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1.  Education level and survival after oesophageal cancer surgery: a prospective population-based cohort study 
BMJ Open  2013;3(12):e003754.
Objectives
This study aimed to investigate whether a higher education level is associated with an improved long-term survival after oesophagectomy for cancer.
Design
A prospective, population-based cohort study.
Setting
Sweden—nationwide.
Participants
90% of all patients with oesophageal and cardia cancer who underwent a resection in Sweden in 2001–2005 were enrolled in this study (N=600; 80.3% male) and followed up until death or the end of the study period (2012). The study exposure was level of education, defined as compulsory (≤9 years), moderate (10–12 years) or high (≥13 years).
Outcome measures
The main outcome measure was overall 5-year survival after oesophagectomy. Cox regression was used to estimate the associations between education level and mortality, expressed as HRs with 95% CIs, with adjustment for sex, age, tumour stage, histological type, complications, comorbidities and annual surgeon volume. The patient group with highest education was used as the reference category.
Results
Among the 600 included patients, 281 (46.8%) had compulsory education, 238 (39.7%) had moderate education and 81 (13.5%) had high education. The overall 5-year survival rate was 23.1%, 24.4% and 32.1% among patients with compulsory, moderate and high education, respectively. After adjustment for confounders, a slightly higher, yet not statistically significantly increased point HR was found among the compulsory educated patients (HR 1.08, 95% CI 0.80 to 1.47). In patients with tumour stage IV, increased adjusted HRs were found for compulsory (HR 2.88, 95% CI 1.07 to 7.73) and moderately (HR 2.83, 95% CI 1.15 to 6.95) educated patients. No statistically significant associations were found for the other tumour stages.
Conclusions
This study provides limited evidence of an association between lower education and worse long-term survival after oesophagectomy for cancer.
doi:10.1136/bmjopen-2013-003754
PMCID: PMC3855588  PMID: 24302504
2.  Clinical Use of HIV Integrase Inhibitors: A Systematic Review and Meta-Analysis 
PLoS ONE  2013;8(1):e52562.
Background
Optimal regimen choice of antiretroviral therapy is essential to achieve long-term clinical success. Integrase inhibitors have swiftly been adopted as part of current antiretroviral regimens. The purpose of this study was to review the evidence for integrase inhibitor use in clinical settings.
Methods
MEDLINE and Web-of-Science were screened from April 2006 until November 2012, as were hand-searched scientific meeting proceedings. Multiple reviewers independently screened 1323 citations in duplicate to identify randomized controlled trials, nonrandomized controlled trials and cohort studies on integrase inhibitor use in clinical practice. Independent, duplicate data extraction and quality assessment were conducted.
Results
48 unique studies were included on the use of integrase inhibitors in antiretroviral therapy-naive patients and treatment-experienced patients with either virological failure or switching to integrase inhibitors while virologically suppressed. On the selected studies with comparable outcome measures and indication (n = 16), a meta-analysis was performed based on modified intention-to-treat (mITT), on-treatment (OT) and as-treated (AT) virological outcome data. In therapy-naive patients, favorable odds ratios (OR) for integrase inhibitor-based regimens were observed, (mITT OR 0.71, 95% CI 0.59–0.86). However, integrase inhibitors combined with protease inhibitors only did not result in a significant better virological outcome. Evidence further supported integrase inhibitor use following virological failure (mITT OR 0.27; 95% CI 0.11–0.66), but switching to integrase inhibitors from a high genetic barrier drug during successful treatment was not supported (mITT OR 1.43; 95% CI 0.89–2.31). Integrase inhibitor-based regimens result in similar immunological responses compared to other regimens. A low genetic barrier to drug-resistance development was observed for raltegravir and elvitegravir, but not for dolutegravir.
Conclusion
In first-line therapy, integrase inhibitors are superior to other regimens. Integrase inhibitor use after virological failure is supported as well by the meta-analysis. Careful use is however warranted when replacing a high genetic barrier drug in treatment-experienced patients switching successful treatment.
doi:10.1371/journal.pone.0052562
PMCID: PMC3541389  PMID: 23341902
3.  The rising problem of antimicrobial resistance in the intensive care unit 
Mainly due to its extremely vulnerable population of critically ill patients, and the high use of (invasive) procedures, the intensive care unit (ICU) is the epicenter of infections. These infections are associated with an important rise in morbidity, mortality, and healthcare costs. The additional problem of multidrug-resistant pathogens boosts the adverse impact of infections in ICUs. Several factors influence the rapid spread of multidrug-resistant pathogens in the ICU, e.g., new mutations, selection of resistant strains, and suboptimal infection control. Among gram-positive organisms, the most important resistant microorganisms in the ICU are currently methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. In gram-negative bacteria, the resistance is mainly due to the rapid increase of extended-spectrum Beta-lactamases (ESBLs) in Klebsiella pneumonia, Escherichia coli, and Proteus species and high level third-generation cephalosporin Beta-lactamase resistance among Enterobacter spp. and Citrobacter spp., and multidrug resistance in Pseudomonas aeruginosa and Acinetobacter species. To conclude, additional efforts are needed in the future to slow down the emergence of antimicrobial resistance. Constant evaluation of current practice on basis of trends in MDR and antibiotic consumption patterns is essential to make progress in this problematic matter.
doi:10.1186/2110-5820-1-47
PMCID: PMC3231873  PMID: 22112929
4.  Severe burn injury in europe: a systematic review of the incidence, etiology, morbidity, and mortality 
Critical Care  2010;14(5):R188.
Introduction
Burn injury is a serious pathology, potentially leading to severe morbidity and significant mortality, but it also has a considerable health-economic impact. The aim of this study was to describe the European hospitalized population with severe burn injury, including the incidence, etiology, risk factors, mortality, and causes of death.
Methods
The systematic literature search (1985 to 2009) involved PubMed, the Web of Science, and the search engine Google. The reference lists and the Science Citation Index were used for hand searching (snowballing). Only studies dealing with epidemiologic issues (for example, incidence and outcome) as their major topic, on hospitalized populations with severe burn injury (in secondary and tertiary care) in Europe were included. Language restrictions were set on English, French, and Dutch.
Results
The search led to 76 eligible studies, including more than 186,500 patients in total. The annual incidence of severe burns was 0.2 to 2.9/10,000 inhabitants with a decreasing trend in time. Almost 50% of patients were younger than 16 years, and ~60% were male patients. Flames, scalds, and contact burns were the most prevalent causes in the total population, but in children, scalds clearly dominated. Mortality was usually between 1.4% and 18% and is decreasing in time. Major risk factors for death were older age and a higher total percentage of burned surface area, as well as chronic diseases. (Multi) organ failure and sepsis were the most frequently reported causes of death. The main causes of early death (<48 hours) were burn shock and inhalation injury.
Conclusions
Despite the lack of a large-scale European registration of burn injury, more epidemiologic information is available about the hospitalized population with severe burn injury than is generally presumed. National and international registration systems nevertheless remain necessary to allow better targeting of prevention campaigns and further improvement of cost-effectiveness in total burn care.
doi:10.1186/cc9300
PMCID: PMC3219295  PMID: 20958968

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