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Current Cardiology Reviews 2022The Fontan procedure is currently the mainstay therapy for single functional ventricles. However, with prolonged follow-up duration, various complications have been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The Fontan procedure is currently the mainstay therapy for single functional ventricles. However, with prolonged follow-up duration, various complications have been observed that seriously influence the quality of life of patients.
OBJECTIVES
The aim of this meta-analysis is to compare the effectiveness of pharmacologic agents in improving exercise capacity in patients with Fontan circulation.
METHODS
This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and has been registered in the International Prospective Register for Systematic Reviews database with registration no. 282352. Quality assessments of the included studies were assessed using the Strengthening Reporting of Observational Studies in Epidemiology (STROBE) statement.
RESULTS
Twelve studies met the predetermined inclusion criteria and were included in this metaanalysis. This meta-analysis found that treatment with bosentan significantly improved New York Heart Association Functional Class (NYHA FC) in Fontan patients (standard mean difference - 0.59, 95% CI -0.94 - -0.25; P=0.0008; I = 1%). However, the use of bosentan (P=0.66) and sildenafil (P=0.13) did not show a significant improvement in the maximum rate of oxygen consumption (VO max).
CONCLUSION
This meta-analysis shows that people with Fontan circulation may benefit from using bosentan as it decreases postexercise heart rate and improves NYHA FC and 6-minute walking test results. Therefore, indirectly improving exercise capacity. Nonetheless, considerable work is required to strengthen our knowledge in improving the exercise capacity of Fontan patients.
Topics: Bosentan; Exercise Test; Exercise Tolerance; Fontan Procedure; Heart Defects, Congenital; Humans; Quality of Life; Sildenafil Citrate; Sulfonamides; Treatment Outcome
PubMed: 35379155
DOI: 10.2174/1573403X18666220404101610 -
Critical Reviews in Oncology/hematology Apr 2022Chemotherapy is ineffective in treating patients with Gastrointestinal Stromal Tumor (GIST). However, several types of tyrosine kinase inhibitors have been investigated... (Review)
Review
BACKGROUND
Chemotherapy is ineffective in treating patients with Gastrointestinal Stromal Tumor (GIST). However, several types of tyrosine kinase inhibitors have been investigated since the approval of imatinib in 2001. The purpose of this report was to systematically review studies on the efficacy of neoadjuvant, adjuvant, and lifelong medical oncological treatment of GIST.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed throughout the review process. The protocol was submitted to the International prospective register of systematic reviews database (ID 251724). A systematic literature search was performed, including phase II- and III studies of biological treatment, reporting on treatment effect in patients with GIST.
RESULTS
Of 308 identified publications, 42 studies were included in this review.
CONCLUSION
This review gives an overview of the existing evidence for approved lines of oncological treatments and potential alternatives for patients with GIST in the neoadjuvant-, adjuvant- and life-long setting.
Topics: Antineoplastic Agents; Benzamides; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Piperazines; Pyrimidines
PubMed: 35283299
DOI: 10.1016/j.critrevonc.2022.103650 -
PloS One 2022Sub-Saharan Africa has the highest burden of malaria in the world. Artemisinin-based combination therapies (ACTs) have been the cornerstone in the efforts to reduce the... (Meta-Analysis)
Meta-Analysis
Therapeutic efficacy of artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine in the treatment of uncomplicated Plasmodium falciparum malaria in Sub-Saharan Africa: A systematic review and meta-analysis.
BACKGROUND
Sub-Saharan Africa has the highest burden of malaria in the world. Artemisinin-based combination therapies (ACTs) have been the cornerstone in the efforts to reduce the global burden of malaria. In the effort to facilitate early detection of resistance for artemisinin derivatives and partner drugs, WHO recommends monitoring of ACT's efficacy in the malaria endemic countries. The present systematic meta-analysis study summarises the evidence of therapeutic efficacy of the commonly used artemisinin-based combinations for the treatment of uncomplicated P. falciparum malaria in Sub-Saharan Africa after more than a decade since the introduction of the drugs.
METHODS
Fifty two studies carried out from 2010 to 2020 on the efficacy of artemether-lumefantrine or dihydro-artemisinin piperaquine or artesunate amodiaquine in patients with uncomplicated P. falciparum malaria in Sub-Saharan Africa were searched for using the Google Scholar, Cochrane Central Register of controlled trials (CENTRAL), PubMed, Medline, LILACS, and EMBASE online data bases. Data was extracted by two independent reviewers. Random analysis effect was performed in STATA 13. Heterogeneity was established using I2 statistics.
RESULTS
Based on per protocol analysis, unadjusted cure rates in malaria infected patients treated with artemether-lumefantrine (ALU), artesunate-amodiaquine (ASAQ) and dihydroartemisinin-piperaquine (DHP) were 89%, 94% and 91% respectively. However, the cure rates after PCR correction were 98% for ALU, 99% for ASAQ and 99% for DHP.
CONCLUSION
The present meta-analysis reports the overall high malaria treatment success for artemether-lumefantrine, artesunate-amodiaquine and dihydroartemisinin-piperaquine above the WHO threshold value in Sub-Saharan Africa.
Topics: Africa South of the Sahara; Amodiaquine; Antimalarials; Artemether; Artemether, Lumefantrine Drug Combination; Artemisinins; Artesunate; Drug Combinations; Ethanolamines; Humans; Malaria; Malaria, Falciparum; Piperazines; Plasmodium falciparum; Quinolines
PubMed: 35271592
DOI: 10.1371/journal.pone.0264339 -
Advances in Therapy May 2022Dementia-related psychosis (DRP) is characterized by hallucinations and delusions, which may increase the debilitating effects of underlying dementia. This network... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Dementia-related psychosis (DRP) is characterized by hallucinations and delusions, which may increase the debilitating effects of underlying dementia. This network meta-analysis (NMA) evaluated the comparative efficacy, safety, and acceptability of atypical antipsychotics (AAPs) commonly used off label to treat DRP.
METHODS
We included 22 eligible studies from a systematic literature review of AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) used off label to treat DRP. Study outcomes were: (1) efficacy-neuropsychiatric inventory-nursing home (NPI-NH psychosis subscale), (2) safety-mortality, cerebrovascular events (CVAEs), and others (somnolence, falls, fractures, injuries, etc.), and (3) acceptability-discontinuations due to all causes, lack of efficacy, and adverse events (AEs). We used random-effects modeling to estimate pooled standardized mean differences (SMDs) for NPI-NH psychosis subscale scores and odds ratios (OR) for other dichotomous outcomes, with their respective 95% confidence intervals (CIs).
RESULTS
Compared with placebo, aripiprazole (SMD - 0.12; 95% CI - 0.31, 0.06), and olanzapine (SMD - 0.17; 95% CI - 0.04; 0.02) demonstrated small, non-significant numerical improvements in NPI-NH psychosis scores (5 studies; n = 1891), while quetiapine (SMD 0.04; 95% CI - 0.23, 0.32) did not improve symptoms. The odds of mortality (15 studies, n = 4989) were higher for aripiprazole (OR 1.58; 95% CI 0.62, 4.04), brexpiprazole (OR 2.22; 95% CI 0.30, 16.56), olanzapine (OR 2.21; 95% CI 0.84, 5.85), quetiapine (OR 1.68; 95% CI 0.70, 4.03), and risperidone (OR 1.63; 95% CI 0.93, 2.85) than for placebo. Risperidone (OR 3.68; 95% CI 1.68, 8.95) and olanzapine (OR 4.47; 95% CI 1.36, 14.69) demonstrated significantly greater odds of CVAEs compared to placebo. Compared with placebo, odds of all-cause discontinuation were significantly lower for aripiprazole (OR 0.71; 95% CI 0.51, 0.98; 20 studies; 5744 patients) and higher for other AAPs. Aripiprazole (OR 0.5; 95% CI 0.31, 0.82) and olanzapine (OR 0.48; 95% CI 0.31, 0.74) had significantly lower odds of discontinuation due to lack of efficacy (OR 12 studies; n = 4382) compared to placebo, while results for quetiapine and risperidone were not significant. Compared with placebo, the odds of discontinuation due to AEs (19 studies, n = 5445) were higher for olanzapine (OR 2.62; 95% CI 1.75, 3.92), brexpiprazole (OR 1.80; 95% CI 0.80, 4.07), quetiapine (OR 1.25; 95% CI 0.82, 1.91), aripiprazole (OR 1.38; 95% CI 0.90, 2.13), and risperidone (OR 1.41; 95% CI 1.02, 1.94).
CONCLUSIONS
Overall results demonstrate that, compared with placebo, quetiapine is not associated with improvement in psychosis in patients with dementia, while olanzapine and aripiprazole have non-significant small numerical improvements. These off-label AAPs (quetiapine, risperidone, olanzapine, aripiprazole, and brexpiprazole) are associated with greater odds of mortality, CVAEs, and discontinuations due to AEs than placebo. These results underscore the ongoing unmet need for newer pharmacological options with a more favorable benefit-risk profile for the treatment of DRP.
Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dementia; Humans; Network Meta-Analysis; Off-Label Use; Olanzapine; Psychotic Disorders; Quetiapine Fumarate; Risperidone; Treatment Outcome
PubMed: 35247186
DOI: 10.1007/s12325-022-02075-8 -
Annals of Palliative Medicine Jan 2022The prognosis of patients with untreated pulmonary arterial hypertension (PAH) has historically been poor. Previous studies have recommended that sildenafil was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prognosis of patients with untreated pulmonary arterial hypertension (PAH) has historically been poor. Previous studies have recommended that sildenafil was beneficial, but the dose varies greatly. In this study, we aimed to evaluate the safety and effectiveness of sildenafil [dose: 20 mg/three times a day (TID)] for adult Asian PAH patients.
METHODS
Electronic databases (MEDLINE, Embase, Web of Science, the Cochrane Library, CBM, CNKI, and Wanfang Data) were searched from their inception to January 2022. We recruited all randomized controlled trials and non-randomized studies of interventions that compared sildenafil (20 mg/TID) versus placebo or symptomatic treatment for adult Asian PAH patients.
RESULTS
A total of 10 studies involving 480 participants were included. Compared to symptomatic treatment, sildenafil-treated patients were more likely to walk 57.68 meters further in six-minute walk distance [mean difference (MD) =57.68 m, 95% confidence interval (CI): 41.55 to 73.81], achieve an improvement in systemic arterial oxygen saturation (MD =2.48%, 95% CI: 1.26 to 3.71), and increase the score of the Borg scale for dyspnea (MD =-0.99 points, 95% CI: -1.45 to -0.53). The total number of patients with World Health Organization class III and IV also exhibited a downtrend. Compared to the placebo, sildenafil was associated with a reduction in the mean pulmonary artery pressure (MD =-4.13 mmHg, 95% CI: -6.52 to -1.74) and the level of brain natriuretic peptide (MD =-86.16 pg/mL, 95% CI: -103.39 to -68.93). The most common adverse events were headache, flushing, dyspepsia, and diarrhea, which were relatively mild.
DISCUSSION
Sildenafil at a dose of 20 mg/TID is well tolerated in adult Asian PAH patients, and is associated with statistically significant improvements in exercise capacity, cardio-pulmonary function, and haemodynamic indices. The long-term prognosis still needs to be evaluated and confirmed by further trials.
Topics: Adult; Dyspnea; Humans; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Quality of Life; Sildenafil Citrate; Treatment Outcome
PubMed: 35144425
DOI: 10.21037/apm-21-3979 -
Frontiers in Public Health 2021The introduction of tyrosine kinase inhibitor (TKI) therapy has dramatically improved the clinical effectiveness of patients with locally advanced and/or metastatic...
The introduction of tyrosine kinase inhibitor (TKI) therapy has dramatically improved the clinical effectiveness of patients with locally advanced and/or metastatic gastrointestinal stromal tumors (GIST), and this systematic review was conducted aiming at the cost-effectiveness analysis of TKIs in GIST. A thorough literature search of online databases was performed, using appropriate terms such as "gastrointestinal stromal tumor or GIST," "cost-effectiveness," and "economic evaluation." Data extraction was conducted independently by two authors, and completeness of reporting and quality of the evaluation were assessed. The systematic review was conducted following the PRISMA statement. Published between 2005 and 2020, 15 articles were incorporated into the systematic review. For advanced GIST, imatinib followed by sunitinib was considered cost-effective, and regorafenib was cost-effective compared with imatinib re-challenge therapy in the third-line treatment. For resectable GIST, 3-year adjuvant imatinib therapy represented a cost-effective treatment option. The precision medicine-assisted imatinib treatment was cost-effective compared with empirical treatment. Although identified studies varied in predicted costs and quality-adjusted life years, there was general agreement in study conclusions. More cost-effectiveness analysis should be conducted regarding more TKIs that have been approved for the treatment of GIST. https://www.crd.york.ac.uk/, PROSPERO: CRD42021225253.
Topics: Antineoplastic Agents; Benzamides; Cost-Benefit Analysis; Gastrointestinal Stromal Tumors; Humans; Imatinib Mesylate; Protein Kinase Inhibitors
PubMed: 35083189
DOI: 10.3389/fpubh.2021.768765 -
Tropical Medicine & International... Mar 2022Lymphatic filariasis is a serious public health issue. Recent studies showed that a single dosage of triple therapy (Ivermectin, Diethylcarbamazepine, and Albendazole)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Lymphatic filariasis is a serious public health issue. Recent studies showed that a single dosage of triple therapy (Ivermectin, Diethylcarbamazepine, and Albendazole) is more effective than dual therapy (Ivermectin plus Albendazole or Diethylcarbamazepine plus Albendazole) for clearing microfilaria from the blood. We aimed to evaluate the efficacy and safety of triple therapy versus dual therapy in patients infected with microfilaria and communities endemic to lymphatic filariasis.
METHODS
For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, SCOPUS, Cochrane Central Register of Controlled Trials, and Web of Science until 24th June 2021. We included randomized control trials that compared triple with dual therapy given to patients with lymphatic filariasis or endemic communities. This study was registered with PROSPERO (CRD42021266724).
RESULTS
We included eight articles after the screening process. Triple therapy caused more clearance of microfilaria in the blood (RR: 1.52; 95% CI: 1.15, 2.02; p = 0.003), while dual therapy caused more clearance of the circulating filariae antigen in the blood (RR: 0.76; 95% CI: 0.65, 0.88; p = 0.0003), both 12 months after drug administration. The triple therapy had a similar adverse effect compared with the dual therapy group.
CONCLUSION
Based on the greater efficacy in the clearance of microfilaria and the safety of triple therapy, it constitutes a better strategy for the eradication programs of lymphatic filariasis in endemic regions. However, further studies are needed to confirm our results.
Topics: Albendazole; Animals; Diethylcarbamazine; Drug Therapy, Combination; Elephantiasis, Filarial; Filaricides; Humans; Ivermectin; Microfilariae
PubMed: 35080325
DOI: 10.1111/tmi.13727 -
The British Journal of Psychiatry : the... Aug 2022Aripiprazole augmentation is proven effective for antidepressant-refractory depression, but its licensed dose range is wide and optimal dosage remains unclear. (Meta-Analysis)
Meta-Analysis Review
Optimal dose of aripiprazole for augmentation therapy of antidepressant-refractory depression: preliminary findings based on a systematic review and dose-effect meta-analysis.
BACKGROUND
Aripiprazole augmentation is proven effective for antidepressant-refractory depression, but its licensed dose range is wide and optimal dosage remains unclear.
AIMS
To find the optimal dosage of aripiprazole augmentation.
METHOD
Multiple electronic databases were searched (from inception to 16 February 2021) to identify all assessor-masked randomised controlled trials evaluating aripiprazole augmentation therapy in adults (≥18 years old, both genders) with major depressive disorder showing inadequate response to at least one antidepressant treatment. A random-effects, one-stage dose-effect meta-analysis with restricted cubic splines was conducted. Outcomes were efficacy (treatment response: ≥50% reduction in depression severity), tolerability (drop-out due to adverse effects) and acceptability (drop-out for any reason) after 8 weeks of treatment (range 4-12 weeks).
RESULTS
Ten studies met the inclusion criteria. All were individually randomised, placebo-controlled, multi-centre, parallel studies including 2625 participants in total. The maximum target dose-efficacy curve showed an increase up to doses between 2 mg (odds ratio OR = 1.46, 95% CI 1.15-1.85) and 5 mg (OR = 1.93, 95% CI 1.33-2.81), and then a non-increasing trend through the higher licensed doses up to 20 mg (OR = 1.90, 95% CI 1.52-2.37). Tolerability showed a similar trend with greater uncertainty. Acceptability showed no significant difference through the examined dose range. Certainty of evidence was low to moderate.
CONCLUSIONS
Low-dose aripiprazole as augmentation treatment might achieve the optimal balance between efficacy, tolerability and acceptability in the acute treatment of antidepressant-refractory depression. However, the small number of included studies and the overall moderate to high risk of bias seriously compromise the reliability of the results. Further research is required to investigate the benefits of low versus high dose.
Topics: Adolescent; Adult; Antidepressive Agents; Aripiprazole; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Female; Humans; Male; Reproducibility of Results
PubMed: 35049482
DOI: 10.1192/bjp.2021.165 -
JCO Precision Oncology Jan 2022Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have revolutionized the treatment of hormone-positive metastatic breast cancers (mBCs). They are currently...
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have revolutionized the treatment of hormone-positive metastatic breast cancers (mBCs). They are currently established as standard therapies in combination with endocrine therapy as first- and second-line systemic treatment options for both endocrine-sensitive and endocrine-resistant mBC populations. In the first-line metastatic setting, the median progression-free survival for the three currently approved CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, with aromatase inhibitors is greater than 2 years (palbociclib 27.6 months; ribociclib 25.3 months; and abemaciclib 28.18 months). Although CDK4/6 inhibitors have significant clinical benefits and enable physicians to delay starting chemotherapy, they are expensive and can be associated with drug toxicities. Here, we have performed a systemic review of the reported molecular markers predictive of drug response including intrinsic and acquired resistance for CDK4/6 inhibition in mBC. The rapidly emerging molecular landscape is captured through next-generation sequencing of breast cancers (DNA with or without RNA), liquid biopsies (circulating tumor DNA), and protein analyses. Individual molecular candidates with robust and reliable evidence are discussed in more depth.
Topics: Aminopyridines; Antineoplastic Agents; Benzimidazoles; Biomarkers, Tumor; Breast Neoplasms; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Drug Resistance, Neoplasm; Female; Humans; Piperazines; Prognosis; Purines; Pyridines
PubMed: 35005994
DOI: 10.1200/PO.21.00002 -
Computational and Mathematical Methods... 2021The treatment with 2nd-generation tyrosine kinase inhibitors (2G-TKIs), namely, dasatinib and nilotinib, has been reported to have faster and deeper responses in newly... (Meta-Analysis)
Meta-Analysis
Second-Generation Tyrosine Kinase Inhibitor Discontinuation in Chronic Myeloid Leukemia Patients with Stable Deep Molecular Response: A Systematic Review and a Meta-Analysis.
The treatment with 2nd-generation tyrosine kinase inhibitors (2G-TKIs), namely, dasatinib and nilotinib, has been reported to have faster and deeper responses in newly diagnosed chronic phase-chronic myeloid leukemia (CP-CML) patients as compared with imatinab. A number of studies on the discontinuation of 2G-TKIs have been conducted and recently published. A meta-analysis was conducted in this study to assess the rate of treatment-free remission (TFR) rate as well as the long-term safety of 2G-TKI discontinuation in CML patients with stable deep molecular response (DMR). 517 patients were recruited in 5 single-armed, prospective cohort studies. The overall weighted mean TFR rate at the follow-up of 12 months reached 57% (95% CI 51-64%; = 56.4%). The weighted mean TFR rate at the 24-month follow-up was 53% (95% CI 47-60%; = 47.1%). The loss of TFR was primarily concentrated in the first 12 months. 96.5% of patients, having restarted TKI therapy after a molecular relapse, achieved major molecular response (MMR) rapidly. There were four deaths at the two-year follow-up. As suggested from the results of the final study, 2G-TKI discontinuation in CML patients with stable DMR was reported to be feasible. Relapsed patients were retreated with 2G-TKI, and over 95% of patients could reach MMR. Almost no deaths occurred due to adverse events in two years after discontinuation, and more than half of the patients could maintain a TFR.
Topics: Antineoplastic Agents; Computational Biology; Dasatinib; Disease-Free Survival; Duration of Therapy; Female; Humans; Imatinib Mesylate; Leukemia, Myeloid, Chronic-Phase; Male; Protein Kinase Inhibitors; Pyrimidines; Recurrence; Remission Induction
PubMed: 34956393
DOI: 10.1155/2021/3110622