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The American Journal of Gastroenterology Jun 2021Constipation is commonly treated with over-the-counter (OTC) products whose efficacy and safety remain unclear. We performed a systematic review of OTC therapies for...
INTRODUCTION
Constipation is commonly treated with over-the-counter (OTC) products whose efficacy and safety remain unclear. We performed a systematic review of OTC therapies for chronic constipation and provide evidence-based recommendations.
METHODS
We searched PubMed and Embase for randomized controlled trials of ≥4-week duration that evaluated OTC preparations between 2004 and 2020. Studies were scored using the US Preventive Services Task Force criteria (0-5 scale) including randomization, blinding, and withdrawals. The strengths of evidence were adjudicated within each therapeutic category, and recommendations were graded (A, B, C, D, and I) based on the level of evidence (level I, good; II, fair; or III, poor).
RESULTS
Of 1,297 studies identified, 41 met the inclusion criteria. There was good evidence (grade A recommendation) for the use of the osmotic laxative polyethylene glycol (PEG) and the stimulant senna; moderate evidence (grade B) for psyllium, SupraFiber, magnesium salts, stimulants (bisacodyl and sodium picosulfate), fruit-based laxatives (kiwi, mango, prunes, and ficus), and yogurt with galacto-oligosaccharide/prunes/linseed oil; and insufficient evidence (grade I) for polydextrose, inulin, and fructo-oligosaccharide. Diarrhea, nausea, bloating, and abdominal pain were common adverse events, but no serious adverse events were reported.
DISCUSSION
The spectrum of OTC products has increased and quality of evidence has improved, but methodological issues including variability in study design, primary outcome measures, trial duration, and small sample sizes remain. We found good evidence to recommend polyethylene glycol or senna as first-line laxatives and moderate evidence supporting fiber supplements, fruits, stimulant laxatives, and magnesium-based products. For others, further validation with more rigorously designed studies is warranted.
Topics: Bisacodyl; Cathartics; Chronic Disease; Citrates; Constipation; Defecation; Fruit; Gastrointestinal Agents; Glucans; Humans; Inulin; Laxatives; Magnesium; Nonprescription Drugs; Oligosaccharides; Organometallic Compounds; Picolines; Polyethylene Glycols; Psyllium; Senna Extract; Yogurt
PubMed: 33767108
DOI: 10.14309/ajg.0000000000001222 -
Clinical Optometry 2023Artificial tears are the mainstay of dry eye disease management, but also have a role in corneal abrasion and wound healing, pain and inflammation management,... (Review)
Review
Artificial tears are the mainstay of dry eye disease management, but also have a role in corneal abrasion and wound healing, pain and inflammation management, conjunctivitis, keratitis, contact lens rewetting and removal, and foreign body removal. A systematic review of randomized controlled trials (PROSPERO registration CRD42022369619) comparing the efficacy of artificial tears in patients with dry eye to inform prescribing choices using Web of Science, PubMed and Medline databases identified 64 relevant articles. There is good evidence that artificial tears improve symptoms of dry eye disease within a month of regular use, applied about four times a day, but signs generally take several months to improve. Not all patients with dry eye disease benefit from artificial tears, so if there is no benefit over a month, alternative management should be considered. Combination formulations are more effective than single active ingredient artificial tears. Artificial tears containing polyethylene glycol are more effective than those containing carboxymethylcellulose/carmellose sodium and hydroxypropyl methylcellulose. Those classified as having evaporative dry eye disease, benefit from artificial tears with liposomes, especially of higher concentration. The data available is limited by the definition of dry eye disease applied in published studies being variable, as well as the disease severity examined and compliance with artificial tears being rarely quantified.
PubMed: 36647552
DOI: 10.2147/OPTO.S350185 -
Journal of Neurogastroenterology and... Oct 2021Constipation is a common gastrointestinal problem in the elderly. Because of the limitations of life style modifications and the comorbidity, laxative use is also very... (Review)
Review
BACKGROUND/AIMS
Constipation is a common gastrointestinal problem in the elderly. Because of the limitations of life style modifications and the comorbidity, laxative use is also very common. Therefore, this study reviews the latest literature on the effect and safety of laxative in the elderly.
METHODS
A systematic review of randomized controlled trials investigating the effectiveness and safety of laxatives for constipation in elderly patients over 65 years old were performed using the following databases: PubMed, EMBASE, and the Cochrane Library.
RESULTS
Twenty-three randomized controlled trials were included in this review. Among the selected studies, 9 studies compared laxative with placebo and 5 studies compared laxatives of the same type. Four studies compared different types of laxatives or compared combination agents. Five studies compared novel medications such as prucalopride, lubiprostone, and elobixibat with placebo. Psyllium, calcium polycarbophil, lactulose syrup, lactitol, polyethylene glycol, magnesium hydroxide, stimulant laxative with or without fiber, and other medications were more effective than placebo in elderly constipation patients in short-term. Generally, the frequency and severity of adverse effects of laxative were similar between the arms of studies.
CONCLUSIONS
Bulk laxative, osmotic laxative, stimulant laxative with or without fiber, and other medications can be used in elderly patients in short-term within 3 months with reasonable safety. However, the quality of included studies was not high and most of studies was conducted in a small number of patients. Among these laxatives, polyethylene glycol seems to be safe and effective in long-term use of about 6 months in elderly patients.
PubMed: 34642269
DOI: 10.5056/jnm20210 -
BMJ Open Gastroenterology May 2021Hepatic encephalopathy (HE) is defined as brain dysfunction that occurs because of acute liver failure or liver cirrhosis and is associated with significant morbidity... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatic encephalopathy (HE) is defined as brain dysfunction that occurs because of acute liver failure or liver cirrhosis and is associated with significant morbidity and mortality. Lactulose is the standard of care till this date; however, polyethylene glycol (PEG) has gained the attention of multiple investigators.
METHODS
We screened five databases namely PubMed, Scopus, Web of Science, Cochrane Library and Embase from inception to 10 February 2021. Dichotomous and continuous data were analysed using the Mantel-Haenszel and inverse variance methods, respectively, which yielded a meta-analysis comparing PEG versus lactulose in the treatment of HE.
RESULTS
Four trials with 229 patients were included. Compared with lactulose, the pooled effect size demonstrated a significantly lower average HE Scoring Algorithm (HESA) Score at 24 hours (Mean difference (MD)=-0.68, 95% CI (-1.05 to -0.31), p<0.001), a higher proportion of patients with reduction of HESA Score by ≥1 grade at 24 hours (risk ratio (RR)=1.40, 95% CI (1.17 to 1.67), p<0.001), a higher proportion of patients with a HESA Score of grade 0 at 24 hours (RR=4.33, 95% CI (2.27 to 8.28), p<0.0010) and a shorter time to resolution of HE group (MD=-1.45, 95% CI (-1.72 to -1.18), p<0.001) in favour of patients treated with PEG.
CONCLUSION
PEG leads to a higher drop in the HESA Score and thus leads to a faster resolution of HE compared with lactulose.
Topics: Hepatic Encephalopathy; Humans; Lactulose; Liver Cirrhosis; Polyethylene Glycols
PubMed: 34006606
DOI: 10.1136/bmjgast-2021-000648 -
BioMed Research International 2022This study is aimed at performing a systematic review and a network meta-analysis of the effects of several membranes on vertical bone regeneration and clinical... (Meta-Analysis)
Meta-Analysis Review
This study is aimed at performing a systematic review and a network meta-analysis of the effects of several membranes on vertical bone regeneration and clinical complications in guided bone regeneration (GBR) or guided tissue regeneration (GTR). We compared the effects of the following membranes: high-density polytetrafluoroethylene (d-PTFE), expanded polytetrafluoroethylene (e-PTFE), crosslinked collagen membrane (CCM), noncrosslinked collagen membrane (CM), titanium mesh (TM), titanium mesh plus noncrosslinked (TM + CM), titanium mesh plus crosslinked (TM + CCM), titanium-reinforced d-PTFE, titanium-reinforced e-PTFE, polylactic acid (PLA), polyethylene glycol (PEG), and polylactic acid 910 (PLA910). Using the PICOS principles to help determine inclusion criteria, articles are collected using PubMed, Web of Science, and other databases. Assess the risk of deviation and the quality of evidence using the Cochrane Evaluation Manual, and GRADE. 27 articles were finally included. 19 articles were included in a network meta-analysis with vertical bone increment as an outcome measure. The network meta-analysis includes network diagrams, paired-comparison forest diagrams, funnel diagrams, surface under the cumulative ranking curve (SUCRA) diagrams, and sensitivity analysis diagrams. SUCRA indicated that titanium-reinforced d-PTFE exhibited the highest vertical bone increment effect. Meanwhile, we analyzed the complications of 19 studies and found that soft tissue injury and membrane exposure were the most common complications.
Topics: Bone Regeneration; Collagen; Guided Tissue Regeneration, Periodontal; Membranes, Artificial; Network Meta-Analysis; Polytetrafluoroethylene; Titanium
PubMed: 35872861
DOI: 10.1155/2022/7742687 -
The Cochrane Database of Systematic... Feb 2023Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anaemia in people with chronic kidney disease (CKD). However, their use has been associated with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Erythropoiesis-stimulating agents (ESAs) are commonly used to treat anaemia in people with chronic kidney disease (CKD). However, their use has been associated with cardiovascular events. This is an update of a Cochrane review first published in 2014.
OBJECTIVES
To compare the efficacy and safety of ESAs (epoetin alfa, epoetin beta, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, and biosimilar ESAs against each other, placebo, or no treatment) to treat anaemia in adults with CKD.
SEARCH METHODS
In this update, we searched the Cochrane Kidney and Transplant Register of Studies up to 29 April 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that included a comparison of an ESA (epoetin alfa, epoetin beta, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, a biosimilar epoetin or a biosimilar darbepoetin alfa) with another ESA, placebo or no treatment in adults with CKD were considered for inclusion.
DATA COLLECTION AND ANALYSIS
Two independent authors screened the search results and extracted data. Data synthesis was performed using random-effects pairwise meta-analysis (expressed as odds ratios (OR) and their 95% confidence intervals (CI)) and network meta-analysis. We assessed for heterogeneity and inconsistency within meta-analyses using standard techniques and planned subgroup and meta-regression to explore sources of heterogeneity or inconsistency. We assessed certainty in treatment estimates for the primary outcomes (preventing blood transfusions and death (any cause)) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Sixty-two new studies (9237 participants) were included in this update, so the review now includes 117 studies with 25,237 participants. Most studies were at high or unclear risk of bias in most methodological domains. Overall, results remain similar in this update compared to our previous review in 2014. For preventing blood transfusion, epoetin alfa (OR 0.28, 95% CI 0.13 to 0.61; low certainty evidence) and epoetin beta (OR 0.19, 95% CI 0.08 to 0.47; low certainty evidence) may be superior to placebo, and darbepoetin alfa was probably superior to placebo (OR 0.27, 95% CI 0.11 to 0.67; moderate certainty evidence). Methoxy polyethylene glycol-epoetin beta (OR 0.33, 95% CI 0.11 to 1.02; very low certainty evidence), a biosimilar epoetin (OR 0.34, 95% CI 0.11 to 1.03; very low certainty evidence) and a biosimilar darbepoetin alfa (OR 0.37, 95% CI 0.07 to 1.91; very low certainty evidence) had uncertain effects on preventing blood transfusion compared to placebo. The comparative effects of ESAs compared with another ESA on preventing blood transfusions were uncertain, in low to very low certainty evidence. Effects on death (any cause) were uncertain for epoetin alfa (OR 0.79, 95% CI 0.51 to 1.22; low certainty evidence), epoetin beta (OR 0.69, 95% CI 0.40 to 1.20; low certainty evidence), methoxy polyethylene glycol-epoetin beta (OR 1.07, 95% CI 0.67 to 1.71; very low certainty evidence), a biosimilar epoetin (OR 0.80, 95% CI 0.47 to 1.36; low certainty evidence) and a biosimilar darbepoetin alfa (OR 1.63, 95% CI 0.51 to 5.23; very low certainty evidence) compared to placebo. There was probably no difference between darbepoetin alfa and placebo on the odds of death (any cause) (OR 0.99, 95% CI 0.81 to 1.21; moderate certainty evidence). The comparative effects of ESAs compared with another ESA on death (any cause) were uncertain in low to very low certainty evidence. Epoetin beta probably increased the odds of hypertension when compared to placebo (OR 2.17, 95% CI 1.17 to 4.00; moderate certainty evidence). Compared to placebo, epoetin alfa (OR 2.10, 95% CI 1.22 to 3.59; very low certainty evidence), darbepoetin alfa (OR 1.88, 95% CI 1.12 to 3.14; low certainty evidence) and methoxy polyethylene glycol-epoetin beta (OR 1.98, 95% CI 1.05 to 3.74; low certainty evidence) may increase the odds of hypertension, but a biosimilar epoetin (OR 1.88, 95% CI 0.96 to 3.67; low certainty evidence) and biosimilar darbepoetin alfa (OR 1.98, 95% CI 0.84 to 4.66; low certainty evidence) had uncertain effects on hypertension. The comparative effects of all ESAs compared with another ESA, placebo or no treatment on cardiovascular death, myocardial infarction, stroke, vascular access thrombosis, kidney failure, and breathlessness were uncertain. Network analysis for fatigue was not possible due to sparse data. AUTHORS' CONCLUSIONS: The comparative effects of different ESAs on blood transfusions, death (any cause and cardiovascular), major cardiovascular events, myocardial infarction, stroke, vascular access thrombosis, kidney failure, fatigue and breathlessness were uncertain.
Topics: Adult; Humans; Hematinics; Epoetin Alfa; Darbepoetin alfa; Biosimilar Pharmaceuticals; Network Meta-Analysis; Erythropoiesis; Anemia; Renal Insufficiency, Chronic; Hypertension; Thrombosis; Dyspnea; Myocardial Infarction
PubMed: 36791280
DOI: 10.1002/14651858.CD010590.pub3 -
Frontiers in Endocrinology 2023This study aimed to perform a network meta-analysis to objectively evaluate the efficacy and safety of 10 Glucagon-like peptide-1 receptor agonists (GLP-1RAs) in... (Comparative Study)
Comparative Study Meta-Analysis Review
PURPOSE
This study aimed to perform a network meta-analysis to objectively evaluate the efficacy and safety of 10 Glucagon-like peptide-1 receptor agonists (GLP-1RAs) in combination with metformin that is approved for use worldwide in patients with type 2 diabetes and to provide evidence-based support and reference for the selection of clinical treatment.
METHODS
Three databases (PubMed, Embase, and Cochrane Library) were searched from their respective inception until September 30, 2022. Only randomized controlled trials comparing the efficacy and safety of GLP-1RAs for treating type 2 diabetes (T2D) were included. The 10 GLP-1RAs are exenatide (including exenatide twice daily and once weekly), liraglutide, lixisenatide, dulaglutide, PEX168, semaglutide (subcutaneous and oral semaglutide), tirzepatide and albiglutide.
RESULTS
34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA). According to the NMA, tirzepatide 15 mg, semaglutide 1.0 mg, PEX168-200μg, oral semaglutide 14 and dulaglutide 1.5 mg reduced HbA1c by -2.23%, -1.57%, -1.12%, -1.10%, -1.09% and body weight by -11.33 kg, -5.99 kg, +0.40 kg, -3.95 kg, -1.87 kg, respectively. There was no significant difference in the rate of adverse events for tirzepatide 15 mg, oral-semaglutide 14 mg, and semaglutide 1.0 mg. PEX168-200μg, tirzepatide 15mg, and oral semaglutide 14mg had Surface Under the Cumulative Ranking (SUCRA) values greater than placebo, and only tirzepatide 15mg and oral semaglutide 14mg were significantly different from placebo in the rate of serious adverse events. All GLP-1RA did not lead to increased incidence of hypoglycemia. Albiglutide 30mg and semaglutide 1.0mg significantly differed from placebo in Adverse Event (AE) withdrawal. Finally, the sensitivity analysis and publication bias analysis results indicate that the study results are reliable.
CONCLUSION
This study's results showed that GLP-1RAs were effective in lowering HbA1c and reducing body weight without increased incidence of hypoglycemic reactions. In addition, this study may provide reference and evidence-based medical evidence for clinicians to select GLP-1RAs in patients with T2D and high body mass index (BMI). Based on the NMA results, tirzepatide 15mg and semaglutide 1.0mg may be preferred.
Topics: Humans; Body Weight; Diabetes Mellitus, Type 2; Exenatide; Glucagon-Like Peptide-1 Receptor; Glycated Hemoglobin; Metformin
PubMed: 37701904
DOI: 10.3389/fendo.2023.1244432 -
The Saudi Dental Journal Nov 2021Fracture resistance of endodontically treated tooth is affected due to large cavity designs and access cavities and an appropriate material capable to resist fracture... (Review)
Review
BACKGROUND
Fracture resistance of endodontically treated tooth is affected due to large cavity designs and access cavities and an appropriate material capable to resist fracture plays an important role. This review aims to evaluate the effect of fibre-reinforced composite (FRC) as a post-obturation material on fracture resistance of endodontically treated teeth.
OBJECTIVES
To systematically gather and evaluate the fracture resistance of fibre-reinforced composite as a post-obturation restorative material in endodontically treated teeth.
DATA SOURCES
A systematic search was conducted using PubMed, Ebsco Host, Scopus, Google Scholar, Hinari and manual search library resources from 1st Jan 2000 to 30th November 2019 to identify appropriate studies.
RESULT
A total of 157 articles were examined out of which 55 articles were selected after reading the title. After removing the duplicates, 27 articles were screened for abstract and 1 article was eliminated as it did not meet the eligibility criteria. A thorough reading of the full text of the remaining 26 selected articles was assessed for eligibility. Amongst these, 1 article was then excluded from the study as the full text was not accessible. Lastly, 25 articles were included in the study.
CONCLUSION
FRC as a core material increases fracture resistance of endodontically treated teeth but they do not have the fracture resistance similar to the intact tooth. Both polyethylene and short fibre-reinforced composites showed greater fracture resistance when compared to glass FRC and restoration without reinforcement. Also, the fracture resistance increases if restored with FRC along with retention slots and are placed on the occlusal third surfaces of cavities. Also, favourable fractures were most commonly seen and it usually occurred at the level of enamel and dentin and adhesive fractures were seen.
PubMed: 34803275
DOI: 10.1016/j.sdentj.2021.07.006 -
Journal of the American Association of... Sep 2022Chronic constipation is a common gastrointestinal condition, and most individuals self-treat with multiple over-the-counter (OTC) laxatives prior to consulting a health...
Chronic constipation is a common gastrointestinal condition, and most individuals self-treat with multiple over-the-counter (OTC) laxatives prior to consulting a health care provider. This brief report is a synopsis of an updated systematic review the authors conducted of published data on the efficacy and safety of OTC treatments to provide evidence-based recommendations. After applying the selection criteria, 41 randomized controlled clinical trials of ≥ 4-week duration were identified and analyzed. Standardized definitions of constipation were applied across these studies; however, definitions for stool frequency and consistency varied. Overall, the short- and long-term efficacy of polyethylene glycol-based preparations and senna were supported by good (grade A) evidence suggesting their use as first-line laxatives. Modest evidence (grade B) supported the use of other agents including the stimulants bisacodyl and sodium picosulfate, fiber, fruit-based laxatives, and magnesium oxide. Additional evidence from rigorously designed studies is needed to support the use of other options for chronic constipation. The OTC products studied were generally well tolerated with common adverse effects being abdominal pain, cramping, bloating, diarrhea, and nausea.
Topics: Constipation; Dietary Fiber; Humans; Laxatives; Nonprescription Drugs; Polyethylene Glycols; Treatment Outcome
PubMed: 35943487
DOI: 10.1097/JXX.0000000000000760 -
Frontiers in Immunology 2023Cytokines are pivotal mediators of cell communication in the tumor microenvironment. Multiple cytokines are involved in the host antitumor response, but the production... (Review)
Review
Cytokines are pivotal mediators of cell communication in the tumor microenvironment. Multiple cytokines are involved in the host antitumor response, but the production and function of these cytokines are usually dysregulated during malignant tumor progression. Considering their clinical potential and the early successful use of cytokines in cancer immunotherapy, such as interferon alpha-2b (IFNα-2b; IntronA) and IL-2 (Proleukin), cytokine-based therapeutics have been extensively evaluated in many follow-up clinical trials. Following these initial breakthroughs, however, clinical translation of these natural messenger molecules has been greatly limited owing to their high-degree pleiotropic features and complex biological properties in many cell types. These characteristics, coupled with poor pharmacokinetics (a short half-life), have hampered the delivery of cytokines via systemic administration, particularly because of severe dose-limiting toxicities. New engineering approaches have been developed to widen the therapeutic window, prolong pharmacokinetic effects, enhance tumor targeting and reduce adverse effects, thereby improving therapeutic efficacy. In this review, we focus on the recent progress and competitive landscape in cytokine engineering strategies and preclinical/clinical therapeutics for cancer. In addition, aiming to promote engineered cytokine-based cancer immunotherapy, we present a profound discussion about the feasibility of recently developed methods in clinical medicine translation.
Topics: Humans; Cytokines; Neoplasms; Immunotherapy; Tumor Microenvironment
PubMed: 37483629
DOI: 10.3389/fimmu.2023.1218082