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3.
Gut Microbes ; : 1-12, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31696774

RESUMO

There is increasing evidence for the role of gut microbial composition in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH) is the most serious form of NAFLD where inflammation causes liver damage that can progress to cirrhosis. We have characterized the gut microbiome composition in UK patients with biopsy-proven NASH (n = 65) and compared it to that in healthy controls (n = 76). We report a 7% lower Shannon alpha diversity in NASH patients without cirrhosis (n = 40) compared to controls (p = 2.7x 10-4) and a 14% drop in NASH patients with cirrhosis (n = 25, p = 5.0x 10-4). Beta diversity (Unweighted UniFrac distance) was also significantly reduced in both NASH (p = 5.6x 10-25) and NASH-cirrhosis (p = 8.1x 10-7) groups. The genus most strongly associated with NASH in this study was Collinsella (0.29% abundance in controls, 3.45% in NASH without cirrhosis (False Discovery Rate (FDR) p = .008), and 4.38% in NASH with cirrhosis (FDR p = .02)). This genus, which has been linked previously to obesity and atherosclerosis, was also positively correlated with fasting levels of triglycerides (p = .01) and total cholesterol (p = 1.2x 10-4) and negatively correlated with high-density lipoprotein cholesterol (p = 2.8x 10-6) suggesting that some of the pathways present in this microbial genus may influence lipid metabolism in the host. In patients, we also found decreased abundance of some of the Ruminococcaceae which are known to produce high levels of short-chain fatty acids which can lower inflammation. This may thus contribute to pathology associated with NASH.

4.
Cochrane Database Syst Rev ; 10: CD005154, 2017 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-29025197

RESUMO

BACKGROUND: People with supraventricular tachycardia (SVT) frequently are symptomatic and present to the emergency department for treatment. Although vagal manoeuvres may terminate SVT, they often fail, and subsequently adenosine or calcium channel antagonists (CCAs) are administered. Both are known to be effective, but both have a significant side effect profile. This is an update of a Cochrane review previously published in 2006. OBJECTIVES: To review all randomised controlled trials (RCTs) that compare effects of adenosine versus CCAs in terminating SVT. SEARCH METHODS: We identified studies by searching CENTRAL, MEDLINE, Embase, and two trial registers in July 2017. We checked bibliographies of identified studies and applied no language restrictions. SELECTION CRITERIA: We planned to include all RCTs that compare adenosine versus a CCA for patients of any age presenting with SVT. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. Two review authors independently checked results of searches to identify relevant studies and resolved differences by discussion with a third review author. At least two review authors independently assessed each included study and extracted study data. We entered extracted data into Review Manager 5. Primary outcomes were rate of reversion to sinus rhythm and major adverse effects of adenosine and CCAs. Secondary outcomes were rate of recurrence, time to reversion, and minor adverse outcomes. We measured outcomes by calculating odds ratios (ORs) and assessed the quality of primary outcomes using the GRADE approach through the GRADEproGDT website. MAIN RESULTS: We identified two new studies for inclusion in the review update; the review now includes seven trials with 622 participants who presented to an emergency department with SVT. All included studies were RCTs, but only three described the randomisation process, and none had blinded participants, personnel, or outcome assessors to the intervention given. Moderate-quality evidence shows no differences in the number of people reverting to sinus rhythm who were treated with adenosine or CCA (89.7% vs 92.9%; OR 1.51, 95% confidence interval (CI) 0.85 to 2.68; participants = 622; studies = 7; I2 = 36%). Low-quality evidence suggests no appreciable differences in major adverse event rates between CCAs and adenosine. Researchers reported only one case of hypotension in the CCA group and none in the adenosine group (0.66% vs 0%; OR 3.09, 95% CI 0.12 to 76.71; participants = 306; studies = 3; I2 = 0%). Included trials did not report length of stay in hospital nor patient satisfaction. AUTHORS' CONCLUSIONS: Moderate-quality evidence shows no differences in effects of adenosine and calcium channel antagonists for treatment of SVT on reverting to sinus rhythm, and low-quality evidence suggests no appreciable differences in the incidence of hypotension. A study comparing patient experiences and prospectively studied adverse events would provide evidence on which treatment is preferable for management of SVT.


Assuntos
Adenosina/uso terapêutico , Antiarrítmicos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Taquicardia Supraventricular/tratamento farmacológico , Adenosina/efeitos adversos , Adulto , Antiarrítmicos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Humanos , Hipotensão/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Verapamil/efeitos adversos , Verapamil/uso terapêutico
5.
Cochrane Database Syst Rev ; 1: CD010447, 2017 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-28079254

RESUMO

BACKGROUND: Pharmacological prophylaxis has been proven to reduce the risk of cardiovascular events in individuals with atherosclerotic occlusive arterial disease. However, the role of prophylaxis in individuals with abdominal aortic aneurysm (AAA) remains unclear. Several studies have shown that despite successful repair, those people with AAA have a poorer rate of survival than healthy controls. People with AAA have an increased prevalence of coronary heart disease and risk of cardiovascular events. Despite this association, little is known about the effectiveness of pharmacological prophylaxis in reducing cardiovascular risk in people with AAA. This is an update of a Cochrane review first published in 2014. OBJECTIVES: To determine the long-term effectiveness of antiplatelet, antihypertensive or lipid-lowering medication in reducing mortality and cardiovascular events in people with abdominal aortic aneurysm (AAA). SEARCH METHODS: For this update the Cochrane Vascular Information Specialist (CIS) searched the Cochrane Vascular Specialised Register (14 April 2016). In addition, the CIS searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 3) and trials registries (14 April 2016) and We also searched the reference lists of relevant articles. SELECTION CRITERIA: Randomised controlled trials in which people with AAA were randomly allocated to one prophylactic treatment versus another, a different regimen of the same treatment, a placebo, or no treatment were eligible for inclusion in this review. Primary outcomes included all-cause mortality and cardiovascular mortality. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion, and completed quality assessment and data extraction. We resolved any disagreements by discussion. Only one study met the inclusion criteria of the review, therefore we were unable to perform meta-analysis. MAIN RESULTS: No new studies met the inclusion criteria for this update. We included one randomised controlled trial in the review. A subgroup of 227 participants with AAA received either metoprolol (N = 111) or placebo (N = 116). There was no clear evidence that metoprolol reduced all-cause mortality (odds ratio (OR) 0.17, 95% confidence interval (CI) 0.02 to 1.41), cardiovascular death (OR 0.20, 95% CI 0.02 to 1.76), AAA-related death (OR 1.05, 95% CI 0.06 to 16.92) or increased nonfatal cardiovascular events (OR 1.44, 95% CI 0.58 to 3.57) 30 days postoperatively. Furthermore, at six months postoperatively, estimated effects were compatible with benefit and harm for all-cause mortality (OR 0.71, 95% CI 0.26 to 1.95), cardiovascular death (OR 0.73, 95% CI 0.23 to 2.39) and nonfatal cardiovascular events (OR 1.41, 95% CI 0.59 to 3.35). Adverse drug effects were reported for the whole study population and were not available for the subgroup of participants with AAA. We considered the study to be at a generally low risk of bias. We downgraded the quality of the evidence for all outcomes to low. We downgraded the quality of evidence for imprecision as only one study with a small number of participants was available, the number of events was small and the result was consistent with benefit and harm. AUTHORS' CONCLUSIONS: Due to the limited number of included trials, there is insufficient evidence to draw any conclusions about the effectiveness of cardiovascular prophylaxis in reducing mortality and cardiovascular events in people with AAA. Further good-quality randomised controlled trials that examine many types of prophylaxis with long-term follow-up are required before firm conclusions can be made.


Assuntos
Aneurisma da Aorta Abdominal/complicações , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Metoprolol/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Aneurisma da Aorta Abdominal/mortalidade , Doenças Cardiovasculares/mortalidade , Causas de Morte , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
6.
Cochrane Database Syst Rev ; (1): CD010447, 2014 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-24449038

RESUMO

BACKGROUND: Pharmacological prophylaxis has been proven to reduce the risk of cardiovascular events in patients with atherosclerotic occlusive arterial disease. However, the role of prophylaxis in patients with abdominal aortic aneurysm (AAA) remains unclear. Several studies have shown that despite successful repair, those with AAA have a poorer rate of survival than healthy controls. People with AAA have an increased prevalence of coronary heart disease and risk of cardiovascular events. Despite this association, little is known about the effectiveness of pharmacological prophylaxis in reducing cardiovascular risk in people with AAA. OBJECTIVES: To determine the long-term effectiveness of antiplatelet, antihypertensive or lipid-lowering medication in reducing mortality and cardiovascular events in people with abdominal aortic aneurysm (AAA). SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched April 2013) and CENTRAL (2013, Issue 3). Reference lists of relevant articles were also checked. SELECTION CRITERIA: Randomised controlled trials in which people with AAA were randomly allocated to one prophylactic treatment versus another, a different regimen of the same treatment, a placebo, or no treatment were eligible for inclusion in this review. Primary outcomes included all-cause mortality and cardiovascular mortality. DATA COLLECTION AND ANALYSIS: Selection of the studies, quality assessment and data extraction were completed independently by two review authors. Any disagreements were resolved by discussion. Only one study was included in the review, therefore meta-analysis could not be performed. MAIN RESULTS: One randomised controlled study was included in the review. A subgroup of 227 patients with AAA received either metoprolol (N = 111) or placebo (N = 116). There was no clear evidence that metoprolol reduced all-cause mortality (odds ratio (OR) 0.17, 95% confidence interval (CI) 0.02 to 1.41), cardiovascular death (OR 0.20, 95% CI 0.02 to 1.76), AAA-related death (OR 1.05, 95% CI 0.06 to 16.92) or increased nonfatal cardiovascular events (OR 1.44, 95% CI 0.58 to 3.57) 30 days postoperatively. Furthermore, at six months postoperatively, estimated effects were compatible with benefit and harm for all-cause mortality (OR 0.71, 95% CI 0.26 to 1.95), cardiovascular death (OR 0.73, 95% CI 0.23 to 2.39) and nonfatal cardiovascular events (OR 1.41, 95% CI 0.59 to 3.35). Adverse drug effects were reported for the whole study population and were not available for the subgroup of participants with AAA. The study was deemed to be at a generally low risk of bias. AUTHORS' CONCLUSIONS: Due to the limited number of trials, there is insufficient evidence to draw any conclusions about the effectiveness of cardiovascular prophylaxis in reducing mortality and cardiovascular events in people with AAA. Further good-quality randomised controlled trials examining many types of prophylaxis with long-term follow-up are required before firm conclusions can be made.


Assuntos
Aneurisma da Aorta Abdominal/complicações , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Metoprolol/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Aneurisma da Aorta Abdominal/mortalidade , Doenças Cardiovasculares/mortalidade , Causas de Morte , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
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