-
Expert Opinion on Drug Safety Jul 2022Sexual dysfunction (SD) is a symptom of depression in ≈70% of patients presenting with major depressive disorder (MDD). Antidepressant medications (AD) and adjunctive...
INTRODUCTION
Sexual dysfunction (SD) is a symptom of depression in ≈70% of patients presenting with major depressive disorder (MDD). Antidepressant medications (AD) and adjunctive treatments may further contribute to SD and complicate evaluation and management.
AREAS COVERED
A systematic literature search of PubMed, Ovid MEDLINE and Cochrane databases for MDD, SD, classes of antidepressants, etc. was performed with a focus on 2014 to June 2021. SSRIs are associated with 70% treatment-emergent sexual dysfunction (TESD), SNRIs and tricyclics have rates of TESD of 40-45%, and antidepressant medications without SRI effects or with additional unique mechanisms of action have rates similar to placebo (<10%). Appropriate assessment at baseline and throughout treatment, consideration of patient preferences in prescribing, addressing modifiable factors (comorbid medical/psychiatric conditions, substances, relationship difficulties), and utilizing management strategies of switching to an AD with less SD, adding an antidote/adjunctive therapy or lowering the dose are discussed.
EXPERT OPINION
MDD and antidepressant treatment contribute to SD in a high percentage of patients. Treating to remission reduces SD as a symptom of depression. Frequent assessment and targeted management strategies may be effective in preventing or addressing SD. Secondary outcomes like impact on adherence, relationships and self-image should also be considered.
Topics: Antidepressive Agents; Depressive Disorder, Major; Humans; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Sexual Dysfunction, Physiological
PubMed: 35255754
DOI: 10.1080/14740338.2022.2049753 -
The Cochrane Database of Systematic... Jun 2014Phosphorus burns are rarely encountered in usual clinical practice and occur mostly in military and industrial settings. However, these burns can be fatal, even with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Phosphorus burns are rarely encountered in usual clinical practice and occur mostly in military and industrial settings. However, these burns can be fatal, even with minimal burn area, and are often associated with prolonged hospitalisation.
OBJECTIVES
To summarise the evidence of effects (beneficial and harmful) of all interventions for treating people with phosphorus burns.
SEARCH METHODS
In October 2013 for this first update we searched the Cochrane Wounds Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library);Ovid OLDMEDLINE; Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL and Conference Proceedings Citation Index - Science (CPCI-S). We did not apply any methodological filters or restrictions on the basis of study design, language, date of publication or publication status.
SELECTION CRITERIA
Any comparisons of different ways of managing phosphorus burns including, but not restricted, to randomised trials.
DATA COLLECTION AND ANALYSIS
We found two non-randomised comparative studies, both comparing patients treated with and without copper sulphate.
MAIN RESULTS
These two comparative studies provide no evidence to support the use of copper sulphate in managing phosphorus burns. Indeed the small amount of available evidence suggests that it may be harmful.
AUTHORS' CONCLUSIONS
First aid for phosphorus burns involves the common sense measures of acting promptly to remove the patient's clothes, irrigating the wound(s) with water or saline continuously, and removing phosphorus particles. There is no evidence that using copper sulphate to assist visualisation of phosphorus particles for removal is associated with better outcome, and some evidence that systemic absorption of copper sulphate may be harmful. We have so far been unable to identify any other comparisons relevant to informing other aspects of the care of patients with phosphorus burns. Future versions of this review will take account of information in articles published in languages other than English, which may contain additional evidence based on treatment comparisons.
Topics: Antidotes; Burns, Chemical; Copper Sulfate; Humans; Phosphorus; Retrospective Studies
PubMed: 24896368
DOI: 10.1002/14651858.CD008805.pub3 -
Alimentary Pharmacology & Therapeutics Dec 2006D-Penicillamine is used for patients with primary biliary cirrhosis due to its ability to decrease hepatic copper and modulate the immune response. The results on... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
D-Penicillamine is used for patients with primary biliary cirrhosis due to its ability to decrease hepatic copper and modulate the immune response. The results on effects of D--penicillamine in randomized-clinical trials of primary biliary cirrhosis patients are inconsistent.
AIM
To systematically evaluate the benefits and harms of D-penicillamine for patients with primary biliary cirrhosis.
METHODS
We have performed a systematic review with meta-analyses of randomized-clinical trials to evaluate the effects of D-penicillamine for primary biliary cirrhosis. The primary outcomes are mortality and mortality or liver transplantation. We analysed the data by fixed-effect and random-effect models.
RESULTS
Seven randomized trials including 706 patients were analysed. d-Penicillamine was without significant effects on mortality (RR 1.08, 95% CI: 0.82-1.43, P = 0.56), mortality or liver transplantation (RR 1.11, 95% CI: 0.74-1.68, P = 0.62), pruritus, liver complications, progression of liver histological stage and liver biochemical variables. D--Penicillamine significantly decreased serum alanine aminotransferase activity (weighted mean difference -45 IU/L, 95% CI: -75 to -15, P < 0.05) and led to significantly more adverse events (RR 4.18, 95% CI: 1.38-12.69, P = 0.01).
CONCLUSION
D-Penicillamine did not appear to reduce the risk of mortality or morbidity, and led to more adverse events in patients with primary biliary cirrhosis.
Topics: Chelating Agents; Female; Humans; Liver Cirrhosis, Biliary; Male; Middle Aged; Penicillamine; Randomized Controlled Trials as Topic
PubMed: 17206942
DOI: 10.1111/j.1365-2036.2006.03164.x -
Current Reviews in Clinical and... May 2024There is a lack of evidence on the effectiveness of antidotes in the management of organophosphate and carbamate (OPC) poisoning. We aimed to review the efficacy and...
OBJECTIVE
There is a lack of evidence on the effectiveness of antidotes in the management of organophosphate and carbamate (OPC) poisoning. We aimed to review the efficacy and safety of glycopyrrolate in the management of OPC poisoning.
METHODOLOGY
Databases such as PubMed, Scopus, Embase, and Cochrane Library were extensively searched from inception to November 2022 and updated till October 2023. Interventional, observational, and descriptive studies assessing the efficacy and safety of glycopyrrolate administered in any dose, route, and duration for the management of OPC poisoning published in the English language were considered for this review. The treatment with any other regimen that did not include glycopyrrolate was regarded as the comparator. The survival, intensive care unit (ICU) days and ventilatory outcomes were considered efficacy outcomes, and adverse effects were considered safety outcomes. Suitable quality assessment tools were used to assess the risk of bias in the included studies. Two independent reviewers were involved in the study selection, data extraction, and quality assessment and any discrepancies were resolved through mutual discussion or consultation with a third reviewer.
RESULTS
A total of 9 studies (2 RCTs, 4 cohorts, 1 case series, and 2 case reports) out of 591 nonduplicate records were considered for this review. Overall, the RCTs were observed to have a moderate quality, and observational studies and descriptive studies were found to have good quality. All the included studies used atropine administration as a standard treatment option along with glycopyrrolate. The OPC patients treated with glycopyrrolate had a fewer hospitalization days with comparable recovery and ventilatory outcomes than those that had not been treated with glycopyrrolate. The occurrence of adverse events and complications was lower in the glycopyrrolate group than in the control group.
CONCLUSION
Currently, there is a lack of comparative studies to recommend the use of glycopyrrolate in OPC poisoning, and further interventional studies are required to make an evidencebased recommendation on this topic.
PubMed: 38797902
DOI: 10.2174/0127724328290595240509051331 -
European Journal of Cardio-thoracic... Oct 2023Literature is scarce on the management of patients using direct oral anticoagulants (DOACs) undergoing elective, urgent and emergency surgery. Therefore, we summarize... (Review)
Review
OBJECTIVES
Literature is scarce on the management of patients using direct oral anticoagulants (DOACs) undergoing elective, urgent and emergency surgery. Therefore, we summarize the current evidence and provide literature-based recommendations for the management of patients on DOACs in the perioperative phase.
METHODS
A general literature review was conducted on the pharmacology of DOACs and for recommendations on the management of cardiac surgical patients on DOACs. Additionally, we performed a systematic review for studies on the use of direct DOAC reversal agents in the emergency cardiac surgical setting.
RESULTS
When surgery is elective, the DOAC cessation strategy is relatively straightforward and should be adapted to the renal function. The same approach applies to urgent cases, but additional DOAC activity drug level monitoring tests may be useful. In emergency cases, idarucizumab can be safely administered to patients on dabigatran in any of the perioperative phases. However, andexanet alfa, which is not registered for perioperative use, should not be administered in the preoperative phase to reverse the effect of factor Xa inhibitors, as it may induce temporary heparin resistance. Finally, the administration of (activated) prothrombin complex concentrate may be considered in all patients on DOACs, and such concentrates are generally readily available.
CONCLUSIONS
DOACs offer several advantages over vitamin K antagonists, but care must be taken in patients undergoing cardiac surgery. Although elective and urgent cases can be managed relatively straightforwardly, the management of emergency cases requires particular attention.
Topics: Humans; Administration, Oral; Anticoagulants; Cardiac Surgical Procedures; Dabigatran; Hemorrhage; Heparin
PubMed: 37812245
DOI: 10.1093/ejcts/ezad340 -
JAMA Oncology Jul 2017The combination of fluorouracil, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI-Bev) is an established and effective first-line chemotherapy regimen for... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
The combination of fluorouracil, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI-Bev) is an established and effective first-line chemotherapy regimen for metastatic colorectal cancer. However, resection rates of metastases and overall survival with this schedule have never been systematically evaluated in published studies including, but not limited to, the TRIBE (TRIplet plus BEvacizumab) trial.
OBJECTIVE
To assess the clinical efficacy of FOLFOXIRI-Bev, including outcomes and rates of surgical conversions.
DATA SOURCES
A systematic review was conducted in October 2016 in concordance with the PRISMA guidelines of PubMed, the Cochrane Central Register of Controlled Trials, SCOPUS, Web of Science, Google Scholar, CINAHL, Ovid, and EMBASE using the terms FOLFOXIRI and bevacizumab and (colorectal cancer).
STUDY SELECTION
Clinical trials, retrospective case series, and prospective case series that used FOLFOXIRI-Bev for the treatment of initially unresectable metastatic colorectal cancer in humans were included. Individual case reports and retrospective case series with fewer than 10 patients were excluded.
DATA EXTRACTION AND SYNTHESIS
Data were extracted independently by 2 reviewers on a predesigned, standardized form. Ultimately, data were aggregated to obtain the pooled effect size of efficacy, according to the random-effects model and weighted for the number of patients included in each trial.
MAIN OUTCOMES AND MEASURES
Median overall survival and progression-free survival, overall response rates, and rates of R0 surgical conversions and overall surgical conversions.
RESULTS
Eleven FOLFOXIRI-Bev studies published between 2010 and 2016 met the inclusion criteria and were pooled for analysis. The studies included 889 patients, with 877 patients clinically evaluable for overall response rates. The objective response rate to FOLFOXIRI-Bev was 69% (95% CI, 65%-72%; I2 = 25%). The rate of overall surgical conversions was 39.1% (95% CI, 26.9%-52.8%), and the rate of R0 surgical conversions was 28.1% (95% CI, 18.1%-40.8%). Median pooled overall survival was 30.2 months (95% CI, 26.5-33.7 months) in 6 trials with data available, and progression-free survival was 12.4 months (95% CI, 10.0-14.3 months) in 9 trials with data available. In meta-regression analysis, variables significantly associated with conversion surgery were disease limited to the liver and a higher median number of cycles (close to 12).
CONCLUSIONS AND RELEVANCE
For patients with surgically unresectable metastatic colorectal cancer, FOLFOXIRI-Bev is associated with a significant overall response rate. Such an effective regimen leads to a probability of surgical conversion of distant metastases approaching 40%, with more than one-fourth of patients having an R0 resection.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Fluorouracil; Hepatectomy; Humans; Leucovorin; Liver Neoplasms; Organoplatinum Compounds; Survival Analysis; Treatment Outcome
PubMed: 28542671
DOI: 10.1001/jamaoncol.2017.0278 -
Annals of Surgical Oncology Dec 2016FOLFIRINOX prolongs survival in patients with metastatic pancreatic cancer and may also benefit patients with locally advanced pancreatic cancer (LAPC). Furthermore, it... (Review)
Review
BACKGROUND
FOLFIRINOX prolongs survival in patients with metastatic pancreatic cancer and may also benefit patients with locally advanced pancreatic cancer (LAPC). Furthermore, it may downstage a proportion of LAPC into (borderline) resectable disease, however data are lacking. This review assessed outcomes after FOLFIRINOX-based therapy in LAPC.
METHODS
The PubMed, EMBASE and Cochrane library databases were systematically searched for studies published to 31 August 2015. Primary outcome was the (R0) resection rate.
RESULTS
Fourteen studies involving 365 patients with LAPC were included; three studies administered a modified FOLFIRINOX regimen. Of all patients, 57 % (n = 208) received radiotherapy. The pooled resection rate was 28 % (n = 103, 77 % R0), with a perioperative mortality of 3 % (n = 2), and median overall survival ranged from 8.9 to 25.0 months. Survival data after resection were scarce, with only one study reporting a median overall survival of 24.9 months in 28 patients. A complete pathologic response was found in 6 of 85 (7 %) resected specimens. Dose reductions were described in up to 65 % of patients, grade 3-4 toxicity occurred in 23 % (n = 51) of patients, and 2 % (n = 5) had to discontinue treatment. Data of patients treated solely with FOLFIRINOX, without additional radiotherapy, were available from 292 patients: resection rate was 12 % (n = 29, 70 % R0), with 15.7 months median overall survival and 19 % (n = 34) grade 3-4 toxicity.
CONCLUSIONS
Outcomes after FOLFIRINOX-based therapy in patients with LAPC seem very promising but further prospective studies are needed, especially with regard to survival after resection.
Topics: Antineoplastic Combined Chemotherapy Protocols; CA-19-9 Antigen; Camptothecin; Carcinoma, Pancreatic Ductal; Chemotherapy, Adjuvant; Fluorouracil; Humans; Irinotecan; Leucovorin; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Pancreatectomy; Pancreatic Neoplasms; Radiotherapy; Radiotherapy, Adjuvant; Survival Rate
PubMed: 27370653
DOI: 10.1245/s10434-016-5373-2 -
Oncotarget Sep 2015Most comprehensive treatments for PBC include UDCA, combination of methotrexate (MTX), corticosteroids (COT), colchicine (COC) or bezafibrate (BEF), cyclosporin A (CYP),... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Most comprehensive treatments for PBC include UDCA, combination of methotrexate (MTX), corticosteroids (COT), colchicine (COC) or bezafibrate (BEF), cyclosporin A (CYP), D-penicillamine (DPM), methotrexate (MTX), or azathioprine (AZP). Since the optimum treatment regimen remains inconclusive, we aimed to compare these therapies in terms of patient mortality or liver transplantation (MOLT) and adverse event (AE).
METHODS
We searched PubMed, Embase, Scopus and the Cochrane Library for randomized controlled trials until August 2014. We estimated HRs for MOLT and ORs for AE. The sensitivity analysis based on dose of UDCA was also performed.
RESULTS
The search identified 49 studies involving 12 different treatment regimens and 4182 patients. Although no statistical significance can be found in MOLT, COT plus UDCA was ranked highest for efficacy outcome amongst all the treatment regimes. While for AEs, compared with OBS or UDCA, monotherapy with COC (OR 5.6, P < 0.001; OR 5.89, P < 0.001), CYP (OR 3.24, P < 0.001; OR 3.42, P < 0.001), DPM (OR 8.00, P < 0.001; OR 8.45, P < 0.001) and MTX (OR 5.31, P < 0.001; OR 5.61, P < 0.001) were associated with statistically significant increased risk of AEs. No significant differences were found for other combination regimes. Effect estimates from indirect comparisons matched closely to estimates derived from pairwise comparisons. Consistently, in the sensitivity analysis, results closely resembled our primary analysis.
CONCLUSIONS
COT plus UDCA was the most efficacious among treatment regimens both for MOLT and AEs.
Topics: Adrenal Cortex Hormones; Adult; Aged; Azathioprine; Bezafibrate; Bile Ducts; Colchicine; Cyclosporine; Drug Therapy, Combination; Female; Humans; Liver Cirrhosis, Biliary; Male; Methotrexate; Middle Aged; Penicillamine; Treatment Outcome; Ursodeoxycholic Acid
PubMed: 26109432
DOI: 10.18632/oncotarget.4528 -
European Journal of Neurology Oct 2018Intracranial hemorrhage (ICH) is the most feared complication in patients treated with oral anticoagulants due to non-valvular atrial fibrillation. Non-vitamin K oral... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
Intracranial hemorrhage (ICH) is the most feared complication in patients treated with oral anticoagulants due to non-valvular atrial fibrillation. Non-vitamin K oral anticoagulants (NOACs) reduce the risk of ICH compared with vitamin K antagonists (VKAs). We performed a systematic review and meta-analysis to evaluate the risk of fatal NOAC-related ICH compared with VKA-related ICH.
METHODS
We calculated the corresponding risk ratios (RRs) in each included study to express the relative risk of fatal ICH amongst all patients receiving oral anticoagulation with either NOACs or VKAs. We additionally evaluated the mortality rates in NOAC-related ICH in patients treated with and without NOAC-specific reversal agents (idarucizumab and factor Xa inhibitors antidote). Case fatality was evaluated at 30-90 days following symptom onset.
RESULTS
Our literature search identified six eligible studies (four randomized controlled trials and two open-label trials of NOAC-specific reversal agents). In pairwise analyses, NOACs were found to have a lower risk of fatal ICH compared with VKAs [RR, 0.46; 95% confidence interval (CI), 0.36-0.58] with no heterogeneity (I = 0%) across included randomized controlled trials. However, the case fatality rate was similar in NOAC-related and VKA-related (RR, 1.00; 95% CI, 0.84-1.19) ICH with no evidence of heterogeneity (I = 0%). In the indirect analysis, the case fatality rate of NOAC-related ICH in patients treated with specific reversal agents was lower compared with the remainder of the patients [17% (95% CI, 11-24%) vs. 41% (95% CI, 34-49%); P < 0.001].
CONCLUSIONS
Non-vitamin K oral anticoagulants halve the risk of fatal ICH in patients with non-valvular atrial fibrillation compared with VKAs, whereas indirect comparisons indicate that NOAC-specific reversal agents may be associated with a lower case fatality rate in NOAC-related ICH.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Intracranial Hemorrhages; Risk
PubMed: 29953696
DOI: 10.1111/ene.13742 -
Pharmaceutical Biology Aug 2016Spirulina (Arthrospira) exerts a wide spectrum of pharmacological activities which are mainly attributed to its antioxidant effect. However, Spirulina has also been... (Review)
Review
CONTEXT
Spirulina (Arthrospira) exerts a wide spectrum of pharmacological activities which are mainly attributed to its antioxidant effect. However, Spirulina has also been reported (both in preclinical and in clinical scenarios) to exhibit other bioactive effects, including an antitoxic potential.
OBJECTIVE
We performed a systematic review of the literature, conducted in TOXNET, PubMed/MEDLINE, and Science Direct-Scopus; all available years were included. Searching criteria included the effects of Spirulina on experimental poisonings from arsenic, cadmium, carbon tetrachloride, deltamethrin, fluoride, hexachlorocyclohexane, iron, lead, lindane, and mercury.
RESULTS
In all cases, it was established that the blue-green alga, and its isolated compounds, effectively counteracted these pollutants toxic effects on the exposed organisms. Some molecular mechanisms are proposed, although they have not been fully elucidated yet.
CONCLUSION
Spirulina could be a useful coadjuvant agent within clinical practice for treatment of these or other pollutants poisonings.
Topics: Animals; Antidotes; Antioxidants; Environmental Exposure; Environmental Pollutants; Humans; Occupational Exposure; Poisoning; Spirulina
PubMed: 26439611
DOI: 10.3109/13880209.2015.1077464