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Pharmaceuticals (Basel, Switzerland) Jan 2022The potential of gossypol and of its R-(-)-enantiomer (R-(-)-gossypol acetic acid, AT-101), has been evaluated for treatment of cancer as an independent agent and in... (Review)
Review
The potential of gossypol and of its R-(-)-enantiomer (R-(-)-gossypol acetic acid, AT-101), has been evaluated for treatment of cancer as an independent agent and in combination with standard chemo-radiation-therapies, respectively. This review assesses the evidence for safety and clinical effectiveness of oral gossypol/AT-101 in treating various types of cancer. The databases PubMed, MEDLINE, Cochrane, and ClinicalTrials.gov were examined. Phase I and II trials as well as single arm and randomized trials were included in this review. Results were screened to determine if they met inclusion criteria and then summarized using a narrative approach. A total of 17 trials involving 759 patients met the inclusion criteria. Overall, orally applied gossypol/AT-101 at low doses (30 mg daily or lower) was determined as well tolerable either as monotherapy or in combination with chemo-radiation. Adverse events should be strictly monitored and were successfully managed by dose-reduction or treating symptoms. There are four randomized trials, two performed in patients with advanced non-small cell lung cancer, one in subjects with head and neck cancer, and one in patients with metastatic castration-resistant prostate cancer. Thereby, standard chemotherapy (either docetaxel (two trials) or docetaxel plus cisplatin or docetaxel plus prednisone) was tested with and without AT-101. Within these trials, a potential benefit was observed in high-risk patients or in some patients with prolongation in progression-free survival or in overall survival. Strikingly, the most recent clinical trial combined low dose AT-101 with docetaxel, fluorouracil, and radiation, achieving complete responses in 11 of 13 patients with gastroesophageal carcinoma (median duration of 12 months) and a median progression-free survival of 52 months. The promising results shown in subsets of patients supports the need of further specification of AT-101 sensitive cancers as well as for the establishment of effective AT-101-based therapy. In addition, the lowest recommended dose of gossypol and its precise toxicity profile need to be confirmed in further studies. Randomized placebo-controlled trials should be performed to validate these data in large cohorts.
PubMed: 35215257
DOI: 10.3390/ph15020144 -
BMJ Open Jan 2022National and international asthma guidelines recommend adjusting asthma treatment based on levels of control, yet no guidance is given regarding the stepping-down of...
BACKGROUND
National and international asthma guidelines recommend adjusting asthma treatment based on levels of control, yet no guidance is given regarding the stepping-down of montelukast in children and young people (CYP).
OBJECTIVE
To systematically review evidence regarding deprescribing montelukast in CYP with established asthma.
DESIGN
Systematic review.
DATA SOURCES
Embase, Medline, PubMed and CINAHL were searched up to October 2020.
STUDY SELECTION
Eligible studies contained patients aged 0-18 years with a diagnosis of asthma, who had been administering montelukast before it was withdrawn. All reasons for withdrawal were included.
RESULTS
The search identified 197 papers. After deduplication, five papers were included (three randomised control studies and two cohort studies). Four studies observed the impact of montelukast withdrawal for 2 weeks, and one study for 8 weeks. The impact of withdrawal was measured in the studies using a combination of lung tests (eg, forced expiratory volume in 1 s (FEV1), fractional exhaled nitric oxide (FeNO)), asthma scoring methods and exercise challenges. Of the 17 domains in the Core Outcome Set for Clinical Trials in Childhood Asthma, eight outcomes were measured in at least one of the five studies, with all five studies measuring the outcome of 'Lung Function'. No significant differences were found between the montelukast and placebo groups following montelukast withdrawal. Significant differences between the comparator points within the test group were found in nine outcomes across four studies; FEV1/forced vital capacity, FEV1, forced expiratory flows (25%-75%), asthma score (study specific), maximum % fall in FEV1 and time to recovery (post exercise) significantly decreased whereas FEV1/bronchodilator response, FeNO and eNO significantly increased.
CONCLUSION
Only limited, contradictory and short-term effects of deprescribing montelukast in CYP with established asthma are presented in literature. Definitive studies determining clinical stability, and impact of deprescribing montelukast in CYP are imperative to improve the safety of asthma treatment in CYP.
PROSPERO REGISTRATION NUMBER
CRD42020213971.
Topics: Acetates; Adolescent; Anti-Asthmatic Agents; Asthma; Child; Child, Preschool; Cyclopropanes; Deprescriptions; Forced Expiratory Volume; Humans; Infant; Infant, Newborn; Quinolines; Sulfides
PubMed: 35105629
DOI: 10.1136/bmjopen-2021-053112 -
Drugs Feb 2022Brivaracetam (BRV), cenobamate (CNB), eslicarbazepine acetate (ESL), lacosamide (LCM) and perampanel (PER) are antiseizure medications (ASMs) approved for adjunctive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Brivaracetam (BRV), cenobamate (CNB), eslicarbazepine acetate (ESL), lacosamide (LCM) and perampanel (PER) are antiseizure medications (ASMs) approved for adjunctive treatment of focal-onset seizures. So far, no randomised controlled trial directly compared the efficacy and safety of these drugs.
OBJECTIVE
We estimated the comparative efficacy and safety of these ASMs for the treatment of focal-onset seizures in adults with epilepsy using a network meta-analysis (NMA).
METHODS
We systematically searched (June week 4, 2021) MEDLINE (accessed by PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and the US National Institutes of Health Clinical Trials Registry ( http://www.clinicaltrials.gov ). There were no date limitations or language restrictions. Randomised, double-blinded, controlled, parallel-group, add-on studies that compared oral BRV, CNB, ESL, LCM, and PER versus any comparator over maintenance periods of at least 12 weeks and included adult patients with focal seizures uncontrolled by concomitant ASMs were identified. The efficacy outcomes were the proportions of patients with ≥ 50% and 100% reduction in baseline seizure frequency during the maintenance period. The tolerability outcomes were the proportions of participants who experienced at least one treatment-emergent adverse event (TEAE) and experienced at least one TEAE leading to discontinuation. Effect sizes were estimated by network meta-analyses within a frequentist framework. The hierarchy of competing interventions was established using the surface under the cumulative ranking curve (SUCRA).
RESULTS
Sixteen trials (BRV: n = 3, CNB: n = 1, ESL: n = 4, LCM: n = 4, PER: n = 4) were included, overall enrolling 4507 patients randomised to add-on active treatments (BRV = 803, CNB = 221, ESL =9 90, LCM = 1104, and PER = 1389) and 2246 to add-on placebo. Cenobamate was associated with a higher rate of ≥ 50% seizure frequency reduction than BRV [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.11-3.66], ESL (OR 1.93, 95% CI 1.07-3.48), LCM (OR 1.86, 95% CI 1.04-3.32), and PER (OR 2.07, 95% CI 1.16-3.70). There was a not statistically significant trend favouring CNB over ESL, LCM and PER for the seizure freedom outcome. Brivaracetam (OR 0.61, 95% CI 0.44-0.86) and LCM (OR 0.60, 95% CI 0.40-0.88) were associated with a lower proportion of participants experiencing TEAEs compared to ESL, and patients treated with PER were associated with a higher risk to experience at least one TEAE (OR 1.42, 95% CI 1.02-1.96) than BRV. According to SUCRA, CNB had the greatest likelihood of being the best option for the ≥ 50% and 100% seizure frequency reduction, and BRV and LCM had the highest probabilities of being the best-tolerated treatments.
CONCLUSIONS
Cenobamate ranked best for efficacy, and BRV and LCM were best tolerated over the other comparators. Although NMAs cannot replace direct comparisons, they may support physicians in clinical decision making.
Topics: Adult; Anticonvulsants; Carbamates; Chlorophenols; Dibenzazepines; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lacosamide; Male; Middle Aged; Network Meta-Analysis; Nitriles; Pyridones; Pyrrolidinones; Randomized Controlled Trials as Topic; Seizures; Tetrazoles
PubMed: 35061214
DOI: 10.1007/s40265-021-01661-4 -
Seizure Feb 2022To estimate the safety and efficacy of sodium valproate combined with levetiracetam in paediatric patients with epilepsy based on randomized controlled trials (RCTs). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To estimate the safety and efficacy of sodium valproate combined with levetiracetam in paediatric patients with epilepsy based on randomized controlled trials (RCTs).
METHODS
The Cochrane Library, PubMed, Web of Science, Chinese Journal Full-Text Database (CNKI), WANGFANG DATA and Sino Med were searched between January 1946 and May 2021. The included literature was randomized controlled clinical trials focusing on sodium valproate combined with levetiracetam in paediatric patients with epilepsy. Two evaluators separately collected the data based on the retrieval strategy, filtered the literature in accordance with the inclusion and exclusion criteria, and summarized the literature that satisfied the criteria. The statistical programme used for the meta-analysis was Stata V14.0.
RESULTS
Of 577 original titles screened, data were extracted from 7 studies (617 participants). Compared with sodium valproate alone or sodium valproate combined with topiramate, the application of sodium valproate combined with levetiracetam in the treatment of paediatric epilepsy significantly improved the overall therapeutic effect (RR=1.24, 95% CI: 1.16 to 1.33, p=0.927). The observation group significantly reduced the occurrence of adverse drug reactions (ADRs) (RR=0.54, 95% CI: 0.37 to 0.79, p=0.602). Egger's regression test of the overall therapeutic effect showed no potential publication bias (p=0.122).
CONCLUSION
Based on this meta-analysis, compared with sodium valproate alone or sodium valproate with topiramate, the application of sodium valproate combined with levetiracetam in the treatment of paediatric epilepsy can significantly improve the overall therapeutic effect and simultaneously reduce the occurrence of ADR. Therefore, we recommend sodium valproate combined with levetiracetam for the therapy of paediatric patients with epilepsy.
Topics: Anticonvulsants; Child; Epilepsy; Humans; Levetiracetam; Topiramate; Valproic Acid
PubMed: 34971912
DOI: 10.1016/j.seizure.2021.12.003 -
International Journal of Environmental... Dec 2021Biofilms in burns are major problems: bacterial communities rapidly develop antibiotic resistance, and 60% of burn mortality is attributed to biofilms. Key pathogens are... (Review)
Review
Reducing Biofilm Infections in Burn Patients' Wounds and Biofilms on Surfaces in Hospitals, Medical Facilities and Medical Equipment to Improve Burn Care: A Systematic Review.
Biofilms in burns are major problems: bacterial communities rapidly develop antibiotic resistance, and 60% of burn mortality is attributed to biofilms. Key pathogens are , methicillin-resistant , and multidrug-resistant Purpose: identify current and novel interventions to reduce biofilms on patients' burns and hospital surfaces and equipment. Medline and Embase were searched without date or language limits, and 31 possible interventions were prioritised: phages, nano-silver, AgSD-NLs@Cur, Acticoat and Mepilex silver, acetic acid, graphene-metal combinations, CuCoSO nanoparticles, Chlorhexidene acetate nanoemulsion, a hydrogel with moxifloxacin, carbomer, Chitosan and Boswellia, LED light therapy with nano-emodin or antimicrobial blue light + Carvacrol to release reactive oxygen species, mannosidase + trypsin, NCK-10 (a napthalene compound with a decyl chain), antimicrobial peptide PV3 (includes two snake venoms), and polypeptides P03 and PL2. Most interventions aimed to penetrate cell membranes and reported significant reductions in biofilms in cfu/mL or biofilm mass or antibiotic minimal inhibitory concentrations or bacterial expression of virulence or quorum sensing genes. Scanning electron microscopy identified important changes in bacterial surfaces. Patients with biofilms need isolating and treating before full admission to hospital. Cleaning and disinfecting needs to include identifying biofilms on keyboards, tablets, cell phones, medical equipment (especially endoscopes), sinks, drains, and kitchens.
Topics: Anti-Bacterial Agents; Antimicrobial Peptides; Biofilms; Burns; Hospitals; Humans; Methicillin-Resistant Staphylococcus aureus; Pseudomonas aeruginosa
PubMed: 34948803
DOI: 10.3390/ijerph182413195 -
JCO Global Oncology Dec 2021Smartphones are used in cervical screening for visual inspection after acetic acid or Lugol's iodine (VIA/VILI) application to capture and share images to improve the... (Meta-Analysis)
Meta-Analysis
Accuracy of Smartphone Images of the Cervix After Acetic Acid Application for Diagnosing Cervical Intraepithelial Neoplasia Grade 2 or Greater in Women With Positive Cervical Screening: A Systematic Review and Meta-Analysis.
PURPOSE
Smartphones are used in cervical screening for visual inspection after acetic acid or Lugol's iodine (VIA/VILI) application to capture and share images to improve the sensitivity and interobserver variability of VIA/VILI. We undertook a systematic review and meta-analysis assessing the diagnostic accuracy of smartphone images of the cervix at the time of VIA/VILI (termed S-VIA) in the detection of precancerous lesions in women undergoing cervical screening.
METHODS
This systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies from January 1, 2010, to June 30, 2020, were assessed. MEDLINE/PubMed, Embase, CINAHL, Cochrane, and LILACS were searched. Cohort and cross-sectional studies were considered. S-VIA was compared with the reference standard of histopathology. We excluded studies where additional technology was added to the smartphone including artificial intelligence, enhanced visual assessment, and other algorithms to automatically diagnose precancerous lesions. The primary outcome was the accuracy of S-VIA for the diagnosis of cervical intraepithelial neoplasia grade 2 or greater (CIN 2+). Data were extracted, and we plotted the sensitivity, specificity, negative predictive value, and positive predictive value of S-VIA using forest plots. This study was prospectively registered with The International Prospective Register of Systematic Reviews:CRD42020204024.
RESULTS
Six thousand three studies were screened, 71 full texts assessed, and eight studies met criteria for inclusion, with six included in the final meta-analysis. The sensitivity of S-VIA for the diagnosis of CIN 2+ was 74.56% (95% CI, 70.16 to 78.95; I 61.30%), specificity was 61.75% (95% CI, 56.35 to 67.15; I 95.00%), negative predictive value was 93.71% (95% CI, 92.81 to 94.61; I 0%), and positive predictive value was 26.97% (95% CI, 24.13 to 29.81; I 61.3%).
CONCLUSION
Our results suggest that S-VIA has accuracy in the detection of CIN 2+ and may provide additional support to health care providers delivering care in low-resource settings.
Topics: Acetic Acid; Artificial Intelligence; Cervix Uteri; Coloring Agents; Cross-Sectional Studies; Early Detection of Cancer; Female; Humans; Male; Precancerous Conditions; Smartphone; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Vaginal Smears
PubMed: 34936374
DOI: 10.1200/GO.21.00168 -
Seizure Jan 2022Antiseizure medications (ASM) have long been examined for their potential to induce thyroid dysfunction. The aim of this systematic review and meta-analysis was to... (Meta-Analysis)
Meta-Analysis
PURPOSE
Antiseizure medications (ASM) have long been examined for their potential to induce thyroid dysfunction. The aim of this systematic review and meta-analysis was to assess the prevalence of thyroid disease in children up to 16 years receiving monotherapy with valproate (VPA), carbamazepine (CBZ) and levetiracetam (LEV).
METHODS
PubMed/MEDLINE, Cochrane/CENTRAL databases and the gray literature were searched to identify observational studies providing the prevalence of thyroid dysfunction in the target population under VPA, CBZ, or LEV monotherapy schemes. The results were pooled using a random-effects model, and additional subgroup analyses were performed for the three ASM groups.
RESULTS
Fifteen and thirteen studies met inclusion criteria for the qualitative and the quantitative analysis, respectively, with a total of 945 pediatric patients with prevalence data. Only VPA and CBZ were associated with thyroid dysfunction. The overall prevalence of thyroid abnormality was higher in children receiving ASM [odds ratio (OR) 6.82, 95% confidence interval (CI) 3.96-11.75]. In the subgroup analysis, the prevalence of biochemical thyroid abnormality with increased TSH was higher in the VPA (OR 9.54, 95%CI 5.25-17.34) and the CBZ group (OR 4.08, 95%CI 1.84-9.04) compared with controls.
CONCLUSION
This study confirms the higher prevalence of biochemical thyroid abnormality in children under VPA and CBZ monotherapy, whereas no such evidence is present for LEV. In children with a predisposition for thyroid disease, LEV should be considered over VPA and CBZ, if appropriate for seizure type and epilepsy syndrome. More studies are needed to reach a consensus on monitoring and management of thyroid dysfunction in children receiving ASM therapy.
Topics: Anticonvulsants; Carbamazepine; Child; Epilepsy; Humans; Levetiracetam; Prevalence; Thyroid Diseases; Valproic Acid
PubMed: 34896814
DOI: 10.1016/j.seizure.2021.11.010 -
Cancers Dec 2021Little is known regarding the usefulness of the smartphone in the detection of uterine cervical lesions or uterine cervical cancer. Therefore, we evaluated the... (Review)
Review
Little is known regarding the usefulness of the smartphone in the detection of uterine cervical lesions or uterine cervical cancer. Therefore, we evaluated the usefulness of the smartphone in the detection of uterine cervical lesions and measured its diagnostic accuracy by comparing its findings with histological findings. We conducted a systematic review to identify studies on the usefulness of the smartphone in detecting uterine cervical lesions indexed in SCOPUS, MEDLINE/PubMed, Cochrane, OVID, Web of Science, and SciELO until November 2020. The risk of bias and applicability was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A total of 16 studies that evaluated the usefulness of the smartphone in the detection of uterine cervical lesions based on the images clicked after visual inspection with acetic acid (VIA), Lugol's iodine (VILI), or VIA/VILI combination were included in the study. Five studies estimated diagnostic sensitivity and specificity, nine described diagnostic concordance, and five described the usefulness of mobile technology. Among the five first studies, the sensitivity ranged between 66.7% (95% confidence interval (CI); 30.0-90.3%) and 94.1% (95% CI; 81.6-98.3%), and the specificity ranged between 24.0% (95% CI; 9.0-45.0%) and 85.7% (95% CI; 76.7-91.6%). The risk of bias was low (20%), and the applicability was high. In conclusion, the smartphone images clicked after a VIA were found to be more sensitive than those following the VILI method or the VIA/VILI combination and naked-eye techniques in detecting uterine cervical lesions. Thus, a smartphone may be useful in the detection of uterine cervical lesions; however, its sensitivity and specificity are still limited.
PubMed: 34885157
DOI: 10.3390/cancers13236047 -
Chinese Medical Journal Nov 2021Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of salmeterol/fluticasone compared with montelukast alone (or add-on therapy to fluticasone) in the treatment of bronchial asthma in children and adolescents: a systematic review and meta-analysis.
BACKGROUND
Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise approaches in asthmatic children, there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years. This study aimed to compare the safety and efficacy of salmeterol/fluticasone (SFC) vs. montelukast (MON), or combination of montelukast and fluticasone (MFC) in children and adolescents aged 4 to 18 years with bronchial asthma.
METHODS
A systematic search was conducted in MEDLINE, EMBASE, the Cochrane Library, China BioMedical Literature Database, Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, and Wanfang for randomized controlled trials (RCTs) published from inception to May 24, 2021. Interventions are as follows: SFC vs. MON, or combination of MFC, with no limitation of dosage or duration. Primary and secondary outcome measures were as follows: the primary outcome of interest was the risk of asthma exacerbation. Secondary outcomes included risk of hospitalization, pulmonary function, asthma control level, quality of life, and adverse events (AEs). A random-effects (I2 ≥ 50%) or fixed-effects model (I2 < 50%) was used to calculate pooled effect estimates, comparing the outcomes between the intervention and control groups where feasible.
RESULTS
Of the 1006 articles identified, 21 studies met the inclusion criteria with 2643 individuals; two were at low risk of bias. As no primary outcomes were similar after an identical treatment duration in the included studies, meta-analysis could not be performed. However, more studies favored SFC, instead of MON, owing to a lower risk of asthma exacerbation in the SFC group. As for secondary outcome, SFC showed a significant improvement of peak expiratory flow (PEF)%pred after 4 weeks compared with MFC (mean difference [MD]: 5.45; 95% confidence interval [CI]: 1.57-9.34; I2 = 95%; P = 0.006). As for asthma control level, SFC also showed a higher full-controlled level (risk ratio [RR]: 1.51; 95% CI: 1.24-1.85; I2 = 0; P < 0.001) and higher childhood asthma control test score after 4 weeks of treatment (MD: 2.30; 95% CI: 1.39-3.21; I2 = 72%; P < 0.001) compared with MFC.
CONCLUSIONS
SFC may be more effective than MFC for the treatment of asthma in children and adolescents, especially in improving asthma control level. However, there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma. Further research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs.
PROSPERO REGISTRATION NUMBER
CRD42019133156.
Topics: Acetates; Administration, Inhalation; Adolescent; Adrenal Cortex Hormones; Albuterol; Anti-Asthmatic Agents; Asthma; Child; Cyclopropanes; Drug Therapy, Combination; Fluticasone; Humans; Quinolines; Salmeterol Xinafoate; Sulfides
PubMed: 34784306
DOI: 10.1097/CM9.0000000000001853 -
European Radiology Mar 2022Effective and non-invasive biomarkers to predict and avoid posthepatectomy liver failure (PHLF) are urgently needed. This systematic review aims to evaluate the efficacy... (Review)
Review
OBJECTIVES
Effective and non-invasive biomarkers to predict and avoid posthepatectomy liver failure (PHLF) are urgently needed. This systematic review aims to evaluate the efficacy of gadoxetic acid-enhanced MRI-derived parameters as an imaging biomarker in preoperative prediction of PHLF.
METHODS
A systematic literature search was performed in the databases of PubMed/Medline, Web of Science, Embase, and Cochrane Library up to 11 December 2020. Studies evaluating the incidence of PHLF on patients who underwent hepatectomy with preoperative liver function assessment using gadoxetic acid-enhanced MRI were included. Data was extracted using pre-designed tables. The Quality In Prognostic Studies (QUIPS) tool was adopted to evaluate the risk of bias.
RESULTS
A total of 15 studies were identified for qualitative synthesis and most studies were marked as low to moderate risk of bias in each domain of QUIPS. The most commonly used parameter was relative liver enhancement or its related parameters. The reported incidence of PHLF ranged from 3.9 to 40%. The predictive sensitivity and specificity of gadoxetic acid-enhanced MRI parameters varied from 75 to 100% and from 54 to 93% in ten reported studies. A majority of the studies revealed that the gadoxetic acid-enhanced MRI parameter was a predictor for PHLF.
CONCLUSIONS
Gadoxetic acid-enhanced MRI showed a high predictive capacity for PHLF and represents a promising imaging biomarker in prediction of PHLF. Multicenter, prospective trials with large sample size and reliable, unified liver function parameters are required to validate the efficacy of individual liver function parameters.
KEY POINTS
• There is an obvious heterogeneity of the published studies, not only in variance of MRI liver function parameters but also in indication and extent of the liver resection. • Signal intensity (SI)-based parameters derived from gadoxetic acid-enhanced MRI are the commonly used method for PHLF prediction. • Gadoxetic acid-enhanced MRI-derived parameters showed high predictive efficacy for PHLF and can potentially serve as a predictor for the incidence of PHLF.
Topics: Contrast Media; Gadolinium DTPA; Hepatectomy; Humans; Liver; Liver Failure; Liver Neoplasms; Magnetic Resonance Imaging; Multicenter Studies as Topic; Postoperative Complications; Prospective Studies; Retrospective Studies
PubMed: 34562137
DOI: 10.1007/s00330-021-08297-8