Pressure support versus T-tube for weaning from mechanical ventilation in adults

BackgroundMechanical ventilation is important in caring for patients with critical illness. Clinical complications, increased mortality, and high costs of health care are associated with prolonged ventilatory support or premature discontinuation of mechanical ventilation. Weaning refers to the process of gradually or abruptly withdrawing mechanical ventilation. the weaning process begins after partial or complete resolution of the underlying pathophysiology precipitating respiratory failure and ends with weaning success (successful extubation in intubated patients or permanent withdrawal of ventilatory support in tracheostomized patients).ObjectivesTo evaluate the effectiveness and safety of two strategies, a T-tube and pressure support ventilation, for weaning adult patients with respiratory failure that required invasive mechanical ventilation for at least 24 hours, measuring weaning success and other clinically important outcomes.Search methodsWe searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 6); MEDLINE (via PubMed) (1966 to June 2012); EMBASE (January 1980 to June 2012); LILACS (1986 to June 2012); CINAHL (1982 to June 2012); SciELO (from 1997 to August 2012); thesis repository of CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior) (http://capesdw.capes.gov.br/capesdw/) (August 2012); and Current Controlled Trials (August 2012).We reran the search in December 2013. We will deal with any studies of interest when we update the review.Selection criteriaWe included randomized controlled trials (RCTs) that compared a T-tube with pressure support (PS) for the conduct of spontaneous breathing trials and as methods of gradual weaning of adult patients with respiratory failure of various aetiologies who received invasive mechanical ventilation for at least 24 hours.Data collection and analysisTwo authors extracted data and assessed the methodological quality of the included studies. Meta-analyses using the random-effects model were conducted for nine outcomes. Relative risk (RR) and mean difference (MD) or standardized mean difference (SMD) were used to estimate the treatment effect, with 95% confidence intervals (CI).Main resultsWe included nine RCTs with 1208 patients; 622 patients were randomized to a PS spontaneous breathing trial (SBT) and 586 to a T-tube SBT. the studies were classified into three categories of weaning: simple, difficult, and prolonged. Four studies placed patients in two categories of weaning. Pressure support ventilation (PSV) and a T-tube were used directly as SBTs in four studies (844 patients, 69.9% of the sample). in 186 patients (15.4%) both interventions were used along with gradual weaning from mechanical ventilation; the PS was gradually decreased, twice a day, until it was minimal and periods with a T-tube were gradually increased to two and eight hours for patients with difficult and prolonged weaning. in two studies (14.7% of patients) the PS was lowered to 2 to 4 cm H2O and 3 to 5 cm H2O based on ventilatory parameters until the minimal PS levels were reached. PS was then compared to the trial with the T-tube (TT).We identified 33 different reported outcomes in the included studies; we took 14 of them into consideration and performed meta-analyses on nine. With regard to the sequence of allocation generation, allocation concealment, selective reporting and attrition bias, no study presented a high risk of bias. We found no clear evidence of a difference between PS and TT for weaning success (RR 1.07, 95% CI 0.97 to 1.17, 9 studies, low quality of evidence), intensive care unit (ICU) mortality (RR 0.81, 95% CI 0.53 to 1.23, 5 studies, low quality of evidence), reintubation (RR 0.92, 95% CI 0.66 to 1.26, 7 studies, low quality evidence), ICU and long-term weaning unit (LWU) length of stay (MD -7.08 days, 95% CI -16.26 to 2.1, 2 studies, low quality of evidence) and pneumonia (RR 0.67, 95% CI 0.08 to 5.85, 2 studies, low quality of evidence). PS was significantly superior to the TT for successful SBTs (RR 1.09, 95% CI 1.02 to 1.17, 4 studies, moderate quality of evidence). Four studies reported on weaning duration, however we were unable to combined the study data because of differences in how the studies presented their data. One study was at high risk of other bias and four studies were at high risk for detection bias. Three studies reported that the weaning duration was shorter with PS, and in one study the duration was shorter in patients with a TT.Authors' conclusionsTo date, we have found evidence of generally low quality from studies comparing pressure support ventilation (PSV) and with a T-tube. the effects on weaning success, ICU mortality, reintubation, ICU and LWU length of stay, and pneumonia were imprecise. However, PSV was more effective than a T-tube for successful spontaneous breathing trials (SBTs) among patients with simple weaning. Based on the findings of single trials, three studies presented a shorter weaning duration in the group undergoing PS SBT, however a fourth study found a shorter weaning duration with a T-tube.

Genetic predisposition to acute respiratory distress syndrome in patients with severe sepsis

The objective of this study was to analyze the association between candidate gene polymorphisms and susceptibility to acute respiratory distress syndrome (ARDS) in patients with severe sepsis. Patients older than 18 years admitted to the intensive care un

Prediction of 30-day mortality in older patients with a first acute myocardial infarction

This study sought predictors of mortality in patients aged >or=75 years with a first ST-segment elevation myocardial infarction (STEMI) and evaluated the validity of the GUSTO-I and TIMI risk models. Clinical variables, treatment and mortality data from 433 consecutive patients were collected. Univariable and multivariable logistic regression analyses were applied to identify baseline factors associated with 30-day mortality. Subsequently a model predicting 30-day mortality was created and compared with the performance of the GUSTO-I and TIMI models. After adjustment, a higher Killip class was the most important predictor (OR 16.1; 95% CI 5.7-45.6). Elevated heart rate, longer time delay to admission, hyperglycemia and older age were also associated with increased risk. Patients with hypercholesterolemia had a significantly lower risk (OR 0.46; 95% CI 0.24-0.86). Discrimination (c-statistic 0.79, 95% CI 0.75-0.84) and calibration (Hosmer-Lemeshow 6, p = 0.5) of our model were good. The GUSTO-I and TIMI risk scores produced adequate discrimination within our dataset (c-statistic 0.76, 95% CI 0.71-0.81, and c-statistic 0.77, 95% CI 0.72-0.82, respectively), but calibration was not satisfactory (HL 21.8, p = 0.005 for GUSTO-I, and HL 20.6, p = 0.008 for TIMI). In conclusion, short-term mortality in elderly patients with a first STEMI depends most importantly on initial clinical and hemodynamic status. The GUSTO-I and TIMI models are insufficiently adequate for providing an exact estimate of 30-day mortality risk.

Volcanic air pollution and mortality in France 1783?1784

Grattan J.P., Rabartin, R., Self, S. & Thordarson, Th. 2005. Volcanic air pollution and mortality in France 1783-84. Comptes Rendu Geosciences. 641-651 This item is available in both English and French in the PDF file.

Illness and elevated Human Mortality in Europe Coincident with the Laki Fissure eruption

Grattan, J. Durand, M. Taylor, S., Illness and elevated Human Mortality in Europe Coincident with the Laki fissure eruption. In: 'Volcanic Degassing: Geological Society, Special Publication 213', Oppenheimer, C., Pyle, D.M. and Barclay, J. (eds). Geological Society, London, Special Publications, 410-414, 2003.

Aspergillus e Aspergilose

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Cancer mortality in IBM endicott plant workers, 1969-2001: An update on a NY production plant

BACKGROUND: In response to concerns expressed by workers at a public meeting, we analyzed the mortality experience of workers who were employed at the IBM plant in Endicott, New York and died between 1969-2001. An epidemiologic feasibility assessment indicated potential worker exposure to several known and suspected carcinogens at this plant. METHODS: We used the mortality and work history files produced under a court order and used in a previous mortality analysis. Using publicly available data for the state of New York as a standard of comparison, we conducted proportional cancer mortality (PCMR) analysis. RESULTS: The results showed significantly increased mortality due to melanoma (PCMR = 367; 95% CI: 119, 856) and lymphoma (PCMR = 220; 95% CI: 101, 419) in males and modestly increased mortality due to kidney cancer (PCMR = 165; 95% CI: 45, 421) and brain cancer (PCMR = 190; 95% CI: 52, 485) in males and breast cancer (PCMR = 126; 95% CI: 34, 321) in females. CONCLUSION: These results are similar to results from a previous IBM mortality study and support the need for a full cohort mortality analysis such as the one being planned by the National Institute for Occupational Safety and Health.

Household Health and Cocoa Production: A Baseline Survey of Smallholder Farming Households in Western Region, Ghana

Background Chronic illness and premature mortality from malaria, water-borne diseases, and respiratory illnesses have long been known to diminish the welfare of individuals and households in developing countries. Previous research has also shown that chronic diseases among farming populations suppress labor productivity and agricultural output. As the illness and death toll from HIV/AIDS continues to climb in most of sub-Saharan Africa, concern has arisen that the loss of household labor it causes will reduce crop yields, impoverish farming households, intensify malnutrition, and suppress growth in the agricultural sector. If chronic morbidity and premature mortality among individuals in farming households have substantial impacts on household production, and if a large number of households are affected, it is possible that an increase in morbidity and mortality from HIV/AIDS or other diseases could affect national aggregate output and exports. If, on the other hand, the impact at the household farm level is modest, or if relatively few households are affected, there is likely to be little effect on aggregate production across an entire country. Which of these outcomes is more likely in West Africa is unknown. Little rigorous, quantitative research has been published on the impacts of AIDS on smallholder farm production, particularly in West Africa. The handful of studies that have been conducted have looked mainly at small populations in areas of very high HIV prevalence in southern and eastern Africa. Conclusions about how HIV/AIDS, and other causes of chronic morbidity and mortality, are affecting agriculture across the continent cannot be drawn from these studies. In view of the importance of agriculture, and particularly smallholder agriculture, in the economies of most African countries and the scarcity of resources for health interventions, it is valuable to identify, describe, and quantify the impact of chronic morbidity and mortality on smallholder production of important crops in West Africa. One such crop is cocoa. In Ghana, cocoa is a crop of national importance that is produced almost exclusively by smallholder households. In 2003, Ghana was the world’s second-largest producer of cocoa. Cocoa accounted for a quarter of Ghana’s export revenues that year and generated 15 percent of employment. The success and growth of the cocoa industry is thus vital to the country’s overall social and economic development. Study Objectives and Methods In February and March 2005, the Center for International Health and Development of Boston University (CIHD) and the Department of Agricultural Economics and Agribusiness (DAEA) of the University of Ghana, with financial support from the Africa Bureau of the U.S. Agency for International Development and from Mars, Inc., which is a major purchaser of West African cocoa, conducted a survey of a random sample of cocoa farming households in the Western Region of Ghana. The survey documented the extent of chronic morbidity and mortality in cocoa growing households in the Western Region of Ghana, the country’s largest cocoa growing region, and analyzed the impact of morbidity and mortality on cocoa production. It aimed to answer three specific research questions. (1) What is the baseline status of the study population in terms of household size and composition, acute and chronic morbidity, recent mortality, and cocoa production? (2) What is the relationship between household size and cocoa production, and how can this relationship be used to understand the impact of adult mortality and chronic morbidity on the production of cocoa at the household level? The study population was the approximately 42,000 cocoa farming households in the southern part of Ghana’s Western Region. A random sample of households was selected from a roster of eligible households developed from existing administrative information. Under the supervision of the University of Ghana field team, enumerators were graduate students of the Department of Agricultural Economics and Agribusiness or employees of the Cocoa Services Division. A total of 632 eligible farmers participated in the survey. Of these, 610 provided complete responses to all questions needed to complete the multivariate statistical analysis reported here.

Optimal assessment of the ability of children with recurrent respiratory tract infections to produce anti-polysaccharide antibodies.

Specific anti-polysaccharide antibody deficiency (SPAD) is an immune disorder. Diagnostic criteria have not yet been defined clearly. One hundred and seventy-six children evaluated for recurrent respiratory tract infections were analysed retrospectively. For each subject, specific anti-pneumococcal antibodies had been measured with two enzyme-linked immunosorbent assays (ELISAs), one overall assay (OA) using the 23-valent pneumococcal polysaccharide vaccine (23-PPSV) as detecting antigen and the other purified pneumococcal polysaccharide serotypes (serotype-specific assay, SSA) (serotypes 14, 19F and 23F). Antibody levels were measured before (n = 176) and after (n = 93) immunization with the 23-PPSV. Before immunization, low titres were found for 138 of 176 patients (78%) with OA, compared to 20 of 176 patients (11%) with the SSA. We found a significant correlation between OA and SSA results. After immunization, 88% (71 of 81) of the patients considered as responders in the OA test were also responders in the SSA; 93% (71 of 76) of the patients classified as responders according to the SSA were also responders in the OA. SPAD was diagnosed in 8% (seven of 93) of patients on the basis of the absence of response in both tests. Thus, we propose to use OA as a screening test for SPAD before 23-PPSV immunization. After immunization, SSA should be used only in case of a low response in OA. Only the absence of or a very low antibody response detected by both tests should be used as a diagnostic criterion for SPAD.

Survival expectations of the obese: Is excess mortality reflected in perceptions?

OBJECTIVE: This study compared self-reported subjective life expectancy (i.e., probability of living to age 75) for normal-weight, overweight, and obese weight groups to examine whether individuals are internalizing information about the health risks due to excessive weight. RESEARCH METHODS AND PROCEDURES: Using data from the Health and Retirement Study, a total of 9035 individuals 51 to 61 years old were analyzed by BMI category. The primary outcome measure was individuals' reports about their own expectations of survival to age 75. Absolute and relative risks of survival were compared with published estimates of survival to age 75. RESULTS: Consistently, higher levels of BMI were associated with lower self-estimated survival probabilities. Differences relative to normal weight ranged from 4.9% (p < 0.01) for male nonsmokers to 8.8% (p < 0.001) for female nonsmokers. However, these differences were substantially less than those obtained from published survival curve estimates, suggesting that obese individuals tended to underestimate mortality risks. DISCUSSION: Individuals appeared to underestimate the mortality risks of excessive weight; thus, knowledge campaigns about the risks of obesity should remain a top priority.

Factors associated with mortality in transplant patients with invasive aspergillosis.

BACKGROUND: Invasive aspergillosis (IA) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The purpose of this study was to evaluate factors associated with mortality in transplant patients with IA. METHODS: Transplant patients from 23 US centers were enrolled from March 2001 to October 2005 as part of the Transplant Associated Infection Surveillance Network. IA cases were identified prospectively in this cohort through March 2006, and data were collected. Factors associated with 12-week all-cause mortality were determined by logistic regression analysis and Cox proportional hazards regression. RESULTS: Six-hundred forty-two cases of proven or probable IA were evaluated, of which 317 (49.4%) died by the study endpoint. All-cause mortality was greater in HSCT patients (239 [57.5%] of 415) than in SOT patients (78 [34.4%] of 227; P<.001). Independent poor prognostic factors in HSCT patients were neutropenia, renal insufficiency, hepatic insufficiency, early-onset IA, proven IA, and methylprednisolone use. In contrast, white race was associated with decreased risk of death. Among SOT patients, hepatic insufficiency, malnutrition, and central nervous system disease were poor prognostic indicators, whereas prednisone use was associated with decreased risk of death. Among HSCT or SOT patients who received antifungal therapy, use of an amphotericin B preparation as part of initial therapy was associated with increased risk of death. CONCLUSIONS: There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials.

Co-regulation of nuclear respiratory factor-1 by NFkappaB and CREB links LPS-induced inflammation to mitochondrial biogenesis.

The nuclear respiratory factor-1 (NRF1) gene is activated by lipopolysaccharide (LPS), which might reflect TLR4-mediated mitigation of cellular inflammatory damage via initiation of mitochondrial biogenesis. To test this hypothesis, we examined NRF1 promoter regulation by NFκB, and identified interspecies-conserved κB-responsive promoter and intronic elements in the NRF1 locus. In mice, activation of Nrf1 and its downstream target, Tfam, by Escherichia coli was contingent on NFκB, and in LPS-treated hepatocytes, NFκB served as an NRF1 enhancer element in conjunction with NFκB promoter binding. Unexpectedly, optimal NRF1 promoter activity after LPS also required binding by the energy-state-dependent transcription factor CREB. EMSA and ChIP assays confirmed p65 and CREB binding to the NRF1 promoter and p65 binding to intron 1. Functionality for both transcription factors was validated by gene-knockdown studies. LPS regulation of NRF1 led to mtDNA-encoded gene expression and expansion of mtDNA copy number. In cells expressing plasmid constructs containing the NRF-1 promoter and GFP, LPS-dependent reporter activity was abolished by cis-acting κB-element mutations, and nuclear accumulation of NFκB and CREB demonstrated dependence on mitochondrial H(2)O(2). These findings indicate that TLR4-dependent NFκB and CREB activation co-regulate the NRF1 promoter with NFκB intronic enhancement and redox-regulated nuclear translocation, leading to downstream target-gene expression, and identify NRF-1 as an early-phase component of the host antibacterial defenses.

Long-term dynamics of death rates of emphysema, asthma, and pneumonia and improving air quality.

BACKGROUND: The respiratory tract is a major target of exposure to air pollutants, and respiratory diseases are associated with both short- and long-term exposures. We hypothesized that improved air quality in North Carolina was associated with reduced rates of death from respiratory diseases in local populations. MATERIALS AND METHODS: We analyzed the trends of emphysema, asthma, and pneumonia mortality and changes of the levels of ozone, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and particulate matters (PM2.5 and PM10) using monthly data measurements from air-monitoring stations in North Carolina in 1993-2010. The log-linear model was used to evaluate associations between air-pollutant levels and age-adjusted death rates (per 100,000 of population) calculated for 5-year age-groups and for standard 2000 North Carolina population. The studied associations were adjusted by age group-specific smoking prevalence and seasonal fluctuations of disease-specific respiratory deaths. RESULTS: Decline in emphysema deaths was associated with decreasing levels of SO2 and CO in the air, decline in asthma deaths-with lower SO2, CO, and PM10 levels, and decline in pneumonia deaths-with lower levels of SO2. Sensitivity analyses were performed to study potential effects of the change from International Classification of Diseases (ICD)-9 to ICD-10 codes, the effects of air pollutants on mortality during summer and winter, the impact of approach when only the underlying causes of deaths were used, and when mortality and air-quality data were analyzed on the county level. In each case, the results of sensitivity analyses demonstrated stability. The importance of analysis of pneumonia as an underlying cause of death was also highlighted. CONCLUSION: Significant associations were observed between decreasing death rates of emphysema, asthma, and pneumonia and decreases in levels of ambient air pollutants in North Carolina.

Menthol attenuates respiratory irritation and elevates blood cotinine in cigarette smoke exposed mice.

Addition of menthol to cigarettes may be associated with increased initiation of smoking. The potential mechanisms underlying this association are not known. Menthol, likely due to its effects on cold-sensing peripheral sensory neurons, is known to inhibit the sensation of irritation elicited by respiratory irritants. However, it remains unclear whether menthol modulates cigarette smoke irritancy and nicotine absorption during initial exposures to cigarettes, thereby facilitating smoking initiation. Using plethysmography in a C57Bl/6J mouse model, we examined the effects of L-menthol, the menthol isomer added to cigarettes, on the respiratory sensory irritation response to primary smoke irritants (acrolein and cyclohexanone) and smoke of Kentucky reference 2R4 cigarettes. We also studied L-menthol's effect on blood levels of the nicotine metabolite, cotinine, immediately after exposure to cigarette smoke. L-menthol suppressed the irritation response to acrolein with an apparent IC₅₀ of 4 ppm. Suppression was observed even at acrolein levels well above those necessary to produce a maximal response. Cigarette smoke, at exposure levels of 10 mg/m³ or higher, caused an immediate and marked sensory irritation response in mice. This response was significantly suppressed by L-menthol even at smoke concentrations as high as 300 mg/m³. Counterirritation by L-menthol was abolished by treatment with a selective inhibitor of Transient Receptor Potential Melastatin 8 (TRPM8), the neuronal cold/menthol receptor. Inclusion of menthol in the cigarette smoke resulted in roughly a 1.5-fold increase in plasma cotinine levels over those observed in mice exposed to smoke without added menthol. These findings document that, L-menthol, through TRPM8, is a strong suppressor of respiratory irritation responses, even during highly noxious exposures to cigarette smoke or smoke irritants, and increases blood cotinine. Therefore, L-menthol, as a cigarette additive, may promote smoking initiation and nicotine addiction.

Ventricular conduction and long-term heart failure outcomes and mortality in African Americans: insights from the Jackson Heart Study.

BACKGROUND: QRS prolongation is associated with adverse outcomes in mostly white populations, but its clinical significance is not well established for other groups. We investigated the association between QRS duration and mortality in African Americans. METHODS AND RESULTS: We analyzed data from 5146 African Americans in the Jackson Heart Study stratified by QRS duration on baseline 12-lead ECG. We defined QRS prolongation as QRS≥100 ms. We assessed the association between QRS duration and all-cause mortality using Cox proportional hazards models and reported the cumulative incidence of heart failure hospitalization. We identified factors associated with the development of QRS prolongation in patients with normal baseline QRS. At baseline, 30% (n=1528) of participants had QRS prolongation. The cumulative incidences of mortality and heart failure hospitalization were greater with versus without baseline QRS prolongation: 12.6% (95% confidence interval [CI], 11.0-14.4) versus 7.1% (95% CI, 6.3-8.0) and 8.2% (95% CI, 6.9-9.7) versus 4.4% (95% CI, 3.7-5.1), respectively. After risk adjustment, QRS prolongation was associated with increased mortality (hazard ratio, 1.27; 95% CI, 1.03-1.56; P=0.02). There was a linear relationship between QRS duration and mortality (hazard ratio per 10 ms increase, 1.06; 95% CI, 1.01-1.12). Older age, male sex, prior myocardial infarction, lower ejection fraction, left ventricular hypertrophy, and left ventricular dilatation were associated with the development of QRS prolongation. CONCLUSIONS: QRS prolongation in African Americans was associated with increased mortality and heart failure hospitalization. Factors associated with developing QRS prolongation included age, male sex, prior myocardial infarction, and left ventricular structural abnormalities.