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Lancet (London, England) Sep 2019Schizophrenia is one of the most common, burdensome, and costly psychiatric disorders in adults worldwide. Antipsychotic drugs are its treatment of choice, but there is... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis.
BACKGROUND
Schizophrenia is one of the most common, burdensome, and costly psychiatric disorders in adults worldwide. Antipsychotic drugs are its treatment of choice, but there is controversy about which agent should be used. We aimed to compare and rank antipsychotics by quantifying information from randomised controlled trials.
METHODS
We did a network meta-analysis of placebo-controlled and head-to-head randomised controlled trials and compared 32 antipsychotics. We searched Embase, MEDLINE, PsycINFO, PubMed, BIOSIS, Cochrane Central Register of Controlled Trials (CENTRAL), WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov from database inception to Jan 8, 2019. Two authors independently selected studies and extracted data. We included randomised controlled trials in adults with acute symptoms of schizophrenia or related disorders. We excluded studies in patients with treatment resistance, first episode, predominant negative or depressive symptoms, concomitant medical illnesses, and relapse-prevention studies. Our primary outcome was change in overall symptoms measured with standardised rating scales. We also extracted data for eight efficacy and eight safety outcomes. Differences in the findings of the studies were explored in metaregressions and sensitivity analyses. Effect size measures were standardised mean differences, mean differences, or risk ratios with 95% credible intervals (CrIs). Confidence in the evidence was assessed using CINeMA (Confidence in Network Meta-Analysis). The study protocol is registered with PROSPERO, number CRD42014014919.
FINDINGS
We identified 54 417 citations and included 402 studies with data for 53 463 participants. Effect size estimates suggested all antipsychotics reduced overall symptoms more than placebo (although not statistically significant for six drugs), with standardised mean differences ranging from -0·89 (95% CrI -1·08 to -0·71) for clozapine to -0·03 (-0·59 to 0·52) for levomepromazine (40 815 participants). Standardised mean differences compared with placebo for reduction of positive symptoms (31 179 participants) varied from -0·69 (95% CrI -0·86 to -0·52) for amisulpride to -0·17 (-0·31 to -0·04) for brexpiprazole, for negative symptoms (32 015 participants) from -0·62 (-0·84 to -0·39; clozapine) to -0·10 (-0·45 to 0·25; flupentixol), for depressive symptoms (19 683 participants) from -0·90 (-1·36 to -0·44; sulpiride) to 0·04 (-0·39 to 0·47; flupentixol). Risk ratios compared with placebo for all-cause discontinuation (42 672 participants) ranged from 0·52 (0·12 to 0·95; clopenthixol) to 1·15 (0·36 to 1·47; pimozide), for sedation (30 770 participants) from 0·92 (0·17 to 2·03; pimozide) to 10·20 (4·72 to 29·41; zuclopenthixol), for use of antiparkinson medication (24 911 participants) from 0·46 (0·19 to 0·88; clozapine) to 6·14 (4·81 to 6·55; pimozide). Mean differences compared to placebo for weight gain (28 317 participants) ranged from -0·16 kg (-0·73 to 0·40; ziprasidone) to 3·21 kg (2·10 to 4·31; zotepine), for prolactin elevation (21 569 participants) from -77·05 ng/mL (-120·23 to -33·54; clozapine) to 48·51 ng/mL (43·52 to 53·51; paliperidone) and for QTc prolongation (15 467 participants) from -2·21 ms (-4·54 to 0·15; lurasidone) to 23·90 ms (20·56 to 27·33; sertindole). Conclusions for the primary outcome did not substantially change after adjusting for possible effect moderators or in sensitivity analyses (eg, when excluding placebo-controlled studies). The confidence in evidence was often low or very low.
INTERPRETATION
There are some efficacy differences between antipsychotics, but most of them are gradual rather than discrete. Differences in side-effects are more marked. These findings will aid clinicians in balancing risks versus benefits of those drugs available in their countries. They should consider the importance of each outcome, the patients' medical problems, and preferences.
FUNDING
German Ministry of Education and Research and National Institute for Health Research.
Topics: Administration, Oral; Antipsychotic Agents; Comparative Effectiveness Research; Humans; Randomized Controlled Trials as Topic; Schizophrenia; Treatment Outcome
PubMed: 31303314
DOI: 10.1016/S0140-6736(19)31135-3 -
JAMA Jun 2016Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited. (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited.
OBJECTIVE
To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta-analysis.
DATA SOURCES
MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries.
STUDY SELECTION
Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration-approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo.
DATA EXTRACTION AND SYNTHESIS
Two investigators identified studies and independently abstracted data using a predefined protocol. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria.
MAIN OUTCOMES AND MEASURES
Proportions of patients with at least 5% weight loss and at least 10% weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year.
RESULTS
Twenty-eight randomized clinical trials with 29 018 patients (median age, 46 years; 74% women; median baseline body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A median 23% of placebo participants had at least 5% weight loss vs 75% of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95% credible interval [CrI], 6.63-12.85; SUCRA, 0.95), 63% of participants taking liraglutide (OR, 5.54; 95% CrI, 4.16-7.78; SUCRA, 0.83), 55% taking naltrexone-bupropion (OR, 3.96; 95% CrI, 3.03-5.11; SUCRA, 0.60), 49% taking lorcaserin (OR, 3.10; 95% CrI, 2.38-4.05; SUCRA, 0.39), and 44% taking orlistat (OR, 2.70; 95% CrI, 2.34-3.09; SUCRA, 0.22). All active agents were associated with significant excess weight loss compared with placebo at 1 year-phentermine-topiramate, 8.8 kg (95% CrI, -10.20 to -7.42 kg); liraglutide, 5.3 kg (95% CrI, -6.06 to -4.52 kg); naltrexone-bupropion, 5.0 kg (95% CrI, -5.94 to -3.96 kg); lorcaserin, 3.2 kg (95% CrI, -3.97 to -2.46 kg); and orlistat, 2.6 kg (95% CrI, -3.04 to -2.16 kg). Compared with placebo, liraglutide (OR, 2.95; 95% CrI, 2.11-4.23) and naltrexone-bupropion (OR, 2.64; 95% CrI, 2.10-3.35) were associated with the highest odds of adverse event-related treatment discontinuation. High attrition rates (30%-45% in all trials) were associated with lower confidence in estimates.
CONCLUSIONS AND RELEVANCE
Among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5% weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving at least 5% weight loss.
Topics: Anti-Obesity Agents; Bayes Theorem; Benzazepines; Drug Combinations; Female; Fructose; Humans; Lactones; Liraglutide; Male; Middle Aged; Naltrexone; Obesity; Orlistat; Phentermine; Randomized Controlled Trials as Topic; Topiramate; Weight Loss
PubMed: 27299618
DOI: 10.1001/jama.2016.7602 -
Ophthalmologica. Journal International... 2014Keratoconus (KCN) is an ectatic disorder with progressive corneal thinning and a clinical picture of corneal protrusion, progressive irregular astigmatism, corneal... (Review)
Review
Keratoconus (KCN) is an ectatic disorder with progressive corneal thinning and a clinical picture of corneal protrusion, progressive irregular astigmatism, corneal fibrosis and visual deterioration. Other ectatic corneal disorders include: post-LASIK ectasia (PLE) and pellucid marginal degeneration (PMD). Corneal crosslinking (CXL) is a procedure whereby riboflavin sensitization with ultraviolet A radiation induces stromal crosslinks. This alters corneal biomechanics, causing an increase in corneal stiffness. In recent years, CXL has been an established treatment for the arrest of KCN, PLE and PMD progression. CXL has also been shown to be effective in the treatment of corneal infections, chemical burns, bullous keratopathy and other forms of corneal edema. This is a current review of CXL - its biomechanical principles, the evolution of CXL protocols in the past, present and future, indications for treatment, treatment efficacy and safety.
Topics: Collagen; Cornea; Corneal Stroma; Cross-Linking Reagents; Elasticity; Humans; Keratoconus; Photosensitizing Agents; Riboflavin; Ultraviolet Rays
PubMed: 24751584
DOI: 10.1159/000357979 -
Indian Dermatology Online Journal 2023Melasma is an acquired disorder, which presents with well-demarcated, brown-colored hyperpigmented macules, commonly involving the sun-exposed areas such as the face. It... (Review)
Review
INTRODUCTION
Melasma is an acquired disorder, which presents with well-demarcated, brown-colored hyperpigmented macules, commonly involving the sun-exposed areas such as the face. It is a chronic and distressing condition, affecting the patients' quality of life, and has been conventionally treated with "first-line" agents including hydroquinone (HQ) alone or as a part of a triple combination cream (TCC), while "second-line" options include chemical peels, and third line options include laser therapy.
MATERIALS AND METHODS
A systematic search was performed for all topical and systemic treatments for melasma up till May 4, 2021, using the PubMed and EMBASE databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The search terms "melasma" and "treatment" were used to search for the relevant articles on both these databases, and a total of 4020 articles were identified. After removing the duplicate entries and screening the titles, abstracts, and full-text articles, we identified 174 randomized controlled trials (RCTs) or controlled clinical trials.
RESULTS
Based on our review, HQ, TCCs, sunscreens, kojic acid (KA), and azelaic acid receive grade A recommendation. Further large-scale studies are required to clearly establish the efficacy of topical vitamin C, resorcinol, and topical tranexamic acid (TXA). Several newer topical agents may play a role only as an add-on or second-line drugs or as maintenance therapy. Oral TXA has a strong recommendation, provided there are no contraindications. Procyanidins, Polypodium leucotomos (PL), and even synbiotics may be taken as adjuncts.
DISCUSSION
Several newer topical and systemic agents with multimodal mechanisms of action have now become available, and the balance seems to be tipping in favor of these innovative modalities. However, it is worth mentioning that the choice of agent should be individualized and subject to availability in a particular country.
PubMed: 38099013
DOI: 10.4103/idoj.idoj_490_22 -
The Cochrane Database of Systematic... Apr 2010The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The National Institute for Health and Clinical Excellence clinical practice guideline on the treatment of depressive disorder recommended that selective serotonin reuptake inhibitors should be the first-line option when drug therapy is indicated for a depressive episode. Preliminary evidence suggested that sertraline might be slightly superior in terms of effectiveness.
OBJECTIVES
To assess the evidence for the efficacy, acceptability and tolerability of sertraline in comparison with tricyclics (TCAs), heterocyclics, other SSRIs and newer agents in the acute-phase treatment of major depression.
SEARCH STRATEGY
MEDLINE (1966 to 2008), EMBASE (1974 to 2008), the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to July 2008. No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were hand-searched. Pharmaceutical companies and experts in this field were contacted for supplemental data.
SELECTION CRITERIA
Randomised controlled trials allocating patients with major depression to sertraline versus any other antidepressive agent.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data. Discrepancies were resolved with another member of the team. A double-entry procedure was employed by two reviewers. Information extracted included study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy (the number of patients who responded or remitted), acceptability (the number of patients who failed to complete the study) and tolerability (side-effects).
MAIN RESULTS
A total of 59 studies, mostly of low quality, were included in the review, involving multiple treatment comparisons between sertraline and other antidepressant agents. Evidence favouring sertraline over some other antidepressants for the acute phase treatment of major depression was found, either in terms of efficacy (fluoxetine) or acceptability/tolerability (amitriptyline, imipramine, paroxetine and mirtazapine). However, some differences favouring newer antidepressants in terms of efficacy (mirtazapine) and acceptability (bupropion) were also found. In terms of individual side effects, sertraline was generally associated with a higher rate of participants experiencing diarrhoea.
AUTHORS' CONCLUSIONS
This systematic review and meta-analysis highlighted a trend in favour of sertraline over other antidepressive agents both in terms of efficacy and acceptability, using 95% confidence intervals and a conservative approach, with a random effects analysis. However, the included studies did not report on all the outcomes that were pre-specified in the protocol of this review. Outcomes of clear relevance to patients and clinicians were not reported in any of the included studies.
Topics: Antidepressive Agents; Depression; Diarrhea; Humans; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Sertraline; Treatment Outcome
PubMed: 20393946
DOI: 10.1002/14651858.CD006117.pub4 -
Emergency Medicine Australasia : EMA Apr 2020Vasopressor medications have traditionally been administered via central venous catheters (CVCs), primarily due to concerns of peripheral extravasation of...
OBJECTIVE
Vasopressor medications have traditionally been administered via central venous catheters (CVCs), primarily due to concerns of peripheral extravasation of vasoconstrictive medications. Recent studies have suggested that vasopressor administration via peripheral intravenous catheters (PiVCs) may be a feasible and safe alternative. This systematic review evaluates the safety of delivering vasopressor medications via PiVCs.
METHODS
We performed a systematic review to assess the frequency of complications associated with the delivery of vasopressors via PiVCs. A literature search for prospective and retrospective studies of vasopressor infusions in adults was performed. We included studies of continuous infusions of vasopressor medications (noradrenaline, adrenaline, metaraminol, phenylephrine, dopamine and vasopressin) delivered via a PiVCs that included at least 20 patients. Data on patient factors, cannulation approach, monitoring protocols, vasopressor dosing and dilutions and adverse events were collected and summarised.
RESULTS
Seven studies were identified that fulfilled the inclusion criteria, including 1382 patients. No study fulfilled all of the validity criteria. Noradrenaline was the most commonly administered agent (n = 702 episodes of administration), followed by phenylephrine (n = 546), dopamine (n = 108), metaraminol (n = 74) and vasopressin and adrenaline (<5 patients). Mean duration of infusion was 22 h (95% confidence interval [CI] 8-36 h). Extravasation occurred in 3.4% (95% CI 2.5-4.7%) of patients. There were no reported episodes of tissue necrosis or limb ischaemia. All extravasation events were successfully managed conservatively or with vasodilatory medications.
CONCLUSIONS
Reports of the administration of vasopressors via PiVCs, when given for a limited duration, under close observation, suggest that extravasation is uncommon and is unlikely to lead to major complications.
Topics: Adult; Catheterization, Peripheral; Humans; Hypotension; Prospective Studies; Retrospective Studies; Vasoconstrictor Agents
PubMed: 31698544
DOI: 10.1111/1742-6723.13406 -
Frontiers in Oral Health 2022and studies have demonstrated the effectiveness of some irrigation protocols in reducing the bacterial load in the root canal system. However, standardized protocols...
BACKGROUND
and studies have demonstrated the effectiveness of some irrigation protocols in reducing the bacterial load in the root canal system. However, standardized protocols have not yet been defined for the real clinical context due to many irrigation procedures available.
OBJECTIVE
To evaluate the clinical endodontic protocols and limitations of irrigating solutions in the disinfection of the root canal system in patients with apical periodontitis.
METHODS
PubMed, Scopus, Embase, Web of Science, and Cochrane databases were searched for randomized controlled trials (RCT) published until January 2021. Hand searching was also performed. Studies focused on evaluating the effectiveness of irrigating solutions and/or irrigation activation methods in reducing the bacterial load in the root canal system were considered. The Cochrane risk-of-bias tool for randomized trials (RoB2) was used to assess the quality of the studies.
RESULTS
Four hundred and twenty eight published articles were identified. After removing the duplicate studies and analyzing full texts, seven RCTs were selected. Two studies compared pure NaOCl with some combination of NaOCl with HEDP and MTAD. Two studies analyzed the antibacterial efficacy of NaOCl and chlorhexidine (CHX). Three studies compared conventional needle irrigation with different irrigation activation methods (PUI, XP-endo finisher, F-file activator, EndoVac activator). The review attained a satisfactory methodology. The main results of each included study were described.
DISCUSSION
Activation methods provide significantly higher biofilm reduction than conventional needle irrigation methods. Combinations of NaOCl with different chelating agents were ineffective in terms of antimicrobial, but it could potentially increase the risk of irrigant extrusion. However, the irrigating protocols were not carefully detailed, especially those regarding the irrigants application time or total volume. The existing literature lacks high-quality studies. The level of evidence is moderate.
CONCLUSIONS
The available data is too heterogeneous to compare and identify the superiority of specific valuable irrigation protocols in each clinical context. Application time, volume, and activation methods should be standardized to determine the optimal irrigating procedures to reduce the bacterial load and ensure higher predictability of the endodontic treatment.
SYSTEMATIC REVIEW REGISTRATION
(https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=218555), PROSPERO registration: CRD42020218555.
PubMed: 35174355
DOI: 10.3389/froh.2022.838043 -
The Cochrane Database of Systematic... Aug 2017Gastric cancer is the fifth most common cancer worldwide. In "Western" countries, most people are either diagnosed at an advanced stage, or develop a relapse after... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Gastric cancer is the fifth most common cancer worldwide. In "Western" countries, most people are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. In people with advanced disease, significant benefits from targeted therapies are currently limited to HER-2 positive disease treated with trastuzumab, in combination with chemotherapy, in first-line. In second-line, ramucirumab, alone or in combination with paclitaxel, demonstrated significant survival benefits. Thus, systemic chemotherapy remains the mainstay of treatment for advanced gastric cancer. Uncertainty remains regarding the choice of the regimen.
OBJECTIVES
To assess the efficacy of chemotherapy versus best supportive care (BSC), combination versus single-agent chemotherapy and different chemotherapy combinations in advanced gastric cancer.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials, MEDLINE and Embase up to June 2016, reference lists of studies, and contacted pharmaceutical companies and experts to identify randomised controlled trials (RCTs).
SELECTION CRITERIA
We considered only RCTs on systemic, intravenous or oral chemotherapy versus BSC, combination versus single-agent chemotherapy and different chemotherapy regimens in advanced gastric cancer.
DATA COLLECTION AND ANALYSIS
Two review authors independently identified studies and extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information.
MAIN RESULTS
We included 64 RCTs, of which 60 RCTs (11,698 participants) provided data for the meta-analysis of overall survival. We found chemotherapy extends overall survival (OS) by approximately 6.7 months more than BSC (hazard ratio (HR) 0.3, 95% confidence intervals (CI) 0.24 to 0.55, 184 participants, three studies, moderate-quality evidence). Combination chemotherapy extends OS slightly (by an additional month) versus single-agent chemotherapy (HR 0.84, 95% CI 0.79 to 0.89, 4447 participants, 23 studies, moderate-quality evidence), which is partly counterbalanced by increased toxicity. The benefit of epirubicin in three-drug combinations, in which cisplatin is replaced by oxaliplatin and 5-FU is replaced by capecitabine is unknown.Irinotecan extends OS slightly (by an additional 1.6 months) versus non-irinotecan-containing regimens (HR 0.87, 95% CI 0.80 to 0.95, 2135 participants, 10 studies, high-quality evidence).Docetaxel extends OS slightly (just over one month) compared to non-docetaxel-containing regimens (HR 0.86, 95% CI 0.78 to 0.95, 2001 participants, eight studies, high-quality evidence). However, due to subgroup analyses, we are uncertain whether docetaxel-containing combinations (docetaxel added to a single-agent or two-drug combination) extends OS due to moderate-quality evidence (HR 0.80, 95% CI 0.71 to 0.91, 1466 participants, four studies, moderate-quality evidence). When another chemotherapy was replaced by docetaxel, there is probably little or no difference in OS (HR 1.05; 0.87 to 1.27, 479 participants, three studies, moderate-quality evidence). We found there is probably little or no difference in OS when comparing capecitabine versus 5-FU-containing regimens (HR 0.94, 95% CI 0.79 to 1.11, 732 participants, five studies, moderate-quality evidence) .Oxaliplatin may extend (by less than one month) OS versus cisplatin-containing regimens (HR 0.81, 95% CI 0.67 to 0.98, 1105 participants, five studies, low-quality evidence). We are uncertain whether taxane-platinum combinations with (versus without) fluoropyrimidines extend OS due to very low-quality evidence (HR 0.86, 95% CI 0.71 to 1.06, 482 participants, three studies, very low-quality evidence). S-1 regimens improve OS slightly (by less than an additional month) versus 5-FU-containing regimens (HR 0.91, 95% CI 0.83 to 1.00, 1793 participants, four studies, high-quality evidence), however since S-1 is used in different doses and schedules between Asian and non-Asian population, the applicability of this finding to individual populations is uncertain.
AUTHORS' CONCLUSIONS
Chemotherapy improves survival (by an additional 6.7 months) in comparison to BSC, and combination chemotherapy improves survival (by an additional month) compared to single-agent 5-FU. Testing all patients for HER-2 status may help to identify patients with HER-2-positive tumours, for whom, in the absence of contraindications, trastuzumab in combination with capecitabine or 5-FU in combination with cisplatin has been shown to be beneficial. For HER-2 negative people, all different two-and three-drug combinations including irinotecan, docetaxel, oxaliplatin or oral 5-FU prodrugs are valid treatment options for advanced gastric cancer, and consideration of the side effects of each regimen is essential in the treatment decision. Irinotecan-containing combinations and docetaxel-containing combinations (in which docetaxel was added to a single-agent or two-drug (platinum/5-FUcombination) show significant survival benefits in the comparisons studied above. Furthermore, docetaxel-containing three-drug regimens have increased response rates, but the advantages of the docetaxel-containing three-drug combinations (DCF, FLO-T) are counterbalanced by increased toxicity. Additionally, oxaliplatin-containing regimens demonstrated a benefit in OS as compared to the same regimen containing cisplatin, and there is a modest survival improvement of S-1 compared to 5-FU-containing regimens.Whether the survival benefit for three-drug combinations including cisplatin, 5-FU, and epirubicin as compared to the same regimen without epirubicin is still valid when second-line therapy is routinely administered and when cisplatin is replaced by oxaliplatin and 5-FU by capecitabine is questionable. Furthermore, the magnitude of the observed survival benefits for the three-drug regimens is not large enough to be clinically meaningful as defined recently by the American Society for Clinical Oncology (Ellis 2014). In contrast to the comparisons in which a survival benefit was observed by adding a third drug to a two-drug regimen at the cost of increased toxicity, the comparison of regimens in which another chemotherapy was replaced by irinotecan was associated with a survival benefit (of borderline statistical significance), but without increased toxicity. For this reason irinotecan/5-FU-containing combinations are an attractive option for first-line treatment. Although they need to be interpreted with caution, subgroup analyses of one study suggest that elderly people have a greater benefit form oxaliplatin, as compared to cisplatin-based regimens, and that people with locally advanced disease or younger than 65 years might benefit more from a three-drug regimen including 5-FU, docetaxel, and oxaliplatin as compared to a two-drug combination of 5-FU and oxaliplatin, a hypothesis that needs further confirmation. For people with good performance status, the benefit of second-line chemotherapy has been established in several RCTs.
Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Docetaxel; Fluorouracil; Humans; Irinotecan; Randomized Controlled Trials as Topic; Stomach Neoplasms; Taxoids
PubMed: 28850174
DOI: 10.1002/14651858.CD004064.pub4 -
Psychiatria Polska 2016BPSD (Behavioral and Psychological Symptoms in Dementia) affects virtually all patients with dementia. The aim of this review is to present information on epidemiology,... (Review)
Review
BPSD (Behavioral and Psychological Symptoms in Dementia) affects virtually all patients with dementia. The aim of this review is to present information on epidemiology, consequences and evidence-based non-pharmacological and pharmacological treatment approaches. The review also covers recent literature derived from a systematic literature Medline search on BPSD. Results indicate that BPSD are major risk factors for an earlier placement of affected individuals in nursing homes and a potentially more severe course of dementia over time. Treatment of BPSD is complex and includes both strategies.
Topics: Aggression; Anticonvulsants; Antipsychotic Agents; Behavioral Symptoms; Clinical Protocols; Conduct Disorder; Dementia; Dopamine Antagonists; Female; Geriatric Psychiatry; Humans; Male; Neurocognitive Disorders; Severity of Illness Index
PubMed: 27847922
DOI: 10.12740/PP/64477 -
BMJ (Clinical Research Ed.) Nov 2018To provide a complete toxicity profile, toxicity spectrum, and a safety ranking of immune checkpoint inhibitor (ICI) drugs for treatment of cancer. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To provide a complete toxicity profile, toxicity spectrum, and a safety ranking of immune checkpoint inhibitor (ICI) drugs for treatment of cancer.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) were systematically searched to include relevant studies published in English between January 2007 and February 2018.
REVIEW METHODS
Only head-to-head phase II and III randomised controlled trials comparing any two or three of the following treatments or different doses of the same ICI drug were included: nivolumab, pembrolizumab, ipilimumab, tremelimumab, atezolizumab, conventional therapy (chemotherapy, targeted therapy, and their combinations), two ICI drugs, or one ICI drug with conventional therapy. Eligible studies must have reported site, organ, or system level data on treatment related adverse events. High quality, single arm trials and placebo controlled trials on ICI drugs were selected to establish a validation group.
RESULTS
36 head-to-head phase II and III randomised trials (n=15 370) were included. The general safety of ICI drugs ranked from high to low for all adverse events was as follows: atezolizumab (probability 76%, pooled incidence 66.4%), nivolumab (56%, 71.8%), pembrolizumab (55%, 75.1%), ipilimumab (55%, 86.8%), and tremelimumab (54%, not applicable). The general safety of ICI drugs ranked from high to low for severe or life threatening adverse events was as follows: atezolizumab (49%, 15.1%), nivolumab (46%, 14.1%), pembrolizumab (72%, 19.8%), ipilimumab (51%, 28.6%), and tremelimumab (28%, not applicable). Compared with conventional therapy, treatment-related adverse events for ICI drugs occurred mainly in the skin, endocrine, hepatic, and pulmonary systems. Taking one ICI drug was generally safer than taking two ICI drugs or one ICI drug with conventional therapy. Among the five ICI drugs, atezolizumab had the highest risk of hypothyroidism, nausea, and vomiting. The predominant treatment-related adverse events for pembrolizumab were arthralgia, pneumonitis, and hepatic toxicities. The main treatment-related adverse events for ipilimumab were skin, gastrointestinal, and renal toxicities. Nivolumab had a narrow and mild toxicity spectrum, mainly causing endocrine toxicities. Integrated evidence from the pooled incidences, subgroup, and sensitivity analyses implied that nivolumab is the best option in terms of safety, especially for the treatment of lung cancer.
CONCLUSIONS
Compared with other ICI drugs used to treat cancer, atezolizumab had the best safety profile in general, and nivolumab had the best safety profile in lung cancer when taking an integrated approach. The safety ranking of treatments based on ICI drugs is modulated by specific treatment-related adverse events.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42017082553.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Ipilimumab; Neoplasms; Network Meta-Analysis; Nivolumab; Randomized Controlled Trials as Topic
PubMed: 30409774
DOI: 10.1136/bmj.k4226