Pneumonia Deaths Research Articles

Automatic classification of diseases from free-text death certificates for real-time surveillance.

BackgroundDeath certificates provide an invaluable source for mortality statistics which can be used for surveillance and early warnings of increases in disease activity and to support the development and monitoring of prevention or response strategies. However, their value can be realised only if accurate, quantitative data can be extracted from death certificates, an aim hampered by both the volume and variable nature of certificates written in natural language. This study aims to develop a set of machine learning and rule-based methods to automatically classify death certificates according to four high impact diseases of interest: diabetes, influenza, pneumonia and HIV.MethodsTwo classification methods are presented: i) a machine learning approach, where detailed features (terms, term n-grams and SNOMED CT concepts) are extracted from death certificates and used to train a set of supervised machine learning models (Support Vector Machines); and ii) a set of keyword-matching rules. These methods were used to identify the presence of diabetes, influenza, pneumonia and HIV in a death certificate. An empirical evaluation was conducted using 340,142 death certificates, divided between training and test sets, covering deaths from 2000–2007 in New South Wales, Australia. Precision and recall (positive predictive value and sensitivity) were used as evaluation measures, with F-measure providing a single, overall measure of effectiveness. A detailed error analysis was performed on classification errors.ResultsClassification of diabetes, influenza, pneumonia and HIV was highly accurate (F-measure 0.96). More fine-grained ICD-10 classification effectiveness was more variable but still high (F-measure 0.80). The error analysis revealed that word variations as well as certain word combinations adversely affected classification. In addition, anomalies in the ground truth likely led to an underestimation of the effectiveness.ConclusionsThe high accuracy and low cost of the classification methods allow for an effective means for automatic and real-time surveillance of diabetes, influenza, pneumonia and HIV deaths. In addition, the methods are generally applicable to other diseases of interest and to other sources of medical free-text besides death certificates.

Solar-powered oxygen delivery: study protocol for a randomized controlled trial.

BackgroundPneumonia is a leading cause of childhood mortality globally. Oxygen therapy improves survival in children with pneumonia, yet its availability remains limited in many resource-constrained settings where most deaths occur. Solar-powered oxygen delivery could be a sustainable method to improve oxygen delivery in remote areas with restricted access to a supply chain of compressed oxygen cylinders and reliable electrical power.Methods/DesignThis study is a randomized controlled trial (RCT). Solar-powered oxygen delivery systems will be compared to a conventional method (oxygen from cylinders) in patients with hypoxemic respiratory illness. Enrollment will occur at two sites in Uganda: Jinja Regional Referral Hospital and Kambuga District Hospital. The primary outcome will be the length of hospital stay. Secondary study endpoints will be mortality, duration of supplemental oxygen therapy (time to wean oxygen), proportion of patients successfully oxygenated, delivery system failure, cost, system maintenance and convenience.DiscussionThe RCT will provide useful data on the feasibility and noninferiority of solar-powered oxygen delivery. This technological innovation uses freely available inputs, the sun and the air, to oxygenate children with pneumonia, and can be applied “off the grid” in remote and/or resource-constrained settings where most pneumonia deaths occur. If proven successful, solar-powered oxygen delivery systems could be scaled up and widely implemented for impact on global child mortality.Trial registrationClinicaltrials.gov registration number NCT0210086 (date of registration: 27 March, 2014)

Sex and Age Differences in Mortality in Southern China, 2004-2010.

The purpose of this study was to describe the mortality patterns in the southern provinces of China, and to provide epidemiologic data on sex and age differences of death outcomes. Reliable mortality and population data from January 2004 to December 2010 were obtained from 12 Disease Surveillance Point (DSP) sites in four provinces of China. Death data from all causes and respiratory disease, chronic obstructive pulmonary disease (COPD), pneumonia and influenza, circulatory disease, and ischemic heart disease, were stratified by year, month of death occurrence and sex, seven age groups, and summarized by descriptive statistics. The mean annual mortality rates of the selected 12 DSP sites in the southernmost provinces of China were 543.9 (range: 423.9–593.6) deaths per 100,000 population. The death rates show that noted sex differences were higher in the male population for all-cause, COPD and circulatory diseases. Pneumonia and influenza death rates present a different sex- and age-related distribution, with higher rates in male aged 65–74 years; whereas the death rates were opposite in elderly aged ≥75 years, and relatively higher in young children. This study had practical implications for recommending target groups for public health interventions.

Burden of Severe Pneumonia, Pneumococcal Pneumonia and Pneumonia Deaths in Indian States: Modelling Based Estimates.

The burden of severe pneumonia in terms of morbidity and mortality is unknown in India especially at sub-national level. In this context, we aimed to estimate the number of severe pneumonia episodes, pneumococcal pneumonia episodes and pneumonia deaths in children younger than 5 years in 2010. We adapted and parameterized a mathematical model based on the epidemiological concept of potential impact fraction developed CHERG for this analysis. The key parameters that determine the distribution of severe pneumonia episode across Indian states were state-specific under-5 population, state-specific prevalence of selected definite pneumonia risk factors and meta-estimates of relative risks for each of these risk factors. We applied the incidence estimates and attributable fraction of risk factors to population estimates for 2010 of each Indian state. We then estimated the number of pneumococcal pneumonia cases by applying the vaccine probe methodology to an existing trial. We estimated mortality due to severe pneumonia and pneumococcal pneumonia by combining incidence estimates with case fatality ratios from multi-centric hospital-based studies. Our results suggest that in 2010, 3.6 million (3.3–3.9 million) episodes of severe pneumonia and 0.35 million (0.31–0.40 million) all cause pneumonia deaths occurred in children younger than 5 years in India. The states that merit special mention include Uttar Pradesh where 18.1% children reside but contribute 24% of pneumonia cases and 26% pneumonia deaths, Bihar (11.3% children, 16% cases, 22% deaths) Madhya Pradesh (6.6% children, 9% cases, 12% deaths), and Rajasthan (6.6% children, 8% cases, 11% deaths). Further, we estimated that 0.56 million (0.49–0.64 million) severe episodes of pneumococcal pneumonia and 105 thousand (92–119 thousand) pneumococcal deaths occurred in India. The top contributors to India’s pneumococcal pneumonia burden were Uttar Pradesh, Bihar, Madhya Pradesh and Rajasthan in that order. Our results highlight the need to improve access to care and increase coverage and equity of pneumonia preventing vaccines in states with high pneumonia burden.

PIN60 - Cost-Effectiveness Analysis of Oseltamivir in the Influenza Pneumonia Prevention In Colombia

Influenza disease may result in a severe disease causing hospitalization and deaths in younger children and older adults. Early antiviral treatment may improve clinical outcomes. Our goal was to estimate the oseltamivir cost-effectiveness in the prevention of pneumonia due to influenza in the Colombian children and elderly population. A probabilistic decision-tree model to simulate Influenza-Like Syndrome (ILS) burden of disease and influenza pneumonia complications in Colombian population was programmed in excel. Transition probabilities and care costs for Colombia were obtained from a literature review and surveillance databases. Oseltamivir effectiveness was meta-analyzed from randomized trials and observational studies. Incremental cost-effectiveness ratio (ICER) for oseltamivir in the prevention of pneumonia complication in population under five years of age and older than 65 year old with ILS was estimated. Monte Carlo simulation with 10,000 iterations were used to estimate 95% confidence interval. Costs were expressed in 2013 USD. A total of 275,788 ILS cases in children and 86,675 in elderly population were estimated for 2014. Whit no oseltamivir would occur 75,789 and 62,817 pneumonias in children and elderly, respectively, and a total 22,719 deaths. Including the oseltamivir treatment at 90% coverage would avert 33,462 pneumonias and 6639 pneumonia deaths. The oseltamivir cost were estimated on US$ 6,419,552, and it would be a cost-saving intervention in population younger than 5 years old and equal or older than 65 years old with an ICER of US$ -953 (IC95% US$-934 to -759). The use of oseltamivir in children and elderly whit ILS appear to be a cost-saving strategy in Colombia, to prevent pneumonia and death complications, when it is administrated between 48 hours of symptoms onset.

Cost-effectiveness analysis of pneumococcal conjugate vaccine introduction in Paraguay

ObjectiveTo describe a cost-effectiveness analysis of 10- or 13-valent pneumococcal conjugate vaccine (PCV10 or 13) introduction in Paraguay compared to no vaccination. MethodsThe integrated TRIVAC vaccine cost-effectiveness model (version 2.0) jointly developed by the Pan American Health Organization's ProVac Initiative and the London School of Hygiene & Tropical Medicine was applied from the government and societal perspectives to estimate the cost-effectiveness (CE) of PCV introduction during 2010 and 2011. The cost-effectiveness ratios of PCV10 and PCV13 were separately compared to non-vaccination. The model calculated health and economic benefits of vaccination for 10 birth cohorts of children <5 years of age. A base case scenario with two primary doses at 2 and 4 months and a booster dose at 12 months (2+1 schedule) and alternate scenarios with varying parameters were considered. ResultsWith PCV10 introduction, the incremental costs of the vaccination program would be approximately US$ 67 million to vaccinate all 10 cohorts of children; with PCV13, US$ 87 million. Health services costs avoided by the government with PCV10 would be US$ 19.5 million; with PCV 13, US$ 17.7 million. From the societal perspective, savings were much greater: with PCV10, US$ 43 million; with PCV13, US$ 35 million. For the higher priced PCV13, the average cost-effectiveness ratio was better than for PCV10 when compared to no vaccination, but regardless both were cost effective for government and society based on a threshold of 3× GDP per capita in Paraguay (2009 US$ 2516). The number of averted meningitis and all-cause pneumonia cases and deaths was greater with PCV13 than with PCV10 when compared to no vaccination. ConclusionThe introduction of either PCV10 or PCV13 would be cost effective when compared to no vaccination, and in some scenarios, highly cost effective in Paraguay. The outcomes of these analyses demonstrate that a pneumococcal vaccine could substantially reduce morbidity and mortality in children <5 years in Paraguay.

Modelling Based Estimates for Severe Pneumonia and Pneumonia Deaths in Indian States

This presentation highlights the use of mathematical model to estimate burden of disease in absence of surveillance data. We estimated that in 2010, 3.57 million severe pneumonia cases and 0.45 million all cause pneumonia deaths occurred in children under age 5 years. Among these cases, the contribution of pneumococcal pneumonia was 15.8% to all cause pneumonia cases and 20.8% to all cause pneumonia deaths. Three states requires specific mention, Uttar Pradesh contributes (24% cases, 24% deaths), Bihar (16% cases, 17% deaths) and MP (9% cases, 10% deaths) to the national figures. They were top contributors to pneumococcal pneumonia burden also.

Reluctance to Advance the Age of Measles Immunisation: Ethics of Best Bargain, Policies of Denial, and Programs of Verticality

There is much expectation that the unprecedented social and political mobilization of polio initiative must be channelized to eliminate and eradicate measles. However, the fact file of measles in low and middle income countries (LMICs) raises several concerns. Measles surveillance in many of these countries is largely outbreakcentric and measles associated mortality is underestimated because several events are documented as pneumonia deaths even after verbal autopsies. Besides vaccine hesitancy, the social and cultural resistance against polio supplementary immunisation activities (SIAs) witnessed in certain pockets is likely to be higher in case of measles immunisation drives. The timing of measles containing vaccines (MCV1 and MCV2) in the immunisation schedules is also surrounded by some technical and ethical issues that we have been ignoring for decades. A small proportion of measles infection is borne by young infants before reaching eligibility for vaccination. Eradicating measles is going to be a tougher challenge on epidemiological grounds also. With basic reproduction number (R0) ranging from 12 to 18 and herd immunity threshold from 92% to 94%, maintaining very high routine immunisation (RI) coverage for a long period will require a cross-sectoral commitment at all levels of operation in LMICs. There are serious ethical issues related to policy, program and governance as well. Health systems in most of the LMICs are historically conditioned in the culture of verticality to an extent that even those who have an ethical responsibility to represent context-specific local voices end up taking an easier route of generic global narrative. An unstated and unappreciated divide between public health and people’s health looks too big to be bridged in such a milieu of governance. The endgame success of any global disease eradication program would decisively depend on two constituencies-frontline health workers and non-utilizer clients who could have been the utilizers.

Test of an electronic program to query clinicians about nonspecific causes reported for pneumonia deaths, New York City, 2012.

We tested an electronic cause-of-death query system at a hospital in New York City to evaluate clinicians’ reporting of cause of death. We used the system to query clinicians about all deaths assigned International Classification of Disease code J189 (pneumonia, unspecified) as the underlying cause of death. Of 29 death certificates that generated queries, 28 were updated with additional information, which led to revisions in the underlying cause of 27 deaths. The electronic system for querying reported cause of death was feasible and enabled quicker than usual responses; however, follow-up with clinicians to ensure timely, accurate, and complete responses was labor-intensive. Educating clinicians and enforcing reporting standards would reduce the time and effort required to ensure accurate and timely cause-of-death reporting.

Nursing and organizational barriers to daily interruption of sedation in U.S. hospitals: A thematic review of the literature

Despite focused attention on hospital-acquired infections, ventilator-associated pneumonia (VAP) infections and deaths continueto be a problem in U.S. hospitals. Research indicates that protocols are in place across hospitals but actual implementationlags behind. The inconsistencies in protocol implementation may be due to workarounds created during the process of dailyinterruption of sedation (DIS), which is the process of stopping the ventilated patient’s sedation at a prescribed time each day toevaluate the patient’s ability to wean. The purpose of this thematic synthesis of the literature was to understand how nursing andorganizational barriers may affect adherence to DIS protocols in U.S. hospitals. We conducted a search using the CumulativeIndex of Nursing and Allied Health Literature, using terms related to sedation and mechanical ventilation, then coded andcategorized the study findings, and developed themes. Three themes emerged: (1) organizational structure does not influenceDIS at either the hospital or unit level, (2) a collaborative, multidisciplinary culture may be needed to influence changes insedation practices, and (3) the gap between evidence and practice may be due to lack of nursing education and experience. Toimprove outcomes, intensive care units should evaluate the impact of multidisciplinary ventilator rounding teams that includenursing, on DIS adherence and VAP rates, and ensure that nurses are up-to-date on the evidence around all aspects of sedationmanagement.

Global, regional, and national estimates of pneumonia burden in HIV-infected children in 2010: a meta-analysis and modelling study

SummaryBackgroundGlobally, pneumonia is a leading cause of mortality and morbidity in children younger than 5 years. Underlying HIV infection is an important risk factor for pneumonia morbidity and mortality in children. There are, however, no global or country level estimates of pneumonia burden in HIV-infected children. We assessed the role of HIV in pneumonia incidence and mortality and estimated the number of pneumonia cases and deaths in HIV-infected children younger than 5 years in 133 high pneumonia-burden countries in 2010.MethodsWe estimated the risk of hospital admission and case fatality rate caused by pneumonia in HIV-infected children compared with HIV-uninfected children from a systematic review of studies published in Medline, Embase, and Global Health between Jan 1, 1980, and Aug 31, 2013. We estimated nationwide pneumonia incidence and mortality with two different models that incorporated several risk factors for paediatric pneumonia hospital admission and mortality (including HIV infection). We then estimated the number of pneumonia episodes and deaths that occurred in HIV-infected children in 2010.FindingsThe odds ratio (OR) for hospital admission for all-cause pneumonia in HIV-infected children compared with HIV-uninfected children was 6·5 (95% CI 5·9–7·2). The risk of death was higher in children with pneumonia and HIV compared with those with pneumonia only (OR 5·9, 95% CI 2·7–12·7). In 2010, 1·4 million pneumonia episodes (uncertainty range [UR] 0·6 million to 3·3 million) and 88 000 pneumonia deaths (UR 47 400–153 000) occurred in HIV-infected children in low-income countries. Of these, 1·2 million pneumonia episodes (UR 0·5 million–2·7 million) and 85 400 deaths (UR 46 000–147 300) were directly attributable to HIV. 1·3 million (90%) pneumonia episodes and 82 400 (93%) pneumonia deaths in HIV-infected children aged younger than 5 years occurred in the WHO African region.InterpretationGlobally, a small proportion of pneumonia episodes and pneumonia deaths occur in HIV-infected children. However, in the highest HIV-burden countries in sub-Saharan Africa (ie, Swaziland, Lesotho, and Zimbabwe) up to a fifth of all pneumonia cases and 60% of pneumonia deaths occur in HIV-infected children. In these countries, major reductions in child pneumonia mortality can be achieved only if the systemic challenges plaguing the health system (poor coverage of early infant testing for HIV, of antiretroviral drugs in pregnant women and young children, of co-trimoxazole prophylaxis, and of pneumococcal vaccination) can be overcome.FundingWHO.

Objective Assessment of Stove Use with Temperature Sensors in a Multi-Stove Study — Kenya, 2012–2013

Background: Household air pollution (HAP) caused by burning biomass fuel for cooking accounts for 500,000 annual pediatric pneumonia deaths in the developing world. The Global Health Alliance aims to reduce HAP and improve health outcomes by installing 100 million improved cookstoves by 2020. However, data on stove preference and stove acceptability are limited. We analyzed data from data-logging temperature sensors to assess improved cookstove use objectively during a multi-stove intervention study. Methods: Up to six different improved cookstoves (Ecochula, Ecozoom, Envirofit, Philips, Prakti, RTI TECA) were installed in a cross-over study during six 2-week periods in 43 households in two rural Kenyan villages; traditional stoves remained available for use. Temperature sensors logged traditional and improved cookstove temperatures and ambient temperature every 10 minutes. Recorded stove temperatures were adjusted for ambient temperature and cooking events were identified using a temperature-change algorithm. Preliminary analyses using ANOVA and chi-squared tests were conducted to compare stove use across improved cookstoves. Results: The 1,247 days with complete data were categorized as: improved cookstove only (24%), traditional stove only (27%), both stoves (42%), and neither stove (7%). Days with any improved stove use (alone or with traditional stove) ranged from 58% to 72% across stove types (P&lt;.05). When improved cookstoves were used, daily improved cookstove cooking events ranged from 1.8 to 2.8 across stove types (P&lt;.0001). Conclusion: Improved stoves were used frequently, but days when only improved stoves were used were not common. This study identified two improved stoves that were used more often, suggesting increased acceptability within study households. Integration of these results with HAP exposure reduction and qualitative data will help determine if one or more improved cookstoves could be used in a longitudinal health study.

Trend analysis on mortality and the mortal causes among children under 5 in Sichuan province, from 2001 to 2013

To study the mortality of children under five and the causes of death together with related trend of dynamics, from 2001 to 2013 in Sichuan province. Using the Children Death Monitoring Network under five in Sichuan province to obtain basic data. Descriptive statistics and chi-square were used to describe the mortalities in children and infants as well as the causes of death, in both rural and urban areas of Sichuan province. In Sichuan province, the mortality of children under five decreased from 35.30‰ in 2001 to 11.77‰ in 2013. In 2013, mortality in the rural areas was 2.37 times more than that in the urban area. The proportion of neonatal deaths among the mortality in children under five was 44.72%. Pneumonia, congenital heart diseases and premature or low birth weigh were the top three causes of death for children under five. Among them, the top three causes of death for urban area were congenital heart disease, drowning, and premature or low birth weight/birth asphyxia. Meanwhile, the top three causes of death in rural areas were pneumonia, premature birth/low birth weight and birth asphyxia. Overall, the mortality rates of birth asphyxia, pneumonia and low birth weight gradually decreasd but drowning, diarrhea and traffic accidents fluctuated. The mortality of children under five in Sichuan province was 13‰, which had already met the goal set for the year 2020. However, reducing the mortality in rural areas, narrowing the gap between urban and rural areas seemed the main part of the future endeavor while focus of prevention should be adjusted according to the causes of death.

Maternal outcomes in pregnancies affected by varicella zoster virus infections: population-based study on 7.7 million pregnancy admissions.

Previous estimates of the incidence of varicella zoster virus (VZV) pneumonia and maternal death associated with VZV infection among the pregnant population have varied considerably and been based predominantly on reports from case series. We sought to measure the incidence of VZV-related morbidity and mortality to provide more representative population estimates. We carried out a large cohort study on all births using the United States Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database between 2003 and 2010. Descriptive statistics were used to measure baseline characteristics and outcomes of women with VZV infection. Multivariate logistic regression analyses were used to identify risk factors for the development of VZV-related morbidity and mortality. We identified 935 patients admitted for VZV infection among 7.7 million pregnancy admissions, representing an incidence of 1.21 cases/10 000 pregnancies (95% confidence interval [CI], 1.13-1.29). The incidence of VZV pneumonia was 2.5% (95% CI, 1.6-3.7). No maternal deaths were recorded during the 8-year study period. There were no significant risk factors identified for those who developed VZV pneumonia compared to those who had an uncomplicated VZV infection during pregnancy. The incidence of VZV pneumonia and VZV infection associated with maternal death is significantly lower than previously estimated and may reflect better immunization and earlier interventions.

Childhood very severe pneumonia and meningitis related hospitalization and death in Yemen, before and after introduction of H. influenzae type b [Hib] vaccine

Haemophilus influenzae type b (Hib) vaccine was included in the Yemen immunization programme in 2005. This study compared the rates of very severe pneumonia and all-cause meningitis hospitalization and death, before and after introduction of conjugate Hib vaccine, and reports the results of the 2010 bacterial meningitis surveillance. A retrospective analysis was made of data collected for 2000-2010 for all children aged 2-60 months in the main children's hospital in Sana'a. Compared with the pre-Hib vaccination period, the post-Hib period showed significant and impressive reductions in the rates of hospitalization and death for all-cause meningitis. However, hospitalization and death for very severe pneumonia improved only modestly, and there was evidence of a decreasing but non-significant trend indicting that very severe pneumonia was a non-specific endpoint with multi-etiologies (both viral and bacterial). Very severe pneumonia remains the leading cause of severe morbidity and death for young children, particularly those aged < 12 months.

Thermal Taste and Anti-Aspiration Drugs: A Novel Drug Discovery Against Pneumonia

Despite the development of strong antibiotics, the pneumonia death is increasing all over the world in these decades. Among the people who died of pneumonia, the majority were 65 years old or over. Although pneumonia is recently categorized into several entities, aspiration pneumonia includes all entities. Therefore, targeting dysphagia and aspiration to treat pneumonia is a promising strategy and anti-aspiration drugs will be a part of pneumonia treatment. The swallowing reflex in elderly people was temperature-sensitive and the improvement of swallowing reflex by temperature stimuli could be mediated by the thermosensing TRP channels at pharynx. The administration of capsaicin as an agonist stimulus of TRPV1, a warm temperature receptor, decreased the delay in swallowing reflex. Red wine polyphenols improved swallowing reflex by enhancing TRPV1 response. Food with menthol, agonist of TRPM8 which is a cold temperature receptor, also decreased the delay in swallowing reflex. Olfactory stimulation such as black pepper was useful to improve the swallowing reflex for people with low ADL levels or with decreased consciousness. Thus, recent advancement of geriatrics found several anti-aspiration drugs such as thermosensing TRP channel agonists, black pepper odor, amantadine, cilostazol, theophylline and angiotensin- converting enzymes inhibitors. Thermosensing TRP channel agonists include capsaicin, capsiate, menthol, and red wine polyphenols. Controls of swallowing are mediated by various stages of neural system from peripheral sensory nerves to the entire cerebral cortex. Each anti-aspiration drug acts on various sites of neural axis of swallowing reflex. The combination of various anti-aspiration drugs may improve dysphagia and prevent aspiration pneumonia.

Risk of pneumonia with inhaled corticosteroid versus long-acting bronchodilator regimens in chronic obstructive pulmonary disease: a new-user cohort study.

IntroductionObservational studies using case-control designs have showed an increased risk of pneumonia associated with inhaled corticosteroid (ICS)-containing medications in patients with chronic obstructive pulmonary disease (COPD). New-user observational cohort designs may minimize biases associated with previous case-control designs.ObjectiveTo estimate the association between ICS and pneumonia among new users of ICS relative to inhaled long-acting bronchodilator (LABD) monotherapy.MethodsPneumonia events in COPD patients ≥45 years old were compared among new users of ICS medications (n = 11,555; ICS, ICS/long-acting β2-agonist [LABA] combination) and inhaled LABD monotherapies (n = 6,492; LABA, long-acting muscarinic antagonists) using Cox proportional hazards models, with propensity scores to adjust for confounding. Setting: United Kingdom electronic medical records with linked hospitalization and mortality data (2002–2010). New users were censored at earliest of: pneumonia event, death, changing/discontinuing treatment, or end of follow-up. Outcomes: severe pneumonia (primary) and any pneumonia (secondary).ResultsFollowing adjustment, new use of ICS-containing medications was associated with an increased risk of pneumonia hospitalization (n = 322 events; HR = 1.55, 95% CI: 1.14, 2.10) and any pneumonia (n = 702 events; HR = 1.49, 95% CI: 1.22, 1.83). Crude incidence rates of any pneumonia were 48.7 and 30.9 per 1000 person years among the ICS-containing and LABD cohorts, respectively. Excess risk of pneumonia with ICS was reduced when requiring ≥1 month or ≥ 6 months of new use. There was an apparent dose-related effect, with greater risk at higher daily doses of ICS. There was evidence of channeling bias, with more severe patients prescribed ICS, for which the analysis may not have completely adjusted.ConclusionsThe results of this new-user cohort study are consistent with published findings; ICS were associated with a 20–50% increased risk of pneumonia in COPD, which reduced with exposure time. This risk must be weighed against the benefits when prescribing ICS to patients with COPD.

Reduced Total and Cause-Specific Mortality from Walking and Running in Diabetes

This study aimed to assess the relationships of running and walking to mortality in diabetic subjects. We studied the mortality surveillance between January 1, 1989 and December 31, 2008, of 2160 participants of the National Walkers' and Runners' Health Studies who reported using diabetic medications at baseline. Hazard ratios (HR) and 95% confidence intervals (95% CI) were obtained from Cox proportional hazard analyses for mortality versus exercise energy expenditure (MET-hours per day, 1 MET·h ∼1-km run or a 1.5-km brisk walk). Three hundred and thirty-one diabetic individuals died during a 9.8-yr average follow-up. Merely meeting the current exercise recommendations was not associated with lower all-cause mortality (P = 0.61), whereas exceeding the recommendations was associated with lower all-cause mortality (HR = 0.64, 95% CI = 0.49-0.82, P = 0.0005). Greater MET-hours per day ran or walked was associated with 40% lower risk for all chronic kidney disease-related deaths (HR = 0.60 per MET·h·d(-1), 95% CI = 0.35-0.91, P = 0.02), 31% lower risk for all sepsis-related deaths (HR = 0.69, 0.47-0.94, P = 0.01), and 31% lower risk for all pneumonia and influenza-related deaths (HR = 0.69, 95% CI = 0.45-0.97, P = 0.03). Running or walking ≥1.8 MET·h·d(-1) was associated with 57% reduction in cardiovascular disease (CVD) as an underlying cause of death and 46% lower risk for all CVD-related deaths versus <1.07 MET·h·d. All results remained significant: 1) adjusted for baseline BMI and 2) excluding all deaths within 3 yr of baseline. These results suggest that 1) exercise is associated with significantly lower all-cause, CVD, chronic kidney disease, sepsis, and pneumonia, and influenza mortality in diabetic patients and 2) higher exercise standards may be warranted for diabetic patients than currently provided to the general population.

An overview of respiratory syncytial virus.

Respiratory Syncytial Virus (RSV), a member of the Paramyxoviridae family, is the leading cause of lower respiratory tract illness (LRI) in infants. From 1993 to 2008, the total RSV hospitalization rate in the United States across all age groups was 55 per 100,000 person-years, slightly lower than the rate of 64 per 100,000 personyears for influenza viruses [1]. In infants, the hospitalization rate was 2,345 per 100,000 person-years for RSV compared to 151 for influenza, consistent with reports that RSV hospitalizes 1–2% of infants in the US each winter, a staggering statistic [1]. RSV disease is not limited to infants. RSV resulted in more hospitalizations in 1– 4-year-olds than influenza [1]. One in 13 children under the age of five in the US required medical attention for RSV each year, and 60% of office visits were for 2–5-year-olds [2]. RSV remains a significant cause of death. Over all age groups, influenza caused three times as many deaths as RSV in the US from 1990 to 1999, mostly in the elderly [3]. RSV caused 137 deaths per year in the US in children less than 4 years old, compared to 38 per year in this age group for influenza [3]. Globally, RSV was estimated to have caused 66,000 to 199,000 pneumonia deaths in children less than 5 years old in 2005, making RSV the third most important cause of deadly childhood pneumonia after Streptococcus pneumonia and Haemophilus influenza [4]. RSV is increasingly recognized as a global health priority. Other than ribavirin, there are no licensed RSV vaccines or therapeutics. The monoclonal antibody (mAb) palivizumab is a neutralizing mAb against a conserved epitope in the viral fusion (F) surface glycoprotein. Palivizumab is administered prophylactically to high-risk infants, such as those with chronic lung disease of prematurity, congenital heart disease, or premature birth at less than 36 weeks gestational age, but it costs $4,500 per patient treatment course [5].

The initial report of RTOG 0524: Phase I/II trial of a combination of paclitaxel and trastuzumab with daily irradiation or paclitaxel alone with daily irradiation following transurethral surgery for noncystectomy candidates with muscle-invasive bladder cancer.

LBA287 Background: Most patients (pts) with muscle-invasive bladder urothelial carcinoma (UC) undergo definitive local treatment with radical cystectomy. Up to 50% of pts with UC overexpress HER2/neu, which may be associated with reduced responsiveness to chemoradiation and reduced survival. Many pts with UC have comorbidities that preclude surgery, creating a traditionally underserved population with worse outcomes. RTOG 0524 evaluated the safety and efficacy of trimodality, organ-preserving therapy in pts not suitable for cystectomy. Methods: Pts with invasive bladder UC (stages T2-T4a, N0-1, M0) underwent cystoscopic tumor resection. Tumors were analyzed by HER2/neu immunohistochemistry (IHC) and assigned to chemotherapy group I (IHC 2+ or 3+; paclitaxel and trastuzumab) or II (IHC negative or 1+; paclitaxel alone). Concurrent weekly paclitaxel (50 mg/m2), weekly trastuzumab (group I only) and daily radiation (64.8 Gy total in 36 fractions) were given for seven consecutive weeks. Results: 21 eligible patients were entered in group I and 47 in group 2, with median ages of 80 and 73, respectively. The primary endpoint was acute protocol-defined toxicity related to treatment. Acute toxicity was observed in 7/21 pts (33%) in group I and 14/47 pts (30%) in group II. Most common grade &gt; 3 adverse events in groups I and II were marrow suppression (43% and 17%), diarrhea (33% and 30%), and hyponatremia (14% and 4%). Three deaths on study were attributed to colonic perforation, pneumonia, and sudden death. Radiation completion rates were 72% and 85% in the two groups, and full-dose chemotherapy completion rates were 52% and 51%. Evaluation by cystoscopy and/or tumor biopsy at 12 weeks noted complete response in 9/13 pts (69%) in group I, in 19/33 pts (58%) in group II, and was not performed in the remaining pts. Conclusions: Trimodality bladder-preserving therapy is an appropriate treatment in noncystectomy candidates with invasive UC. The response rate for HER2/neu-targeted therapy is encouraging but may increase certain adverse events in this challenging population. Clinical trial information: NCT00238420.