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Molecular Psychiatry Jan 2023A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to... (Meta-Analysis)
Meta-Analysis
A systematic review and random-effects model network meta-analysis were conducted to compare the efficacy, acceptability, tolerability, and safety of antidepressants to treat adults with major depressive disorder (MDD) in the maintenance phase. This study searched the PubMed, Cochrane Library, and Embase databases and included only double-blind, randomized, placebo-controlled trials with an enrichment design: patients were stabilized on the antidepressant of interest during the open-label study and then randomized to receive the same antidepressant or placebo. The outcomes were the 6-month relapse rate (primary outcome, efficacy), all-cause discontinuation (acceptability), discontinuation due to adverse events (tolerability), and the incidence of individual adverse events. The risk ratio with a 95% credible interval was calculated. The meta-analysis comprised 34 studies (n = 9384, mean age = 43.80 years, and %females = 68.10%) on 20 antidepressants (agomelatine, amitriptyline, bupropion, citalopram, desvenlafaxine, duloxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, vilazodone, and vortioxetine) and a placebo. In terms of the 6-month relapse rate, amitriptyline, citalopram, desvenlafaxine, duloxetine, fluoxetine, fluvoxamine, mirtazapine, nefazodone, paroxetine, reboxetine, sertraline, tianeptine, venlafaxine, and vortioxetine outperformed placebo. Compared to placebo, desvenlafaxine, paroxetine, sertraline, venlafaxine, and vortioxetine had lower all-cause discontinuation; however, sertraline had a higher discontinuation rate due to adverse events. Compared to placebo, venlafaxine was associated with a lower incidence of dizziness, while desvenlafaxine, sertraline, and vortioxetine were associated with a higher incidence of nausea/vomiting. In conclusion, desvenlafaxine, paroxetine, venlafaxine, and vortioxetine had reasonable efficacy, acceptability, and tolerability in the treatment of adults with stable MDD.
Topics: Female; Humans; Adult; Depressive Disorder, Major; Duloxetine Hydrochloride; Sertraline; Citalopram; Venlafaxine Hydrochloride; Vortioxetine; Fluoxetine; Paroxetine; Mirtazapine; Amitriptyline; Desvenlafaxine Succinate; Fluvoxamine; Reboxetine; Network Meta-Analysis; Antidepressive Agents; Randomized Controlled Trials as Topic
PubMed: 36253442
DOI: 10.1038/s41380-022-01824-z -
The Cochrane Database of Systematic... Oct 2022Motion sickness is a syndrome that occurs as a result of passive body movement in response to actual motion, or the illusion of motion when exposed to virtual and moving... (Review)
Review
BACKGROUND
Motion sickness is a syndrome that occurs as a result of passive body movement in response to actual motion, or the illusion of motion when exposed to virtual and moving visual environments. The most common symptoms are nausea and vomiting. Antihistamines have been used in the management of motion sickness for decades, however studies have shown conflicting results regarding their efficacy.
OBJECTIVES
To assess the effectiveness of antihistamines in the prevention and treatment of motion sickness in adults and children.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 7 December 2021.
SELECTION CRITERIA
Randomised controlled trials (RCTs) in susceptible adults and children in whom motion sickness was induced under natural conditions such as air, sea and land transportation. We also included studies in which motion sickness was induced under experimental conditions (analysed separately). Antihistamines were included regardless of class, route or dosage and compared to no treatment, placebo or any other pharmacological or non-pharmacological interventions.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1) the proportion of susceptible participants who did not experience any motion sickness symptoms; 2) the proportion of susceptible participants who experienced a reduction or resolution of existing symptoms. Secondary outcomes were 1) physiological measures (heart rate, core temperature and gastric tachyarrhythmia (electrogastrography)) and 2) adverse effects (sedation, impaired cognition, blurred vision). We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We included nine RCTs (658 participants). Studies were conducted across seven countries, with an overall age range of 16 to 55 years. Motion sickness was induced naturally in six studies and experimentally in four studies (rotating chair). All the naturally induced studies only evaluated first-generation antihistamines (cinnarizine and dimenhydrinate). Risk of bias across the studies varied, with mostly low risk for random sequence generation and allocation concealment, and mostly high risk for selective reporting. Only the experimentally induced studies measured physiological parameters and only the naturally induced studies evaluated adverse effects. There were no studies that clearly assessed the paediatric population. Antihistamines versus placebo or no treatment Antihistamines are probably more effective than placebo at preventing motion sickness symptoms under natural conditions (symptoms prevented: 25% placebo; 40% antihistamines) (risk ratio (RR) 1.81, 95% confidence interval (CI) 1.23 to 2.66; 3 studies; 240 participants) (moderate-certainty). The evidence is very uncertain about the effect of antihistamines on preventing motion sickness under experimental conditions (standardised mean difference (SMD) 0.32, 95% CI -0.18 to 0.83; 2 studies; 62 participants) (very low-certainty). No studies reported results on the resolution of existing motion sickness symptoms. Antihistamines may result in little or no difference in gastric tachyarrhythmia under experimental conditions (mean difference (MD) -2.2, 95% CI -11.71 to 7.31; 1 study; 42 participants) (low-certainty). No studies reported results for any other physiological measures. When compared to placebo, antihistamines may be more likely to cause sedation (sedation: 44% placebo; 66% antihistamines) (RR 1.51, 95% CI 1.12 to 2.02; 2 studies; 190 participants) (low-certainty); they may result in little or no difference in blurred vision (blurred vision: 12.5% placebo; 14% antihistamines) (RR 1.14, 95% CI 0.53 to 2.48; 2 studies; 190 participants) (low-certainty); and they may result in little or no difference in terms of impaired cognition (impaired cognition: 33% placebo; 29% antihistamines) (RR 0.89, 95% CI 0.58 to 1.38; 2 studies; 190 participants) (low-certainty). Antihistamines versus scopolamine The evidence is very uncertain about the effect of antihistamines on preventing motion sickness under natural conditions when compared to scopolamine (symptoms prevented: 81% scopolamine; 71% antihistamines) (RR 0.89, 95% CI 0.68 to 1.16; 2 studies; 71 participants) (very low-certainty). No studies were performed under experimental conditions. No studies reported results on the resolution of existing motion sickness symptoms. The evidence is very uncertain about the effect of antihistamines on heart rate under natural conditions (narrative report, 1 study; 20 participants; "No difference in pulse frequency"; very low-certainty). No studies reported results for any other physiological measures. When compared to scopolamine, the evidence is very uncertain about the effect of antihistamines on sedation (sedation: 21% scopolamine; 30% antihistamines) (RR 0.82, 95% CI 0.07 to 9.25; 2 studies; 90 participants) (very low-certainty) and on blurred vision (narrative report: not a significant difference; 1 study; 51 participants; very low-certainty). No studies evaluated impaired cognition. Antihistamines versus antiemetics Antihistamines may result in little or no difference in the prevention of motion sickness under experimental conditions (MD -0.20, 95% CI -10.91 to 10.51; 1 study; 42 participants) (low-certainty). The evidence is of low certainty due to imprecision as the sample size is small and the confidence interval crosses the line of no effect. No studies assessed the effects of antihistamines versus antiemetics under natural conditions. No studies reported results on the resolution of existing motion sickness symptoms. Antihistamines may result in little or no difference in gastric tachyarrhythmia (MD 4.56, 95% CI -3.49 to 12.61; 1 study; 42 participants) (low-certainty). No studies reported results for any other physiological measures. No studies evaluated sedation, impaired cognition or blurred vision. One study reported physiological data for this outcome, evaluating gastric tachyarrhythmia specifically. Antihistamines may result in little or no difference in gastric tachyarrhythmia (MD 4.56, 95% CI -3.49 to 12.61; 1 study; 42 participants; low-certainty evidence). This evidence is of low certainty due to imprecision as the sample size is small and the confidence interval crosses the line of no effect. Antihistamines versus acupuncture The evidence is very uncertain about the effects of antihistamines on the prevention of motion sickness under experimental conditions when compared to acupuncture (RR 1.32, 95% CI 1.12 to 1.57; 1 study; 100 participants) (very low-certainty). This study did not assess the prevention of motion sickness under natural conditions, nor the resolution of existing motion sickness symptoms. There was no study performed under natural conditions. Physiological measures and adverse effects were not reported.
AUTHORS' CONCLUSIONS
There is probably a reduction in the risk of developing motion sickness symptoms under naturally occurring conditions of motion when using first-generation antihistamines, in motion sickness-susceptible adults, compared to placebo. Antihistamines may be more likely to cause sedation when compared to placebo. No studies evaluated the treatment of existing motion sickness, and there are few data on the effect of antihistamines in children. The evidence for all other outcomes and comparisons (versus scopolamine, antiemetics and acupuncture) was of low or very low certainty and we are therefore uncertain about these effects of antihistamines.
Topics: Adolescent; Adult; Antiemetics; Child; Cinnarizine; Dimenhydrinate; Histamine Antagonists; Humans; Middle Aged; Motion Sickness; Scopolamine Derivatives; Young Adult
PubMed: 36250781
DOI: 10.1002/14651858.CD012715.pub2 -
Psychopharmacology Nov 2022While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
While one of the basic axioms of pharmacology postulates that there is a relationship between the concentration and effects of a drug, the value of measuring blood levels is questioned by many clinicians. This is due to the often-missing validation of therapeutic reference ranges.
OBJECTIVES
Here, we present a prototypical meta-analysis of the relationships between blood levels of aripiprazole, its target engagement in the human brain, and clinical effects and side effects in patients with schizophrenia and related disorders.
METHODS
The relevant literature was systematically searched and reviewed for aripiprazole oral and injectable formulations. Population-based concentration ranges were computed (N = 3,373) and pharmacokinetic influences investigated.
RESULTS
Fifty-three study cohorts met the eligibility criteria. Twenty-nine studies report blood level after oral, 15 after injectable formulations, and nine were positron emission tomography studies. Conflicting evidence for a relationship between concentration, efficacy, and side effects exists (assigned level of evidence low, C; and absent, D). Population-based reference ranges are well in-line with findings from neuroimaging data and individual efficacy studies. We suggest a therapeutic reference range of 120-270 ng/ml and 180-380 ng/ml, respectively, for aripiprazole and its active moiety for the treatment of schizophrenia and related disorders.
CONCLUSIONS
High interindividual variability and the influence of CYP2D6 genotypes gives a special indication for Therapeutic Drug Monitoring of oral and long-acting aripiprazole. A starting dose of 10 mg will in most patients result in effective concentrations in blood and brain. 5 mg will be sufficient for known poor metabolizers.
Topics: Humans; Aripiprazole; Schizophrenia; Reference Values; Antipsychotic Agents; Cytochrome P-450 CYP2D6
PubMed: 36195732
DOI: 10.1007/s00213-022-06233-2 -
Journal of Interventional Cardiology 2022This systematic review and meta-analysis evaluates the safety and efficacy of dual antiplatelet therapy (DAPT) in elderly patients with acute coronary syndrome (ACS). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This systematic review and meta-analysis evaluates the safety and efficacy of dual antiplatelet therapy (DAPT) in elderly patients with acute coronary syndrome (ACS).
BACKGROUND
The safety and efficacy of DAPT in elderly patients with ACS is not well characterized.
METHODS
We performed a systematic literature review to identify clinical studies that reported safety and efficacy outcomes after DAPT for ACS in elderly patients. The primary outcomes of primary efficacy endpoint rates and bleeding event rates were reported as random effects risk ratio (RR) with 95% confidence interval. No prior ethical approval was required since all data are public.
RESULTS
Our search yielded 660 potential studies. We included 8 studies reporting on 29,217 patients. There was a higher risk of bleeding event rates in elderly patients treated with prasugrel or ticagrelor when compared to clopidogrel with a risk ratio of 1.17 (95% CI 1.08 to 1.27, < 0.05). There was no difference in primary efficacy endpoint rates between elderly patients treated with prasugrel or ticagrelor when compared to clopidogrel with a risk ratio of 0.85 (95% CI 0.68 to 1.07, =0.17).
CONCLUSIONS
This systematic review and meta-analysis suggests that DAPT with prasugrel or ticagrelor compared to clopidogrel is associated with a higher risk of bleeding events in elderly patients with ACS. There was no difference in the primary efficacy endpoints between the two treatment groups.
Topics: Acute Coronary Syndrome; Aged; Clopidogrel; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Risk Assessment; Ticagrelor; Treatment Outcome
PubMed: 36176329
DOI: 10.1155/2022/3111840 -
The Cochrane Database of Systematic... Sep 2022This review is the third update of a previously published Cochrane Review. The original review, looking at all possible cardioprotective agents, was split and this part... (Review)
Review
BACKGROUND
This review is the third update of a previously published Cochrane Review. The original review, looking at all possible cardioprotective agents, was split and this part now focuses on dexrazoxane only. Anthracyclines are effective chemotherapeutic agents in the treatment of numerous malignancies. Unfortunately, their use is limited by a dose-dependent cardiotoxicity. In an effort to prevent or reduce this cardiotoxicity, different cardioprotective agents have been studied, including dexrazoxane.
OBJECTIVES
To assess the efficacy of dexrazoxane to prevent or reduce cardiotoxicity and determine possible effects of dexrazoxane on antitumour efficacy, quality of life and toxicities other than cardiac damage in adults and children with cancer receiving anthracyclines when compared to placebo or no additional treatment.
SEARCH METHODS
We searched CENTRAL, MEDLINE and Embase to May 2021. We also handsearched reference lists, the proceedings of relevant conferences and ongoing trials registers.
SELECTION CRITERIA
Randomised controlled trials (RCTs) in which dexrazoxane was compared to no additional therapy or placebo in adults and children with cancer receiving anthracyclines.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, data extraction, risk of bias and GRADE assessment of included studies. We analysed results in adults and children separately. We performed analyses according to the Cochrane Handbook for Systematic Reviews of Interventions.
MAIN RESULTS
For this update, we identified 548 unique records. We included three additional RCTs: two paediatric and one adult. Therefore, we included a total of 13 eligible RCTs (five paediatric and eight adult). The studies enrolled 1252 children with leukaemia, lymphoma or a solid tumour and 1269 participants, who were mostly diagnosed with breast cancer. In adults, moderate-quality evidence showed that there was less clinical heart failure with the use of dexrazoxane (risk ratio (RR) 0.22, 95% confidence interval (CI) 0.11 to 0.43; 7 studies, 1221 adults). In children, we identified no difference in clinical heart failure risk between treatment groups (RR 0.20, 95% CI 0.01 to 4.19; 3 studies, 885 children; low-quality evidence). In three paediatric studies assessing cardiomyopathy/heart failure as the primary cause of death, none of the children had this outcome (1008 children, low-quality evidence). In the adult studies, different definitions for subclinical myocardial dysfunction and clinical heart failure combined were used, but pooled analyses were possible: there was a benefit in favour of the use of dexrazoxane (RR 0.37, 95% CI 0.24 to 0.56; 3 studies, 417 adults and RR 0.46, 95% CI 0.33 to 0.66; 2 studies, 534 adults, respectively, moderate-quality evidence). In the paediatric studies, definitions of subclinical myocardial dysfunction and clinical heart failure combined were incomparable, making pooling impossible. One paediatric study showed a benefit in favour of dexrazoxane (RR 0.33, 95% CI 0.13 to 0.85; 33 children; low-quality evidence), whereas another study showed no difference between treatment groups (Fischer exact P = 0.12; 537 children; very low-quality evidence). Overall survival (OS) was reported in adults and overall mortality in children. The meta-analyses of both outcomes showed no difference between treatment groups (hazard ratio (HR) 1.04, 95% 0.88 to 1.23; 4 studies; moderate-quality evidence; and HR 1.01, 95% CI 0.72 to 1.42; 3 studies, 1008 children; low-quality evidence, respectively). Progression-free survival (PFS) was only reported in adults. We subdivided PFS into three analyses based on the comparability of definitions, and identified a longer PFS in favour of dexrazoxane in one study (HR 0.62, 95% CI 0.43 to 0.90; 164 adults; low-quality evidence). There was no difference between treatment groups in the other two analyses (HR 0.95, 95% CI 0.64 to 1.40; 1 study; low-quality evidence; and HR 1.18, 95% CI 0.97 to 1.43; 2 studies; moderate-quality evidence, respectively). In adults, there was no difference in tumour response rate between treatment groups (RR 0.91, 95% CI 0.79 to 1.04; 6 studies, 956 adults; moderate-quality evidence). We subdivided tumour response rate in children into two analyses based on the comparability of definitions, and identified no difference between treatment groups (RR 1.01, 95% CI 0.95 to 1.07; 1 study, 206 children; very low-quality evidence; and RR 0.92, 95% CI 0.84 to 1.01; 1 study, 200 children; low-quality evidence, respectively). The occurrence of secondary malignant neoplasms (SMN) was only assessed in children. The available and worst-case analyses were identical and showed a difference in favour of the control group (RR 3.08, 95% CI 1.13 to 8.38; 3 studies, 1015 children; low-quality evidence). In the best-case analysis, the direction of effect was the same, but there was no difference between treatment groups (RR 2.51, 95% CI 0.96 to 6.53; 4 studies, 1220 children; low-quality evidence). For other adverse effects, results also varied. None of the studies evaluated quality of life. If not reported, the number of participants for an analysis was unclear.
AUTHORS' CONCLUSIONS
Our meta-analyses showed the efficacy of dexrazoxane in preventing or reducing cardiotoxicity in adults treated with anthracyclines. In children, there was a difference between treatment groups for one cardiac outcome (i.e. for one of the definitions used for clinical heart failure and subclinical myocardial dysfunction combined) in favour of dexrazoxane. In adults, no evidence of a negative effect on tumour response rate, OS and PFS was identified; and in children, no evidence of a negative effect on tumour response rate and overall mortality was identified. The results for adverse effects varied. In children, dexrazoxane may be associated with a higher risk of SMN; in adults this was not addressed. In adults, the quality of the evidence ranged between moderate and low; in children, it ranged between low and very low. Before definitive conclusions on the use of dexrazoxane can be made, especially in children, more high-quality research is needed. We conclude that if the risk of cardiac damage is expected to be high, it might be justified to use dexrazoxane in children and adults with cancer who are treated with anthracyclines. However, clinicians and patients should weigh the cardioprotective effect of dexrazoxane against the possible risk of adverse effects, including SMN, for each individual. For children, the International Late Effects of Childhood Cancer Guideline Harmonization Group has developed a clinical practice guideline.
Topics: Adult; Anthracyclines; Antibiotics, Antineoplastic; Cardiotonic Agents; Cardiotoxicity; Child; Dexrazoxane; Heart Failure; Humans; Leukemia, Myeloid, Acute; Polyketides; Systematic Reviews as Topic
PubMed: 36162822
DOI: 10.1002/14651858.CD014638.pub2 -
Molecular Psychiatry Jan 2023People with mood disorders have increased risk of comorbid medical diseases versus the general population. It is paramount to identify interventions to improve physical...
The impact of pharmacological and non-pharmacological interventions on physical health outcomes in people with mood disorders across the lifespan: An umbrella review of the evidence from randomised controlled trials.
OBJECTIVE
People with mood disorders have increased risk of comorbid medical diseases versus the general population. It is paramount to identify interventions to improve physical health in this population.
METHODS
Umbrella review of meta-analyses of randomised controlled trials (RCTs) on pharmacological/non-pharmacological interventions for physical health outcomes/intolerability-related discontinuation in mood disorders (any age).
RESULTS
Ninety-seven meta-analyses were included. Among youths, against placebo, in depression, antidepressants/antipsychotics had higher discontinuation rates; in bipolar depression, olanzapine+fluoxetine worsened total cholesterol (TC)/triglycerides/weight gain (WG) (large ES). In adults with bipolar disorder, olanzapine worsened HbA1c/TC/WG (moderate/large ES); asenapine increased fasting glucose (small ES); quetiapine/cariprazine/risperidone induced WG (small/moderate ES). In bipolar depression, lurasidone was metabolically neutral. In depression, psychological interventions improved physical health-related quality of life (PHQoL) (small ES), fasting glucose/HbA1c (medium/large ES); SSRIs improved fasting glucose/HbA1c, readmission for coronary disease, pain (small ES); quetiapine/aripiprazole/olanzapine induced WG (small to large ES). Exercise improved cardiorespiratory fitness (moderate ES). In the elderly, fluoxetine yielded more detrimental cardiovascular effects than sertraline/escitalopram (large ES); antidepressants were neutral on exercise tolerance and PHQoL. In mixed age groups, in bipolar disorder aripiprazole was metabolically neutral; in depression, SSRIs lowered blood pressure versus placebo and serotonin-noradrenaline reuptake inhibitors (small ES); brexpiprazole augmentation caused WG and was less tolerated (small ES); exercise improved PHQoL (moderate ES).
CONCLUSIONS
Some interventions (psychological therapies, exercise and SSRIs) improve certain physical health outcomes in mood disorders, few are neutral, but various pharmacological interventions are associated with negative effects. Evidence from this umbrella review has limitations, should consider evidence from other disorders and should be integrated with recent evidence from individual RCTs, and observational evidence. Effective treatments with either beneficial or physically neutral profiles should be prioritized.
Topics: Adult; Humans; Aged; Adolescent; Fluoxetine; Olanzapine; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Aripiprazole; Longevity; Glycated Hemoglobin; Antipsychotic Agents; Antidepressive Agents; Bipolar Disorder; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic
PubMed: 36138129
DOI: 10.1038/s41380-022-01770-w -
Frontiers in Endocrinology 2022The dipeptidyl peptidase-4 inhibitor (DPP-4i) drugs, such as evogliptin, as the second-line drugs for type 2 diabetes mellitus (T2DM) treatment have been reported to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The dipeptidyl peptidase-4 inhibitor (DPP-4i) drugs, such as evogliptin, as the second-line drugs for type 2 diabetes mellitus (T2DM) treatment have been reported to facilitate insulin secretion by reducing glucagon and inhibiting glucagon like peptides. With a vague consensus, the advantageous and non-inferior effects of evogliptin relative to other DPP-4i drugs were recently demonstrated on hemoglobin A1c (HbA1c) levels and overall adverse events in T2DM patients. Thus, the aim was to evaluate the overall influence of evogliptin on HbA1c levels and the adverse events in T2DM patients compared to sitagliptin and linagliptin.
METHODS
Complying with PRISMA guidelines, we conducted a systematic literature search in databases and a meta-analysis. Data about HbA1c levels and the adverse events of T2DM patients were collected and analyzed.
RESULTS
From 1,397 studies, we found five matched studies involving 845 subjects (mean age: 54.7 ± 3 years). The meta-analysis revealed that evogliptin was non-inferior to sitagliptin/linagliptin with a mean difference of 0.062 (95% CI: -0.092 to 0.215. I: 0%. = 0.431) regarding the HbA1c level reduction, and the risk ratio was -0.006 (95% CI: -0.272 to 0.260. I: 1.7%. = 0.966) regarding the adverse effects, indicating no significant difference between evogliptin and linagliptin or sitagliptin in affecting the HbA1c level and adverse effects.
CONCLUSION
The study provides preliminary evidence regarding the similarity in the efficacy of evogliptin compared to other DPP-4i drugs, including sitagliptin and linagliptin, for managing HbA1c levels and adverse events.
Topics: Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Linagliptin; Middle Aged; Piperazines; Sitagliptin Phosphate
PubMed: 36060938
DOI: 10.3389/fendo.2022.962385 -
The Cochrane Database of Systematic... Sep 2022Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of... (Review)
Review
BACKGROUND
Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus, and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, and their many side effects are well-documented. A group of compounds, the azoles, have activity against A fumigatus, and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been used in aerosolised form to treat invasive infection with A fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review.
OBJECTIVES
The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); and 2. do not have unacceptable adverse effects. If benefit was demonstrated, we planned to assess the optimal type, duration, and dose of antifungal therapy.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals, and abstract books of conference proceedings. Date of the most recent search of the Group's Trials Register was 28 September 2021. We searched ongoing trials registries, most recently on 11 March 2022. Earlier, we also approached pharmaceutical companies regarding possible unpublished trials.
SELECTION CRITERIA
Published or unpublished randomised controlled trials, in which antifungal treatments were compared to either placebo or no treatment, or where different doses of the same treatment were used in the treatment of ABPA in people with cystic fibrosis.
DATA COLLECTION AND ANALYSIS
The searches identified six trials; none of which met the inclusion criteria for the review.
MAIN RESULTS
We included no completed randomised controlled trials. There is currently one ongoing trial, which we may find eligible for a future update.
AUTHORS' CONCLUSIONS
At present, there are no randomised controlled trials that evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although one trial is currently ongoing. Trials with clear outcome measures are needed to properly evaluate the use of corticosteroids in people with ABPA and cystic fibrosis.
Topics: Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Cystic Fibrosis; Humans; Itraconazole
PubMed: 36053129
DOI: 10.1002/14651858.CD002204.pub5 -
Scientific Reports Aug 2022Trazodone has been widely prescribed for off-label use as a sleep aid. Identifying how trazodone impacts the performance of polysomnographic sleep architecture in... (Meta-Analysis)
Meta-Analysis
Trazodone has been widely prescribed for off-label use as a sleep aid. Identifying how trazodone impacts the performance of polysomnographic sleep architecture in insomnia disorder will provide additional data that can be used to guide clinical application. To assess the efficacy of trazodone in altering the polysomnographic sleep architecture in insomnia disorder so that sleep can be facilitated. PubMed, EMBASE, Web of Science, PsycINFO, Cochrane Library, Chinese Biomedical Literature Database (SinoMed), China National Knowledge Infrastructure, Wanfang Database, and the China Science and Technology Journal Database were searched for articles published between inception and June 2022. RCTs in patients with insomnia disorder applying trazodone in one arm of interventions at least 1 week, and reporting PSG parameters in the outcomes were eligible. RoB 2 was used to evaluate the risk of bias. The results of quality of evidence assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. When I < 50%, the fixed effects model was used. When I ≥ 50%, the random effects model was used. The mean differences (MD) or standardized mean differences (SMD) and odds ratios (OR) with 95% confidence intervals (CIs) were estimated. Eleven randomized controlled trials were selected and participants were 466. Risk of bias was low in 5 trials (45.5%), and was moderate in 6 (54.5%). Compared with the control group, trazodone significantly increased total sleep time (TST, min) (MD = 39.88, 95% CI 14.44-65.32, P = 0.002) and non-rapid eye movement stage 3 (N3, mixed min and %) (SMD = 1.61, 95% CI 0.69-2.53, P = 0.0006); trazodone significantly decreased latency to onset of persistent sleep (LPS, min) (MD = - 19.30, 95% CI - 37.28 to - 1.32, P = 0.04), non-rapid eye movement stage 1 (N1, mixed min and %) (SMD = - 0.62, 95% CI - 1.13 to - 0.12, P = 0.02), the number of awakenings (NAs, including both arousal times and arousal index) (SMD = - 0.67, 95% CI - 0.91 to - 0.42, P < 0.00001), and waking time after persistent sleep onset (WASO, mixed min and %) (SMD = - 0.42, 95% CI - 0.81, - 0.03, P = 0.04), with no obvious effect on non-rapid eye movement stage 2 (N2, mixed min and %) (SMD = - 0.15, 95% CI - 0.41 to 0.11, P = 0.25), rapid eye movement (REM, mixed min and %) (SMD = 0.22, 95% CI - 0.26 to 0.70, P = 0.37), rapid eye movement latency (REML, min) (MD = 2.33, 95% CI - 27.56 to 32.22, P = 0.88), or apnea-hypopnea index (AHI) (MD = - 4.21, 95% CI - 14.02 to 5.59, P = 0.40). Daytime drowsiness (OR = 2.53, 95% CI 1.14-5.64, P = 0.02) and decreased appetite (OR = 2.81, 95% CI 1.14-6.92, P = 0.02) occurred with greater frequency in the trazodone group as compared to the control group, and the differences were significant. The results of quality of evidence were very low in TST, N3 and AHI, were low in LPS, WASO and REM, and were moderate in N1 and NAs. The sources of heterogeneity in TST and N3 were not found out from sensitive and subgroup analysis and there was no high quality of evidence in outcomes by GRADE Assessment. Trials with combination of other therapy could be a problem in this meta-analysis as the possibility of interactions were found from sungroup analysis. Trazodone could improve sleep by changing the sleep architecture in insomnia disorder, but it should be used with caution due to the adverse events that may occur.PROSPERO registration register name: The effect of trazodone on polysomnography sleep architecture in patients with insomnia: a systematic review and meta-analysis protocol; Registration Number CRD42020215332.
Topics: Arousal; Humans; Lipopolysaccharides; Randomized Controlled Trials as Topic; Sleep; Sleep Initiation and Maintenance Disorders; Trazodone
PubMed: 36002579
DOI: 10.1038/s41598-022-18776-7 -
The International Journal of... Dec 2022Dementia and depression are increasingly common worldwide, and their effective control could ease the burden on economies, public health systems, and support networks.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dementia and depression are increasingly common worldwide, and their effective control could ease the burden on economies, public health systems, and support networks. Vortioxetine is a new antidepressant with multipharmacologic actions that elevate the concentration of serotonin and modulate multiple neurotransmitter receptors in the brain. We conducted a meta-analysis to explore whether the cognitive function of patients with major depressive disorder (MDD) treated with vortioxetine would improve.
METHODS
We systematically reviewed randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to assess the treatment effects of vortioxetine on the cognitive function of patients with MDD. The outcome measures included the Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire (PDQ), and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pooled results were calculated using a fixed-effects or random-effects model according to the heterogeneity of the included trials.
RESULTS
Six RCTs with a total of 1782 patients were included in the meta-analysis, which demonstrated that vortioxetine improved DSST, PDQ, and MADRS scores in patients with MDD. The results were consistent at the 10- and 20-mg doses. In the 20-mg group, the decrease in MADRS scores was more significant than that in the placebo group.
CONCLUSIONS
Both the 10- and 20-mg doses of vortioxetine can significantly increase DSST scores and decrease PDQ and MADRS scores in patients with MDD and cognitive dysfunction, but further studies with longer follow-up periods to assess mental function are required.
Topics: Humans; Vortioxetine; Depressive Disorder, Major; Piperazines; Sulfides; Randomized Controlled Trials as Topic; Cognitive Dysfunction; Treatment Outcome; Double-Blind Method
PubMed: 35981958
DOI: 10.1093/ijnp/pyac054