed the risk of bias. The quality of the evidence was assessed by GRADE. Network meta-analyses were performed using the Stata v.14.2. Twenty-six articles were selected (NSAIDs = 21 and corticoids = 5). Naproxen 1,000 improved physical function, reduced pain and the number of painful joints compared to placebo. Etoricoxib 90 reduced the number of painful joints compared to placebo. Naproxen 750 reduced the number of swollen joints, except for etoricoxib 90. Naproxen 1,000, etoricoxib 90 and diclofenac 150 were better than placebo regarding patient assessment. Assessment physician showed that NSAIDs were better than placebo. Meta-analyses were not performed for prednisolone and prednisone. Naproxen 1,000 was the most effective drug and celecoxib 200 showed fewer adverse events. However, the low quality of the evidence observed for the outcomes with NSAIDs, the absence of meta-analyses to assess the outcomes with corticoids, as well as the risk of bias observed, indicate that future RCT can confirm such findings.
Topics: Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Female; Humans; Male; Middle Aged; Network Meta-Analysis
PubMed: 33826610
DOI: 10.1371/journal.pone.0248866 -
Journal of Osteopathic Medicine Apr 2023Rheumatoid arthritis (RA) is a systemic autoimmune disease that commonly affects joints. Although many treatment options exist, the most common, disease-modifying... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Rheumatoid arthritis (RA) is a systemic autoimmune disease that commonly affects joints. Although many treatment options exist, the most common, disease-modifying antirheumatic drugs (DMARDs), have been associated with pulmonary infections. These types of infections (specifically pneumonia) can be detrimental to RA patients. This leads providers to utilize other treatment modalities such as glucocorticoids (GCs). GCs are commonly utilized to treat RA; however, the role of GCs in the onset of pneumonia in RA patients is not fully understood.
OBJECTIVES
The goal of this study was to systematically review and statistically analyze pooled data documenting pneumonia as an adverse event in RA patients on DMARDs as a monotherapy vs RA patients on DMARDs and GCs as combination therapy utilizing the Population, Intervention, Comparison, and Outcomes (PICO) framework.
METHODS
On August 1, 2021, a search was conducted and completed on six databases: Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, International Pharmaceutical Abstracts (IPA), and ClinicalTrials.gov. A total of 12 researchers were involved with the search and screening of articles (K.E., P.R.; V.A., D.P.C.; C.B., D.C.; T.A., E.S.; S.H., L.B.; K.S., C.S.). Search terms were identified utilizing Medical Subject Headings (MeSH) and Emtree and included "glucocorticoids," "rheumatoid arthritis," "pneumonia," and "respiratory tract infections," Inclusion criteria included human subjects over the age of 18 with seropositive RA, on a combination of GC (prednisone, methylprednisolone, or prednisolone) with DMARD (methotrexate [MTX], hydroxychloroquine [HCQ], or sulfasalazine [SSZ]) and developed pneumonia of bacterial, viral, or fungal origin. The control groups were on a DMARD monotherapy regimen. Articles were excluded if they were not in English, had less than 20 participants, were case reports or literature reviews, included animal subjects, and did not adhere to the established PICO framework. Five teams of two researchers individually sorted through abstracts of articles based on the inclusion and exclusion criteria. The same teams individually sorted through full-text articles of selected abstracts based on the same criteria. Conflicts between each team were resolved by a separate researcher. Odds ratios were utilized to quantify the effect sizes of combined studies from a random effects model. Chi-square tests and I2 statistics were utilized to analyze heterogeneity.
RESULTS
A total of 3360 articles were identified from all databases, and 416 duplicate articles were removed. Thus, a total of 2944 articles abstracts were screened, of which 2819 articles either did not meet the inclusion criteria or did meet the exclusion criteria. A total of 125 articles were retrieved and assessed for full-text eligibility, of which only three observational articles were included for meta-analysis. Statistical results revealed that patients treated with DMARDs monotherapy are 95% (95% CI: 0.65-0.99) less likely to develop pneumonia compared to patients treated with a DMARD and GCs (p=0.002).
CONCLUSIONS
Our data suggest that RA patients have a higher probability of developing pneumonia on combination therapy with GCs, compared to monotherapy with DMARDs. To our knowledge, our findings are the first to systematically review and statistically evaluate the relationship between the use of GCs and show an increased chance of developing pneumonia.
Topics: Humans; Adult; Middle Aged; Glucocorticoids; Arthritis, Rheumatoid; Antirheumatic Agents; Methotrexate; Pneumonia
PubMed: 36691851
DOI: 10.1515/jom-2022-0177 -
Journal of Nephrology Jul 2023Acute pyelonephritis is a common infection in children that may cause renal scarring. The aim of this systematic review and meta-analysis was to analyse the use of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute pyelonephritis is a common infection in children that may cause renal scarring. The aim of this systematic review and meta-analysis was to analyse the use of corticosteroid treatment to prevent renal scarring.
METHODS
We searched the PubMED, SCOPUS, Cochrane CENTRAL and Web of Science databases in June 2022 for (corticosteroid* or dexamethasone or prednisolone* or prednisone* or hydrocortisone*) AND pyelonephritis. Randomised controlled trials focusing on children were included. The intervention was corticosteroid treatment with antibiotics compared to antibiotics with or without a placebo. The main outcome was the presence of renal scars on dimercaptosuccinic acid scanning at follow-up. The evidence quality was assessed using the GRADE methodology and risk of bias 2.0 tool. We calculated the risk ratio (RR), absolute risk difference (RD) with 95% confidence intervals (CI) and the number needed to treat (NNT). We applied a fixed effects model due to low heterogeneity.
RESULTS
We screened 872 abstracts and included five full texts. Renal scarring at follow-up was found in 31/220 (14.1%) patients in the corticosteroid groups and 76/278 (27.3%) in the control groups (RR 0.65, CI 0.44-0.96, RD - 13.2%, NNT 8). The evidence quality was moderate. Two studies reported adverse events with no differences between the groups. The risk of bias analysis showed some concerns in four studies.
CONCLUSION
We found moderate quality evidence that adjuvant corticosteroid treatment could prevent renal scarring. Adverse events were insufficiently reported, and more research on their effectiveness and harm is therefore needed before using corticosteroids in clinical settings.
Topics: Child; Humans; Cicatrix; Adrenal Cortex Hormones; Prednisolone; Anti-Bacterial Agents; Pyelonephritis; Randomized Controlled Trials as Topic
PubMed: 36692666
DOI: 10.1007/s40620-022-01552-1