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Journal of Parkinson's Disease 2021Long-term physiotherapy is acknowledged to be crucial to manage motor symptoms for Parkinson's disease (PD) patients, but its effectiveness is not well understood. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Long-term physiotherapy is acknowledged to be crucial to manage motor symptoms for Parkinson's disease (PD) patients, but its effectiveness is not well understood.
OBJECTIVE
This systematic review and meta-analysis aimed to assess the evidence regarding the effectiveness of long-term physiotherapy to improve motor symptoms and reduce antiparkinsonian medication dose in PD patients.
METHODS
Pubmed, Cochrane, PEDro, and CINAHL were searched for randomized controlled trials before August 31, 2020 that investigated the effectiveness of physiotherapy for 6 months or longer on motor symptoms and levodopa-equivalent dose (LED) in PD patients with Hoehn and Yahr stage 1- 3. We performed random effects meta-analyses for long-term physiotherapy versus no/control intervention and estimated standard mean differences with 95% confidence intervals (CIs). Levels of evidence were rated by the Grading of Recommendation Assessment, Development and Evaluation approach.
RESULTS
From 2,940 studies, 10 studies involving 663 PD patients were assessed. Long-term physiotherapy had favorable effects on motor symptoms in off medication state [- 0.65, 95% CI - 1.04 to - 0.26, p = 0.001] and LED [- 0.49, 95% CI - 0.89to - 0.09, p = 0.02]. Subgroup analyses demonstrated favorable effects on motor symptoms in off medication state by aerobic exercise [- 0.42, 95% CI - 0.64 to - 0.20, p < 0.001] and LED by multidisciplinary rehabilitation of primarily physiotherapy [- 1.00, 95% CI - 1.44 to - 0.56, p < 0.001]. Quality of evidence for aerobic exercise and multidisciplinary rehabilitation were low and very low.
CONCLUSION
This review provided evidence that long-term physiotherapy has beneficial impact on motor symptoms and antiparkinsonian medication dose in PD patients and could motivate implementation of long-term physiotherapy.
Topics: Antiparkinson Agents; Humans; Levodopa; Parkinson Disease; Physical Therapy Modalities
PubMed: 34366377
DOI: 10.3233/JPD-212782 -
The Cochrane Database of Systematic... Apr 2012Ingrowing toenails are a common problem in which part of the nail penetrates the skinfold alongside the nail, creating a painful area. Different non-surgical and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ingrowing toenails are a common problem in which part of the nail penetrates the skinfold alongside the nail, creating a painful area. Different non-surgical and surgical interventions for ingrowing toenails are available, but there is no consensus about a standard first-choice treatment.
OBJECTIVES
To evaluate the effects of non-surgical and surgical interventions in a medical setting for ingrowing toenails, with the aim of relieving symptoms and preventing regrowth of the nail edge or recurrence of the ingrowing toenail.
SEARCH METHODS
We updated our searches of the following databases to January 2010: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE, and EMBASE. We also updated our searches of CINAHL, WEB of SCIENCE, ongoing trials databases, and reference lists of articles.
SELECTION CRITERIA
Randomised controlled trials of non-surgical and surgical interventions for ingrowing toenails, which are also known by the terms 'unguis incarnatus' and 'onychocryptosis', and those comparing postoperative treatment options. Studies must have had a follow-up period of at least one month.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We analysed outcomes as risk ratios (RR) with 95% confidence intervals (CI).
MAIN RESULTS
This is an update of the Cochrane review 'Surgical treatments for ingrowing toenails'. In this update we included 24 studies, with a total of 2826 participants (of which 7 were also included in the previous review). Five studies were on non-surgical interventions, and 19 were on surgical interventions.The risk of bias of each included study was assessed; this is a measure of the methodological quality of several characteristics in these studies. It was found to be unclear for several items, due to incomplete reporting. Participants were not blinded to the treatment they received because of the nature of the interventions, e.g. surgery or wearing a brace on the toe. Outcome assessors were reported to be blinded in only 9 of the 24 studies.None of the included studies addressed our primary outcomes of 'relief of symptoms' or 'regrowth', but 16 did address 'recurrence'. Not all of the included studies addressed all of our secondary outcomes (healing time, postoperative complications - infection and haemorrhage, pain of operation/postoperative pain, participant satisfaction), and two studies did not address any of the secondary outcomes.Surgical interventions were better at preventing recurrence than non-surgical interventions with gutter treatment (or gutter removal), and they were probably better than non-surgical treatments with orthonyxia (brace treatment).In 4 of the 12 studies in which a surgical intervention with chemical ablation (e.g. phenol) was compared with a surgical intervention without chemical ablation, a significant reduction of recurrence was found. The surgical interventions on both sides in these comparisons were not equal, so it is not clear if the reduction was caused by the addition of the chemical ablation.In only one study, a comparison was made of a surgical intervention known as partial nail avulsion with matrix excision compared to the same surgical intervention with phenol. In this study of 117 participants, the surgical intervention with phenol was significantly more effective in preventing recurrence than the surgical intervention alone (14% compared to 41% respectively, RR 0.34, 95% CI 0.17 to 0.69).None of the postoperative interventions described, such as the use of antibiotics or manuka honey; povidone-iodine with paraffin; hydrogel with paraffin; or paraffin gauze, showed any significant difference when looking at infection rates, pain, or healing time.
AUTHORS' CONCLUSIONS
Surgical interventions are more effective than non-surgical interventions in preventing the recurrence of an ingrowing toenail.In the studies comparing a surgical intervention to a surgical intervention with the application of phenol, the addition of phenol is probably more effective in preventing recurrence and regrowth of the ingrowing toenail. Because there is only one study in which the surgical interventions in both study arms were equal, more studies have to be done to confirm these outcomes.Postoperative interventions do not decrease the risk of postoperative infection, postoperative pain, or healing time.
Topics: Combined Modality Therapy; Humans; Nails, Ingrown; Phenol; Postoperative Care; Randomized Controlled Trials as Topic; Secondary Prevention; Toes
PubMed: 22513901
DOI: 10.1002/14651858.CD001541.pub3 -
The Cochrane Database of Systematic... Apr 2018Scabies is an intensely itchy parasitic infection of the skin. It occurs worldwide, but is particularly problematic in areas of poor sanitation, overcrowding, and social... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Scabies is an intensely itchy parasitic infection of the skin. It occurs worldwide, but is particularly problematic in areas of poor sanitation, overcrowding, and social disruption. In recent years, permethrin and ivermectin have become the most relevant treatment options for scabies.
OBJECTIVES
To assess the efficacy and safety of topical permethrin and topical or systemic ivermectin for scabies in people of all ages.
SEARCH METHODS
We searched the following databases up to 25 April 2017: the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and IndMED. We searched the World Health Organization International Clinical Trials Registry Platform, the ISRCTN registry, CenterWatch Clinical Trials Listing, ClinicalTrials.gov, TrialsCentral, and the UK Department of Health National Research Register for ongoing trials. We also searched multiple sources for grey literature and checked reference lists of included studies for additional trials.
SELECTION CRITERIA
We included randomized controlled trials that compared permethrin or ivermectin against each other for people with scabies of all ages and either sex.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the identified records, extracted data, and assessed the risk of bias for the included trials.The primary outcome was complete clearance of scabies. Secondary outcomes were number of participants re-treated, number of participants with at least one adverse event, and number of participants withdrawn from study due to an adverse event.We summarized dichotomous outcomes using risk ratios (RR) with 95% confidence intervals (CI). If it was not possible to calculate the point estimate, we described the data qualitatively. Where appropriate, we calculated combined effect estimates using a random-effects model and assessed heterogeneity. We calculated numbers needed to treat for an additional beneficial outcome when we found a difference.We assessed the certainty of the evidence using the GRADE approach. We used the control rate average to provide illustrative clearance rates in the comparison groups.
MAIN RESULTS
Fifteen studies (1896 participants) comparing topical permethrin, systemic ivermectin, or topical ivermectin met the inclusion criteria. Overall, the risk of bias in the included trials was moderate: reporting in many studies was poor. Nearly all studies were conducted in South Asia or North Africa, where the disease is more common, and is associated with poverty.EfficacyOral ivermectin (at a standard dose of 200 μg/kg) may lead to slightly lower rates of complete clearance after one week compared to permethrin 5% cream. Using the average clearance rate of 65% in the trials with permethrin, the illustrative clearance with ivermectin is 43% (RR 0.65, 95% CI 0.54 to 0.78; 613 participants, 6 studies; low-certainty evidence). However, by week two there may be little or no difference (illustrative clearance of permethrin 74% compared to ivermectin 68%; RR 0.91, 95% CI 0.76 to 1.08; 459 participants, 5 studies; low-certainty evidence). Treatments with one to three doses of ivermectin or one to three applications of permethrin may lead to little or no difference in rates of complete clearance after four weeks' follow-up (illustrative cures with 1 to 3 applications of permethrin 93% and with 1 to 3 doses of ivermectin 86%; RR 0.92, 95% CI 0.82 to 1.03; 581 participants, 5 studies; low-certainty evidence).After one week of treatment with oral ivermectin at a standard dose of 200 μg/kg or one application of permethrin 5% lotion, there is probably little or no difference in complete clearance rates (illustrative cure rates: permethrin 73%, ivermectin 68%; RR 0.93, 95% CI 0.74 to 1.17; 120 participants, 1 study; moderate-certainty evidence). After two weeks of treatment, one dose of systemic ivermectin compared to one application of permethrin lotion may lead to similar complete clearance rates (extrapolated cure rates: 67% in both groups; RR 1.00, 95% CI 0.78 to 1.29; 120 participants, 1 study; low-certainty evidence).There is probably little or no difference in rates of complete clearance between systemic ivermectin at standard dose and topical ivermectin 1% lotion four weeks after initiation of treatment (illustrative cure rates: oral ivermectin 97%, ivermectin lotion 96%; RR 0.99, 95% CI 0.95 to 1.03; 272 participants, 2 studies; moderate-certainty evidence). Likewise, after four weeks, ivermectin lotion probably leads to little or no difference in rates of complete clearance when compared to permethrin cream (extrapolated cure rates: permethrin cream 94%, ivermectin lotion 96%; RR 1.02, 95% CI 0.96 to 1.08; 210 participants, 1 study; moderate-certainty evidence), and there is little or no difference among systemic ivermectin in different doses (extrapolated cure rates: 2 doses 90%, 1 dose 87%; RR 0.97, 95% CI 0.83 to 1.14; 80 participants, 1 study; high-certainty evidence).SafetyReporting of adverse events in the included studies was suboptimal. No withdrawals due to adverse events occurred in either the systemic ivermectin or the permethrin group (moderate-certainty evidence). Two weeks after treatment initiation, there is probably little or no difference in the proportion of participants treated with systemic ivermectin or permethrin cream who experienced at least one adverse event (55 participants, 1 study; moderate-certainty evidence). After four weeks, ivermectin may lead to a slightly larger proportion of participants with at least one adverse event (extrapolated rates: permethrin 4%, ivermectin 5%; RR 1.30, 95% CI 0.35 to 4.83; 502 participants, 4 studies; low-certainty evidence).Adverse events in participants treated with topical ivermectin were rare and of mild intensity and comparable to those with systemic ivermectin. For this comparison, it is uncertain whether there is any difference in the number of participants with at least one adverse event (very low-certainty evidence). No withdrawals due to adverse events occurred (62 participants, 1 study; moderate-certainty evidence).It is uncertain whether topical ivermectin or permethrin differ in the number of participants with at least one adverse event (very low-certainty evidence). We found no studies comparing systemic ivermectin in different doses that assessed safety outcomes.
AUTHORS' CONCLUSIONS
We found that for the most part, there was no difference detected in the efficacy of permethrin compared to systemic or topical ivermectin. Overall, few and mild adverse events were reported. Our confidence in the effect estimates was mostly low to moderate. Poor reporting is a major limitation.
Topics: Administration, Oral; Administration, Topical; Antiparasitic Agents; Humans; Ivermectin; Permethrin; Randomized Controlled Trials as Topic; Scabies; Treatment Outcome
PubMed: 29608022
DOI: 10.1002/14651858.CD012994 -
British Journal of Sports Medicine May 2018To compare the efficacy and safety of topical non-steroidal anti-inflammatory drugs (NSAIDs), including salicylate, for the treatment of osteoarthritis (OA). (Meta-Analysis)
Meta-Analysis Review
Relative efficacy and safety of topical non-steroidal anti-inflammatory drugs for osteoarthritis: a systematic review and network meta-analysis of randomised controlled trials and observational studies.
OBJECTIVES
To compare the efficacy and safety of topical non-steroidal anti-inflammatory drugs (NSAIDs), including salicylate, for the treatment of osteoarthritis (OA).
METHODS
PubMed, Embase, Cochrane Library and Web of Science were searched from 1966 to January 2017. Randomised controlled trials (RCTs) comparing topical NSAIDs with placebo or each other in patients with OA and observational studies comparing topical NSAIDs with no treatment or each other irrespective of disease were included. Two investigators identified studies and independently extracted data. Bayesian network and conventional meta-analyses were conducted. The primary outcomes were pain relief for RCTs and risk of adverse effects (AEs) for observational studies.
RESULTS
43 studies, comprising 36 RCTs (7 900 patients with OA) and seven observational studies (218 074 participants), were included. Overall, topical NSAIDs were superior to placebo for relieving pain (standardised mean difference (SMD)=-0.30, 95% CI -0.40 to -0.20) and improving function (SMD=-0.35, 95% CI -0.45 to -0.24) in OA. Of all topical NSAIDs, diclofenac patches were most effective for OA pain (SMD=-0.81, 95% CI -1.12 to -0.52) and piroxicam was most effective for functional improvement (SMD=-1.04, 95% CI -1.60 to -0.48) compared with placebo. Although salicylate gel was associated with higher withdrawal rates due to AEs, the remaining topical NSAIDs were not associated with any increased local or systemic AEs.
CONCLUSIONS
Topical NSAIDs were effective and safe for OA. Diclofenac patches may be the most effective topical NSAID for pain relief. No serious gastrointestinal and renal AEs were observed in trials or the general population. However, confirmation of the cardiovascular safety of topical NSAIDs still warrants further observational study.
Topics: Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal; Bayes Theorem; Humans; Network Meta-Analysis; Osteoarthritis; Pain; Randomized Controlled Trials as Topic; Salicylates; Transdermal Patch
PubMed: 29436380
DOI: 10.1136/bjsports-2017-098043 -
The Cochrane Database of Systematic... Jul 2017Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their... (Review)
Review
BACKGROUND
Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their quality of life. Opioid (morphine-like) drugs are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. The most commonly-used opioid drugs are buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, tramadol, and tapentadol.
OBJECTIVES
To provide an overview of the analgesic efficacy of opioids in cancer pain, and to report on adverse events associated with their use.
METHODS
We identified systematic reviews examining any opioid for cancer pain published to 4 May 2017 in the Cochrane Database of Systematic Reviews in the Cochrane Library. The primary outcomes were no or mild pain within 14 days of starting treatment, withdrawals due to adverse events, and serious adverse events.
MAIN RESULTS
We included nine reviews with 152 included studies and 13,524 participants, but because some studies appeared in more than one review the number of unique studies and participants was smaller than this. Most participants had moderate or severe pain associated with a range of different types of cancer. Studies in the reviews typically compared one type of opioid or formulation with either a different formulation of the same opioid, or a different opioid; few included a placebo control. Typically the reviews titrated dose to effect, a balance between pain relief and adverse events. Various routes of administration of opioids were considered in the reviews; oral with most opioids, but transdermal administration with fentanyl, and buprenorphine. No review included studies of subcutaneous opioid administration. Pain outcomes reported were varied and inconsistent. The average size of included studies varied considerably between reviews: studies of older opioids, such as codeine, morphine, and methadone, had low average study sizes while those involving newer drugs tended to have larger study sizes.Six reviews reported a GRADE assessment (buprenorphine, codeine, hydromorphone, methadone, oxycodone, and tramadol), but not necessarily for all comparisons or outcomes. No comparative analyses were possible because there was no consistent placebo or active control. Cohort outcomes for opioids are therefore reported, as absolute numbers or percentages, or both.Reviews on buprenorphine, codeine with or without paracetamol, hydromorphone, methadone, tramadol with or without paracetamol, tapentadol, and oxycodone did not have information about the primary outcome of mild or no pain at 14 days, although that on oxycodone indicated that average pain scores were within that range. Two reviews, on oral morphine and transdermal fentanyl, reported that 96% of 850 participants achieved that goal.Adverse event withdrawal was reported by five reviews, at rates of between 6% and 19%. Participants with at least one adverse event were reported by three reviews, at rates of between 11% and 77%.Our GRADE assessment of evidence quality was very low for all outcomes, because many studies in the reviews were at high risk of bias from several sources, including small study size.
AUTHORS' CONCLUSIONS
The amount and quality of evidence around the use of opioids for treating cancer pain is disappointingly low, although the evidence we have indicates that around 19 out of 20 people with moderate or severe pain who are given opioids and can tolerate them should have that pain reduced to mild or no pain within 14 days. This accords with the clinical experience in treating many people with cancer pain, but overstates to some extent the effectiveness found for the WHO pain ladder. Most people will experience adverse events, and help may be needed to manage the more common undesirable adverse effects such as constipation and nausea. Perhaps between 1 in 10 and 2 in 10 people treated with opioids will find these adverse events intolerable, leading to a change in treatment.
Topics: Acetaminophen; Administration, Cutaneous; Administration, Oral; Analgesics, Opioid; Buprenorphine; Cancer Pain; Codeine; Fentanyl; Humans; Hydromorphone; Methadone; Oxycodone; Phenols; Review Literature as Topic; Tapentadol; Tramadol
PubMed: 28683172
DOI: 10.1002/14651858.CD012592.pub2 -
Dental and Medical Problems 2020Burning mouth syndrome (BMS) is idiopathic chronic oral pain, associated with depression, anxiety and pain symptoms. The BMS symptoms include a burning sensation in the...
Burning mouth syndrome (BMS) is idiopathic chronic oral pain, associated with depression, anxiety and pain symptoms. The BMS symptoms include a burning sensation in the tongue and/or other oral mucosa with no underlying medical or dental reasons. As many BMS patients suffer from psychiatric comorbidities, several psychotropic drugs are included in the management of BMS, reducing the complaint, while managing anxiety, depression and pain disorders. In this review, a search of the published literature regarding the management of BMS was conducted. We discuss the BMS etiology, clinically associated symptoms and available treatment options. The current evidence supports some BMS interventions, including alpha-lipoic acid (ALA), clonazepam, capsaicin, and low-level laser therapy (LLLT); however, there is a lack of robust scientific evidence, and large-scale clinical trials with long follow-up periods are needed to establish the role of these BMS management options. This knowledge could raise the awareness of dentists, psychiatrists and general practitioners about these challenges and the available kinds of treatment to improve multidisciplinary management for better health outcomes.
Topics: Burning Mouth Syndrome; Capsaicin; Clonazepam; Humans; Low-Level Light Therapy; Pain
PubMed: 33113291
DOI: 10.17219/dmp/120991 -
Frontiers in Immunology 2022Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dietary polyphenol treatment of non-alcoholic fatty liver disease (NAFLD) is a novel direction, and the existing clinical studies have little effective evidence for its therapeutic effect, and some studies have inconsistent results. The effectiveness of dietary polyphenols in the treatment of NAFLD is still controversial. The aim of this study was to evaluate the therapeutic efficacy of oral dietary polyphenols in patients with NAFLD.
METHODS
The literature (both Chinese and English) published before 30 April 2022 in PubMed, Cochrane, Medline, CNKI, and other databases on the treatment of NAFLD with dietary polyphenols was searched. Manual screening, quality assessment, and data extraction of search results were conducted strictly according to the inclusion and exclusion criteria. RevMan 5.3 software was used to perform the meta-analysis.
RESULTS
The RCTs included in this study involved dietary supplementation with eight polyphenols (curcumin, resveratrol, naringenin, anthocyanin, hesperidin, catechin, silymarin, and genistein) and 2,173 participants. This systematic review and meta-analysis found that 1) curcumin may decrease body mass index (BMI), Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Triglycerides (TG) total cholesterol (TC), and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) compared to placebo; and curcumin does not increase the occurrence of adverse events. 2) Although the meta-analysis results of all randomized controlled trials (RCTs) did not reveal significant positive changes, individual RCTs showed meaningful results. 3) Naringenin significantly decreased the percentage of NAFLD grade, TG, TC, and low-density lipoprotein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C) but had no significant effect on AST and ALT, and it is a safe supplementation. 4) Only one team presents a protocol about anthocyanin (from L. fruit extract) in the treatment of NAFLD. 5) Hesperidin may decrease BMI, AST, ALT, TG, TC, HOMA-IR, and so on. 6) Catechin may decrease BMI, HOMA-IR, and TG level, and it was well tolerated by the patients. 7) Silymarin was effective in improving ALT and AST and reducing hepatic fat accumulation and liver stiffness in NAFLD patients.
CONCLUSION
Based on current evidence, curcumin can reduce BMI, TG, TC, liver enzymes, and insulin resistance; catechin can reduce BMI, insulin resistance, and TG effectively; silymarin can reduce liver enzymes. For resveratrol, naringenin, anthocyanin, hesperidin, and catechin, more RCTs are needed to further evaluate their efficacy and safety.
Topics: Alanine Transaminase; Anthocyanins; Aspartate Aminotransferases; Catechin; Cholesterol, HDL; Cholesterol, LDL; Curcumin; Dietary Supplements; Genistein; Hesperidin; Humans; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Plant Extracts; Polyphenols; Resveratrol; Silymarin; Triglycerides
PubMed: 36159792
DOI: 10.3389/fimmu.2022.949746 -
Nutrients Jul 2018Oxidative stress has been considered a key causing factor of liver damage induced by a variety of agents, including alcohol, drugs, viral infections, environmental... (Review)
Review
Oxidative stress has been considered a key causing factor of liver damage induced by a variety of agents, including alcohol, drugs, viral infections, environmental pollutants and dietary components, which in turn results in progression of liver injury, non-alcoholic steatohepatitis, non-alcoholic liver disease, liver fibrosis and cirrhosis. During the past 30 years and even after the major progress in the liver disease management, millions of people worldwide still suffer from an acute or chronic liver condition. Curcumin is one of the most commonly used indigenous molecules endowed by various shielding functionalities that protects the liver. The aim of the present study is to comprehensively review pharmacological effects and molecular mechanisms, as well as clinical evidence, of curcumin as a lead compound in the prevention and treatment of oxidative associated liver diseases. For this purpose, electronic databases including “Scopus,” “PubMed,” “Science Direct” and “Cochrane library” were extensively searched with the keywords “curcumin or curcuminoids” and “hepatoprotective or hepatotoxicity or liver” along with “oxidative or oxidant.” Results showed that curcumin exerts remarkable protective and therapeutic effects of oxidative associated liver diseases through various cellular and molecular mechanisms. Those mechanisms include suppressing the proinflammatory cytokines, lipid perodixation products, PI3K/Akt and hepatic stellate cells activation, as well as ameliorating cellular responses to oxidative stress such as the expression of Nrf2, SOD, CAT, GSH, GPx and GR. Taking together, curcumin itself acts as a free radical scavenger over the activity of different kinds of ROS via its phenolic, β-diketone and methoxy group. Further clinical studies are still needed in order to recognize the structure-activity relationships and molecular mechanisms of curcumin in oxidative associated liver diseases.
Topics: Animals; Antioxidants; Curcumin; Humans; Liver; Liver Diseases; Oxidative Stress; Signal Transduction
PubMed: 29966389
DOI: 10.3390/nu10070855 -
The Cochrane Database of Systematic... Jul 2016Randomized trials investigating the efficacy of aminosalicylates for the treatment of mildly to moderately active Crohn's disease have yielded conflicting results. A... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Randomized trials investigating the efficacy of aminosalicylates for the treatment of mildly to moderately active Crohn's disease have yielded conflicting results. A systematic review was conducted to critically examine current available data on the efficacy of sulfasalazine and mesalamine for inducing remission or clinical response in these patients.
OBJECTIVES
To evaluate the efficacy of aminosalicylates compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) for the treatment of mildly to moderately active Crohn's disease.
SEARCH METHODS
We searched PubMed, EMBASE, MEDLINE and the Cochrane Central Library from inception to June 2015 to identify relevant studies. There were no language restrictions. We also searched reference lists from potentially relevant papers and review articles, as well as proceedings from annual meetings (1991-2015) of the American Gastroenterological Association and American College of Gastroenterology.
SELECTION CRITERIA
Randomized controlled trials that evaluated the efficacy of sulfasalazine or mesalamine in the treatment of mildly to moderately active Crohn's disease compared to placebo, corticosteroids, and other aminosalicylates (alone or in combination with corticosteroids) were included.
DATA COLLECTION AND ANALYSIS
Data extraction and assessment of methodological quality was independently performed by the investigators and any disagreement was resolved by discussion and consensus. We assessed methodological quality using the Cochrane risk of bias tool. The overall quality of the evidence supporting the outcomes was evaluated using the GRADE criteria. The primary outcome measure was a well defined clinical endpoint of induction of remission or response to treatment. Secondary outcomes included mean Crohn's disease activity index (CDAI) scores, adverse events, serious adverse events and withdrawal due to adverse events. For dichotomous outcomes we calculated the pooled risk ratio (RR) and corresponding 95% confidence interval (CI) using a random-effects model. For continuous outcomes we calculated the mean difference (MD) and 95% CI using a random-effects model. Sensitivity analyses based on a fixed-effect model and duration of therapy were conducted where appropriate.
MAIN RESULTS
Twenty studies (2367 patients) were included. Two studies were judged to be at high risk of bias due to lack of blinding. Eight studies were judged to be at high risk of bias due to incomplete outcomes data (high drop-out rates) and potential selective reporting. The other 10 studies were judged to be at low risk of bias. A non-significant trend in favour of sulfasalazine over placebo for inducing remission was observed, with benefit confined mainly to patients with Crohn's colitis. Forty-five per cent (63/141) of sulfasalazine patients entered remission at 17-18 weeks compared to 29% (43/148) of placebo patients (RR 1.38, 95% CI 1.00 to 1.89, 2 studies). A GRADE analysis rated the overall quality of the evidence supporting this outcome as moderate due to sparse data (106 events). There was no difference between sulfasalazine and placebo in adverse event outcomes. Sulfasalazine was significantly less effective than corticosteroids and inferior to combination therapy with corticosteroids (RR 0.64, 95% CI 0.47 to 0.86, 1 study, 110 patients). Forty-three per cent (55/128) of sulfasalazine patients entered remission at 17 to 18 weeks compared to 60% (79/132) of corticosteroid patients (RR 0.68, 95% CI 0.51 to 0.91; 2 studies, 260 patients). A GRADE analysis rated the overall quality of the evidence supporting this outcome as moderate due to sparse data (134 events). Sulfasalazine patients experienced significantly fewer adverse events than corticosteroid patients (RR 0.43, 95% CI 0.22 to 0.82; 1 study, 159 patients). There was no difference between sulfasalazine and corticosteroids in serious adverse events or withdrawal due to adverse events. Olsalazine was less effective than placebo in a single trial (RR 0.36, 95% CI 0.18 to 0.71; 91 patients). Low dose mesalamine (1 to 2 g/day) was not superior to placebo for induction of remission. Twenty-three per cent (43/185) of low dose mesalamine patients entered remission at week 6 compared to 15% (18/117) of placebo patients (RR = 1.46, 95% CI 0.89 to 2.40; n = 302). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to risk of bias (incomplete outcome data) and sparse data (61 events). There was no difference between low dose mesalamine and placebo in the proportion of patients who had adverse events (RR 1.33, 95% CI 0.91 to 1.96; 3 studies, 342 patients) or withdrew due to adverse events (RR 1.21, 95% CI 0.75 to 1.95; 3 studies, 342 patients). High dose controlled-release mesalamine (4 g/day) was not superior to placebo, inducing a clinically non significant reduction in CDAI (MD -19.8 points, 95% CI -46.2 to 6.7; 3 studies, 615 patients), and was also inferior to budesonide (RR 0.56, 95% CI 0.40 to 0.78; 1 study, 182 patients, GRADE = low). While high dose delayed-release mesalamine (3 to 4.5 g/day) was not superior to placebo for induction of remission (RR 2.02, 95% CI 0.75 to 5.45; 1 study, 38 patients, GRADE = very low), no significant difference in efficacy was found when compared to conventional corticosteroids (RR 1.04, 95% CI 0.79 to 1.36; 3 studies, 178 patients, GRADE = moderate) or budesonide (RR 0.89, 95% CI 0.76 to 1.05; 1 study, 307 patients, GRADE = moderate). However, these trials were limited by risk of bias (incomplete outcome data) and sparse data (small numbers of events). There was a lack of good quality clinical trials comparing sulfasalazine with other mesalamine formulations. Adverse events that were commonly reported included headache, nausea, vomiting, abdominal pain and diarrhea.
AUTHORS' CONCLUSIONS
Sulfasalazine is only modestly effective with a trend towards benefit over placebo and is inferior to corticosteroids for the treatment of mildly to moderately active Crohn's disease. Olsalazine and low dose mesalamine (1 to 2 g/day) are not superior to placebo. High dose mesalamine (3.2 to 4 g/day) is not more effective than placebo for inducing response or remission. However, trials assessing the efficacy of high dose mesalamine (4 to 4.5 g/day) compared to budesonide yielded conflicting results and firm conclusions cannot be made. Future large randomized controlled trials are needed to provide definitive evidence on the efficacy of aminosalicylates in active Crohn's disease.
Topics: Aminosalicylic Acids; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Crohn Disease; Delayed-Action Preparations; Gastrointestinal Agents; Humans; Induction Chemotherapy; Mesalamine; Randomized Controlled Trials as Topic; Sulfasalazine
PubMed: 27372735
DOI: 10.1002/14651858.CD008870.pub2 -
JAMA May 2018Vasopressin is an alternative to catecholamine vasopressors for patients with distributive shock-a condition due to excessive vasodilation, most frequently from severe... (Comparative Study)
Comparative Study Meta-Analysis Review
Association of Vasopressin Plus Catecholamine Vasopressors vs Catecholamines Alone With Atrial Fibrillation in Patients With Distributive Shock: A Systematic Review and Meta-analysis.
IMPORTANCE
Vasopressin is an alternative to catecholamine vasopressors for patients with distributive shock-a condition due to excessive vasodilation, most frequently from severe infection. Blood pressure support with a noncatecholamine vasopressor may reduce stimulation of adrenergic receptors and decrease myocardial oxygen demand. Atrial fibrillation is common with catecholamines and is associated with adverse events, including mortality and increased length of stay (LOS).
OBJECTIVES
To determine whether treatment with vasopressin + catecholamine vasopressors compared with catecholamine vasopressors alone was associated with reductions in the risk of adverse events.
DATA SOURCES
MEDLINE, EMBASE, and CENTRAL were searched from inception to February 2018. Experts were asked and meta-registries searched to identify ongoing trials.
STUDY SELECTION
Pairs of reviewers identified randomized clinical trials comparing vasopressin in combination with catecholamine vasopressors to catecholamines alone for patients with distributive shock.
DATA EXTRACTION AND SYNTHESIS
Two reviewers abstracted data independently. A random-effects model was used to combine data.
MAIN OUTCOMES AND MEASURES
The primary outcome was atrial fibrillation. Other outcomes included mortality, requirement for renal replacement therapy (RRT), myocardial injury, ventricular arrhythmia, stroke, and LOS in the intensive care unit and hospital. Measures of association are reported as risk ratios (RRs) for clinical outcomes and mean differences for LOS.
RESULTS
Twenty-three randomized clinical trials were identified (3088 patients; mean age, 61.1 years [14.2]; women, 45.3%). High-quality evidence supported a lower risk of atrial fibrillation associated with vasopressin treatment (RR, 0.77 [95% CI, 0.67 to 0.88]; risk difference [RD], -0.06 [95% CI, -0.13 to 0.01]). For mortality, the overall RR estimate was 0.89 (95% CI, 0.82 to 0.97; RD, -0.04 [95% CI, -0.07 to 0.00]); however, when limited to trials at low risk of bias, the RR estimate was 0.96 (95% CI, 0.84 to 1.11). The overall RR estimate for RRT was 0.74 (95% CI, 0.51 to 1.08; RD, -0.07 [95% CI, -0.12 to -0.01]). However, in an analysis limited to trials at low risk of bias, RR was 0.70 (95% CI, 0.53 to 0.92, P for interaction = .77). There were no significant differences in the pooled risks for other outcomes.
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, the addition of vasopressin to catecholamine vasopressors compared with catecholamines alone was associated with a lower risk of atrial fibrillation. Findings for secondary outcomes varied.
Topics: Atrial Fibrillation; Catecholamines; Drug Therapy, Combination; Female; Humans; Length of Stay; Male; Publication Bias; Shock; Vasoconstrictor Agents; Vasopressins
PubMed: 29801010
DOI: 10.1001/jama.2018.4528