OSA has emerged as a highly prevalent public health problem that imposes important mid- and long-term consequences, namely cardiovascular, metabolic, cognitive, and cancer-related alterations. OSA is ...characterized by increased upper airway resistance, alveolar hypoventilation, and recurrent upper airway obstruction during sleep. Recurrent collapse of the upper airway develops with sleep onset and is associated with both intermittent hypoxemia and sleep fragmentation. The microbiome is a vast and complex polymicrobial ecosystem that coexists with the human organism, and it has been identified as playing significant roles in the development of host immunologic phenotypes. In humans and animal models, changes in gut microbial communities occur with lifestyle behaviors, such as smoking, long-distance travel, dietary preferences, physical exercise, and circadian rhythm disturbances. In parallel, diseases previously attributed in part to lifestyle such as obesity, coronary heart disease, depression, and asthma (also associated with OSA) are now claimed as microbiota related. We therefore posit that altered patterns of sleep and oxygenation, as seen in OSA, will promote specific alterations in gut microbiota that in turn will elicit the immunologic alterations that lead to OSA-induced end-organ morbidities. The present article assesses the potential mechanistic links between OSA-induced changes in gut microbiota and its morbid phenotypes.
This is an updated version of the original review published in Issue 4, 2004. The use of concurrent chemotherapy and radiotherapy in non-small cell lung cancer (NSCLC) might be seen as a way of ...increasing the effectiveness of radical radiotherapy at the same time as reducing the risks of metastatic disease.
To determine the effectiveness of concurrent chemoradiotherapy as compared to radiotherapy alone with regard to overall survival, tumour control and treatment-related morbidity. To determine the effectiveness of concurrent versus sequential chemoradiotherapy.
For this update we ran a new search in October 2009, using a search strategy adapted from the design in the original review. We searched: CENTRAL (accessed through The Cochrane Library, 2009, Issue 4), MEDLINE (accessed through PubMed), and EMBASE (accessed through Ovid).
Randomised trials of patients with stage I-III NSCLC undergoing radical radiotherapy and randomised to receive concurrent chemoradiotherapy versus radiotherapy alone, or concurrent versus sequential chemoradiotherapy.
Study selection, data extraction and assessment of risk of bias was performed independently by two authors. Pooled hazard ratios and relative risks were calculated according to a random-effects model.
Nineteen randomised studies (2728 participants) of concurrent chemoradiotherapy versus radiotherapy alone were included. Chemoradiotherapy significantly reduced overall risk of death (HR 0.71, 95% CI 0.64 to 0.80; I(2) 0%; 1607 participants) and overall progression-free survival at any site (HR 0.69, 95% CI 0.58 to 0.81; I(2) 45%; 1145 participants). Incidence of acute oesophagitis, neutropenia and anaemia were significantly increased with concurrent chemoradiation. Six trials (1024 patients) of concurrent versus sequential chemoradiation were included. A significant benefit of concurrent treatment was shown in overall survival (HR 0.74, 95% CI 0.62 to 0.89; I(2) 0%; 702 participants). This represented a 10% absolute survival benefit at 2 years. More treatment-related deaths (4% vs 2%) were reported in the concurrent arm without statistical significance (RR 2.02, 95% CI 0.90 to 4.52; I(2) 0%; 950 participants). There was increased severe oesophagitis with concurrent treatment (RR 4.96, 95%CI 2.17 to 11.37; I(2) 66%; 947 participants).
This update of the review published in 2004 incorporates additional trials and more mature data. It demonstrates the benefit of concurrent chemoradiation over radiotherapy alone or sequential chemoradiotherapy. Patient selection is an important consideration in view of the added toxicity of concurrent treatment. Uncertainty remains as to how far this is purely due to a radiosensitising effect and whether similar benefits could be achieved by using modern radiotherapy techniques and more dose intensive accelerated and/ or hyperfractionated radiotherapy regimens.
Aims
Heart failure (HF) is one of the diseases with greater healthcare expenditure. However, little is known about the cost of HF at a population level. Hence, our aim was to study the ...population‐level distribution and predictors of healthcare expenditure in patients with HF.
Methods and results
This was a population‐based longitudinal study including all prevalent HF cases in Catalonia (Spain) on 31 December 2012 (n = 88 195). We evaluated 1‐year healthcare resource use and expenditure using the Health Department (CatSalut) surveillance system that collects detailed information on healthcare usage for the entire population. Mean age was 77.4 (12) years; 55% were women. One‐year mortality rate was 14%. All‐cause emergency department visits and unplanned hospitalizations were required at least once in 53.4% and 30.8% of patients, respectively. During 2013, a total of €536.2 million were spent in the care of HF patients (7.1% of the total healthcare budget). The main source of expenditure was hospitalization (39% of the total) whereas outpatient care represented 20% of the total expenditure. In the general population, outpatient care and hospitalization were the main expenses. In multivariate analysis, younger age, higher presence of co‐morbidities, and a recent HF or all‐cause hospitalization were independently associated with higher healthcare expenditure.
Conclusions
In Catalonia, a large portion of the annual healthcare budget is devoted to HF patients. Unplanned hospitalization represents the main source of healthcare‐related expenditure. The knowledge of how expenditure is distributed in a non‐selected HF population might allow health providers to plan the distribution of resources in patients with HF.
Obstructive sleep apnea (OSA) has been associated with heart failure (HF). Sleep fragmentation (SF), one of the main hallmarks of OSA, induces systemic inflammation, oxidative stress and sympathetic ...activation, hence potentially participating in OSA-induced cardiovascular consequences. However, whether SF
is deleterious to heart function is unknown. The aim of this study was to non-invasively evaluate the effect of SF mimicking OSA on heart function in healthy mice and in mice with HF.
Forty C57BL/6J male mice were randomized into 4 groups: control sleep (C), sleep fragmentation (SF), isoproterenol-induced heart failure (HF), and mice subjected to both SF+HF. Echocardiography was performed at baseline and after 30 days to evaluate left ventricular end-diastolic (LVEDD) and end-systolic (LVESD) diameters, left ventricular ejection fraction (LVEF) and fraction shortening (FS). The effects of SF and HF on these parameters were assessed by two-way ANOVA. Mice with isoproterenol-induced HF had significant increases in LVEDD and LVESD, as well as a decreases in LVEF and FS (
= 0.013,
= 0.006,
= 0.027, and
= 0.047, respectively). However, no significant effects emerged with SF (
= 0.480,
= 0.542,
= 0.188, and
= 0.289, respectively).
Chronic SF mimicking OSA did not induce echocardiographic changes in cardiac structure and function in both healthy and HF mice. Thus, the deleterious cardiac consequences of OSA are likely induced by other perturbations associated with this prevalent condition, or result from interactions with underlying comorbidities in OSA patients.
Exercise training (ET) is a critical component of cardiac rehabilitation (CR), but it remains underused. The aim of this study was to compare clinical outcomes between patients who completed ET ...(A-T), those who accepted ET but did not complete it (A-NT), and those who did not accept to undergo it (R-NT), and to analyze reasons for rejecting or not completing ET.
A unicenter ambispective observational registry study of 497 patients with acute coronary syndrome (ACS) was carried out in Barcelona, Spain, from 2016 to 2019. The primary endpoint was a composite of all-cause mortality, hospitalization for ACS, or need for revascularization during follow-up. Multivariable analysis was carried out to identify variables independently associated with the primary outcome. Initially, 70% of patients accepted participating in the ET, but only 50.5% completed it. The A-T group were younger and had fewer comorbidities. Baseline characteristics in A-NT and R-NT groups were very similar. The main reason for not undergoing or completing ET was rejection (reason unknown) or work/schedule incompatibility. The median follow-up period was 31 months. Both the composite primary endpoint and mortality were significantly lower in the A-T group compared to the A-NT and R-NT (primary endpoint: 3.6% vs. 23.2% vs. 20.4%,
< 0.001, respectively; mortality: 0.8% vs. 9.1% vs. 8.2%,
< 0.001; respectively). During multivariable analysis, the only variables that remained statistically significant with the composite endpoint were ET completion, previous ACS, and anemia.
Completion of ET after ACS was associated with improved prognosis. Only half of the patients completed the ET program, with the leading reasons for not completing it being refusal (reason unknown) and work/schedule incompatibility. These results highlight the need to focus on the needs of patients in order to guarantee that structural barriers to ET no longer exist.
•Extracapsular spread (ECS) and lymph node ratio (LNR) had prognostic capacity in patients treated with a neck dissection.•We classified patients according to the ECS status and LNR ...value.•Classification according to ECS and LNR improves the prognostic capacity of the 8th edition of the TNM Classification.
The presence of nodes with extracapsular spread (ECS) and the lymph node ratio (LNR) have prognostic competence in the pathologic evaluation of patients with a head and neck squamous cell carcinoma (HNSCC) treated with a neck dissection. The purpose of this study is to assess the effect of ECS & LNR on prognosis of HPV negative HNSCC patients treated with neck dissection and to compare to 8th edition TNM/AJCC classification.
We carried out a retrospective study of 1383 patients with HNSCC treated with a neck dissection between 1985 and 2013. We developed a classification of the patients according to the presence of nodes with ECS and the LNR value with a recursive partitioning analysis (RPA) model.
We obtained a classification tree with four terminal nodes: for patients without ECS (including patients pN0) the cut-off point for LNR was 1.6%, while for patients with lymph nodes with ECS it was 11.4%. The 5-year disease-specific survival for patients without ECS/LNR < 1.6% was 83.3%; for patients without ECS/LNR ≥ 1.6% it was 61.5%; for patients with ECS/LNR < 11.4% it was 33.7%; and for patients with ECS/LNR ≥ 11.4% it was 18.5%. The classification obtained with RPA had better discrimination between categories than the 8th edition of the TNM/AJCC classification.
ECS status and LNR value proved high prognostic capacity in the pathological evaluation of the neck dissection. The combination of ECS and LNR improved the predictive capacity of the 8th edition of the TNM/AJCC classification in HPV-negative HNSCC patients.
Heart failure (HF) is a common condition associated with a high rate of hospitalizations and adverse outcomes. HF is characterized by impairments of either the cardiac ventricular filling, ejection ...of blood capacity or both. Sleep fragmentation (SF) involves a series of short sleep interruptions that lead to fatigue and contribute to cognitive impairments and dementia. Both conditions are known to be associated with increased inflammation and dysbiosis of the gut microbiota. In the present study, mice were distributed into four groups, and subjected for four weeks to either HF, SF, both HF and SF, or left unperturbed as controls. We used 16S metabarcoding to assess fecal microbiome composition before and after the experiments. Evidence for distinct alterations in several bacterial groups and an overall decrease in alpha diversity emerged in HF and SF treatment groups. Combined HF and SF conditions, however, showed no synergism, and observed changes were not always additive, suggesting preliminarily that some of the individual effects of either HF or SF cancel each other out when applied concomitantly.
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