No abstract

Objective-To determine the distribution and importance of various factors, especially the preventable ones, that contribute to cardiac decompensation and subsequent hospital admission for heart failure. Methods-During a one year period patients were prospectively recruited and evaluated during their hospital stay by means of a structured personal interview by trained medical staV and through clinical examination and laboratory investigation. Setting-The cardiological department at a teaching aYliated general community hospital in Berlin, Germany. Patients-Consecutive sample of 179 patients admitted to hospital with acute decompensation of pre-existing heart failure. Main outcome measures-Proportional distribution of causative factors leading to hospital admission for heart failure; relative importance of preventable factors; details of patient compliance with diet and medication, and knowledge about medication. Results-Mean (SD) age was 75.4 (9.9) years. Potential causative factors for decompensated heart failure were identified in 85.5% of patients. Lack of adherence to the medical regimen was the most commonly identified factor and was regarded as the cause of the cardiac decompensation in 41.9% of cases. Non-compliance with drugs was found in 23.5% of patients. Other factors related to hospital admission were coronary ischaemia (13.4%), cardiac arrhythmias (6.1%), uncontrolled hypertension (5.6%), and inadequate preadmission treatment (12.3%). In all, 54.2% of admissions could be regarded as preventable. Conclusions-Many hospital admissions for decompensation of chronic heart failure in patients at a district hospital in Berlin are preventable. Measures are necessary to improve this situation and evaluation of programmes that include patient education, patient follow up, and physician training is needed. (Heart 1998;80:437-441)

No abstract

The reliability of free energy simulations (FES) is limited by two factors: (a) the need for correct sampling and (b) the accuracy of the computational method employed. Classical methods (e.g., force fields) are typically used for FES and present a myriad of challenges, with parametrization being a principle one. On the other hand, parameter-free quantum mechanical (QM) methods tend to be too computationally expensive for adequate sampling. One widely used approach is a combination of methods, where the free energy difference between the two end states is computed by, e.g., molecular mechanics (MM), and the end states are corrected by more accurate methods, such as QM or hybrid QM/MM techniques. Here we report two new approaches that significantly improve the aforementioned scheme; with a focus on how to compute corrections between, e.g., the MM and the more accurate QM calculations. First, a molecular dynamics trajectory that properly samples relevant conformational degrees of freedom is generated. Next, potential energies of each trajectory frame are generated with a QM or QM/MM Hamiltonian. Free energy differences are then calculated based on the QM or QM/MM energies using either a non-Boltzmann Bennett approach (QM-NBB) or non-Boltzmann free energy perturbation (NB-FEP). Both approaches are applied to calculate relative and absolute solvation free energies in explicit and implicit solvent environments. Solvation free energy differences (relative and absolute) between ethane and methanol in explicit solvent are used as the initial test case for QM-NBB. Next, implicit solvent methods are employed in conjunction with both QM-NBB and NB-FEP to compute absolute solvation free energies for 21 compounds. These compounds range from small molecules such as ethane and methanol to fairly large, flexible solutes, such as triacetyl glycerol. Several technical aspects were investigated. Ultimately some best practices are suggested for improving methods that seek to connect MM to QM (or QM/MM) levels of theory in FES.