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The Cochrane Database of Systematic... May 2020Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Several agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action is unknown. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed and it is now available in Australia and some countries in Europe. This is an update of a previous review.
OBJECTIVES
To assess whether inhaled dry powder mannitol is well tolerated, whether it improves the quality of life and respiratory function in people with cystic fibrosis and which adverse events are associated with the treatment.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic databases, handsearching relevant journals and abstracts from conferences. Date of last search: 12 December 2019.
SELECTION CRITERIA
All randomised controlled studies comparing mannitol with placebo, active inhaled comparators (for example, hypertonic saline or dornase alfa) or with no treatment.
DATA COLLECTION AND ANALYSIS
Authors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias in included studies. The quality of the evidence was assessed using GRADE.
MAIN RESULTS
Six studies (reported in 36 unique publications) were included with a total of 784 participants. Duration of treatment in the included studies ranged from 12 days to six months, with open-label treatment for an additional six months in two of the studies. Five studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol) and the final study compared mannitol to dornase alfa alone and to mannitol plus dornase alfa. Two large studies had a similar parallel design and provided data for 600 participants, which could be pooled where data for a particular outcome and time point were available. The remaining studies had much smaller sample sizes (ranging from 22 to 95) and data could not be pooled due to differences in design, interventions and population. Pooled evidence from the two large parallel studies was judged to be of low to moderate quality and from the smaller studies was judged to be of low to very low quality. In all studies, there was an initial test to see if participants tolerated mannitol, with only those who could tolerate the drug being randomised; therefore, the study results are not applicable to the cystic fibrosis population as a whole. While the published papers did not provide all the data required for our analysis, additional unpublished data were provided by the drug's manufacturer and the author of one of the studies. Pooling the large parallel studies comparing mannitol to control, up to and including six months, lung function (forced expiratory volume at one second) measured in both mL and % predicted was significantly improved in the mannitol group compared to the control group (moderate-quality evidence). Beneficial results were observed in these studies in adults and in both concomitant dornase alfa users and non-users in these studies. In the smaller studies, statistically significant improvements in lung function were also observed in the mannitol groups compared to the non-respirable mannitol groups; however, we judged this evidence to be of low to very low quality. For the comparisons of mannitol and control, we found no consistent differences in health-related quality of life in any of the domains except for burden of treatment, which was less for mannitol up to four months in the two pooled studies of a similar design; this difference was not maintained at six months. It should be noted that the tool used to measure health-related quality of life was not designed to assess mucolytics and pooling of the age-appropriate tools (as done in some of the included studies) may not be valid so results were judged to be low to very low quality and should be interpreted with caution. Cough, haemoptysis, bronchospasm, pharyngolaryngeal pain and post-tussive vomiting were the most commonly reported side effects in both treatment groups. Where rates of adverse events could be compared, statistically no significant differences were found between mannitol and control groups; although some of these events may have clinical relevance for people with CF. For the comparisons of mannitol to dornase alfa alone and to mannitol plus dornase alfa, very low-quality evidence from a 12-week cross-over study of 28 participants showed no statistically significant differences in the recorded domains of health-related quality of life or measures of lung function. Cough was the most common side effect in the mannitol alone arm but there was no occurrence of cough in the dornase alfa alone arm and the most commonly reported reason of withdrawal from the mannitol plus dornase alfa arm was pulmonary exacerbations. In terms of secondary outcomes of the review (pulmonary exacerbations, hospitalisations, symptoms, sputum microbiology), evidence provided by the included studies was more limited. For all comparisons, no consistent statistically significant and clinically meaningful differences were observed between mannitol and control treatments (including dornase alfa).
AUTHORS' CONCLUSIONS
There is moderate-quality evidence to show that treatment with mannitol over a six-month period is associated with an improvement in some measures of lung function in people with cystic fibrosis compared to control. There is low to very low-quality evidence suggesting no difference in quality of life for participants taking mannitol compared to control. This review provides very low-quality evidence suggesting no difference in lung function or quality of life comparing mannitol to dornase alfa alone and to mannitol plus dornase alfa. The clinical implications from this review suggest that mannitol could be considered as a treatment in cystic fibrosis; but further research is required in order to establish who may benefit most and whether this benefit is sustained in the longer term. Furthermore, studies comparing its efficacy against other (established) mucolytic therapies need to be undertaken before it can be considered for mainstream practice.
Topics: Administration, Inhalation; Adult; Child; Cystic Fibrosis; Deoxyribonuclease I; Forced Expiratory Volume; Humans; Mannitol; Mucociliary Clearance; Powders; Randomized Controlled Trials as Topic; Recombinant Proteins; Respiratory Function Tests; Vital Capacity
PubMed: 32358807
DOI: 10.1002/14651858.CD008649.pub4 -
JAMA Pediatrics Sep 2020The current rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection justifies the global effort to identify effective preventive...
IMPORTANCE
The current rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection justifies the global effort to identify effective preventive strategies and optimal medical management. While data are available for adult patients with coronavirus disease 2019 (COVID-19), limited reports have analyzed pediatric patients infected with SARS-CoV-2.
OBJECTIVE
To evaluate currently reported pediatric cases of SARS-CoV-2 infection.
EVIDENCE REVIEW
An extensive search strategy was designed to retrieve all articles published from December 1, 2019, to March 3, 2020, by combining the terms coronavirus and coronavirus infection in several electronic databases (PubMed, Cochrane Library, and CINAHL), and following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Retrospective cross-sectional and case-control studies, case series and case reports, bulletins, and national reports about the pediatric SARS-CoV-2 infection were included. The risk of bias for eligible observational studies was assessed according to the Strengthening the Reporting of Observational Studies in Epidemiology reporting guideline.
FINDINGS
A total of 815 articles were identified. Eighteen studies with 1065 participants (444 patients were younger than 10 years, and 553 were aged 10 to 19 years) with confirmed SARS-CoV-2 infection were included in the final analysis. All articles reflected research performed in China, except for 1 clinical case in Singapore. Children at any age were mostly reported to have mild respiratory symptoms, namely fever, dry cough, and fatigue, or were asymptomatic. Bronchial thickening and ground-glass opacities were the main radiologic features, and these findings were also reported in asymptomatic patients. Among the included articles, there was only 1 case of severe COVID-19 infection, which occurred in a 13-month-old infant. No deaths were reported in children aged 0 to 9 years. Available data about therapies were limited.
CONCLUSIONS AND RELEVANCE
To our knowledge, this is the first systematic review that assesses and summarizes clinical features and management of children with SARS-CoV-2 infection. The rapid spread of COVID-19 across the globe and the lack of European and US data on pediatric patients require further epidemiologic and clinical studies to identify possible preventive and therapeutic strategies.
Topics: Adolescent; COVID-19; Child; Child, Preschool; Coronavirus Infections; Humans; Infant; Pandemics; Pneumonia, Viral
PubMed: 32320004
DOI: 10.1001/jamapediatrics.2020.1467 -
Journal of Ethnopharmacology Jun 2020Withania somnifera popularly known as Aswagandha or Indian Ginseng/Poison Gooseberry have thousands years of history of use in Indian traditional medicine. Besides,...
ETHNOPHARMACOLOGICAL RELEVANCE
Withania somnifera popularly known as Aswagandha or Indian Ginseng/Poison Gooseberry have thousands years of history of use in Indian traditional medicine. Besides, finding place root of the plant as Indian Ginseng, Ayurveda also uses root of this plant as general health tonic, adaptogenic, nootropic, immunomodulatory etc. With its widespread and growing use, it becomes prudent to scientifically evaluate and document both the efficacy and safety of this plant in humans.
AIM OF THE STUDY
Aswagnadha root is rapidly gaining popularity abroad for use as medicine. Current article attempts to primarily review the human efficacy and safety of Aswagandha generated through clinical trials.
METHODS
A systematic search both for indexed and non-indexed literature was made for W. somnifera using various search engines and databases and the details of research articles pertaining to all clinical trials/human studies, animal studies addressing safety issues of CNS, CVS, general toxicity, mutagenicity, genotoxicity, reproductive safety and herb-drug interactions were reviewed and compiled comprehensively from full texts.
RESULTS
A total of 69 (39 pre-clinical and 30 clinical) studies documenting efficacy and safety aspects were identified and the desired information of these studies is comprehensively presented in this review. Retrieved thirty(30) human studies demonstrated reasonable efficacy of root preparations in subclinical hypothyroidism (1), schizophrenia (3), chronic stress (2), insomnia (2), anxiety (1), memory and cognitive improvement (2), obsessive-compulsive disorder (1), rheumatoid arthritis (2), type-2 diabetes (2), male infertility (6), fertility promotion activity in females (1), adaptogenic (3), growth promoter in children (3) and chemotherapy adjuvant (1). Reasonable safety of root preparations of Aswagandha has been established by these retrieved 30 human trials. No serious adverse events or any changes in haematological, biochemical or vital parameters were reported in these human studies. Only mild and mainly transient type adverse events of somnolence, epigastric pain/discomfort and loose stools were reported as most common (>5%); and giddiness, drowsiness, hallucinogenic, vertigo, nasal congestion (rhinitis), cough, cold, decreased appetite, nausea, constipation, dry mouth, hyperactivity, nocturnal cramps, blurring of vision, hyperacidity, skin rash and weight gain were reported as less common adverse events. Pre-clinical chronic toxicity studies conducted up to 8 months also found root extracts to be safe. No mutagenicity or genotoxicity was reported for the root; only mild CNS depression and increase in thyroxine (T4) levels were reported with rootby some studies. Further, there was no in vitro and in vivo inhibition seen for CYP3A4 and CYP2D6, the two major hepatic drug metabolizing enzymes.
CONCLUSION
Root of the Ayurvedic drug W. somnifera (Aswagandha) appears a promising safe and effective traditional medicine for management of schizophrenia, chronic stress, insomnia, anxiety, memory/cognitive enhancement, obsessive-compulsive disorder, rheumatoid arthritis, type-2 diabetes and male infertility, and bears fertility promotion activity in females adaptogenic, growth promoter activity in children and as adjuvant for reduction of fatigue and improvement in quality of life among cancer patients undergoing chemotherapy. Properly designed, randomized-controlled, large-size, prospective trials with standardized preparations are needed to ascertain efficacy of Aswagandha root in previously studied and other new indications.
Topics: Herb-Drug Interactions; Humans; Patient Safety; Plant Extracts; Plant Roots; Risk Assessment; Risk Factors; Withania
PubMed: 32201301
DOI: 10.1016/j.jep.2020.112768 -
Recenti Progressi in Medicina Jan 2020In recent years there has been an enormous development in the use of electronic cigarettes (e-cig). In Italy, in the 2019, the users of e-cig are about 900.000. E-cig... (Comparative Study)
Comparative Study
BACKGROUND
In recent years there has been an enormous development in the use of electronic cigarettes (e-cig). In Italy, in the 2019, the users of e-cig are about 900.000. E-cig users tend to overlook the absolute risk of the e-cig product in favor of the relative risk compared to traditional ones. This is also due to the fact that at the moment there are large knowledge gaps on the health effects of using e-cig. Recently reports have emerged regarding serious health adverse effects (AE) related to their use. As of December 2019, the American Centers for Disease Control and Prevention (CDC) reported 2409 cases of lung disease associated with the use of e-cig, and 52 deaths.
AIM
To summarize the available evidence on the health effects of electronic cigarettes.
METHODS
We searched systematic reviews (SR) of the literature published up to September 2019.
RESULTS
The systematic searches led to the identification of 14 SRs (1037 studies included of which 77 provided useful information for this review) that met the inclusion criteria. Given the heterogeneity of the comparisons and of the outcome measures considered, the results are described narratively. Effects on the respiratory system: cough, phlegm, asthma and bronchitis symptoms, cases of chronic bronchitis and COPD have also been reported. Effects on the oropharyngeal system: lesions in the oral cavity, villous black tongue, allergic reactions, endogenous formation of carcinogens, development of oral cancer. Effects on the cardiovascular system: increased heart rate, increased systolic and diastolic pressure. Effects on skin and annexes: squamous and pruritic dermatitis. Any adverse effect: the most frequently reported AEs are cough, dry mouth, shortness of breath, irritation of the mouth and throat and headache. Effects of exposure to e-cig passive smoking: increase in cotinine levels in exposed environments.
CONCLUSIONS
These results, based on evidence from very low to moderate, show a series of possible risks linked to the use of e-cig. However, there is a need for further well-conducted studies with longer follow-up periods to confirm these results.
Topics: Electronic Nicotine Delivery Systems; Humans; Risk; Tobacco Smoke Pollution; Vaping
PubMed: 31992902
DOI: 10.1701/3294.32651 -
Indian Journal of Occupational and... 2019We report a 65 year old female patient who had presented with dry cough and shortness of breath for the last 5 years and had also received anti-tubercular therapy but...
We report a 65 year old female patient who had presented with dry cough and shortness of breath for the last 5 years and had also received anti-tubercular therapy but without any benefit. Evaluation revealed the presence of obstructive airway disease with nodular opacities in bilateral lungs. Histopathological examination including electron microscopy was suggestive of domestically acquired pneumoconiosis.A diagnosis of Gujjar lung was made based on history of exposure to wood smoke, characteristic histological and radiological features. Anti-tubercular therapy was stopped and bronchodilators were initiated along with removal from source of exposure to which she showed significant improvement. We also did a systematic review of literature pertaining to Gujjar lung.
PubMed: 31920264
DOI: 10.4103/ijoem.IJOEM_230_18 -
Evidence-based Complementary and... 2019Fr. Schmidt ex Miq, the sole species in the genus (Apiaceae), has long been used in traditional Chinese medicine to treat fatigue, weakness, stomach-yin deficiency,... (Review)
Review
Fr. Schmidt ex Miq, the sole species in the genus (Apiaceae), has long been used in traditional Chinese medicine to treat fatigue, weakness, stomach-yin deficiency, lung heat, cough, dry throat, and thirst. Recently, has also been incorporated into a wide range of Chinese vegetarian cuisines. Based on the comprehensive information, advances in botany, known uses, phytochemistry, pharmacology, and toxicity of , we aim to highlight research gaps and challenges in studying as well as to explore its potential use in plant biotechnology. This may provide more efficient therapeutic agents and health products from . A literature search of SciFinder, ScienceDirect, Scopus, TPL, Google Scholar, Baidu Scholar, and Web of Science, books, PhD and MSc dissertations, and peer-reviewed papers on research was conducted and comprehensively analyzed. We confirmed that the ethnomedical uses of have been recorded in China, Japan, and Korea for thousands of years. A phytochemical investigation revealed that the primary active compounds were phenylpropanoids, coumarins, lignanoids, and flavonoids, organic acids and derivatives, terpenoids, polyacetylenes, steroids, nitrogen compounds, and others. Our analysis also confirmed that the extracts of possess immunoregulatory, antitumor, anti-inflammatory, hepatoprotective, antioxidant, neuroprotective, antibacterial, antifungal, and analgesic properties. Although further studies are required, there is strong evidence of the antitumor and immunoregulatory potential of . Also, more studies are needed to elucidate the mechanisms of action of its active compounds (e.g., falcarinol and panaxydiol) before any clinical studies can be carried out.
PubMed: 31915441
DOI: 10.1155/2019/1253493