Post community hospital discharge rehabilitation attendance: Self-perceived barriers and participation over time.

INTRODUCTION: This study aimed to examine the attendance rates of post-discharge supervised rehabilitation as recommended by the multidisciplinary team at discharge among subacutely disabled adults and the barriers preventing adherence. MATERIALS AND METHODS: Patients were from a community hospital, aged 40 years or older. They had been assessed by a multidisciplinary team to benefit from rehabilitation after discharge, were mentally competent and communicative. We used a sequential qualitative-quantitative mixed methods study design. In the initial qualitative phase, we studied the patient-perceived barriers to adherence to rehabilitation using semi-structured interviews. Emerging themes were then analysed and used to develop a questionnaire to measure the extent of these barriers. In the subsequent quantitative phase, the questionnaire was used with telephone follow-up at 3, 6, 9 and 12 months after discharge. RESULTS: Qualitative phase interviews (n = 41) revealed specific perceived financial, social, physical and health barriers. At the start of the quantitative phase (n = 70), 87.1% of the patients viewed rehabilitation as beneficial, but overall longitudinal attendance rate fell from 100% as inpatient to 20.3% at 3 months, 9.8% at 6 months, 6.3% at 9 months and 4.3% at 12 months. The prevalence of physical and social barriers were high initially but decreased with time. In contrast, the prevalence of financial and perceptual barriers increased with time. CONCLUSION: Attendance of post-hospitalisation rehabilitation in Singapore is low. Self-perceived barriers to post-discharge rehabilitation attendance were functional, social, financial and perceptual, and their prevalence varied with time.

Characterization of SARS-CoV main protease and identification of biologically active small molecule inhibitors using a continuous fluorescence-based assay.

Severe acute respiratory syndrome associated coronavirus main protease (SARS-CoV Mpro) has been proposed as a prime target for anti-SARS drug development. We have cloned and overexpressed the SARS-CoV Mpro in Escherichia coli, and purified the recombinant Mpro to homogeneity. The kinetic parameters of the recombinant SARS-CoV Mpro were characterized by high performance liquid chromatography-based assay and continuous fluorescence-based assay. Two novel small molecule inhibitors of the SARS-CoV Mpro were identified by high-throughput screening using an internally quenched fluorogenic substrate. The identified inhibitors have Ki values at low microM range with comparable anti-SARS-CoV activity in cell-based assays.

Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics.

The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) infected more than 8,000 people across 29 countries and caused more than 900 fatalities. Based on the concept of chemical genetics, we screened 50,240 structurally diverse small molecules from which we identified 104 compounds with anti-SARS-CoV activity. Of these 104 compounds, 2 target the SARS-CoV main protease (M(pro)), 7 target helicase (Hel), and 18 target spike (S) protein-angiotensin-converting enzyme 2 (ACE2)-mediated viral entry. The EC(50) of the majority of the 104 compounds determined by SARS-CoV plaque reduction assay were found to be at low micromolar range. Three selected compounds, MP576, HE602, and VE607, validated to be inhibitors of SARS-CoV M(pro), Hel, and viral entry, respectively, exhibited potent antiviral activity (EC(50) < 10 microM) and comparable inhibitory activities in target-specific in vitro assays.