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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 -
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 -
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 -
Journal of Veterinary Emergency and... Jan 2019To systematically examine the evidence for use of a specific protocol (dose, frequency, route) of selected antithrombotic drugs, in comparisons to no therapy or to other...
OBJECTIVES
To systematically examine the evidence for use of a specific protocol (dose, frequency, route) of selected antithrombotic drugs, in comparisons to no therapy or to other antithrombotic therapies, to reduce the risk of complications or improve outcomes in dogs and cats at risk for thrombosis.
DESIGN
Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence (LOE) and quality (Good, Fair, or Poor), and development of consensus on conclusions via a Delphi-style survey for application of the concepts to clinical practice.
SETTINGS
Academic and referral veterinary medical centers.
RESULTS
Databases searched included Medline via PubMed and CAB abstracts. Eight different antithrombotic drugs were investigated using a standardized Patient, Intervention, Comparison, Outcome (PICO) question format both for dogs and cats, including aspirin, clopidogrel, warfarin, unfractionated heparin (UFH), dalteparin, enoxaparin, fondaparinux, and rivaroxaban, generating a total of 16 worksheets. Most studies identified were experimental controlled laboratory studies in companion animals (LOE 3) with only four randomized controlled clinical trials in companion animals (LOE 1).
CONCLUSIONS
Overall, evidence-based recommendations concerning specific protocols could not be formulated for most antithrombotic drugs evaluated, either because of the wide range of dosage reported (eg, aspirin in dogs) or the lack of evidence in the current literature. However, clopidogrel administration in dogs and cats at risk of arterial thrombosis, notably in cats at risk of cardiogenic thromboembolism, is supported by the literature, and specific protocols were recommended. Comparably, aspirin should not be used as a sole antithrombotic in cats with cardiomyopathy. Using the available safety profile information contained in the literature, the panel reached consensus on suggested dosage schemes for most antithrombotics. Significant knowledge gaps were highlighted, which will hopefully drive novel research.
Topics: Animals; Anticoagulants; Cat Diseases; Cats; Clinical Protocols; Critical Care; Dog Diseases; Dogs; Fibrinolytic Agents; Heparin; Practice Patterns, Physicians'; Veterinary Medicine
PubMed: 30654416
DOI: 10.1111/vec.12795 -
International Journal of Clinical... Apr 2022Background Surgical site infections account for 14-17% of all healthcare-associated infections. Antimicrobial stewardship (AMS) are complementary strategies developed to... (Review)
Review
Background Surgical site infections account for 14-17% of all healthcare-associated infections. Antimicrobial stewardship (AMS) are complementary strategies developed to optimize the use of antimicrobials. Aim to evaluate the effectiveness of AMS in promoting adherence to surgical antibiotic prophylaxis protocols in hospitalized patients, reducing surgical site infection rate and cost-benefit ratio. Method This systematic review of randomized clinical trials, non-randomized clinical trials and before and after studies was performed using Pubmed, Cochrane, Web of Science, Scopus, Embase, Google Scholar and ClinicalTrials.gov, in addition to reference lists of included studies. The risk of bias of studies was measured by the ROBINS-I checklist and the quality of the evidence synthesis by GRADE. Results Fourteen before and after design studies were included. In 85.7% of the studies, AMS was effective in increasing adherence to surgical antibiotic prophylaxis protocols and in 28.5%, there was reduction in surgical site infection rate. Three studies evaluated cost-benefit ratio and found a favorable impact. Eight (57%) studies were at risk of moderate bias and six had severe bias. The evaluation of the synthesis of evidence showed quality ranging from low to very low. Conclusion AMS, such as audit, feedback, education, implementation of a protocol, and a computer-assisted decision support methodology, appear to be effective in promoting adherence to surgical antibiotic prophylaxis protocols, reducing surgical site infection rate with a positive economic impact. However, more studies, particularly randomized clinical trials, are needed to improve the level of evidence of available information on AMS in order to favor decision-making.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antibiotic Prophylaxis; Antimicrobial Stewardship; Humans; Surgical Wound Infection
PubMed: 34843035
DOI: 10.1007/s11096-021-01358-4 -
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 -
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 -
Journal of Oral Rehabilitation Oct 2019To compare the treatments used to treat dentin hypersensitivity (DH), based on its efficacy and effect duration. (Review)
Review
OBJECTIVES
To compare the treatments used to treat dentin hypersensitivity (DH), based on its efficacy and effect duration.
METHODS
Medline/PubMed, Cochrane Library, EMBASE and ClinicalTrials were searched for articles published between 1 January 2008 and 14 November 2018, in English, Portuguese or Spanish, reporting clinical trials, completed and with results. This systematic review protocol was registered in PROSPERO, number CRD42019121986.
RESULTS
Seventy-four randomised clinical trials were included in the systematic review, reporting patients from 16 to 65 years old, with a clinical diagnosis of DH, that evaluate the efficacy of a desensitising product, compared to pre-treatment, used the evaporative method stimulation and the visual analogue scale. These studies evaluated 5366 patients and at least 9167 teeth. Seven follow-up periods were considered corresponding to an immediate, medium or long-time effect. Sixty-six studies were included in the quantitative synthesis. Glutaraldehyde with HEMA, glass ionomer cements and Laser present significant immediate (until 7 days) DH reduction. Medium-term (until 1 month) reduction was observed in stannous fluoride, glutaraldehyde with HEMA, hydroxyapatite, glass ionomer cements and Laser groups. Finally, long-term significant reduction was seen at potassium nitrate, arginine, glutaraldehyde with HEMA, hydroxyapatite, adhesive systems, glass ionomer cements and LASER.
CONCLUSIONS
All active ingredients show efficacy in DH reduction in different follow-up times. Only in-office treatments are effective in immediate DH reduction, maintaining its efficacy over time. For long-time effects, at-home treatments can also be used. More standardised evaluation protocols should be implemented to increase the robustly of the results.
Topics: Adolescent; Adult; Aged; Dentin; Dentin Desensitizing Agents; Dentin Sensitivity; Follow-Up Studies; Glass Ionomer Cements; Humans; Middle Aged; Treatment Outcome; Young Adult
PubMed: 31216069
DOI: 10.1111/joor.12842 -
In Vivo (Athens, Greece) 2023Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment, resulting in pain, numbness, instability, and thus affecting quality of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIM
Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer treatment, resulting in pain, numbness, instability, and thus affecting quality of life (QoL), occasionally leading to discontinuation of chemotherapy. Pharmacological treatments are not sufficient. Non-pharmacological interventions (NPIs) have also been tried. This study aimed to systematically review the efficacy of NPIs on pain and QoL in patients suffering from CIPN.
MATERIALS AND METHODS
The databases searched were Pubmed, Cohrane, and Scopus for randomized controlled trials (RCTs) published in the last 5 years (2017-2022). Studies were considered eligible, if they assessed adult patients suffering from CIPN because of any chemotherapeutic drug for any type and any stage of cancer and if study protocols included non-pharmacological intervention with a structured protocol.
RESULTS
A total of 1,496 records were identified. Finally, 10 RCTs including 495 patients (253 in the intervention group and 242 in the control group) were included for meta-analysis. Intervention protocols included acupuncture (n=6), exercise (n=3), and yoga (n=1). NPIs significantly reduced neuropathic pain. However, the effect on QoL was not significant.
CONCLUSION
NPIs are beneficial in the treatment of pain in patients with CIPN but their impact on QoL is not statistically supported. Larger sample sizes, more homogenous in outcome measures and interventions are needed to further explore NPIs' efficacy on CIPN symptoms.
Topics: Adult; Humans; Antineoplastic Agents; Neoplasms; Polyneuropathies; Neuralgia; Quality of Life
PubMed: 36593011
DOI: 10.21873/invivo.13053 -
American Journal of Obstetrics and... Aug 2019To compare the treatment success and failure rates, as well as side effects and surgery rates, between methotrexate protocols. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the treatment success and failure rates, as well as side effects and surgery rates, between methotrexate protocols.
DATA SOURCES
PubMed, Embase, and the Cochrane library searched up to July 2018.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials that compared women with ectopic pregnancies receiving the single-dose, two-dose, or multi-dose methotrexate protocols.
STUDY APPRAISAL AND SYNTHESIS METHODS
Odds of treatment success, treatment failure, side effects, and surgery for tubal rupture, as well as length of follow-up until treatment success, were compared using random and fixed effects meta-analysis. Sensitivity analyses compared treatment success in the groups with high human chorionic gonadatropin (hCG) values and a large adnexal mass, as defined by individual studies. The Cochrane Collaboration tool was used to assess risk of bias.
RESULTS
The 2-dose protocol was associated with higher treatment success compared to the single-dose protocol (odds ratio [OR], 1.84; 95% CI, 1.13, 3.00). The 2-dose protocol was more successful in women with high hCG (OR, 3.23; 95% CI, 1.53, 6.84) and in women with a large adnexal mass (OR, 2.93; 95% CI, 1.23, 6.9). The odds of surgery for tubal rupture were lower in the 2-dose protocol (OR, 0.65; 95% CI, 0.26, 1.63), but this was not statistically significant. The length of follow-up was 7.9 days shorter for the 2-dose protocol (95% CI, -12.2, -3.5). The odds of side effects were higher in the 2-dose protocol (OR, 1.53; 95% CI, 1.01, 2.30). Compared to the single-dose protocol, the multi-dose protocol was associated with a nonsignificant reduction in treatment failure (OR, 0.56; 95% CI, 0.28, 1.13) and a higher chance of side effects (OR, 2.10; 95% CI, 1.24, 3.54). The odds of surgery for tubal rupture (OR, 1.62; 95% CI, 0.41, 6.49) and time to follow-up (OR, -1.3; 95% CI, -5.4, 2.7) were similar.
CONCLUSION
The 2-dose methotrexate protocol is superior to the single-dose protocol for the treatment of ectopic pregnancy in terms of treatment success and time to success. Importantly, these findings hold true in patients thought to be at a lower likelihood of responding to medical management, such as those with higher hCGs and a large adnexal mass.
Topics: Abortifacient Agents, Nonsteroidal; Chorionic Gonadotropin; Dose-Response Relationship, Drug; Fallopian Tubes; Female; Humans; Methotrexate; Pregnancy; Pregnancy, Ectopic; Randomized Controlled Trials as Topic; Rupture
PubMed: 30629908
DOI: 10.1016/j.ajog.2019.01.002