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European Review For Medical and... Nov 2020Alginate formulations are increasingly being used for treating gastroesophageal reflux disease (GERD). However, the benefits of alginate versus control or proton pump... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Alginate formulations are increasingly being used for treating gastroesophageal reflux disease (GERD). However, the benefits of alginate versus control or proton pump inhibitors (PPIs) are somewhat unclear. We performed a systematic review and meta-analysis to summarize data from recent randomized controlled trials (RCTs) comparing the efficacy and safety of alginate-based formulation with PPIs or control for the treatment of GERD.
MATERIALS AND METHODS
PubMed, Embase, Scopus, BioMed Central, CENTRAL, and Google scholar databases were searched from 1st January 2000 to 15th June 2020. Primary outcome was a reduction of symptoms while secondary outcomes were adverse events and treatment withdrawals. Ten articles with 11 RCTs were included.
RESULTS
Qualitative analysis of four trials indicated better outcomes with alginates vs. placebo/antacids. Our pooled analysis, however, indicated no statistically significant difference between alginates and placebo/antacids for relief of heartburn, regurgitation, or dyspepsia. Similarly, no difference was seen between a combination of alginate and PPI vs. PPI alone for reduction of heartburn, regurgitation, or dyspepsia symptoms. The risk of adverse events and treatment withdrawal did not differ between the two groups in either comparison. Descriptive analysis of studies comparing alginate vs. PPI indicated no difference between the two drugs.
CONCLUSIONS
Our study indicates that alginates may have greater efficacy than placebo/antacids in improving outcomes of GERD. However, current evidence on the efficacy of alginate-based formulations vs. PPI or the role of added alginates with PPI is questionable, and suggests no difference between the two drugs. The risk of adverse events with alginates is no greater than that of placebo or PPIs.
Topics: Alginates; Drug Compounding; Gastroesophageal Reflux; Humans; Proton Pump Inhibitors; Randomized Controlled Trials as Topic
PubMed: 33275256
DOI: 10.26355/eurrev_202011_23841 -
Electroacupuncture for the treatment of functional dyspepsia: A systematic review and meta-analysis.Medicine Nov 2020Functional dyspepsia (FD) is a common functional gastrointestinal disease. Acupuncture, including electroacupuncture (EA) is widely used as a complementary and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Functional dyspepsia (FD) is a common functional gastrointestinal disease. Acupuncture, including electroacupuncture (EA) is widely used as a complementary and alternative treatment for patients with FD. This study aimed to explore the effectiveness of EA for the treatment of FD.
METHODS
We searched Embase, PubMed, and the Cochrane Central Register of Controlled Trials (Cochrane Library) for randomized controlled trials of FD treated by EA from inception to February 3, 2020. Two reviewers will independently screen studies for data extraction and assess the quality and risk of bias. The Cochrane Collaboration's risk of bias tool, RevMan 5.3 software were used for meta-analysis. Data were pooled to calculate relative risk and 95% confidence intervals (CIs) of substantial improvement after treatment for dichotomous data and mean differences (SMDs) and 95% CIs for continuous data.
RESULTS
Seven randomized clinical trials included 853 patients. This meta-analysis investigated the effectiveness of EA alone in the treatment of FD relative to sham-EA or pharmacologic medication (PM). The results showed that EA could significantly improve clinical symptoms. Compared with sham-EA, EA was more effective in reducing symptom scores (SMD -3.44, 95% CI -4.21 to -2.67) and increasing normal slow waves of electrogastrogram (SMD 0.93, 95% CI -0.30 to1.55). When EA was combined with PM, there was no significant difference in reducing symptom scores (SMD -0.18, 95% CI -0.51 to 0.16), increasing the effective rate of clinical symptoms (risk ratio 1.04, 95% CI 0.96 to 1.13), enhancing the level of plasma motilin (SMD 0.93, 95% CI -0.30 to1.55), and reducing gastric half-emptying time (SMD 0.02, 95% CI -0.16 to 0.20). The results also showed that there were very few adverse events reported.
CONCLUSION
This meta-analysis suggests that EA is better than the placebo (sham-EA) in treating FD, and the therapeutic effect of EA on FD is equivalent to that of PM on FD. Compared with PM, EA for FD is safer and has fewer adverse reactions. Despite limitations due to the quality and number of the included studies, EA might be used as an effective and safe treatment for FD.
Topics: Acupuncture Therapy; Case-Control Studies; Dyspepsia; Electroacupuncture; Humans; Motilin; Placebos; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33157947
DOI: 10.1097/MD.0000000000023014 -
Complementary Medicine Research 2021Einleitung: Ziel dieser systematischen Übersicht war die Bewertung der verfügbaren Evidenz zur Wirkung der Kneipp-Therapie. Methoden: MEDLINE, Embase, Web of Science,...
UNLABELLED
Einleitung: Ziel dieser systematischen Übersicht war die Bewertung der verfügbaren Evidenz zur Wirkung der Kneipp-Therapie. Methoden: MEDLINE, Embase, Web of Science, Cochrane-Library und CAMbase wurden nach relevanten Artikeln, veröffentlicht zwischen 2000 und 2019, durchsucht. Graue Literatur wurde über Google Scholar und andere Tools bezogen. Studien mit jeglicher Art von Studiendesign, die die Effekte der Kneipp-Therapie untersuchten, wurden eingeschlossen. Die Qualitätsbewertung erfolgte mittels EPHPP-QAT. Ergebnisse: 25 Quellen, darunter 14 kontrol-lierte Studien, wurden eingeschlossen. Gemäß EPHPP-QAT wurden 3 Studien "stark", 13 "moderat" und 9 "schwach" bewertet. Neun (64%) der kontrollierten Studien berichteten signifikante Verbesserungen nach Kneipp-Therapie im Gruppenvergleich bei chronisch-venöser Insuffizienz, Hypertonie, leichter Herzinsuffizienz, menopausalen Be-schwerden und Schlafstörungen in verschiedenen Patientenkollektiven sowie verbesserte Immunparameter bei gesunden Probanden. Im Hinblick auf Depression und Angst bei Mammakarzinom-Patientinnen mit klimakterischen Beschwerden, Lebensqualität bei Post-Polio-Syndrom, krankheitsbedingten polyneuropathischen Beschwerden und Inzidenz von Erkältungsepisoden bei Kindern konnten keine signifikanten Gruppenunterschiede festgestellt werden. Elf unkontrollierte Studien berichteten Verbesse-rungen bei allergischen Symptomen, Dyspepsie, Lebens-qualität, Herzratenvariabilität, Infekten, Hypertonie, Wohlbefinden, Schmerz und polyneuropathischen Beschwerden. Diskussion/Schlussfolgerung: Die Kneipp-Therapie scheint bei zahlreichen Beschwerdebildern in verschiedenen Patientenkollektiven positive Effekte zu bewirken. Zukünftige Studien sollten noch stärker auf eine methodisch sorgfältige Studienplanung achten (Kontrollgruppen, Randomisierung, adäquate Fallzahlen, Verblindung), um Verzerrungen entgegenzuwirken.
INTRODUCTION
The aim of this systematic review was to evaluate the available evidence on the effect of Kneipp therapy.
METHODS
MEDLINE, Embase, Web of Science, Cochrane Library and CAMbase were searched for relevant articles published between 2000 and 2019. Grey literature was obtained through Google Scholar and other tools. Studies with any kind of study design that examined the effects of Kneipp therapy were included. The quality assessment was carried out using EPHPP-QAT.
RESULTS
25 sources, including 14 controlled studies, were included. According to EPHPP-QAT, 3 studies were rated as “strong,” 13 as “moderate” and 9 as “weak.” Nine (64%) of the controlled studies reported significant improvements after Kneipp therapy in a between-group comparison in chronic venous insufficiency, hypertension, mild heart failure, menopausal complaints, and sleep disorders in different patient collectives as well as improved immune parameters in healthy subjects. Regarding depression and anxiety in breast cancer patients with climacteric complaints, quality of life in post-polio syndrome, disease-related polyneuropathic complaints and incidence of cold episodes in children, no significant group differences were found. Eleven uncontrolled studies reported improvements in allergic symptoms, dyspepsia, quality of life, heart rate variability, infections, hypertension, well-being, pain and polyneuropathic complaints.
DISCUSSION/CONCLUSION
Kneipp therapy seems to be beneficial for numerous symptoms in different patient groups. Future studies should pay even more attention to methodologically careful study planning (control groups, randomisation, adequate case numbers, blinding) to counteract bias.
Topics: Humans; Hydrotherapy; Phytotherapy; Quality of Life
PubMed: 33049739
DOI: 10.1159/000510452 -
Alimentary Pharmacology & Therapeutics Jan 2021Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy is unknown.
AIM
To perform a systematic review with network meta-analysis to resolve this uncertainty.
METHODS
We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities.
RESULTS
We identified 71 eligible RCTs (19 243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy (RR of remaining symptomatic = 0.71; 95% CI 0.58-0.87, SUCRA 0.87), and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy (RR = 0.49; 95% CI 0.36-0.69, SUCRA 0.99), trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo.
CONCLUSIONS
TCAs, histamine- receptor antagonists, standard- and low-dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD.
Topics: Adult; Dyspepsia; Histamine H2 Antagonists; Humans; Network Meta-Analysis; Pharmaceutical Preparations; Proton Pump Inhibitors
PubMed: 32936964
DOI: 10.1111/apt.16072 -
The Cochrane Database of Systematic... Aug 2020Oral 5-aminosalicylic acid (5-ASA; also known as mesalazine or mesalamine) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Oral 5-aminosalicylic acid (5-ASA; also known as mesalazine or mesalamine) preparations were intended to avoid the adverse effects of sulfasalazine (SASP) while maintaining its therapeutic benefits. In an earlier version of this review, we found that 5-ASA drugs were more effective than placebo for maintenance of remission of ulcerative colitis (UC), but had a significant therapeutic inferiority relative to SASP. In this version, we have rerun the search to bring the review up to date.
OBJECTIVES
To assess the efficacy, dose-responsiveness, and safety of oral 5-ASA compared to placebo, SASP, or 5-ASA comparators for maintenance of remission in quiescent UC and to compare the efficacy and safety of once-daily dosing of oral 5-ASA with conventional (two or three times daily) dosing regimens.
SEARCH METHODS
We performed a literature search for studies on 11 June 2019 using MEDLINE, Embase, and the Cochrane Library. In addition, we searched review articles and conference proceedings.
SELECTION CRITERIA
We included randomized controlled trials with a minimum treatment duration of six months. We considered studies of oral 5-ASA therapy for treatment of participants with quiescent UC compared with placebo, SASP, or other 5-ASA formulations. We also included studies that compared once-daily 5-ASA treatment with conventional dosing of 5-ASA and 5-ASA dose-ranging studies.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. The primary outcome was the failure to maintain clinical or endoscopic remission. Secondary outcomes were adherence, adverse events (AE), serious adverse events (SAE), withdrawals due to AEs, and withdrawals or exclusions after entry. Trials were separated into five comparison groups: 5-ASA versus placebo, 5-ASA versus SASP, once-daily dosing versus conventional dosing, 5-ASA (balsalazide, Pentasa, and olsalazine) versus comparator 5-ASA formulation (Asacol and Salofalk), and 5-ASA dose-ranging. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each outcome. We analyzed data on an intention-to-treat basis, and used GRADE to assess the overall certainty of the evidence.
MAIN RESULTS
The search identified 44 studies (9967 participants). Most studies were at low risk of bias. Ten studies were at high risk of bias. Seven of these studies were single-blind and three were open-label. 5-ASA is more effective than placebo for maintenance of clinical or endoscopic remission. About 37% (335/907) of 5-ASA participants relapsed at six to 12 months compared to 55% (355/648) of placebo participants (RR 0.68, 95% CI 0.61 to 0.76; 8 studies, 1555 participants; high-certainty evidence). Adherence to study medication was not reported for this comparison. SAEs were reported in 1% (6/550) of participants in the 5-ASA group compared to 2% (5/276) of participants in the placebo group at six to 12 months (RR 0.60, 95% CI 0.19 to 1.84; 3 studies, 826 participants; low-certainty evidence). There is probably little or no difference in AEs at six to 12 months' follow-up (RR 0.93, 95% CI 0.73 to 1.18; 5 studies, 1132 participants; moderate-certainty evidence). SASP is more effective than 5-ASA for maintenance of remission. About 48% (416/871) of 5-ASA participants relapsed at six to 18 months compared to 43% (336/784) of SASP participants (RR 1.14, 95% CI 1.03 to 1.27; 12 studies, 1655 participants; high-certainty evidence). Adherence to study medication and SAEs were not reported for this comparison. There is probably little or no difference in AEs at six to 12 months' follow-up (RR 1.07, 95% CI 0.82 to 1.40; 7 studies, 1138 participants; moderate-certainty evidence). There is little or no difference in clinical or endoscopic remission rates between once-daily and conventionally dosed 5-ASA. About 37% (717/1939) of once-daily participants relapsed over 12 months compared to 39% (770/1971) of conventional-dosing participants (RR 0.94, 95% CI 0.88 to 1.01; 10 studies, 3910 participants; high-certainty evidence). There is probably little or no difference in medication adherence rates. About 10% (106/1152) of participants in the once-daily group failed to adhere to their medication regimen compared to 8% (84/1154) of participants in the conventional-dosing group (RR 1.18, 95% CI 0.72 to 1.93; 9 studies, 2306 participants; moderate-certainty evidence). About 3% (41/1587) of participants in the once-daily group experienced a SAE compared to 2% (35/1609) of participants in the conventional-dose group at six to 12 months (RR 1.20, 95% CI 0.77 to 1.87; moderate-certainty evidence). There is little or no difference in the incidence of AEs at six to 13 months' follow-up (RR 0.98, 95% CI 0.92 to 1.04; 8 studies, 3497 participants; high-certainty evidence). There may be little or no difference in the efficacy of different 5-ASA formulations. About 44% (158/358) of participants in the 5-ASA group relapsed at six to 18 months compared to 41% (142/349) of participants in the 5-ASA comparator group (RR 1.08, 95% CI 0.91 to 1.28; 6 studies, 707 participants; low-certainty evidence).
AUTHORS' CONCLUSIONS
There is high-certainty evidence that 5-ASA is superior to placebo for maintenance therapy in UC. There is high-certainty evidence that 5-ASA is inferior compared to SASP. There is probably little or no difference between 5-ASA and placebo, and 5-ASA and SASP in commonly reported AEs such as flatulence, abdominal pain, nausea, diarrhea, headache, and dyspepsia. Oral 5-ASA administered once daily has a similar benefit and harm profile as conventional dosing for maintenance of remission in quiescent UC.
Topics: Administration, Oral; Aminosalicylic Acids; Anti-Inflammatory Agents, Non-Steroidal; Bias; Colitis, Ulcerative; Drug Administration Schedule; Humans; Maintenance Chemotherapy; Medication Adherence; Mesalamine; Patient Dropouts; Placebos; Randomized Controlled Trials as Topic; Recurrence; Remission Induction; Sulfasalazine
PubMed: 32856298
DOI: 10.1002/14651858.CD000544.pub5 -
Alimentary Pharmacology & Therapeutics Sep 2020Prevalence of uninvestigated dyspepsia varies across cross-sectional surveys. This may be due to differences in definitions used or study methodology, rather than global... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prevalence of uninvestigated dyspepsia varies across cross-sectional surveys. This may be due to differences in definitions used or study methodology, rather than global variability.
AIM
To determine the global prevalence of uninvestigated dyspepsia according to Rome criteria.
METHODS
MEDLINE and EMBASE were searched to identify population-based studies reporting prevalence of uninvestigated dyspepsia in adults (≥18 years old) according to Rome I, II, III or IV criteria. Prevalence of uninvestigated dyspepsia was extracted, according to criteria used to define it. Pooled prevalence, according to study location and certain other characteristics, odds ratios (OR), and 95% confidence intervals (CIs) were calculated.
RESULTS
Of 2133 citations evaluated, 67 studies fulfilled eligibility criteria, representing 98 separate populations, comprising 338 383 subjects. Pooled prevalence ranged from 17.6% (95% CI 9.8%-27.1%) in studies defining uninvestigated dyspepsia according to Rome I criteria, to 6.9% (95% CI 5.7%-8.2%) in those using Rome IV criteria. Postprandial distress syndrome was the commonest subtype, occurring in 46.2% of participants using Rome III criteria, and 62.8% with Rome IV. Prevalence of uninvestigated dyspepsia was up to 1.5-fold higher in women, irrespective of the definition used. There was significant heterogeneity between studies in all our analyses, which persisted even when the same criteria were applied and similar methodology was used.
CONCLUSIONS
Even when uniform symptom-based criteria are used to define the presence of uninvestigated dyspepsia, prevalence varies between countries. This suggests that there are environmental, cultural, ethnic, dietary or genetic influences determining symptoms.
Topics: Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Diagnostic Errors; Diagnostic Techniques, Digestive System; Dyspepsia; Female; Humans; Male; Middle Aged; Prevalence; Syndrome; Young Adult
PubMed: 32852839
DOI: 10.1111/apt.16006 -
Journal of Gastroenterology and... Jan 2021Functional dyspepsia (FD) is characterized by chronic and unexplained indigestion at upper abdomen. Because of unsatisfactory effect of conventional treatments, demand... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Functional dyspepsia (FD) is characterized by chronic and unexplained indigestion at upper abdomen. Because of unsatisfactory effect of conventional treatments, demand is growing for complementary and alternative medicine. Rikkunshito (RKT) is a herbal medicine, which has been widely used for FD in Asia; however, the evidence is lacking. We carried out systematic review and meta-analysis to evaluate the effect and safety of RKT in the treatment of FD.
METHODS
Electronic databases were searched in April 2019, including PUBMED, EMBASE, and Cochrane Library. All eligible studies should be randomized controlled trials (RCTs) comparing RKT or combination therapy (RKT and western medicine) group to western medicine group. The primary outcome measure was the total clinical efficacy rate (TCE). The secondary outcomes were total dyspepsia symptom scale, gastric emptying rate, gastrin, motilin, recurrence 6 months after treatment, and Hamilton depression rating scale.
RESULTS
Fifty-two RCTs with 5475 patients were involved in this systematic review and meta-analysis. Compared with western medicine, RKT showed significant better result, with higher TCE (relative risk = 1.21, 95% confidence interval 1.17 to 1.25, P < 0.001). RKT presented higher reduction of total dyspepsia symptom scale, more improved gastric emptying rate, and lower recurrence 6 months after treatment compared with western medicine. However, there was no significant difference in Hamilton depression rating scale between RKT and western medicine group. Combination therapy brought significant symptom improvement with TCE compared with western medicine alone.
CONCLUSIONS
Rikkunshito and combination therapy might be considered an effective alternative treatment for FD. Further rigorously designed and high-quality RCTs are needed.
Topics: Drug Therapy, Combination; Drugs, Chinese Herbal; Dyspepsia; Female; Gastric Emptying; Humans; Male; Phytotherapy; Randomized Controlled Trials as Topic; Recurrence; Treatment Outcome
PubMed: 32767596
DOI: 10.1111/jgh.15208 -
World Journal of Gastroenterology May 2020Functional dyspepsia (FD) is a common digestive disease with limited therapeutic options. According to evidence-based clinical practice, acupuncture or...
BACKGROUND
Functional dyspepsia (FD) is a common digestive disease with limited therapeutic options. According to evidence-based clinical practice, acupuncture or electroacupuncture (EA) seems to be a promising therapy for patients with FD. However, there is still a lack of systematic reviews that have analyzed current clinical trials for a better understanding of mechanisms involved in the ameliorating effect of acupuncture and EA on FD.
AIM
To evaluate the results and qualities of existing clinical evidence for researching the underlying mechanisms of acupuncture/EA in treating FD.
METHODS
A systematic search of the literature was performed to identify randomized controlled trials in which research on the mechanism of acupuncture or EA was conducted in FD patients. Databases searched included PubMed, EMBASE, Cochrane Library, and Web of Science. Data extraction and quality assessment were completed by two investigators independently and the results of quality evaluation were exported through Review Manager V5.3.
RESULTS
Eight studies were included in this review with a total of 17 items for detecting techniques for mechanistic research. Positive effects of acupuncture and EA were observed in regulating gastric motility, gastric accommodation, mental status, gastrointestinal hormones, and central and autonomic functions while improving dyspeptic symptoms and quality of life.
CONCLUSION
The key findings of this systematic review support the potential of acupuncture and EA in altering the heterogeneous pathophysiology in patients with FD. However, high-quality studies with well-planned designs are necessary to provide more credible evidence.
Topics: Acupuncture Therapy; Dyspepsia; Electroacupuncture; Gastrointestinal Motility; Humans; Quality of Life; Randomized Controlled Trials as Topic; Stomach; Treatment Outcome
PubMed: 32476804
DOI: 10.3748/wjg.v26.i19.2440 -
Annals of Palliative Medicine May 2020Functional dyspepsia (FD) is a common, etiologically complex disease which persistently and recurrently attacks the digestive system. However, the efficacy of Western... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Functional dyspepsia (FD) is a common, etiologically complex disease which persistently and recurrently attacks the digestive system. However, the efficacy of Western medicine in treating FD is unsatisfactory and its use is often accompanied with severe side effects. Here, this study conducted a metaanalysis on the clinical efficacy and safety of the treatment of FD with Xin kai bitter method combined with Western medicine, to produce a more objective and comprehensive systematic review to guide clinical application.
METHODS
Systematic searches were conducted of the PubMed, Cochrane Library, EMBASE, Medline, Web of Science, Wanfang Databases, and Weipu (VIP) databases, as well as China National Knowledge Infrastructure (CNKI). Randomized controlled clinical trials (RCTs) of Xin kai bitter method in the treatment of FD were included in the study. The total effective rate and safety were evaluated with relative risk (RR) and the quantitative data were evaluated with standard mean difference (SMD) and 95% confidence interval (CI). The quality of the included literature was evaluated using RevMan5.3 software, and the "meta" package of R3.5.1 software was used for all other statistical analysis.
RESULTS
A total of 24 papers involving 1,044 patients in the treatment group and 989 patients in the control group were included. A total of 23 articles reported the total effective rate after 1 month of treatment (I2 =0%), and the total effective rate in the treatment group was 1.21 times higher than that in the control group (95% CI: 1.17 vs. 1.26). A total of 4 articles reported the safety rate after 1 month of treatment (I2 =27%); the safety rate in the treatment group was 0.43 times than that in the control group (95% CI: 0.23 vs. 0.82). A total of 8 articles reported traditional Chinese medicine (TCM) symptom score or clinical symptoms before and after 1 month of treatment (I2 =91%), and the difference in TCM symptom score before and after treatment in the treatment group was significantly lower than that in the control group, with a SMD of -1.19 (95% CI: -1.71, -0.66). A total of 6 articles reported the motilin (MTL) level before and after 1 month of treatment, and the difference before and after treatment in MTL in the treatment group was not significantly different to that in the control group, with a SMD of 0.92 (95% CI: -0.12, 1.97).
CONCLUSIONS
Compared to conventional treatment, Xin kai bitter method has a higher clinical effect and lower adverse reaction rate in patients with FD, and can improve TCM symptom score. However, highquality RCT research is still needed to further explore the safety of Xin kai bitter method for treating FD.
Topics: China; Drugs, Chinese Herbal; Dyspepsia; Humans; Medicine, Chinese Traditional; Treatment Outcome
PubMed: 32434358
DOI: 10.21037/apm-20-860 -
The Cochrane Database of Systematic... May 2020Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea, and a reduction in lung function, quality of life, and life... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is associated with cough, sputum production or dyspnoea, and a reduction in lung function, quality of life, and life expectancy. Apart from smoking cessation, no other treatments that slow lung function decline are available. Roflumilast and cilomilast are oral phosphodiesterase-4 (PDE₄) inhibitors proposed to reduce the airway inflammation and bronchoconstriction seen in COPD. This Cochrane Review was first published in 2011, and was updated in 2017 and 2020.
OBJECTIVES
To evaluate the efficacy and safety of oral PDE₄ inhibitors for management of stable COPD.
SEARCH METHODS
We identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register (date of last search 9 March 2020). We found other trials at web-based clinical trials registers.
SELECTION CRITERIA
We included RCTs if they compared oral PDE₄ inhibitors with placebo in people with COPD. We allowed co-administration of standard COPD therapy.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Two independent review authors selected trials for inclusion, extracted data, and assessed risk of bias. We resolved discrepancies by involving a third review author. We assessed our confidence in the evidence by using GRADE recommendations. Primary outcomes were change in lung function (minimally important difference (MID) = 100 mL) and quality of life (scale 0 to 100; higher score indicates more limitations).
MAIN RESULTS
We found 42 RCTs that met the inclusion criteria and were included in the analyses for roflumilast (28 trials with 18,046 participants) or cilomilast (14 trials with 6457 participants) or tetomilast (1 trial with 84 participants), with a duration between six weeks and one year or longer. These trials included people across international study centres with moderate to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades II to IV), with mean age of 64 years. We judged risks of selection bias, performance bias, and attrition bias as low overall amongst the 39 published and unpublished trials. Lung function Treatment with a PDE₄ inhibitor was associated with a small, clinically insignificant improvement in forced expiratory volume in one second (FEV₁) over a mean of 40 weeks compared with placebo (mean difference (MD) 49.33 mL, 95% confidence interval (CI) 44.17 to 54.49; participants = 20,815; studies = 29; moderate-certainty evidence). Forced vital capacity (FVC) and peak expiratory flow (PEF) were also improved over 40 weeks (FVC: MD 86.98 mL, 95% CI 74.65 to 99.31; participants = 22,108; studies = 17; high-certainty evidence; PEF: MD 6.54 L/min, 95% CI 3.95 to 9.13; participants = 4245; studies = 6; low-certainty evidence). Quality of life Trials reported improvements in quality of life over a mean of 33 weeks (St George's Respiratory Questionnaire (SGRQ) MD -1.06 units, 95% CI -1.68 to -0.43; participants = 7645 ; moderate-certainty evidence). Incidence of exacerbations Treatment with a PDE₄ inhibitor was associated with a reduced likelihood of COPD exacerbation over a mean of 40 weeks (odds ratio (OR) 0.78, 95% CI 0.73 to 0.84; participants = 20,382; studies = 27; high-certainty evidence), that is, for every 100 people treated with PDE₄ inhibitors, five more remained exacerbation-free during the study period compared with those given placebo (number needed to treat for an additional beneficial outcome (NNTB) 20, 95% CI 16 to 27). No change in COPD-related symptoms nor in exercise tolerance was found. Adverse events More participants in the treatment groups experienced an adverse effect compared with control participants over a mean of 39 weeks (OR 1.30, 95% CI 1.22 to 1.38; participants = 21,310; studies = 30; low-certainty evidence). Participants experienced a range of gastrointestinal symptoms such as diarrhoea, nausea, vomiting, or dyspepsia. Diarrhoea was more commonly reported with PDE₄ inhibitor treatment (OR 3.20, 95% CI 2.74 to 3.50; participants = 20,623; studies = 29; high-certainty evidence), that is, for every 100 people treated with PDE₄ inhibitors, seven more suffered from diarrhoea during the study period compared with those given placebo (number needed to treat for an additional harmful outcome (NNTH) 15, 95% CI 13 to 17). The likelihood of psychiatric adverse events was higher with roflumilast 500 µg than with placebo (OR 2.13, 95% CI 1.79 to 2.54; participants = 11,168; studies = 15 (COPD pool data); moderate-certainty evidence). Roflumilast in particular was associated with weight loss during the trial period and with an increase in insomnia and depressive mood symptoms. Participants treated with PDE₄ inhibitors were more likely to withdraw from trial participation; on average, 14% in the treatment groups withdrew compared with 8% in the control groups. Mortality No effect on mortality was found (OR 0.98, 95% CI 0.77 to 1.24; participants = 19,786; studies = 27; moderate-certainty evidence), although mortality was a rare event during these trials.
AUTHORS' CONCLUSIONS
For this current update, five new studies from the 2020 search contributed to existing findings but made little impact on outcomes described in earlier versions of this review. PDE₄ inhibitors offered a small benefit over placebo in improving lung function and reducing the likelihood of exacerbations in people with COPD; however, they had little impact on quality of life or on symptoms. Gastrointestinal adverse effects and weight loss were common, and the likelihood of psychiatric symptoms was higher, with roflumilast 500 µg. The findings of this review provide cautious support for the use of PDE₄ inhibitors in COPD. In accordance with GOLD 2020 guidelines, they may have a place as add-on therapy for a subgroup of people with persistent symptoms or exacerbations despite optimal COPD management (e.g. people whose condition is not controlled by fixed-dose long-acting beta₂-agonist (LABA) and inhaled corticosteroid (ICS) combinations). More longer-term trials are needed to determine whether or not PDE₄ inhibitors modify FEV₁ decline, hospitalisation, or mortality in COPD.
Topics: Administration, Oral; Aminopyridines; Benzamides; Cyclohexanecarboxylic Acids; Cyclopropanes; Diarrhea; Disease Progression; Forced Expiratory Volume; Humans; Middle Aged; Nitriles; Peak Expiratory Flow Rate; Phosphodiesterase 4 Inhibitors; Pulmonary Disease, Chronic Obstructive; Quality of Life; Randomized Controlled Trials as Topic; Thiazoles; Vital Capacity
PubMed: 32356609
DOI: 10.1002/14651858.CD002309.pub6