Aug 272013
 

Asthma.

Lancet. 2013 Aug 22;

Authors: Martinez FD, Vercelli D

Abstract
Asthma is a heterogeneous group of conditions that result in recurrent, reversible bronchial obstruction. Although the disease can start at any age, the first symptoms occur during childhood in most cases. Asthma has a strong genetic component, and genome-wide association studies have identified variations in several genes that slightly increase the risk of disease. Asthma is often associated with increased susceptibility to infection with rhinoviruses and with changes in the composition of microbial communities colonising the airways, but whether these changes are a cause or consequence of the disease is unknown. There is currently no proven prevention strategy; however, the finding that exposure to microbial products in early life, particularly in farming environments, seems to be protective against asthma offers hope that surrogates of such exposure could be used to prevent the disease. Genetic and immunological studies point to defective responses of lung resident cells, especially those associated with the mucosal epithelium, as crucial elements in the pathogenesis of asthma. Inhaled corticosteroids continue to be the mainstay for the treatment of mild and moderate asthma, but limited adherence to daily inhaled medication is a major obstacle to the success of such therapy. Severe asthma that is refractory to usual treatment continues to be a challenge, but new biological therapies, such as humanised antibodies against IgE, interleukin 5, and interleukin 13, offer hope to improve the quality of life and long-term prognosis of severe asthmatics with specific molecular phenotypes.

PMID: 23972423 [PubMed - as supplied by publisher]

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Aug 212013
 

Future treatment strategies in ST-segment elevation myocardial infarction.

Lancet. 2013 Aug 17;382(9892):644-57

Authors: Windecker S, Bax JJ, Myat A, Stone GW, Marber MS

Abstract
Over the past five decades, management of acute ST-segment elevation myocardial infarction (STEMI) has evolved substantially. Current treatment encompasses a systematic chain of network activation, antithrombotic drugs, and rapid instigation of mechanical reperfusion, although pharmacoinvasive strategies remain relevant. Secondary prevention with drugs and lifestyle modifications completes the contemporary management package. Despite a tangible improvement in outcomes, STEMI remains a frequent cause of morbidity and mortality, justifying the quest to find new therapeutic avenues. Ways to reduce delays in doing coronary angioplasty after STEMI onset include early recognition of symptoms by patients and prehospital diagnosis by paramedics so that the emergency room can be bypassed in favour of direct admission to the catheterisation laboratory. Mechanical reperfusion can be optimised by improvements to stent design, whereas visualisation of infarct size has been improved by developments in cardiac MRI. Novel treatments to modulate the inflammatory component of atherosclerosis and the vulnerable plaque include use of bioresorbable vascular scaffolds and anti-proliferative drugs. Translational efforts to improve patients' outcomes after STEMI in relation to cardioprotection, cardiac remodelling, and regeneration are also being realised.

PMID: 23953388 [PubMed - in process]

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Jun 212013
 
Related Articles

Challenges in the management of acute peptic ulcer bleeding.

Lancet. 2013 Jun 8;381(9882):2033-43

Authors: Lau JY, Barkun A, Fan DM, Kuipers EJ, Yang YS, Chan FK

Abstract
Acute upper gastrointestinal bleeding is a common medical emergency worldwide, a major cause of which are bleeding peptic ulcers. Endoscopic treatment and acid suppression with proton-pump inhibitors are cornerstones in the management of the disease, and both treatments have been shown to reduce mortality. The role of emergency surgery continues to diminish. In specialised centres, radiological intervention is increasingly used in patients with severe and recurrent bleeding who do not respond to endoscopic treatment. Despite these advances, mortality from the disorder has remained at around 10%. The disease often occurs in elderly patients with frequent comorbidities who use antiplatelet agents, non-steroidal anti-inflammatory drugs, and anticoagulants. The management of such patients, especially those at high cardiothrombotic risk who are on anticoagulants, is a challenge for clinicians. We summarise the published scientific literature about the management of patients with bleeding peptic ulcers, identify directions for future clinical research, and suggest how mortality can be reduced.

PMID: 23746903 [PubMed - indexed for MEDLINE]

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Jun 042013
 

Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance.

Lancet. 2013 May 29;

Authors: Hu Y, Lu S, Song Z, Wang W, Hao P, Li J, Zhang X, Yen HL, Shi B, Li T, Guan W, Xu L, Liu Y, Wang S, Zhang X, Tian D, Zhu Z, He J, Huang K, Chen H, Zheng L, Li X, Ping J, Kang B, Xi X, Zha L, Li Y, Zhang Z, Peiris M, Yuan Z

Abstract
BACKGROUND: On March 30, a novel influenza A subtype H7N9 virus (A/H7N9) was detected in patients with severe respiratory disease in eastern China. Virological factors associated with a poor clinical outcome for this virus remain unclear. We quantified the viral load and analysed antiviral resistance mutations in specimens from patients with A/H7N9. METHODS: We studied 14 patients with A/H7N9 disease admitted to the Shanghai Public Health Clinical Centre (SPHCC), China, between April 4, and April 20, 2013, who were given antiviral treatment (oseltamivir or peramivir) for less than 2 days before admission. We investigated the viral load in throat, stool, serum, and urine specimens obtained sequentially from these patients. We also sequenced viral RNA from these specimens to study the mutations associated with resistance to neuraminidase inhibitors and their association with disease outcome. FINDINGS: All patients developed pneumonia, seven of them required mechanical ventilation, and three of them further deteriorated to become dependent on extracorporeal membrane oxygenation (ECMO), two of whom died. Antiviral treatment was associated with a reduction of viral load in throat swab specimens in 11 surviving patients. Three patients with persistently high viral load in the throat in spite of antiviral therapy became ECMO dependent. An Arg292Lys mutation in the virus neuraminidase (NA) gene known to confer resistance to both zanamivir and oseltamivir was identified in two of these patients, both also received corticosteroid treatment. In one of them, wild-type sequence Arg292 was noted 2 days after start of antiviral treatment, and the resistant mutant Lys292 dominated 9 days after start of treatment. INTERPRETATION: Reduction of viral load following antiviral treatment correlated with improved outcome. Emergence of NA Arg292Lys mutation in two patients who also received corticosteroid treatment led to treatment failure and a poor clinical outcome. The emergence of antiviral resistance in A/H7N9 viruses, especially in patients receiving corticosteroid therapy, is concerning, needs to be closely monitored, and considered in pandemic preparedness planning. FUNDING: National Megaprojects of China for Infectious Diseases, Shanghai Municipal Health and Family Planning Commission, the National Key Basic Research Program of China, Ministry of Science and Technology, and National Natural Science Foundation of China.

PMID: 23726392 [PubMed - as supplied by publisher]

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Jun 042013
 

Acute kidney injury: an increasing global concern.

Lancet. 2013 May 30;

Authors: Lameire NH, Bagga A, Cruz D, De Maeseneer J, Endre Z, Kellum JA, Liu KD, Mehta RL, Pannu N, Van Biesen W, Vanholder R

Abstract
Despite an increasing incidence of acute kidney injury in both high-income and low-income countries and growing insight into the causes and mechanisms of disease, few preventive and therapeutic options exist. Even small acute changes in kidney function can result in short-term and long-term complications, including chronic kidney disease, end-stage renal disease, and death. Presence of more than one comorbidity results in high severity of illness scores in all medical settings. Development or progression of chronic kidney disease after one or more episode of acute kidney injury could have striking socioeconomic and public health outcomes for all countries. Concerted international action encompassing many medical disciplines is needed to aid early recognition and management of acute kidney injury.

PMID: 23727171 [PubMed - as supplied by publisher]

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Jun 042013
 

Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials.

Lancet. 2013 May 29;

Authors: Coxib and traditional NSAID Trialists' (CNT) Collaboration

Abstract
BACKGROUND: The vascular and gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors (coxibs) and traditional non-steroidal anti-inflammatory drugs (tNSAIDs), are not well characterised, particularly in patients at increased risk of vascular disease. We aimed to provide such information through meta-analyses of randomised trials. METHODS: We undertook meta-analyses of 280 trials of NSAIDs versus placebo (124 513 participants, 68 342 person-years) and 474 trials of one NSAID versus another NSAID (229 296 participants, 165 456 person-years). The main outcomes were major vascular events (non-fatal myocardial infarction, non-fatal stroke, or vascular death); major coronary events (non-fatal myocardial infarction or coronary death); stroke; mortality; heart failure; and upper gastrointestinal complications (perforation, obstruction, or bleed). FINDINGS: Major vascular events were increased by about a third by a coxib (rate ratio [RR] 1·37, 95% CI 1·14-1·66; p=0·0009) or diclofenac (1·41, 1·12-1·78; p=0·0036), chiefly due to an increase in major coronary events (coxibs 1·76, 1·31-2·37; p=0·0001; diclofenac 1·70, 1·19-2·41; p=0·0032). Ibuprofen also significantly increased major coronary events (2·22, 1·10-4·48; p=0·0253), but not major vascular events (1·44, 0·89-2·33). Compared with placebo, of 1000 patients allocated to a coxib or diclofenac for a year, three more had major vascular events, one of which was fatal. Naproxen did not significantly increase major vascular events (0·93, 0·69-1·27). Vascular death was increased significantly by coxibs (1·58, 99% CI 1·00-2·49; p=0·0103) and diclofenac (1·65, 0·95-2·85, p=0·0187), non-significantly by ibuprofen (1·90, 0·56-6·41; p=0·17), but not by naproxen (1·08, 0·48-2·47, p=0·80). The proportional effects on major vascular events were independent of baseline characteristics, including vascular risk. Heart failure risk was roughly doubled by all NSAIDs. All NSAID regimens increased upper gastrointestinal complications (coxibs 1·81, 1·17-2·81, p=0·0070; diclofenac 1·89, 1·16-3·09, p=0·0106; ibuprofen 3·97, 2·22-7·10, p<0·0001; and naproxen 4·22, 2·71-6·56, p<0·0001). INTERPRETATION: The vascular risks of high-dose diclofenac, and possibly ibuprofen, are comparable to coxibs, whereas high-dose naproxen is associated with less vascular risk than other NSAIDs. Although NSAIDs increase vascular and gastrointestinal risks, the size of these risks can be predicted, which could help guide clinical decision making. FUNDING: UK Medical Research Council and British Heart Foundation.

PMID: 23726390 [PubMed - as supplied by publisher]

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