scholarly journals Real-World Safety of CFTR Modulators in the Treatment of Cystic Fibrosis: A Systematic Review

2020 ◽  
Vol 10 (1) ◽  
pp. 23
Author(s):  
Renée V. E. Dagenais ◽  
Victoria C. Su ◽  
Bradley S. Quon
Keyword(s):  
Systematic Review ◽  
Cystic Fibrosis ◽  
Clinical Trials ◽  
Real World ◽  
Observational Studies ◽  
Case Reports ◽  
Case Series ◽  
Patient Characteristics ◽  
Online Databases ◽  
Cftr Modulators

Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies target the underlying cause of cystic fibrosis (CF), and are generally well-tolerated; however, real-world studies indicate the frequency of discontinuation and adverse events (AEs) may be higher than what was observed in clinical trials. The objectives of this systematic review were to summarize real-world AEs reported for market-available CFTR modulators (i.e., ivacaftor (IVA), lumacaftor/ivacaftor (LUM/IVA), tezacaftor/ivacaftor (TEZ/IVA), and elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA)), and to identify ways in which the pharmacist on CF healthcare teams may contribute to mitigating and managing these AEs. The MEDLINE, EMBASE, CINAHL, and Web of Science Core Collection online databases were searched from 2012 to 1 Aug 2020. Full manuscripts or conference abstracts of observational studies, case series, and case reports were eligible for inclusion. The included full manuscripts and conference abstracts comprised of 54 observational studies, 5 case series, and 9 case reports. The types of AEs reported generally aligned with what have been observed in clinical trials. LUM/IVA was associated with a higher frequency of respiratory-related AE and discontinuation in real-world studies. A signal for mental health and neurocognitive AEs was identified with all 4 CFTR modulators. A systematic approach to monitoring for AEs in people with CF on CFTR modulators in the real-world setting is necessary to help better understand potential AEs, as well as patient characteristics that may be associated with higher risk of certain AEs. Pharmacists play a key role in the safe initiation and monitoring of people with CF on CFTR modulator therapies.

scholarly journals Real-World Outcomes of Ivacaftor Treatment in People with Cystic Fibrosis: A Systematic Review

2021 ◽  
Vol 10 (7) ◽  
pp. 1527
Author(s):  
Jamie Duckers ◽  
Beth Lesher ◽  
Teja Thorat ◽  
Eleanor Lucas ◽  
Lisa J. McGarry ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cystic Fibrosis ◽  
Real World ◽  
Safety Profile ◽  
Clinical Trial Data ◽  
Patient Characteristics ◽  
Healthcare Resource Utilization ◽  
Patient Reported ◽  
Clinical Benefits

Cystic fibrosis (CF) is a rare, progressive, multi-organ genetic disease. Ivacaftor, a small-molecule CF transmembrane conductance regulator modulator, was the first medication to treat the underlying cause of CF. Since its approval, real-world clinical experience on the use of ivacaftor has been documented in large registries and smaller studies. Here, we systematically review data from real-world observational studies of ivacaftor treatment in people with CF (pwCF). Searches of MEDLINE and Embase identified 368 publications reporting real-world studies that enrolled six or more pwCF treated with ivacaftor published between January 2012 and September 2019. Overall, 75 publications providing data from 57 unique studies met inclusion criteria and were reviewed. Studies reporting within-group change for pwCF treated with ivacaftor consistently showed improvements in lung function, nutritional parameters, and patient-reported respiratory and sino-nasal symptoms. Benefits were evident as early as 1 month following ivacaftor initiation and were sustained over long-term follow-up. Decreases in pulmonary exacerbations, Pseudomonas aeruginosa prevalence, and healthcare resource utilization also were reported for up to 66 months following ivacaftor initiation. In studies comparing ivacaftor treatment to modulator untreated comparator groups, clinical benefits similarly were reported as were decreases in mortality, organ-transplantation, and CF-related complications. The safety profile of ivacaftor observed in these real-world studies was consistent with the well-established safety profile based on clinical trial data. Our systematic review of real-world studies shows ivacaftor treatment in pwCF results in highly consistent and sustained clinical benefit in both pulmonary and non-pulmonary outcomes across various geographies, study designs, patient characteristics, and follow-up durations, confirming and expanding upon evidence from clinical trials.

scholarly journals Repurposing of drugs for Covid-19: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Pinky Kotecha ◽  
Alexander Light ◽  
Enrico Checcucci ◽  
Daniele Amparore ◽  
Cristian Fiori ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Clinical Improvement ◽  
Case Reports ◽  
Meta Analysis ◽  
Case Series ◽  
Cochrane Library ◽  
Control Group ◽  
Significant Difference

AbstractObjectiveThe aim of this systematic review is to evaluate the data currently available regarding the repurposing of different drugs for Covid-19 treatment. Participants with suspected or diagnosed Covid-19 will be included. The interventions being considered are drugs being repurposed, and comparators will include standard of care treatment or placebo.MethodsWe searched Ovid-MEDLINE, EMBASE, Cochrane library, clinical trial registration site in the UK(NIHR), Europe (clinicaltrialsregister.eu), US (ClinicalTrials.gov) and internationally (isrctn.com), and reviewed the reference lists of articles for eligible articles published up to April 22, 2020. All studies in English that evaluated the efficacy of the listed drugs were included. Cochrane RoB 2.0 and ROBINS-I tool were used to assess study quality. This systematic review adheres to the PRISMA guidelines. The protocol is available at PROSPERO (CRD42020180915).ResultsFrom 708 identified studies or clinical trials, 16 studies and 16 case reports met our eligibility criteria. Of these, 6 were randomized controlled trials (763 patients), 7 cohort studies (321 patients) and 3 case series (191 patients). Chloroquine (CQ) had a 100% discharge rate compared to 50% with lopinavir-ritonavir at day 14, however a trial has recommended against a high dosage due to cardiotoxic events. Hydroxychloroquine (HCQ) has shown no significant improvement in negative seroconversion rate which is also seen in our meta-analysis (p=0.68). Adverse events with HCQ have a significant difference compared to the control group (p=0.001). Lopinavir-ritonavir has shown no improvement in time to clinical improvement which is seen in our meta-analyses (p=0.1). Remdesivir has shown no significant improvement in time to clinical improvement but this trial had insufficient power.DiscussionDue to the paucity in evidence, it is difficult to establish the efficacy of these drugs in the treatment of Covid-19 as currently there is no significant clinical effectiveness of the repurposed drugs. Further large clinical trials are required to achieve more reliable findings. A risk-benefit analysis is required on an individual basis to weigh out the potential improvement in clinical outcome and viral load reduction compared to the risks of the adverse events. (1-16)

scholarly journals Treatment of Tinnitus in Children—A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Max J. Dullaart ◽  
Marijn Kip ◽  
Adriana L. Smit ◽  
Inge Stegeman
Keyword(s):  
Systematic Review ◽  
Randomized Controlled Trials ◽  
Observational Studies ◽  
Case Reports ◽  
Case Series ◽  
Controlled Trials ◽  
Eligibility Criteria ◽  
Subjective Tinnitus ◽  
Randomized Controlled

Objectives: To systematically review studies on the effect of treatment of subjective tinnitus in children.Data Sources: We searched for studies in MEDLINE and EMBASE databases, after which additional studies were hand searched using Scopus databases. The methods are described in the study protocol, which has been registered in the PROSPERO register. PRISMA guidelines were followed in the reporting of this study.Eligibility Criteria: We considered for inclusion randomized controlled trials (RCTs), observational studies, case reports, and case series, with tinnitus as primary outcome in children (0–18 years old) with acute or chronic subjective tinnitus. We excluded studies in which both children and adults participated but outcomes were not specifically reported for children, as well as animal studies, studies with a non-original study design and studies about children with pulsatile or objective tinnitus.Data Selection: Two reviewers independently assessed studies for eligibility and quality, collected and extracted data. Statistical analyses were performed in case of homogeneous outcomes.Results: The search yielded a total of 4,447 studies. Of these, 147 eligible studies were selected. One case report and five observational studies met the eligibility criteria. Three studies applied counseling and (simplified-)TRT and reported improvement in tinnitus outcome in 68 out of 82 children after 3–6 months of treatment. Two studies used pharmacological treatments and reported improvement in 74 out of 86 patients after 10 days to 3 months of treatment. One study reported the outcome of biofeedback therapy, describing an improvement in tinnitus loudness and annoyance after 2 months of treatment.Conclusion: Due to the high risk of bias of the included studies, we cannot determine the effectiveness of the treatment of subjective tinnitus in children. Also, owing to brief follow-up periods, it is not possible to draw conclusions regarding long-term effects. Randomized controlled trials with longer follow-up periods are necessary to provide substantial evidence of the effects of therapies for children affected by tinnitus. https://www.crd.york.ac.uk/prospero/Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier [CRD42020178134].

scholarly journals Therapeutic Management of COVID-19 Patients: A systematic review

2020 ◽  
Author(s):  
Mansour Tobaiqy ◽  
Mohammed Qashqary ◽  
Shrooq Al-Dahery ◽  
Alaa Mujallad ◽  
Almonther Abdullah Hershan ◽  
...  
Keyword(s):  
Systematic Review ◽  
Observational Studies ◽  
Treatment Guidelines ◽  
Case Reports ◽  
Case Series ◽  
Systematic Review Protocol ◽  
Search Terms ◽  
Global Pandemic ◽  
Prisma Statement ◽  
Review Protocol

AbstractBackgroundSARS-CoV-2 is the cause of the COVID-19 that has been declared a global pandemic by the WHO in 2020. The COVID-19 treatment guidelines vary in each country, and yet there is no approved therapeutic for COVID-19.Aims of the studythis review aimed to report any evidence of therapeutics used for the management of COVID-19 patients in clinical practice since the emergence of the virus.MethodsA systematic review protocol was developed based on PRISMA Statement. Articles for review were selected from electronic databases (Embase, Medline and Google Scholar). Readily accessible peer-reviewed full articles in English published from December 1 st, 2019 to March 26 th, 2020 were included. The search terms included combinations of: COVID, SARS-COV-2, glucocorticoids, convalescent plasma, antiviral, antibacterial. There were no restrictions on the type of study design eligible for inclusion.ResultsAs of March 26, 2020, of the initial manuscripts identified (n=449) articles. Forty-one studies were included, of which clinical trials (n=3), (case reports n=7), case series (n=10), retrospective (n=11) and prospective (n=10) observational studies. Thirty-six studies were conducted in China (88%).The most common mentioned and reported medicine in this systematic review was corticosteroids (n=25), followed by Lopinavir (n=21) and oseltamivir (n=16).ConclusionsThis is the first systematic review up to date related to the therapeutics used in COVID-19 patients. Only forty-one research articles on COVID-19 and therapeutics were found eligible to be included, most conducted in China, corticosteroid therapy was found to be the most used medicine in these studies.

scholarly journals Daily Practice Managing Resistant Multiple Sclerosis Spasticity With Delta-9-Tetrahydrocannabinol: Cannabidiol Oromucosal Spray: A Systematic Review of Observational Studies

2019 ◽  
Vol 11 ◽  
pp. 117957351983199 ◽  
Author(s):  
Katja Akgün ◽  
Ute Essner ◽  
Cordula Seydel ◽  
Tjalf Ziemssen
Keyword(s):  
Multiple Sclerosis ◽  
Systematic Review ◽  
Clinical Practice ◽  
Real World ◽  
Observational Studies ◽  
Rating Scale ◽  
Real Life ◽  
Daily Practice ◽  
Patient Characteristics ◽  
Numeric Rating Scale

Background/purpose: Spasticity is one of the most common symptoms in people with multiple sclerosis (MS). Conventional anti-spasticity agents have limitations in their efficacy and tolerability. Delta-9-tetrahydrocannabinol: cannabidiol (THC:CBD) spray, a cannabinoid-based medicine, is approved as an add-on therapy for MS spasticity not adequately controlled by other anti-spasticity medications. The results from randomized controlled trials (RCTs) have demonstrated a reduction in the severity of spasticity and associated symptoms. However, RCTs do not always reflect real-life outcomes. We systematically reviewed the complementary evidence from non-interventional real-world studies. Methods: A systematic literature review was conducted to identify all non-RCT publications on THC:CBD spray between 2011 and 2017. Data on study design, patient characteristics, effectiveness, and safety outcomes were extracted from those publications meeting our inclusion criteria. Results: In total, we reviewed 14 real-world publications including observational studies and treatment registries. The proportion of patients reaching the threshold of minimal clinical important difference (MCID), with at least a 20% reduction of the spasticity Numeric Rating Scale (NRS) score after 4 weeks ranged from 41.9% to 82.9%. The reduction in the mean NRS spasticity score after 4 weeks was maintained over 6-12 months. The average daily dose was five to six sprays. Delta-9-tetrahydrocannabinol: cannabidiol was well tolerated in the evaluated studies in the same way as in the RCTs. No new or unexpected adverse events or safety signals were reported in everyday clinical practice. Conclusions: The data evaluated in this systematic review provide evidence for the efficacy and safety of THC:CBD in clinical practice and confirm results obtained in RCTs.

scholarly journals Assessment of the possibility of vertical transmission of COVID-19: A systematic review and meta-analysis protocol

2020 ◽  
Author(s):  
Sareh Dashti ◽  
Tahereh Fathi Najafi ◽  
Hamid Reza Tohidinik ◽  
Narjes Bahri
Keyword(s):  
Systematic Review ◽  
Pregnant Women ◽  
Vertical Transmission ◽  
Observational Studies ◽  
Case Reports ◽  
Meta Analysis ◽  
Case Series ◽  
World Health ◽  
Free Text ◽  
Care Providers

Abstract BackgroundThe novel coronavirus 2019 (COVID-19) outbreak has put a great burden on global health and healthcare systems. One of the vulnerable groups to COVID-19 infection and complications is the pregnant women. There is controversy regarding the possibility of vertical transmission of COVID-19 from mother to infant. The aim of this systematic review and meta-analysis was to assess the possibility of vertical transmission of COVID-19 based on currently published literature including observational studies. All published articles including case reports, case series,MethodsThis study will be conducted on all published observational studies, including cross-sectional studies, cohort, case-control, case reports, and case series, in peer reviewed journals in any language until the end of March 2020. Editorials, commentaries and letter to editors will be excluded from the review. Search will be conducted in international bibliographic databases including PubMed, Embase, and Web of Science based on preferred reporting items for systematic reviews and meta-analysis (PRISMA) checklist. Primary search will be performed in PubMed and Embase using the Coronavirus 2019 and vertical transmission keywords based on medical subject heading (MeSH) terms along with free text searching in combination with Boolean operations. The search strategy will be improved and finalized based on the results of the primary search. The World Health Organization (WHO) and google scholar websites will be searched as grey literature. Articles will be reviewed by two authors independently for the relevance of titles and abstracts. Data extraction of the included articles will be performed by two researchers using the Zotero and review manager (revMan) software. Heterogeneity of the articles will be assessed using DerSimonian & Laird Q test and I 2 statistic. The pooled estimated prevalence of vertical transmission of COVID-19 will be performed using the Metaprop command. Publication bias will be assessed using the Begg's rank correlation and the Egger weighted regression methods.DiscussionThe findings of this systematic review and meta-analysis will help practitioners and health care providers in decision making for the care and management of COVID-19 infected pregnant women. Systematic review registration In process

scholarly journals Metatarsal Head Resections in Diabetic Foot Patients: A Systematic Review

2020 ◽  
Vol 9 (6) ◽  
pp. 1845 ◽  
Author(s):  
Irene Sanz-Corbalán ◽  
Aroa Tardáguila-García ◽  
Josep M. García-Alamino ◽  
Yolanda García-Álvarez ◽  
Francisco Javier Álvaro-Afonso ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Diabetic Foot ◽  
Observational Studies ◽  
Meta Analysis ◽  
Case Series ◽  
Metatarsal Head ◽  
Inclusion Criteria ◽  
Heterogeneity Test ◽  
Meta Analyses

A systematic review and proportional meta-analysis were carried out to investigate the complications that occur after surgical metatarsal head resection in diabetic foot patients. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist recommendations were applied, and the selected studies were evaluated using a Strengthening the Reporting of Observational studies in Epidemiology (STROBE) checklist. PubMed (Medline) and Embase (Elsevier) were searched in December 2019 to find clinical trials, cohort studies, or case series assessing the efficacy of the metatarsal head resection technique in diabetic foot patients. The systematic review covered 21 studies that satisfied the inclusion criteria and included 483 subjects. The outcomes evaluated were the time to heal, recurrence, reulceration, amputation, and other complications. The proportion of recurrence was 7.2% [confidence interval (CI) 4.0–10.4, p < 0.001], that of reulceration was 20.7% (CI 11.6–29.8, p < 0.001), and that of amputation was 7.6% (CI 3.4–11.8, p < 0.001). A heterogeneity test indicated I2 = 72.6% (p < 0.001) for recurrences, I2 = 94% (p < 0.001) for reulcerations, and I2 = 79% (p < 0.001) for amputations. We conclude that metatarsal head resections in diabetic foot patients are correlated with significant complications, especially reulceration.

scholarly journals The Safety of Cruciferous Plants in Humans: A Systematic Review

2012 ◽  
Vol 2012 ◽  
pp. 1-28 ◽  
Author(s):  
Ori Scott ◽  
Elaine Galicia-Connolly ◽  
Denise Adams ◽  
Soleil Surette ◽  
Sunita Vohra ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Adverse Events ◽  
Drug Metabolism ◽  
Observational Studies ◽  
Case Reports ◽  
Medical Conditions ◽  
Preventative Medicine ◽  
Warfarin Resistance ◽  
Cruciferous Plants

Some cruciferous plants may serve as preventive treatments for several medical conditions; our objective was to systematically investigate their safety in humans. Four electronic databases were searched, and, of 10,831 references identified, 50 were included. Data were extracted by two independent reviewers, whereafter the association between interventions and adverse events was assessed. Adverse events in 53 subjects were identified through clinical trials; of these, altered drug metabolism was rated as certainly/likely caused by cruciferous plants. Adverse events in 1247 subjects were identified through observational studies, of which none received high causality ratings. Adverse events in 35 subjects were identified through case reports, of which allergies and warfarin resistance were rated as certainly/likely caused by cruciferous plants. We conclude that cruciferous plants are safe in humans, with the exception of allergies. Individuals treated with warfarin should consult their physician. Further investigation of uses of cruciferous plants in preventative medicine is warranted.

scholarly journals Efficacy of topical hyaluronic acid for symptomatic oral lichen planus: A systematic Review.

2021 ◽  
Vol 10 (4) ◽  
pp. 1-7
Author(s):  
Sadeq A. Al-Maweri ◽  
◽  
Rawan Alanazi ◽  
Mohammed Nasser Alhajj ◽  
Ammar Daer ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Hyaluronic Acid ◽  
Lichen Planus ◽  
Oral Lichen Planus ◽  
Randomized Clinical Trials ◽  
Case Reports ◽  
Clinical Signs ◽  
Case Series ◽  
Oral Lichen

Background: Oral lichen planus (OLP) is a chronic inflam-matory disorder with a potential of malignant transformation. Despite the extensive research on the topic, the management of OLP is still quite challenging, with no definitive cure. Objective: The present systematic review assessed the efficacy of topical hyaluronic acid in the management of OLP. Material and Methods: A comprehensive search of PubMed, Scopus, Web of Science and Google Scholar was carried out by two independent investigators. All randomized clinical trials that compared the efficacy of hyaluronic acid with other interventions and/or placebo in the management of OLP and fulfilled the following criteria were included: 1) OLP diagnosis was confirmed clinically and histopathologically, 2) the study included systemically healthy patients aged 15 years and older, 3) a minimum sample size of 10, and 4) reporting the main outcomes including pain, erythema, and ulcer size. Case reports, case series, reviews, animal studies, uncontrolled trials were excluded. Results: Four clinical trials involving 234 patients were included. Two studies compared hyaluronic acid with a topical corticosteroid, and two studies compared it with placebo. Only one of the four included studies was at low risk of bias. Overall, topical hyaluronic acid showed good efficacy in alleviating the signs and symptoms of OLP. Two studies found hyaluronic acid significantly more effective in reducing pain and improving clinical signs of OLP compared to placebo. Compared to topical corticosteroids, one study reported comparable results; and one study found hyaluronic acid to be superior to triamcinolone in reducing pain but inferior to triamcinolone in improving the healing time. Conclusion: The limited available evidence suggests that hyaluronic acid may have some benefits in the management of OLP. Further well-designed studies with adequate follow-up periods are highly recommended.

Sign in / Sign up

Export Citation Format

Share Document