1,911 research outputs found

    Demographic characteristics and opportunistic diseases associated with attrition during preparation for antiretroviral therapy in primary health centres in Kibera, Kenya.

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    Using routine data from HIV-positive adult patients eligible for antiretroviral therapy (ART), we report on routinely collected demographic characteristics and opportunistic diseases associated with pre-ART attrition (deaths and loss to follow-up). Among 2471 ART eligible patients, enrolled between January 2005 and November 2008, 446 (18%) were lost to attrition pre-ART. Adjusted risk factors significantly associated with pre-ART attrition included age <35 years (Odds Ratio, OR 1.4, 95% Confidence Interval, CI 1.1-1.8), severe malnutrition (OR 1.5, 95% CI 1.1-2.0), active pulmonary tuberculosis (OR 1.6, 95% CI 1.1-2.4), severe bacterial infections including severe bacterial pneumonia (OR 1.9, 95% CI 1.2-2.8) and prolonged unexplained fever (>1 month), (OR 2.6, 95% CI 1.3-5.2). This study highlights a number of clinical markers associated with pre-ART attrition that could serve as 'pointers' or screening tools to identify patients who merit fast-tracking onto ART and/or closer clinical attention and follow-up

    Viral pathogens and acute lung injury: investigations inspired by the SARS epidemic and the 2009 H1N1 influenza pandemic.

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    Acute viral pneumonia is an important cause of acute lung injury (ALI), although not enough is known about the exact incidence of viral infection in ALI. Polymerase chain reaction-based assays, direct fluorescent antigen (DFA) assays, and viral cultures can detect viruses in samples from the human respiratory tract, but the presence of the virus does not prove it to be a pathogen, nor does it give information regarding the interaction of viruses with the host immune response and bacterial flora of the respiratory tract. The severe acute respiratory syndrome (SARS) epidemic and the 2009 H1N1 influenza pandemic provided a better understanding of how viral pathogens mediate lung injury. Although the viruses initially infect the respiratory epithelium, the relative role of epithelial damage and endothelial dysfunction has not been well defined. The inflammatory host immune response to H1N1 infection is a major contributor to lung injury. The SARS coronavirus causes lung injury and inflammation in part through actions on the nonclassical renin angiotensin pathway. The lessons learned from the pandemic outbreaks of SARS coronavirus and H1N1 capture key principles of virally mediated ALI. There are pathogen-specific pathways underlying virally mediated ALI that converge onto a common end pathway resulting in diffuse alveolar damage. In terms of therapy, lung protective ventilation is the cornerstone of supportive care. There is little evidence that corticosteroids are beneficial, and they might be harmful. Future therapeutic strategies may be targeted to specific pathogens, the pathogenetic pathways in the host immune response, or enhancing repair and regeneration of tissue damage

    Inhaled corticosteriod use and the risk of pneumonia and COPD exacerbations in the UPLIFT study

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    Rationale Unlike many other COPD studies, the 4-year UPLIFT trial permitted inhaled corticosteroid (ICS) use during run-in and treatment phases. This provided the opportunity to prospectively observe the continuing effects of ICS on respiratory events in closely observed COPD population. Objectives We aimed to determine rate and number of episodes of pneumonia and exacerbations of COPD in patients entering the study on no ICS, fluticasone proprionate (FP), and other ICS. Methods The UPLIFT dataset was examined retrospectively, and patients were divided into three groups based on their medications at entry: no ICS, FP and other ICS. Poisson regression was used to compare the frequency of respiratory adverse events. Measurements and main results At entry, the groups were well matched apart from a higher FEV1% predicted (38 vs. 41%; ICS vs. no ICS, respectively) and prevalence of current smoking (26 vs. 36%; ICS vs. no ICS, respectively). Incidence rates of pneumonia were significantly higher in patients taking ICS compared to no ICS (0.068 vs. 0.056 respectively; p = 0.012). When the FP group was compared to the other ICS, the event rate was even higher (0.077 vs. 0.058, respectively; p &lt; 0.001). COPD exacerbations were more frequent in patients taking ICS, with significantly greater rate in the FP group compared to that seen with other ICS (0.93 vs. 0.84 respectively; p = 0.013). Conclusions ICS use was associated an increase in respiratory adverse event rates, but whether this was due to more severe illness at entry is unknown. In subgroup analysis, the excess of morbidity in the ICS group appeared to be mainly associated with those receiving FP at randomisation

    Safety and immunogenicity of a new tuberculosis vaccine, MVA85A, in mycobacterium tuberculosis–infected individuals

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    Copyright © 2009 by the American Thoracic Society.Rationale: An effective new tuberculosis (TB) vaccine regimen must be safe in individuals with latent TB infection (LTBI) and is a priority for global health care. Objectives: To evaluate the safety and immunogenicity of a leading new TB vaccine, recombinant Modified Vaccinia Ankara expressing Antigen 85A (MVA85A) in individuals with LTBI. Methods: An open-label, phase I trial of MVA85A was performed in 12 subjects with LTBI recruited from TB contact clinics in Oxford and London or by poster advertisements in Oxford hospitals. Patients were assessed clinically and had blood samples drawn for immunological analysis over a 52-week period after vaccination with MVA85A. Thoracic computed tomography scans were performed at baseline and at 10 weeks after vaccination. Safety of MVA85A was assessed by clinical, radiological, and inflammatory markers. The immunogenicity of MVA85A was assessed by IFNγ and IL-2 ELISpot assays and FACS. Measurements and Main Results: MVA85A was safe in subjects with LTBI, with comparable adverse events to previous trials of MVA85A. There were no clinically significant changes in inflammatory markers or thoracic computed tomography scans after vaccination. MVA85A induced a strong antigen-specific IFN-γ and IL-2 response that was durable for 52 weeks. The magnitude of IFN-γ response was comparable to previous trials of MVA85A in bacillus Calmette-Guérin–vaccinated individuals. Antigen 85A–specific polyfunctional CD4+ T cells were detectable prior to vaccination with statistically significant increases in cell numbers after vaccination. Conclusions: MVA85A is safe and highly immunogenic in individuals with LTBI. These results will facilitate further trials in TB-endemic areas.Oxford Biomedical Research Centre, Wellcome Trust, and AFTBVAC

    Hyaluronidase: A Potential New Treatment for Acute Respiratory Distress Syndrome

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    Acute respiratory distress syndrome, also known as diffuse alveolar damage, is an acute injury to the lungs. Patients experience severe shortness of breath and require mechanical ventilation. It is not a specific disease, but an acute lung dysfunction associated with a variety of disorders: pneumonia, shock, sepsis, and trauma. A similar lesion occurs in newborn infants, called hyaline disease of the newborn. It occurs in premature babies and has the same pathophysiological mechanism as acute respiratory distress syndrome. Hyaline membranes are a pathologic feature of acute respiratory distress syndrome, consisting of basophilic structures that coat alveolar surfaces. They prevent oxygen exchange and are the basis of the lethality of this disorder. The syndrome is associated with very high levels of hyaluronan in broncho-alveolar lavage specimens. We postulate that the hyaline membranes of acute respiratory distress syndrome are hyaluronan-rich structures associated with serum hyaluronan-binding proteins such as fibrinogen and fibrin. Potent infectious influenza viruses are recurrent pandemics and potential terrorist threats. Lethality of influenza infection correlates with the presence of hyaline membranes. Installation of hyaluronidase as an aerosol would provide a new treatment for acute respiratory respiratory distress syndrome, for which there has been no new treatment in 45 years. The pig is the only species other than humans that develop hyaline membranes. Employing this treatment in the porcine model would provide a direct test of the hypothesis


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    Objective: This study was conducted to generate the data on drug utilization pattern among geriatric inpatients in general medicine department.Methods: The patient's prescriptions and medical record files were randomly selected on the basis of inclusion and exclusion criteria at medicine department of Shri Mahant Indiresh Hospital, Dehradun and the required data for the study were collected in well-designed data collection form and evaluated after the period of 3 months.Results: Among 175 patients, males were predominant and 31.42% patients were in age group of 71-75 years. Cardiovascular diseases (28%) were most common cause of hospitalization followed by, respiratory disorders (20.57%). Hypertension (25.72%) was most commonly diagnosed disease followed by, diabetes mellitus (22.2%) and chronic obstructive pulmonary disease (14.28%).  The most common co-morbidity was hypertension &amp; diabetes mellitus. More than 3 co-morbidities were found in 79 patients. Cardiovascular drugs (22.17%) was most frequently prescribed drug followed by, gastrointestinal drugs (15.30%). Among individual drugs pantoprazole (A02BC02) was most commonly prescribed drugs.  Total of 1581 drugs were prescribed with an average of 9.03 drugs per prescription. Only 9.63% drugs were prescribed by generic name. Antimicrobials were prescribed in 146 prescriptions, among them ceftriaxone (J01DD04) was frequently prescribed.Conclusion: Most of the drugs were utilized by male patients and the rate of polypharmacy was high