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Clinical Therapeutics Nov 2020This systematic review and meta-analysis assesses the pharmacokinetic (PK) summary estimates of isoniazid (INH) between healthy volunteers and patients with tuberculosis... (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review and meta-analysis assesses the pharmacokinetic (PK) summary estimates of isoniazid (INH) between healthy volunteers and patients with tuberculosis (TB), evaluates whether the current INH dose regimen is appropriate in patients with TB, and evaluates the impact of N-acetyl-transferase-2 (NAT2) status on the PK properties of INH.
METHODS
A systematic approach was conducted to find studies with relevant INH PK data published in the English language up to February 2018. The PK properties of INH were extracted with their respective INH dosages and were dose normalized to allow a fair comparison between healthy volunteers and patients with TB. Meta-analysis was then performed for the C and AUC estimates for all INH dosages.
FINDINGS
Ninety studies were included in this systematic review. TB status significantly affected the INH C and AUC estimates. In healthy volunteers, the dose-normalized INH C and AUC were statistically higher than those of patients with TB. No significant differences were found in dose-normalized C and AUC between adults with TB and adults with TB/HIV; however, the AUC in pediatric patients was significantly different between patients with TB and patients with TB/HIV. In addition, no significance was observed comparing the dose-normalized C and AUC of pediatric patients with TB and TB/HIV with their respective adult counterparts. Dose-normalized INH C and AUC in patients with fast and intermediate NAT2 were significantly lower than in patients with slow NAT2.
IMPLICATIONS
The current recommended dosages of INH were found to produce less drug exposure in patients with TB when compared with healthy volunteers. NAT2 polymorphism greatly impacts the PK properties of INH; hence, testing for acetylator status is highly recommended, and therapeutic drug monitoring would help reduce INH toxicity.
Topics: Adult; Antitubercular Agents; Arylamine N-Acetyltransferase; Drug Monitoring; Humans; Isoniazid; Tuberculosis
PubMed: 33032843
DOI: 10.1016/j.clinthera.2020.09.009 -
Psychotherapy and Psychosomatics 2019Major depressive disorder (MDD) is a complex mental illness with unmet therapeutic needs. The antidepressant effects of ω-3 polyunsaturated fatty acids (n-3 PUFAs) have... (Meta-Analysis)
Meta-Analysis
Major depressive disorder (MDD) is a complex mental illness with unmet therapeutic needs. The antidepressant effects of ω-3 polyunsaturated fatty acids (n-3 PUFAs) have been widely reported. The subcommittee of the International Society for Nutritional Psychiatry Research organized an expert panel and conducted a literature review and a Delphi process to develop a consensus-based practice guideline for clinical use of n-3 PUFAs in MDD. The guideline focuses on 5 thematic areas: general concepts, acute treatment strategy, depression recurrence monitoring and prevention, use in special populations, and potential safety issues. The key practice guidelines contend that: (1) clinicians and other practitioners are advised to conduct a clinical interview to validate clinical diagnoses, physical conditions, and measurement-based psychopathological assessments in the therapeutic settings when recommending n-3 PUFAs in depression treatment; (2) with respect to formulation and dosage, both pure eicosapentaenoic acid (EPA) or an EPA/docosahexaenoic acid (DHA) combination of a ratio higher than 2 (EPA/DHA >2) are considered effective, and the recommended dosages should be 1-2 g of net EPA daily, from either pure EPA or an EPA/DHA (>2:1) formula; (3) the quality of n-3 PUFAs may affect therapeutic activity; and (4) potential adverse effects, such as gastrointestinal and dermatological conditions, should be monitored, as well as obtaining comprehensive metabolic panels. The expert consensus panel has agreed on using n-3 PUFAs in MDD treatment for pregnant women, children, and the elderly, and prevention in high-risk populations. Personalizing the clinical application of n-3 PUFAs in subgroups of MDD with a low Omega-3 Index or high levels of inflammatory markers might be regarded as areas that deserve future research.
Topics: Aged; Antidepressive Agents; Biomarkers; Child; Depressive Disorder, Major; Docosahexaenoic Acids; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Humans; Pregnancy; Societies, Medical
PubMed: 31480057
DOI: 10.1159/000502652 -
Annals of the Rheumatic Diseases Jul 2009To review systematically the available literature on the optimal dosage and route of administration of methotrexate in patients with rheumatoid arthritis (RA), as an... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To review systematically the available literature on the optimal dosage and route of administration of methotrexate in patients with rheumatoid arthritis (RA), as an evidence base for generating clinical practice recommendations.
METHODS
A systematic literature search was carried out in MEDLINE, EMBASE, Cochrane Library and American College of Rheumatology/European League Against Rheumatism meeting abstracts, searching for randomised controlled trials evaluating various dosages or routes of administration of methotrexate in RA. Articles that fulfilled predefined inclusion criteria were systematically reviewed and the quality was appraised. Effect sizes and odds ratios for clinical, radiological and toxicity outcomes were calculated and directly or indirectly compared between study groups using methotrexate in different dosages or by different routes.
RESULTS
A total of 38 publications out of 1748 identified references was included in the review. Start doses of 25 mg/week or fast escalation with 5 mg/month to 25-30 mg/week were associated with higher clinical effect sizes and more (gastrointestinal) adverse events in comparison with doses of 5-15 mg/week or slow escalation. Starting with 15 mg/week subcutaneous versus oral methotrexate was associated with higher clinical efficacy but more withdrawal due to toxicity in early RA. In longstanding RA, after failure on 15-20 mg/week orally, a switch to 15 mg/week intramuscularly with subsequent dose escalation did not result in increased efficacy.
CONCLUSIONS
Starting on methotrexate 15 mg/week orally, escalating with 5 mg/month to 25-30 mg/week, or the highest tolerable dose, with a subsequent switch to subcutaneous administration in the case of an insufficient response, seems to be the optimal evidence-based dosing and routing recommendation for methotrexate in RA.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Drug Administration Routes; Drug Administration Schedule; Humans; Methotrexate; Randomized Controlled Trials as Topic
PubMed: 19033290
DOI: 10.1136/ard.2008.092668 -
Phytomedicine : International Journal... Oct 2022Given the challenges on diabetic nephropathy (DN) treatment, research has been carried out progressively focusing on dietary nutrition and natural products as a novel... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Given the challenges on diabetic nephropathy (DN) treatment, research has been carried out progressively focusing on dietary nutrition and natural products as a novel option with the objective of enhancing curative effect and avoiding adverse reactions. As a representative, Quercetin (Qu) has proved to be of great value in current data.
PURPOSE
We aimed to synthetize the evidence regarding the therapeutic effect and specific mechanism of quercetin on DN via systematically reviewing and performing meta-analysis.
METHODS
Preclinical literature published prior to August 2021, was systematical retrieval and manually filtrated across four major databases including PubMed, Web of Science, EMBASE and Cochrane library. Pooled overall effect sizes of results were generated by STATA 16.0, and underlying mechanisms were summarized. Three-dimensional dose/time-effect analyses and radar maps were conducted to examine the dosage/time-response relations between Qu and DN.
RESULTS
This paper pools all current available evidence in a comprehensive way, and shows the therapeutic benefits as well as potential action mechanisms of Qu in protecting the kidney against damage. A total of 304 potentially relevant citations were identified, of which 18 studies were enrolled into analysis. Methodological quality was calculated, resulting in an average score of 7.06/10. This paper provided the preliminary evidence that consumption of Qu could induce a statistical reduction in mesangial index, Scr, BUN, 24-h urinary protein, serum urea, BG, kidney index, TC, TG, LDL-C, AST, MDA, AGE, TNF-α, TGF-β1, TGF-β1 mRNA, CTGF and IL-1β, whereas HDL-C, SOD, GSH, GSH-Px, CAT and smad-7 were significantly increased. Furthermore, Qu could remarkably improve the renal pathology. In terms of the mechanisms underlying therapy of DN, Qu exerts anti-diabetic nephropathy properties possibly through PI3K/PKB, AMPK-P38 MAPK, SCAP/SREBP2/LDLr, mtROS-TRX/TXNIP/NLRP3/IL-1β, TGF-β1/Smad, Nrf2/HO-1, Hippo, mTORC1/p70S6K and SHH pathways. Dose/time-response images predicted a modest association between Qu dosage consumption/administration length and therapeutic efficacy, with the optimal dosage at 90-150 mg/kg/d and administration length ranging from 8 weeks to 12 weeks.
CONCLUSIONS
Quercetin exhibit highly pleiotropic actions, which simultaneously contributes to prevent fundamental progression of DN, such as hyperglycemia, dyslipidemia, inflammation, fibrotic lesions and oxidative stress. The therapeutic effect becomes stronger when Qu administration at higher dosages lasts for longer durations. Taken together, quercetin could be used in patients with DN as a promising agent, which has well-established safety profiles and nontoxicity according to existing literature.
Topics: Animals; Diabetes Mellitus; Diabetic Nephropathies; Flavonoids; Kidney; Quercetin; Rodentia; Transforming Growth Factor beta1
PubMed: 35908521
DOI: 10.1016/j.phymed.2022.154348 -
Climacteric : the Journal of the... Apr 2021A systematic literature search revealed 35 clinical studies and one meta-analysis comprising 43,759 women, of which 13,096 were treated with isopropanolic extract... (Meta-Analysis)
Meta-Analysis
A systematic literature search revealed 35 clinical studies and one meta-analysis comprising 43,759 women, of which 13,096 were treated with isopropanolic extract (iCR). Compared to placebo, iCR was significantly superior for treating neurovegetative and psychological menopausal symptoms, with a standardized mean difference of -0.694 in favor of iCR ( < 0.0001). Effect sizes were larger when higher dosages of iCR as monotherapy or in combination with St. John's wort ( [HP]) were given (-1.020 and -0.999, respectively), suggesting a dose-dependency. For psychological symptoms, the iCR+HP combination was superior to iCR monotherapy. Efficacy of iCR was comparable to low-dose transdermal estradiol or tibolone. Yet, due to its better tolerability, iCR had a significantly better benefit-risk profile than tibolone. Treatment with iCR/iCR+HP was well tolerated with few minor adverse events, with a frequency comparable to placebo. The clinical data did not reveal any evidence of hepatotoxicity. Hormone levels remained unchanged and estrogen-sensitive tissues (e.g. breast, endometrium) were unaffected by iCR treatment. As benefits clearly outweigh risks, iCR/iCR+HP should be recommended as an evidence-based treatment option for natural climacteric symptoms. With its good safety profile in general and at estrogen-sensitive organs, iCR as a non-hormonal herbal therapy can also be used in patients with hormone-dependent diseases who suffer from iatrogenic climacteric symptoms.
Topics: 2-Propanol; Cimicifuga; Female; Hot Flashes; Humans; Menopause; Middle Aged; Phytotherapy; Plant Extracts; Treatment Outcome
PubMed: 33021111
DOI: 10.1080/13697137.2020.1820477 -
Heart (British Cardiac Society) Apr 2024In clinical practice, patients with eosinophilic myocarditis (EM) may forgo the gold standard diagnostic procedure, endomyocardial biopsy (EMB), although it is highly...
OBJECTIVE
In clinical practice, patients with eosinophilic myocarditis (EM) may forgo the gold standard diagnostic procedure, endomyocardial biopsy (EMB), although it is highly recommended in guidelines. This systematic review aims to summarise current approaches in diagnosing and treating EM with a particular emphasis on the utilisation and value of alternative diagnostic methods.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we searched MEDLINE and EMBASE for all peer-reviewed articles using the keywords "eosinophilic myocarditis" from their inception to 10 September 2022.
RESULTS
We included 239 articles, including 8 observational studies and 274 cases, in this review. The median patient age was 45 years. Initial presentations were non-specific, including dyspnoea (50.0%) and chest pain (39.4%). The aetiologies of EM were variable with the most common being idiopathic (28.8%) and eosinophilic granulomatosis polyangiitis (19.3%); others included drug-induced (13.1%) and hypereosinophilic syndrome (12.8%). 82.4% received an EM diagnosis by EMB while 17.6% were diagnosed based on clinical reasoning and cardiac MRI (CMR). CMR-diagnosed patients exhibited a better risk profile at diagnosis, particularly higher left ventricular ejection fraction and less need for inotropic or mechanical circulatory supports. Glucocorticoids were the primary treatment with variability in dosages and regimens.
CONCLUSION
EMB is the mainstay for diagnostic testing for EM. CMR is potentially helpful for screening in appropriate clinical scenarios. Regarding treatment, there is no consensus regarding the optimal dosage of corticosteroids. Large clinical trials are warranted to further explore the utility of CMR in the diagnosis of EM and steroid regimen in treating EM.
Topics: Humans; Myocarditis; Eosinophilia; Biopsy; Myocardium
PubMed: 37963727
DOI: 10.1136/heartjnl-2023-323225 -
The American Journal of Clinical... Mar 2024The optimal dosage range for B-vitamin supplementation for stroke prevention has not received sufficient attention. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The optimal dosage range for B-vitamin supplementation for stroke prevention has not received sufficient attention.
OBJECTIVE
Our aim was to determine the optimal dosage range of a combination of folic acid, vitamin B12, and vitamin B6 supplementation in stroke prevention.
METHODS
We searched PubMed, the Cochrane Central Register of Controlled Trials, and Embase database for randomized controlled trials published between January 1966 and April 2023, whose participants received B-vitamin supplementation and that reported the number of stroke cases. Relative risk (RR) was used to measure the effect of combined supplementation on risk of stroke using a fixed-effects model. Risk of bias was assessed with the Cochrane risk-of-bias algorithm.
RESULTS
The search identified 14 randomized controlled trials of folic acid combined with vitamin B12 and vitamin B6 supplementation for stroke prevention that included 76,664 participants with 2720 stroke cases. In areas without and with partial folic acid fortification, combined B-vitamin supplementation significantly reduced the risk of stroke by 34% [RR: 0.66; 95% confidence interval (CI): 0.50, 0.86] and 11% (RR: 0.89; 95% CI: 0.79, 1.00), respectively. Further analysis showed that a dosage of folic acid ≤0.8 mg/d and vitamin B12 ≤0.4 mg/d was best for stroke prevention (RR: 0.65; 95% CI: 0.48, 0.86) in these areas. In contrast, no benefit of combined supplementation was found in fortified areas (RR: 1.04; 95% CI: 0.94, 1.16).
CONCLUSIONS
Our meta-analysis found that the folic acid combined with vitamin B12 and vitamin B6 supplementation strategy significantly reduced the risk of stroke in areas without and with partial folic acid fortification. Combined dosages not exceeding 0.8 mg/d for folic acid and 0.4 mg/d for vitamin B12 supplementation may be more effective for populations within these areas. This trial was registered at PROSPERO asCRD42022355077.
Topics: Humans; Vitamins; Vitamin B 12; Folic Acid; Vitamin B 6; Stroke; Dietary Supplements
PubMed: 38432716
DOI: 10.1016/j.ajcnut.2023.12.021 -
Current Medical Research and Opinion Aug 2014To compare the efficacy and safety between different dosages of avanafil for the treatment of erectile dysfunction (ED). (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
To compare the efficacy and safety between different dosages of avanafil for the treatment of erectile dysfunction (ED).
METHODS
PubMed, Cochrane Library, and Embase were searched to identify randomized controlled trials which compared avanafil with placebo, or compared different dosages of avanafil for ED. International Index of Erectile Function-Erectile Function domain score (IIEF-EF), Sexual Encounter Profile Question (SEP) questions 2 and 3, and adverse events were considered as the study outcomes. Both pairwise meta-analysis and network meta-analysis were carried out.
RESULTS
Five studies including 2225 patients were assessed. The pairwise meta-analysis suggested that avanafil was more effective than placebo in improving IIEF-EF (mean difference [MD]: 4.47; 95% confidence interval [CI]: 3.51 to 5.43), SEP-2 (MD: 17.41; 95% CI: 14.03 to 20.79), and SEP-3 (MD: 20.01; 95% CI: 22.98 to 37.22), with an evident dose-response relationship. The effectiveness was significantly different between the 50 mg and 100 mg groups, or between the 50 mg and 200 mg groups, for all outcomes. Overall, avanafil was associated with a significantly higher incidence of any adverse event (risk ratio [RR]: 2.56; 95% CI: 1.66 to 3.94), serious adverse event (RR: 2.78; 95% CI: 1.34 to 5.76), flushing (RR: 6.06; 95% CI: 3.37 to 10.88) and headache (RR: 7.54; 95% CI: 3.52 to 16.12) when compared with placebo. No significant difference in safety was found among various dosage groups.
CONCLUSIONS
Avanafil, from 50 to 200 mg, is effective and well tolerated for the treatment of ED, and an increase in dosage is associated with a significant rise in effectiveness but not with significantly more adverse events.
Topics: Dose-Response Relationship, Drug; Drug Administration Schedule; Erectile Dysfunction; Humans; Male; Phosphodiesterase 5 Inhibitors; Pyrimidines; Treatment Outcome
PubMed: 24701971
DOI: 10.1185/03007995.2014.909391 -
International Urology and Nephrology Mar 2023Numerous studies have demonstrated the efficiency of tacrolimus + rituximab and rituximab in idiopathic membranous nephropathy (IMN). But optimal dosages of... (Meta-Analysis)
Meta-Analysis Review
Efficacy of low or heavy rituximab‑based protocols and comparison with seven regimens in idiopathic membranous nephropathy: a systematic review and network meta-analysis.
OBJECTIVE
Numerous studies have demonstrated the efficiency of tacrolimus + rituximab and rituximab in idiopathic membranous nephropathy (IMN). But optimal dosages of rituximab for IMN are still controversial. This network meta-analysis (NMA) was conducted to compare the efficacy of different rituximab dosages and other main treatments in IMN treatment.
METHODS
Randomized controlled trials (RCTs) and observational studies analyzing nine therapeutic regimens for IMN were included from some databases. Network comparisons were performed to analyze the rates of total remission (TR) and relapse rate. The surface under the cumulative ranking area (SUCRA) was calculated to rank interventions.
RESULTS
Twelve RCTs and 12 observational studies involving 1724 patients were pooled for comparison of 9 interventions. This NMA demonstrated steroids + tacrolimus was ranked first in the aspect of total remission at 6 months (92%) and 12 months (81.3%). The total remission rate associated with tacrolimus + rituximab increased rapidly between the sixth (SUCRA 22.5%) and the twelfth month (SUCRA 63.9%). Tacrolimus and cyclosporine A were associated with higher total remission at 6 months (78.8% and 65.4%, separately) and decreased at 12 months (58.1 and 34.9%, separately). Steroids + cyclophosphamide, rituximab (Heavy dose) and rituximab (Low dose) had stable remission rates at 6 (63.7%, 46.6%, and 19.4%) and 12 months (SUCRA 66.9%, 39.6%, and 28.8%). Tacrolimus and cyclosporine A were associated with a significantly higher risk of relapse than that with steroids + cyclophosphamide, rituximab (Heavy dose), and rituximab (Low dose).
CONCLUSIONS
For IMN in adults, steroids + tacrolimus was ranked first in the aspect of total remission, followed by steroids + cyclophosphamide and steroids + cyclosporine A. The TR associated with rituximab (Heavy and Low dosage) at 12 months was higher than that at 6 months. And rituximab (Heavy dose) achieves a higher rate of total remission than that of rituximab (Low dose).
Topics: Adult; Humans; Cyclophosphamide; Cyclosporine; Glomerulonephritis, Membranous; Immunosuppressive Agents; Network Meta-Analysis; Rituximab; Tacrolimus; Treatment Outcome
PubMed: 36161550
DOI: 10.1007/s11255-022-03372-5 -
Frontiers in Pharmacology 2022The decision of vancomycin dosage for central nervous system (CNS) infections is still a challenge because its bactericidal nature in cerebrospinal fluid (CSF) has not... (Review)
Review
The decision of vancomycin dosage for central nervous system (CNS) infections is still a challenge because its bactericidal nature in cerebrospinal fluid (CSF) has not been confirmed by human studies. This study systematically reviewed the literatures on vancomycin in patients with meningitis, ventriculitis, and CNS device-associated infections, to assess efficacy, safety, and pharmacokinetics to better serve as a practical reference. Medline, Embase, and Cochrane Library were searched using terms vancomycin, Glycopeptides, meningitis, and central nervous system infections. Data were extracted including characteristics of participants, causative organism(s), administration, dosage, etc., The clinical response, microbiological response, adverse events and pharmacokinetic parameters were analyzed. Nineteen articles were included. Indications for vancomycin included meningitis, ventriculitis, and intracranial device infections. No serious adverse effects of intravenous (IV) and intraventricular (IVT) vancomycin have been reported. Dosages of IV and IVT vancomycin ranged from 1000-3000 mg/day and 2-20 mg/day. Duration of IV and IVT vancomycin therapy most commonly ranged from 3-27 days and 2-21 days. Therapeutic drug monitoring was conducted in 14 studies. Vancomycin levels in CSF in patients using IV and IVT vancomycin were varied widely from 0.06 to 22.3 mg/L and 2.5-292.9 mg/L. No clear relationships were found between vancomycin CSF levels and efficacy or toxicity. Using vancomycin to treat CNS infections appears effective and safe based on current evidence. However, the optimal regimens are still unclear. Higher quality clinical trials are required to explore the vancomycin disposition within CNS.
PubMed: 36467047
DOI: 10.3389/fphar.2022.1056148