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Danish Medical Journal Dec 2016Refractory coeliac disease (RCD) is a rare and severe malabsorptive disease. The condition has two subtypes: RCDI and RCDII. Different treatments have been tested: and... (Review)
Review
INTRODUCTION
Refractory coeliac disease (RCD) is a rare and severe malabsorptive disease. The condition has two subtypes: RCDI and RCDII. Different treatments have been tested: and because RCD has a poor prognosis due to progress to enteropathy-associated T-cell lymphoma, the aim was to review the epidemiologic aspects and the therapeutic options for RCD.
METHODS
A systematic literature search was performed in 18 databases, and 122 records were identified. Incidence, prevalence, treatment methods and their efficacy were evaluated.
RESULTS
Among coeliac disease patients, the cumulative incidence of RCD is 1-4% per ten-year period and the prevalence is 0.31-0.38%. In the general population, the prevalence of RCD is 0.002%. Treatment of RCDI is azathioprine (effect 100%), mesalamine (effect 60%) or tioguanine (effect 83%). Treatment for RCDII is the antimetabolite cladribine (effect 81%) and autologous haematopoetic stem cell transplantation (effect 85%).
CONCLUSION
RCD is a very rare disease. The current evidence for RCDI treatment includes prednisolone in combination with the immunosuppressants azathioprine, mesalamine or tioguanine. The current evidence for RCDII treatment documents use of the antimetabolite cladribine, and if there is no effect, autologous haematopoetic stem cell transplantation may be attempted. In the future, there is a need for more effective treatments which will also prevent further progression to enteropathy-associated T-cell lymphoma.
Topics: Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Azathioprine; Celiac Disease; Cladribine; Drug Therapy, Combination; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Incidence; Mesalamine; Prednisolone; Prevalence; Thioguanine
PubMed: 27910801
DOI: No ID Found -
The Cochrane Database of Systematic... Oct 2016Depression is a recurrent illness with high rates of chronicity, treatment-resistance and significant economic impact. There is evidence in the literature that... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Depression is a recurrent illness with high rates of chronicity, treatment-resistance and significant economic impact. There is evidence in the literature that S-adenosyl methionine (SAMe), a naturally occurring compound in the human body, has antidepressant efficacy. This product may be an important addition to the armamentarium of antidepressant agents.
OBJECTIVES
To assess the effects of SAMe in comparison with placebo or antidepressants for the treatment of depression in adults.
SEARCH METHODS
We searched the Cochrane Common Mental Disorders Group's Specialised Register (CCMDCTR Studies and Reference Register), MEDLINE, EMBASE, PsycINFO, international trial registers ClinicalTrials.gov and the World Health Organization trials portal (ICTRP). We checked reference lists, performed handsearching and contacted experts in the field. The CCMDCTR literature search was last updated on 5 February 2016.
SELECTION CRITERIA
Randomised controlled trials comparing SAMe with placebo or antidepressants in adults with a diagnosis of major depression.
DATA COLLECTION AND ANALYSIS
Two authors independently performed extraction of data and assessment of risk of bias. We contacted trialists of included studies for additional information.
MAIN RESULTS
This systematic review included eight trials comparing SAMe with either placebo, imipramine, desipramine or escitalopram. We accepted trials that used SAMe as monotherapy or as add-on therapy to selective serotonin reuptake inhibitors (SSRIs), and we accepted both oral and parenteral administration. The review involved 934 adults, of both sexes, from inpatient and outpatient settings.The trials were at low risk of reporting bias. We judged the risk of selection, performance, detection and attrition bias as unclear or low, and one study was at high risk of attrition bias.There was no strong evidence of a difference in terms of change in depressive symptoms from baseline to end of treatment between SAMe and placebo as monotherapy (standardised mean difference (SMD) -0.54, 95% confidence interval (CI) -1.54 to 0.46; P = 0.29; 142 participants; 2 studies; very low quality evidence). There was also no strong evidence of a difference in terms of drop-out rates due to any reason between SAMe and placebo, when used as monotherapy (risk ratio (RR) 0.88, 95% CI 0.61 to 1.29; P = 0.52; 142 participants; 2 studies; low quality evidence).Low quality evidence showed that the change in depressive symptoms from baseline to end of treatment was similar between SAMe and imipramine, both as monotherapy (SMD -0.04, 95% CI -0.34 to 0.27; P = 0.82; 619 participants; 4 studies). There was also no strong evidence of a difference between SAMe and a tricyclic antidepressant in terms of drop-outs due to any reason (RR 0.61, 95% CI 0.28 to 1.31; P = 0.2; 78 participants; 3 studies; very low quality evidence).There was little evidence of a difference in terms of change in depressive symptoms from baseline to end of treatment between SAMe and escitalopram, both as monotherapy (MD 0.12, 95% CI -2.75 to 2.99; P = 0.93; 129 participants; 1 study; low quality evidence). There was no strong evidence of a difference between SAMe and escitalopram in terms of drop-outs due to any reason (RR 0.81, 95% CI 0.57 to 1.16; P = 0.26; 129 participants; 1 study; low quality evidence).There was low quality evidence that SAMe is superior to placebo as add-on to SSRIs in terms of change in depressive symptoms from baseline to end of treatment (MD -3.90, 95% CI -6.93 to -0.87; P = 0.01; 73 participants; 1 study). There was no strong evidence of a difference between SAMe and placebo as adjunctive therapy to an SSRI in terms of drop-outs due to any reason (RR 0.70, 95% CI 0.31 to 1.56; P = 0.38; 73 participants; 1 study; very low quality evidence).For all comparisons, secondary outcome measures of response and remission rates were consistent with these primary outcome measures.With regard to all extractable measures of the acceptability of SAMe, the quality of the evidence was low to very low. SAMe was not different from placebo and established antidepressants. The exception was that compared to imipramine, fewer participants experienced troublesome adverse effects when treated with parenteral SAMe.The specific adverse effects were not detailed in most of the included studies. There were two reports of mania/hypomania recorded for 441 participants in the SAMe arm.
AUTHORS' CONCLUSIONS
Given the absence of high quality evidence and the inability to draw firm conclusions based on that evidence, the use of SAMe for the treatment of depression in adults should be investigated further. Future trials should be in the form of large randomised controlled clinical trials of high methodological quality, with particular attention given to randomisation, allocation concealment, blinding and the handling of missing data. Comparator antidepressants from all classes should be used. Adverse events should be detailed for each participant, bearing in mind that induction of mania is of particular interest.
Topics: Adult; Aged; Aged, 80 and over; Antidepressive Agents; Citalopram; Depression; Humans; Imipramine; Middle Aged; Randomized Controlled Trials as Topic; S-Adenosylmethionine; Selective Serotonin Reuptake Inhibitors
PubMed: 27727432
DOI: 10.1002/14651858.CD011286.pub2 -
Antioxidants & Redox Signaling Apr 20168-Hydroxy-2-deoxyguanosine (8-OHdG) is generated after the repair of ROS-mediated DNA damages and, thus, is one of the most widely recognized biomarkers of oxidative... (Meta-Analysis)
Meta-Analysis Review
SIGNIFICANCE
8-Hydroxy-2-deoxyguanosine (8-OHdG) is generated after the repair of ROS-mediated DNA damages and, thus, is one of the most widely recognized biomarkers of oxidative damage of DNA because guanosine is the most oxidized among the DNA nucleobases. In several pathological conditions, high urinary levels of oxidized DNA-derived metabolites have been reported (e.g., cancer, atherosclerosis, hypertension, and diabetes).
RECENT ADVANCES
Even if published studies have shown that DNA damage is significantly associated with the development of atherosclerosis, the exact role of this damage in the onset and progression of this pathology is not fully understood, and the association of oxidative damage to DNA with cardiovascular disease (CVD) still needs to be more extensively investigated. We performed a meta-analysis of the literature to investigate the association among 8-OHdG levels and CVD.
CRITICAL ISSUES
Fourteen studies (810 CVD patients and 1106 controls) were included in the analysis. We found that CVD patients showed higher 8-OHdG levels than controls (SMD: 1.04, 95%CI: 0.61, 1.47, p < 0.001, I(2) = 94%, p < 0.001). The difference was confirmed both in studies in which 8-OHdG levels were assessed in urine (MD: 4.43, 95%CI: 1.71, 7.15, p = 0.001) and in blood samples (MD: 1.42, 95%CI: 0.64, 2.21, p = 0.0004). Meta-regression models showed that age, hypertension, and male gender significantly impacted on the difference in 8-OHdG levels among CVD patients and controls.
FUTURE DIRECTIONS
8-OHdG levels are higher in patients with CVD than in controls. However, larger prospective studies are needed to test 8-OHdG as a predictor of CVD.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Deoxyguanosine; Humans; Oxidation-Reduction; Oxidative Stress; Prognosis; Publication Bias; Regression Analysis
PubMed: 26650622
DOI: 10.1089/ars.2015.6508 -
The Cochrane Database of Systematic... Nov 2015The review is withdrawn as it was abandoned and has not been updated since its last edition in 2008. A new team of authors resumed the work on the review, and so far, a... (Meta-Analysis)
Meta-Analysis Review
The review is withdrawn as it was abandoned and has not been updated since its last edition in 2008. A new team of authors resumed the work on the review, and so far, a major update to the protocol is published. The review is expected to be finalised towards the end of 2016. The editorial group responsible for this previously published document have withdrawn it from publication.
Topics: Humans; Liver Diseases, Alcoholic; Randomized Controlled Trials as Topic; S-Adenosylmethionine
PubMed: 26560497
DOI: 10.1002/14651858.CD002235.pub3 -
Biology of Blood and Marrow... Apr 2016Oral mucositis (OM) is a debilitating early adverse effect of allogeneic hematopoietic stem cell transplantation (HSCT). The intensity of the conditioning regimen... (Review)
Review
Oral mucositis (OM) is a debilitating early adverse effect of allogeneic hematopoietic stem cell transplantation (HSCT). The intensity of the conditioning regimen correlates with the incidence and severity of OM, but no studies have analyzed this relationship among various conditioning regimens. We performed a systematic review on the incidence and outcomes of OM in allogeneic HSCT patients and analyzed this association. A comprehensive search of several databases (Ovid Medline In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, Cochrane CRCT, Cochrane DSR, Scopus) from 1990 to 2014 for studies of OM in allogeneic HSCT patients was conducted. Professional societies' meeting abstracts were also searched. Grade of OM was analyzed based on the World Health Organization (WHO) or National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events scales. Severe mucositis was defined as either grades 2 to 4 or grades 3 and 4, depending on the studies' definition of severity. Cohorts were analyzed based on regimen intensity; ie, reduced-intensity conditioning (RIC) (including nonmyeloablative) and myeloablative (MA). Random effect (RE) and standard logistic models weighted by the number of patients in each cohort were used for comparisons. A total of 624 studies were generated from the search. Of the 395 patients in 8 eligible MA regimen studies, 73.2% experienced any OM, whereas in 245 patients in the 6 eligible RIC regimen studies, 86.5% experienced any OM (chi-square P < .0001; RE, P = .05). Severe (grades 2 to 4) OM occurred among 79.7% of the WHO/NCI-graded MA patients and 71.5% of RIC patients (chi-square, P = .0421; RE, P < .01). In comparing graft-versus-host disease (GVHD) prophylaxis, only 55.4% of patients receiving nonmethotrexate regimens experienced OM; this was lower (chi-square, P < .0001; RE, P = .06) than that found among patients who received methotrexate (83.4%), either standard or reduced dose. Besides NCI and WHO grading scales, other scales included in the studies were Oral Mucositis Index, the Southwest Oncology Group Criteria, and Eastern Cooperative Oncology Group scale. To our knowledge, this is the first analysis on OM in allogeneic HSCT patients with respect to conditioning regimens, and we observed that RIC regimens led to a high incidence of OM similar to that of MA regimens. Clinical trials on treatment of OM are lacking, emphasizing the essential need for prospective studies in this arena. A significant variance in the criteria for grading OM underscores the importance of establishing a standard grading system for OM measurement in future allogeneic HSCT clinical trials.
Topics: Busulfan; Cyclophosphamide; Graft vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Methotrexate; Mouth Mucosa; Myeloablative Agonists; Severity of Illness Index; Stomatitis; Transplantation Conditioning; Transplantation, Homologous; Vidarabine
PubMed: 26409924
DOI: 10.1016/j.bbmt.2015.09.014 -
The Cochrane Database of Systematic... May 2015Primary percutaneous coronary intervention (PPCI) is the preferred treatment for ST-segment elevation myocardial infarction. Although coronary flow is restored after... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Primary percutaneous coronary intervention (PPCI) is the preferred treatment for ST-segment elevation myocardial infarction. Although coronary flow is restored after PPCI, impaired myocardial perfusion (known as no-reflow) related to poor clinical outcomes is frequently observed. To overcome this phenomenon, drugs, such as atorvastatin, abciximab and others, have been tried as adjunctive treatment to PPCI. Among these drugs, verapamil and adenosine are among the most promising. No other systematic reviews have examined use of these two drugs in people with acute myocardial infarction (AMI) undergoing PPCI. This is an update of the version previously published (2013, Issue 6), for which the people of interest in the review were those treated with PPCI - not those given fibrinolytic therapy.
OBJECTIVES
To study the impact of adenosine and verapamil on no-reflow during PPCI in people with AMI.
SEARCH METHODS
We updated searches of the following databases in June 2014 without language restriction: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science and BIOSIS, China National Knowledge Infrastructure and clinical trials registers (ClinicalTrials.gov, Current Controlled Trials, Australian and New Zealand Clinical Trials Registry, the World Health Organization (WHO) International Clinical Trials Registry Platform). We also handsearched The American Journal of Cardiology.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) in which adenosine or verapamil was the primary intervention. Participants were individuals diagnosed with AMI who were undergoing PPCI.
DATA COLLECTION AND ANALYSIS
Two review authors collected studies and extracted data. When necessary, we contacted trial authors to obtain relevant information. We calculated risk ratios (RRs), P values and 95% confidence intervals (CIs) of dichotomous data.
MAIN RESULTS
We included in our review 11 RCTs (one new study with 59 participants) involving 1027 participants. Ten RCTs were associated with adenosine and one with verapamil. We considered the overall risk of bias of included studies to be moderate. We found no evidence that adenosine reduced short-term all-cause mortality (RR 0.61, 95% CI 0.25 to 1.48, P value = 0.27), long-term all-cause mortality (RR 0.78, 95% CI 0.22 to 2.74, P value = 0.70), short-term non-fatal myocardial infarction (RR 1.32, 95% 0.33 to 5.29, P value = 0.69) or myocardial blush grade (MBG) 0 to 1 after PPCI (RR 0.96, 95% CI 0.76 to 1.22, P value = 0.75). The incidence of thrombolysis in myocardial infarction (TIMI) flow grade < 3 after PPCI (RR 0.62, 95% CI 0.42 to 0.91, P value = 0.01) was decreased. Conversely, adverse events with adenosine, such as bradycardia (RR 6.32, 95% CI 2.98 to 13.41, P value < 0.00001), hypotension (RR 11.43, 95% CI 2.75 to 47.57, P value = 0.0008) and atrioventricular (AV) block (RR 6.78, 95% CI 2.15 to 21.38, P value = 0.001), were significantly increased.Meta-analysis of verapamil as treatment for no-reflow during PPCI was not performed because data were insufficient.
AUTHORS' CONCLUSIONS
It is difficult to draw conclusions because of the insufficient quality and quantity of current research studies. We considered the overall risk of bias of included studies to be moderate. Adenosine as treatment for no-reflow during PPCI could reduce angiographic no-reflow (TIMI flow grade < 3) but was found to increase adverse events. What's more, no evidence could be found to suggest that adenosine reduced all-cause mortality, non-fatal myocardial infarction or the incidence of myocardial blush grade 0 to 1. Additionally, the efficacy of verapamil for no-reflow during PPCI could not be analysed because data were insufficient. Further clinical research into adenosine and verapamil is needed because of the limited numbers of available trials and participants.
Topics: Adenosine; Cause of Death; Humans; Myocardial Infarction; No-Reflow Phenomenon; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Vasodilator Agents; Verapamil
PubMed: 25985145
DOI: 10.1002/14651858.CD009503.pub3 -
Journal of Thrombosis and Haemostasis :... Jun 2015Ticagrelor and prasugrel have shown superiority over clopidogrel. However, it remains unclear if one is superior to another regarding on-treatment platelet reactivity. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ticagrelor and prasugrel have shown superiority over clopidogrel. However, it remains unclear if one is superior to another regarding on-treatment platelet reactivity.
OBJECTIVES
To compare the impact of ticagrelor and prasugrel on high on-treatment platelet reactivity (HTPR).
METHODS
The PubMed and Cochrane databases were searched for eligible studies in December 2014. Studies were eligible if they compared ticagrelor and prasugrel regarding high on-treatment platelet reactivity (HTPR). Pooled estimates were calculated by using a random-effects model with 95% confidence intervals.
RESULTS
We included 14 studies and 1822 patients: 805 and 1017 in the ticagrelor and prasugrel groups, respectively. The rate of HTPR was significantly lower in the ticagrelor group: 1.5% vs. 9.8% (RR = 0.27 [0.14-0.50]). The pre-specified analysis focusing on randomized trials (n = 10) showed consistent results (RR = 0.27 [0.12-0.60]).
CONCLUSION
Our results suggest that ticagrelor allows a higher platelet reactivity inhibition as compared with prasugrel and leads to a further decrease in the rate of HTPR.
Topics: Adenosine; Blood Platelets; Chi-Square Distribution; Drug Resistance; Heart Diseases; Humans; Odds Ratio; Percutaneous Coronary Intervention; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prasugrel Hydrochloride; Predictive Value of Tests; Risk Factors; Ticagrelor; Treatment Outcome
PubMed: 25809392
DOI: 10.1111/jth.12907 -
PloS One 2015It has been well established that S-adenosyl-L-methionine (SAMe) is the principal methyl donor in methyltransferase reactions and that SAMe supplementation restores... (Meta-Analysis)
Meta-Analysis Review
It has been well established that S-adenosyl-L-methionine (SAMe) is the principal methyl donor in methyltransferase reactions and that SAMe supplementation restores hepatic glutathione (GSH) deposits and attenuates liver injury. However, the effectiveness of SAMe therapy in chronic liver disease has not been adequately addressed. We searched globally recognized electronic databases, including PubMed, the Cochrane Database and EMBASE, to retrieve relevant randomized controlled trials (RCTs) of chronic liver disease published in the past 20 years. We then performed a systematic review and meta-analysis of the enrolled trials that met the inclusion criteria.The results showed that twelve RCTs from 11 studies, which examined 705 patients, were included in this research. For liver function, certain results obtained from data synthesis and independent comparisons demonstrated significant differences between the levels of total bilirubin (TBIL) and aspartate transaminase (AST). However, no studies identified significant differences regarding alanine transaminase (ALT) levels. An analysis of the adverse events and long-term prognosis also indicated no significant differences between the SAMe and the placebo groups. In a subgroup analysis of gravidas and children, several of the included data indicated that there was a significant difference in the pruritus score. Furthermore, the results regarding ursodeoxycholic acid (UDCA) and stronger neo-minophagen C (SNMC) indicated that both treatments were more effective than SAMe was in certain chronic liver diseases. These findings suggest that SAMe could be used as the basis of a medication regimen for liver function improvement because of its safety. However, SAMe also demonstrated limited clinical value in the treatment of certain chronic liver diseases.
Topics: Age Factors; Chronic Disease; Humans; Liver Diseases; Liver Function Tests; S-Adenosylmethionine; Treatment Outcome
PubMed: 25774783
DOI: 10.1371/journal.pone.0122124 -
Psychoneuroendocrinology Jan 2015It has been suggested that depressed persons have increased oxidative stress and decreased anti-oxidant defences. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It has been suggested that depressed persons have increased oxidative stress and decreased anti-oxidant defences. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) and F2-isoprostanes, measures of oxidative DNA and lipid damage respectively, are among the most reliable oxidative stress markers, but studies on their association with depression show conflicting results. This meta-analysis quantifies the association between depression and these markers and explores factors that may explain inconsistencies in the results.
METHODS
A systematic literature search was conducted in PubMed, EMBASE and PsycINFO. Studies assessing the association of 8-OHdG or F2-isoprostanes with elevated depressive symptoms, major depressive disorder (MDD) or bipolar disorder (BD) were pooled in two random-effect models.
RESULTS
The pooled effect size (Hedges' g) for the association of depression with oxidative stress was 0.31 (p=0.01, I(2)=75%) for 8-OHdG (10 studies, 1308 subjects) and 0.48 (p=0.001, I(2)=73%) for F2-isoprostanes (8 studies, 2471 subjects), indicating that both markers are increased in depression. There was no indication of publication bias for either marker. The F2-isoprostane results did not differ by type of depression, biological specimen, laboratory method or quality, however subgroup analyses in the 8-OHdG studies showed significantly stronger associations in plasma/serum vs. urine samples (p<0.01), in measurements performed with immuno-assay vs. chromatography-mass spectrometry (p<0.01) and weaker associations in high quality studies vs. low (p=0.02).
CONCLUSION
This meta-analysis finds that oxidative stress, as measured by 8-OHdG and F2-isoprostanes, is increased in depression. Larger-scale studies are needed to extend the evidence on oxidative stress in depression, and examine the potential impact of treatment.
Topics: 8-Hydroxy-2'-Deoxyguanosine; Biomarkers; Bipolar Disorder; Deoxyguanosine; Depression; Depressive Disorder, Major; F2-Isoprostanes; Humans; Oxidative Stress
PubMed: 25462890
DOI: 10.1016/j.psyneuen.2014.09.025 -
Progress in Neuro-psychopharmacology &... Mar 2015Uric acid and purines (such as adenosine) regulate mood, sleep, activity, appetite, cognition, memory, convulsive threshold, social interaction, drive, and impulsivity.... (Review)
Review
Uric acid and purines (such as adenosine) regulate mood, sleep, activity, appetite, cognition, memory, convulsive threshold, social interaction, drive, and impulsivity. A link between purinergic dysfunction and mood disorders was first proposed a century ago. Interestingly, a recent nationwide population-based study showed elevated risk of gout in subjects with bipolar disorder (BD), and a recent meta-analysis and systematic review of placebo-controlled trials of adjuvant purinergic modulators confirmed their benefits in bipolar mania. Uric acid may modulate energy and activity levels, with higher levels associated with higher energy and BD spectrum. Several recent genetic studies suggest that the purinergic system - particularly the modulation of P1 and P2 receptor subtypes - plays a role in mood disorders, lending credence to this model. Nucleotide concentrations can be measured using brain spectroscopy, and ligands for in vivo positron emission tomography (PET) imaging of adenosine (P1) receptors have been developed, thus allowing potential target engagement studies. This review discusses the key role of the purinergic system in the pathophysiology of mood disorders. Focusing on this promising therapeutic target may lead to the development of therapies with antidepressant, mood stabilization, and cognitive effects.
Topics: Adenosine; Adenosine Triphosphate; Animals; Biomarkers; Guanosine; Humans; Models, Neurological; Molecular Targeted Therapy; Mood Disorders; Neuroimaging; Psychotropic Drugs; Receptors, Purinergic
PubMed: 25445063
DOI: 10.1016/j.pnpbp.2014.10.016