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The Cochrane Database of Systematic... Dec 2014This is an updated version of the original Cochrane review published in Issue 3, 2012. Caffeine has been added to common analgesics such as paracetamol, ibuprofen, and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane review published in Issue 3, 2012. Caffeine has been added to common analgesics such as paracetamol, ibuprofen, and aspirin, in the belief that it enhances analgesic efficacy. Evidence to support this belief is limited and often based on invalid comparisons.
OBJECTIVES
To assess the relative efficacy of a single dose of an analgesic plus caffeine against the same dose of the analgesic alone, without restriction on the analgesic used or the pain condition studied. We also assessed serious adverse events.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and EMBASE from inception to 28 August 2014, the Oxford Pain Relief Database, and also carried out Internet searches and contacted pharmaceutical companies known to have carried out trials that have not been published.
SELECTION CRITERIA
We included randomised, double-blind studies that compared a single dose of analgesic plus caffeine with the same dose of the analgesic alone in the treatment of acute pain.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the eligibility and quality of studies, and extracted data. Any disagreements or uncertainties were settled by discussion with a third review author. We sought any validated measure of analgesic efficacy, but particularly the number of participants experiencing at least 50% of the maximum possible pain relief over four to six hours, participants reporting a global evaluation of treatment of very good or excellent, or headache relief after two hours. We pooled comparable data to look for a statistically significant difference, and calculated numbers needed to treat to benefit (NNT) with caffeine. We also looked for any numerical superiority associated with the addition of caffeine, and information about any serious adverse events.
MAIN RESULTS
We identified no new studies with available results for this update. The earlier review included 20 studies (7238 participants) in valid comparisons, but because we used different outcomes for some headache studies, the number of participants in the analyses of the effects of caffeine is now 4262 when previously it was 5243. The studies were generally of good methodological quality, using standard designs and mostly standard scales of pain measurement, although many of those treating postoperative pain were small.Most studies used paracetamol or ibuprofen, with 100 mg to 130 mg caffeine, and the most common pain conditions studied were postoperative dental pain, postpartum pain, and headache. There was a small but statistically significant benefit with caffeine used at doses of 100 mg or more, which was not dependent on the pain condition or type of analgesic. About 5% to 10% more participants achieve a good level of pain relief (at least 50% of the maximum over four to six hours) with the addition of caffeine, giving a NNT of about 14 (high quality evidence).Most comparisons individually demonstrated numerical superiority with caffeine, but not statistical superiority. One serious adverse event was reported with caffeine, but was considered unrelated to any study medication.We know of the existence of around 25 additional studies with almost 12,500 participants for which data for analysis were not obtainable. The additional analgesic effect of caffeine remained statistically significant but clinically less important even if all the known missing data had no effect; the bulk of the unobtainable data are reported to have similar results as this review.
AUTHORS' CONCLUSIONS
The addition of caffeine (≥ 100 mg) to a standard dose of commonly used analgesics provides a small but important increase in the proportion of participants who experience a good level of pain relief.
Topics: Acetaminophen; Acute Pain; Adolescent; Adult; Aged; Analgesics; Caffeine; Chemotherapy, Adjuvant; Diclofenac; Drug Synergism; Dysmenorrhea; Female; Headache; Humans; Ibuprofen; Male; Middle Aged; Pain, Postoperative; Postpartum Period; Pregnancy; Randomized Controlled Trials as Topic; ortho-Aminobenzoates
PubMed: 25502052
DOI: 10.1002/14651858.CD009281.pub3 -
Medicina (Kaunas, Lithuania) Jul 2018Pancreatic cancer is one of the most fatal cancers. Cytotoxic chemotherapy remains the mainstream treatment for unresectable pancreatic cancer. This systematic review...
BACKGROUND AND AIM
Pancreatic cancer is one of the most fatal cancers. Cytotoxic chemotherapy remains the mainstream treatment for unresectable pancreatic cancer. This systematic review evaluated and compared the overall survival (OS) and progression-free survival (PFS) outcomes obtained from recent phase 2 and 3 clinical trials of pancreatic cancer chemotherapy.
MATERIALS AND METHODS
Thirty-two studies were included and compared based on chemotherapy agents or combinations used. Additionally, outcomes of first-line versus second-line chemotherapy in pancreatic cancer were compared.
RESULTS
In studies that investigated the treatments in adjuvant settings, the highest OS reported was for S-1 in patients, who received prior surgical resection (46.5 months). In neoadjuvant settings, the combination of gemcitabine, docetaxel, and capecitabine prior to the surgical resection had promising outcomes (OS of 32.5 months). In non-adjuvant settings, the highest OS reported was for the combination of temsirolimus plus bevacizumab (34.0 months). Amongst studies that investigated second-line treatment, the highest OS reported was for the combination of gemcitabine plus cisplatin (35.5 months), then temsirolimus plus bevacizumab (34.0 months).
CONCLUSIONS
There is a need to develop further strategies besides chemotherapy to improve the outcomes in pancreatic cancer treatment. Future studies should consider surgical interventions, combination chemotherapy, and individualized second-line treatment based on the prior chemotherapy.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Deoxycytidine; Disease-Free Survival; Docetaxel; Female; Humans; Male; Neoadjuvant Therapy; Pancreatic Neoplasms; Survival Analysis; Treatment Outcome; Gemcitabine
PubMed: 30344279
DOI: 10.3390/medicina54030048 -
Biomedicine & Pharmacotherapy =... Mar 2022As the important active ingredients of Astragali Radix (AR), Astragalus polysaccharides (APs) have therapeutic potential for multiple diseases including nervous system...
As the important active ingredients of Astragali Radix (AR), Astragalus polysaccharides (APs) have therapeutic potential for multiple diseases including nervous system diseases, cardiovascular diseases, diabetes mellitus, and cancer. A large number of cell experiments combined with animal experiments have shed light on the therapeutic mechanisms and therapeutic effects of APs on a variety of diseases. However, the clinical application of APs is not widespread, except for the use of injected APs in the clinical adjuvant therapy of cancer. Due to the excessive molecular weight, bulky, low solubility and negatively charged characteristics, APs have low bioavailability which limits their clinical application. With the deepening of researches on the pharmaceutics of APs, the nanocrystals and moderate structural modification enormously boost the bioavailability, which may expand the application of APs. This review summarizes the studies in pharmacodynamic properties and pharmaceutics of APs, with the purpose of providing experimental researches and clinical application data for expanding the clinical development through expounding the therapeutic mechanisms and pharmaceutical researches of APs.
Topics: Animals; Astragalus Plant; Cardiovascular Diseases; Chemistry, Pharmaceutical; Diabetes Mellitus; Gastrointestinal Microbiome; Humans; Hypoxia; Immune Checkpoint Proteins; Immune System Diseases; Metabolic Diseases; Molecular Weight; Nanoparticles; Neoplasms; Neurodegenerative Diseases; Oxidative Stress; Polysaccharides
PubMed: 35086031
DOI: 10.1016/j.biopha.2022.112654 -
JAMA Network Open Oct 2019The role of induction chemotherapy (IC) or adjuvant chemotherapy (AC) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains controversial. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The role of induction chemotherapy (IC) or adjuvant chemotherapy (AC) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC) remains controversial.
OBJECTIVES
To update meta-analyses on the association of survival outcomes with IC and AC regimens in patients with locoregionally advanced NPC and assess whether the current evidence is conclusive by a trial sequential analysis (TSA) approach.
DATA SOURCES
PubMed, Embase, and Web of Science were searched for articles published from inception until June 1, 2019.
STUDY SELECTION
Randomized clinical trials that assessed the efficacy of radiotherapy with or without chemotherapy among previously untreated patients and patients with nondistant metastatic NPC.
DATA EXTRACTION AND SYNTHESIS
Data were extracted by 2 investigators from each trial independently and synthesized by the 2 investigators. All trial results were combined and analyzed by a fixed- or random-effects model.
MAIN OUTCOMES AND MEASURES
Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS).
RESULTS
A total of 8036 patients (median age, 46.5 years; 5872 [73.1%] male) from 28 randomized clinical trials were included in the analysis. Pooled analyses revealed that concurrent chemoradiotherapy (CCRT) was significantly associated with improved OS, PFS, DMFS, and LRFS compared with radiotherapy across all subgroups. The TSA confirmed the treatment outcomes of CCRT compared with radiotherapy. The additional IC regimen was associated with an improvement in OS (hazard ratio [HR], 0.84; 95% CI, 0.74-0.95), PFS (HR, 0.73; 95% CI, 0.64-0.84), DMFS (HR, 0.67; 95% CI, 0.59-0.78), and LRFS (HR, 0.74; 95% CI, 0.64-0.85). These findings were consistent in subgroup analyses of multicenter trials with sample sizes greater than 250, years of survival rate of 5 or greater, median follow-up longer than 5 years, or low risk of bias. However, the additional AC regimen was not associated with a survival benefit in OS (HR, 0.98; 95% CI, 0.78-1.23), PFS (HR, 0.86; 95% CI, 0.70-1.07), DMFS (HR, 0.84; 95% CI, 0.64-1.10), or LRFS (HR, 0.80, 95% CI, 0.59-1.09). The TSA provided sound evidence on the additional benefit of IC but not AC.
CONCLUSIONS AND RELEVANCE
These data suggest a significant association of survival outcomes with CCRT in patients with locoregionally advanced NPC. The addition of IC instead of AC could achieve survival benefits. The potential therapeutic gain of AC should be explored in the future.
Topics: Adult; Chemoradiotherapy; Disease-Free Survival; Female; Humans; Male; Middle Aged; Nasopharyngeal Carcinoma; Randomized Controlled Trials as Topic
PubMed: 31626318
DOI: 10.1001/jamanetworkopen.2019.13619 -
JAMA Pediatrics Mar 2019Incidence of neonatal abstinence syndrome is rising rapidly, and optimal pharmacotherapy may meaningfully reduce length of treatment.
IMPORTANCE
Incidence of neonatal abstinence syndrome is rising rapidly, and optimal pharmacotherapy may meaningfully reduce length of treatment.
OBJECTIVE
To compare pharmacological therapies for neonatal abstinence syndrome.
DATA SOURCES
Systematic review and network meta-analysis of Medline (1946-June 2018), Embase (1974-June 2018), Cochrane CENTRAL (1966-June 2018), Web of Science (1900-June 2018), and ClinicalTrials.gov (June 2018).
STUDY SELECTION
Randomized clinical trials of pharmacological treatments for neonatal abstinence syndrome alone or in combination with adjuvant treatments. Abstract, title, and full-text screening were conducted independently by 2 reviewers (T.D. and C.G.).
DATA EXTRACTION AND SYNTHESIS
Data extraction was conducted independently by 2 reviewers (T.D. and C.G.) according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-Network Meta-Analyses guidelines. Quality was assessed with the Cochrane Risk of Bias tool and data were pooled with fixed-effect models as a result of the low number of trials that were included in the analysis.
MAIN OUTCOMES AND MEASURES
The primary outcome was the length of treatment. The length of stay, need for adjuvant therapy, and adverse events were considered as secondary outcomes.
RESULTS
Eighteen trials (N = 1072) were eligible for inclusion. The treatments that were included in the length of treatment analysis were buprenorphine, clonidine, diluted tincture of opium and clonidine, diluted tincture of opium, morphine, methadone, and phenobarbital. Sublingual buprenorphine was considered the optimal treatment for a reduction in the length of treatment (days: mean difference vs morphine, -12.75 [95% CI, -17.97 to -7.58]; median rank, 1 [3-1]) and length of stay (days: mean difference vs morphine, -11.43 [95% CI, -16.95 to -5.82]; median rank, 1 [3-1]) but not the need for adjuvant treatment (odds ratio vs morphine, 1.23 [95% CI, 0.46-3.44]; median rank, 3 [5-1]). The results were robust to bias but sensitive to imprecision.
CONCLUSIONS AND RELEVANCE
The current evidence suggests that buprenorphine is the optimal treatment for neonatal abstinence treatment, but limitations are considerable and wide-scale adoption requires a large multisite trial. Morphine, which is considered standard of care in most hospitals, was the lowest-ranked opioid for length of treatment and length of stay.
Topics: Analgesics, Opioid; Buprenorphine; Humans; Infant, Newborn; Neonatal Abstinence Syndrome; Network Meta-Analysis; Treatment Outcome
PubMed: 30667476
DOI: 10.1001/jamapediatrics.2018.5044 -
BMC Complementary and Alternative... Nov 2015Shenmai injection (SM), as a traditional Chinese medicine injection, is widely used for chronic cor pulmonale heart failure in mainland China. It is essential to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Shenmai injection (SM), as a traditional Chinese medicine injection, is widely used for chronic cor pulmonale heart failure in mainland China. It is essential to systematically assess the efficacy and safety of SM as an adjuvant treatment for chronic cor pulmonale heart failure.
METHODS
Eight English and Chinese electronic databases were searched, from inception to December 2014, to identify randomized controlled trials (RCTs) of SM for chronic cor pulmonale heart failure. The Cochrane Risk of Bias tool was used to evaluate the methodological quality of eligible studies. Meta-analysis was performed by Review Manager 5.2.
RESULTS
Twenty-seven RCTs with 2045 participants were identified. The methodological quality of the included studies was generally low. Only one trial reported data on death. None of the included trials reported quality of life. The meta-analysis indicated that compared to conventional treatment, the combination of SM and conventional treatment was more effective in terms of the New York Heart Association classification (RR, 1.26; 95% CI, 1.20-1.32; P < 0.00001), Left Ventricular Ejection Fraction (MD, 11.33; 95% CI, 8.59-14.07; p < 0.00001), partial pressure of oxygen (MD, 1.00; 95% CI, 0.64-1.36; P < 0.00001) and partial pressure of carbon dioxide (MD, 0.83; 95 % CI, 0.58-1.08; p < 0.00001). In addition, two trials reported that SM plus conventional treatment was superior to the conventional treatment alone to reduce B-type natriuretic peptide. No serious adverse drug events or reactions were reported.
CONCLUSIONS
SM plus conventional treatment appeared to be effective and relatively safe for chronic cor pulmonale heart failure. However, due to the generally low methodological quality and small sample size, this review didn't find evidence to support routine use of SM as an adjuvant treatment for chronic cor pulmonale heart failure.
Topics: Adjuvants, Pharmaceutic; Chemotherapy, Adjuvant; Drug Combinations; Drugs, Chinese Herbal; Humans; Pulmonary Heart Disease; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 26603978
DOI: 10.1186/s12906-015-0939-2 -
The Lancet. Oncology Mar 2019Although frequently used as a primary endpoint, disease-free survival has not been validated as a surrogate for overall survival in early breast cancer. We investigated... (Meta-Analysis)
Meta-Analysis
Disease-free survival as a surrogate for overall survival in patients with HER2-positive, early breast cancer in trials of adjuvant trastuzumab for up to 1 year: a systematic review and meta-analysis.
BACKGROUND
Although frequently used as a primary endpoint, disease-free survival has not been validated as a surrogate for overall survival in early breast cancer. We investigated this surrogacy in the adjuvant setting of treatment with anti-HER2 antibodies.
METHODS
In a systematic review and meta-analysis, we identified published and non-published randomised controlled trials with completed accrual and available disease-free survival and overall survival results for the intention-to-treat population as of September 2016. Bibliographic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials), clinical trial registries (Clinicaltrials.gov, EU Clinical Trials Register, WHO International Clinical Trials Registry Platform, and PharmNet.Bund), and trial registries from relevant pharmaceutical companies were searched. Eligibility for treatment of HER2-positive early breast cancer required at least one group to have an anti-HER antibody treatment (ie, trastuzumab, pertuzumab, or trastuzumab emtansine) planned for 12 months, and at least one control arm with chemotherapy without the antibody, a lower total dose or duration of the antibody, or observation alone. Units of analysis were contrasts: two-group trials gave rise to one contrast, whereas trials with more than two groups gave rise to more than one contrast. We excluded trials enrolling patients with recurrent, metastatic, or non-invasive disease, and those testing neoadjuvant therapy exclusively. Our primary objective was to estimate patient-level and trial-level correlations between disease-free survival and overall survival. We measured the association between disease-free survival and overall survival using Spearman's correlation coefficient (r), and the association between hazard ratios (HRs) for disease-free survival and overall survival using R. We computed the surrogate threshold effect, the maximum HR for disease-free survival that statistically predicts an HR for overall survival less than 1·00 in a future trial.
FINDINGS
Eight trials (n=21 480 patients) gave rise to a full set (12 contrasts). Patient-level associations between disease-free and overall survival were strong (r=0·90 [95% CI 0·89-0·90]). Trial-level associations gave rise to values of R of 0·75 (95% CI 0·50-1·00) for the full set. Subgroups defined by nodal status and hormone receptor status yielded qualitatively similar results. Depending on the expected number of deaths in a future trial, the surrogate threshold effects ranged from 0·56 to 0·81, based on the full set.
INTERPRETATION
These findings suggest that it is appropriate to continue to use disease-free survival as a surrogate for overall survival in trials in HER-2-positive, early breast cancer. The key limitation of this study is the dependence of its results on the trials included and on the existence of an outlying trial.
FUNDING
Roche Pharma AG.
Topics: Ado-Trastuzumab Emtansine; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Female; Humans; Neoplasm Staging; Proportional Hazards Models; Receptor, ErbB-2; Treatment Outcome
PubMed: 30709633
DOI: 10.1016/S1470-2045(18)30750-2 -
Pain Research & Management 2022To assess if the addition of fentanyl to brachial plexus block has an impact on anesthetic outcomes and complication rates in patients undergoing upper extremity... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To assess if the addition of fentanyl to brachial plexus block has an impact on anesthetic outcomes and complication rates in patients undergoing upper extremity surgeries.
METHODS
We explore the PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases for all randomized controlled trials (RCTs) comparing adjuvant fentanyl with placebo/no drug for patients undergoing upper extremity surgery under brachial plexus block. Outcomes assessed were onset, duration of sensory and motor anesthesia, complications, and postoperative analgesia scores. Meta-analysis was conducted utilizing a random-effects model. The risk of bias was assessed using the Cochrane Collaboration's risk of bias assessment tool 2. Certainty of evidence was assessed using GRADE. Subgroup analysis was conducted depending upon the approach of brachial plexus block and type of local anesthetic.
RESULTS
Twelve RCTs with 660 patients were included. Addition of fentanyl had no effect on onset of sensory anesthesia (11 studies; MD: 0.48; 95% CI: -1.81, 0.85; = 96%; =0.48) but significantly shortened onset of motor anesthesia (8 studies; MD: -2.36; 95% CI: -3.99, -0.74; = 96%; =0.48). Duration of sensory anesthesia (9 studies; MD: 82.81; 95% CI: 41.81, 123.81; = 99%; < 0.0001) and motor anesthesia (7 studies; MD: 93.41; 95% CI: 42.35, 144.46; = 99%; =0.0003) was significantly increased with addition of fentanyl. The certainty of evidence-based on GRADE was deemed to be moderate for both onset and duration of anesthesia. The incidence of overall complications (nausea/vomiting and pruritis) was significantly higher in the fentanyl group (7 studies; OR: 2.14; 95% CI: 1.04, 4.40; = 8%; =0.04) but with low certainty of evidence.
CONCLUSIONS
Adjuvant fentanyl with brachial plexus block improves the onset of motor anesthesia but not sensory anesthesia. The duration of both sensory and motor anesthesia is significantly prolonged with fentanyl by around 83-93 minutes. However, clinicians should be aware that complications such as nausea/vomiting and pruritis are increased twofold with the addition of the drug. Current evidence is limited risk of bias in the RCTs and high heterogeneity in the meta-analyses.
Topics: Adjuvants, Pharmaceutic; Anesthetics, Local; Brachial Plexus Block; Fentanyl; Humans; Upper Extremity
PubMed: 35345625
DOI: 10.1155/2022/8704569 -
Toxins Apr 2023Envenomation caused by venomous animals may trigger significant local complications such as pain, edema, localized hemorrhage, and tissue necrosis, in addition to... (Review)
Review
Envenomation caused by venomous animals may trigger significant local complications such as pain, edema, localized hemorrhage, and tissue necrosis, in addition to complications such as dermonecrosis, myonecrosis, and even amputations. This systematic review aims to evaluate scientific evidence on therapies used to target local effects caused by envenomation. The PubMed, MEDLINE, and LILACS databases were used to perform a literature search on the topic. The review was based on studies that cited procedures performed on local injuries following envenomation with the aim of being an adjuvant therapeutic strategy. The literature regarding local treatments used following envenomation reports the use of several alternative methods and/or therapies. The venomous animals found in the search were snakes (82.05%), insects (2.56%), spiders (2.56%), scorpions (2.56%), and others (jellyfish, centipede, sea urchin-10.26%). In regard to the treatments, the use of tourniquets, corticosteroids, antihistamines, and cryotherapy is questionable, as well as the use of plants and oils. Low-intensity lasers stand out as a possible therapeutic tool for these injuries. Local complications can progress to serious conditions and may result in physical disabilities and sequelae. This study compiled information on adjuvant therapeutic measures and underscores the importance of more robust scientific evidence for recommendations that act on local effects together with the antivenom.
Topics: Animals; Antivenins; Snakes; Scorpions; Insecta; Spiders; Snake Bites
PubMed: 37235348
DOI: 10.3390/toxins15050313 -
Anticancer Research Oct 2023Using statins as antitumor agents is an approach to cancer therapy that has been explored extensively in specific cancer types. Reframing the query to how a statin... (Review)
Review
BACKGROUND/AIM
Using statins as antitumor agents is an approach to cancer therapy that has been explored extensively in specific cancer types. Reframing the query to how a statin interacts with the treatment regimen instead might provide new insight. Given that cell-cycle regulation influences tumorigenesis, it is possible that the cell-cycle phase which a given chemotherapy acts on influences the synergistic effects with adjuvant statin use. In this review, we outline the effect of statins in combination with chemotherapeutic drugs in in vivo animal model studies based on the class of chemotherapy and its relation to the cell cycle.
MATERIALS AND METHODS
This systematic review was conducted using the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 with 23 articles deemed eligible to be included.
RESULTS
Our review suggests that statins influence the success of chemotherapy treatments. Furthermore, enhanced efficacy was demonstrated with chemotherapeutic drugs that act at every phase of the cell cycle.
CONCLUSION
This type of compilation departs from the norm of describing statin influence on named cancer subtypes and instead catalogs how statins interact with categorical chemotherapy agents which might be beneficial for broader therapeutic decision-making across cancer subtypes, possibly contributing to pharmaceutical development, and thereby helping to maximize patient outcomes.
Topics: Animals; Mice; Antineoplastic Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 37772570
DOI: 10.21873/anticanres.16621