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Inhaled antibiotics for long-term therapy in cystic fibrosis.

Background :Inhaled antibiotics are commonly used to treat persistent airway infection that contributes to lung damage in people with cystic fibrosis (CF).

Objectives : To examine the evidence that inhaled antibiotic treatment in people with CF reduces frequency of exacerbations of infection, and improves lung function, quality of life and survival. To examine adverse effects of inhaled antibiotic treatment.

Corticosteroids for pneumonia.

Pneumonia is an acute inflammation of the lungs and treatments differ depending on the type and severity. Corticosteroids can influence immune regulation, carbohydrate metabolism, protein catabolism, electrolyte balance and stress response. However, the benefits of corticosteroids for patients with pneumonia remains unclear.

Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial.

Daily inhaled corticosteroids are an effective treatment for mild persistent asthma, but some children have exacerbations even with good day-to-day control, and many discontinue treatment after becoming asymptomatic. We assessed the effectiveness of an inhaled corticosteroid (beclomethasone dipropionate) used as rescue treatment.

Methods : In this 44-week, randomised, double-blind, placebo-controlled trial we enrolled children and adolescents with mild persistent asthma aged 5—18 years from five clinical centres in the USA. A computer-generated randomisation sequence, stratified by clinical centre and age group, was used to randomly assign participants to one of four treatment groups: twice daily beclomethasone with beclomethasone plus albuterol as rescue (combined group); twice daily beclomethasone with placebo plus albuterol as rescue (daily beclomethasone group); twice daily placebo with beclomethasone plus albuterol as rescue (rescue beclomethasone group); and twice daily placebo with placebo plus albuterol as rescue (placebo group). Twice daily beclomethasone treatment was one puff of beclomethasone (40 μg per puff) or placebo given in the morning and evening. Rescue beclomethasone treatment was two puffs of beclomethasone or placebo for each two puffs of albuterol (180 μg) needed for symptom relief. The primary outcome was time to first exacerbation that required oral corticosteroids. A secondary outcome measured linear growth. Analysis was by intention to treat. This study is registered with clinicaltrials.gov, number NCT00394329.

Results : 843 children and adolescents were enrolled into this trial, of whom 288 were assigned to one of four treatment groups; combined (n=71), daily beclomethasone (n=72), rescue beclomethasone (n=71), and placebo (n=74)—555 individuals were excluded during the run-in, according to predefined criteria. Compared with the placebo group (49%, 95% CI 37—61), the frequency of exacerbations was lower in the daily (28%, 18—40, p=0·03), combined (31%, 21—43, p=0·07), and rescue (35%, 24—47, p=0·07) groups. Frequency of treatment failure was 23% (95% CI 14—43) in the placebo group, compared with 5·6% (1·6—14) in the combined (p=0·012), 2·8% (0—10) in the daily (p=0·009), and 8·5% (2—15) in the rescue (p=0·024) groups. Compared with the placebo group, linear growth was 1·1 cm (SD 0·3) less in the combined and daily arms (p<0·0001), but not the rescue group (p=0·26). Only two individuals had severe adverse events; one in the daily beclomethasone group had viral meningitis and one in the combined group had bronchitis.

Interpretation : Children with mild persistent asthma should not be treated with rescue albuterol alone and the most effective treatment to prevent exacerbations is daily inhaled corticosteroids. Inhaled corticosteroids as rescue medication with albuterol might be an effective step-down strategy for children with well controlled, mild asthma because it is more effective at reducing exacerbations than is use of rescue albuterol alone. Use of daily inhaled corticosteroid treatment and related side-effects such as growth impairment can therefore be avoided.

Can combined (mechanical and pharmacological) modalities prevent fatal VTE?

The aim of this paper was to perform a systemic review and meta-analysis of the efficacy of combined modalities (intermittent pneumatic leg compression and pharmacological prophylaxis, treatment group) against single modalities alone (control group) in preventing pulmonary embolism (PE), including fatal PE and deep-vein thrombosis (DVT) in high-risk patients.

Predictive and Associative Models to Identify Hospitalized Medical Patients at Risk for Venous Thromboembolism.

Acutely ill hospitalized medical patients are at risk for venous thromboembolism (VTE). We assessed the incidence of VTE in the observational IMPROVE study, and derived VTE risk-assessment scores at admission and associative VTE scores during hospitalization.

METHODS: Data from 15,156 medical patients were analyzed to determine the cumulative incidence of clinically observed VTE over 3 months after admission. Multiple regression analysis identified factors associated with VTE risk.

RESULTS: Of the 184 patients who developed symptomatic VTE, 76 had pulmonary embolism and 67 lower-extremity DVT. Cumulative VTE incidence was 1.0%; 45% of events occurred post-discharge. Factors independently associated with VTE included: previous VTE; known thrombophilia; cancer; age >60, lower limb paralysis; immobilization ≥7 days; and admission to an intensive/coronary care unit (first four were available at admission). Points were assigned to each factor identified to give a total risk score for each patient. At admission, 67% of patients had a score ≥1. During hospitalization, 31% had a score ≥2; for a score of 2 or 3, observed VTE risk was 1.5% vs 5.7% for a score ≥4. Observed and predicted rates were similar for both models (c statistics 0.65 and 0.69, respectively. During hospitalization, a score ≥2 was associated with higher overall and VTE-related mortality.

CONCLUSIONS: Weighted VTE risk scores derived from four clinical risk factors at hospital admission can predict VTE risk in acutely ill hospitalized medical patients. Scores derived from seven clinical factors during hospitalization may help us further understand symptomatic VTE risk. These scores require external validation.

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