Coronary artery disease (CAD) remains the leading cause of mortality among cardiovascular diseases, responsible for 16% of the world’s total deaths. According to a statistical report published in 2020, the global prevalence of CAD was estimated at 1655 per 100,000 people and is predicted to exceed 1845 by 2030. Annually, in the United States, CAD accounts for approximately 610,000 deaths and costs more than 200 billion dollars for healthcare services. Most patients with CAD need to be treated over long periods with a combination of drugs. Therefore, the inappropriate use of drugs, or drug-related problems (DRPs), can lead to many consequences that affect these patients’ health, including decreased quality of life, increased hospitalization rates, prolonged hospital stays, increased overall health care costs, and even increased risk of morbidity and mortality. DRPs are common in CAD patients, with a prevalence of over 60%. DRPs must therefore be noticed and recognized by healthcare professionals. This chapter describes common types and determinants of DRPs in CAD patients and recommends interventions to limit their prevalence.
Health-related quality of life (HRQL) is a good indicator to monitor and evaluate healthcare services for adults with HIV/AIDS. This study described HRQL of adults with HIV and its determinants, and compared it with HRQL for the general population. A cross-sectional study with a national multistage sampling of households with and without HIV-positive people was conducted in 2008. Six provinces were purposively selected to represent areas of the country and progressions of HIV epidemics. Households were sampled with probability-proportional-to-size, following the selection of rural and urban districts. A total of 820 HIV-positive and HIV-negative adults (mean age: 32.5; 38.7% female) were interviewed. Among 400 HIV-positive people, 52.3% had a history of injecting drugs, and 56.3% were at AIDS stage and receiving antiretroviral treatment (ART). HRQL was measured using the EuroQOL five-dimension questionnaire (EQ-5D). Multiple regression models were purposefully constructed to examine the determinants of HRQL. The EQ-5D index and visual analog scale (VAS) score in less advanced HIV people (0.90, 69.3) and AIDS patients (0.88, 65.2) were significantly lower than those of the general population (0.96, 81.6) (p<0.001). The frequency of reported problems across EQ-5D dimensions in the HIV population (2.4-30.9%) was significantly higher than in the general population (0.7-12.1%). Compared to ART patients, those at earlier HIV stages reported having problems at similar proportions across four HRQL dimensions, except pain/discomfort, where ART patients had a significantly higher proportion. Injecting drug users taking ART perceived lower HRQL score than non-injecting drug users. Multiple regression determined that joblessness (p<0.01) and inaccessibility to health services (p<0.05) were associated with lower HRQL. In addition, involvements in self-help groups significantly improved HRQL among HIV-positive participants (p<0.05). The findings highlight the need to improve the health service referral system and enhance psychological and social supports for patients in early stages of HIV infection in Vietnam.
Streptococcus mutans employs a key virulence factor, three glucosyltransferase (GtfBCD) enzymes to establish cariogenic biofilms. Therefore, the inhibition of GtfBCD would provide anti-virulence therapeutics. Here a small molecule library of 500,000 small molecule compounds was screened in silico against the available crystal structure of the GtfC catalytic domain. Based on the predicted binding affinities and drug-like properties, small molecules were selected and evaluated for their ability to reduce S. mutans biofilms, as well as inhibit the activity of Gtfs. The most potent inhibitor was further characterized for Gtf binding using OctetRed instrument, which yielded low micromolar KD against GtfB and nanomolar KD against GtfC, demonstrating selectivity towards GtfC. Additionally, the lead compound did not affect the overall growth of S. mutans and commensal oral bacteria, and selectively inhibit the biofilm formation by S. mutans, indicative of its selectivity and non-bactericidal nature. The lead compound also effectively reduced cariogenicity in vivo in a rat model of dental caries. An analog that docked poorly in the GtfC catalytic domain failed to inhibit the activity of Gtfs and S. mutans biofilms, signifying the specificity of the lead compound. This report illustrates the validity and potential of structure-based design of anti-S. mutans virulence inhibitors.
Background: Patient adherence to cardioprotective medications improves outcomes of acute coronary syndrome (ACS), but few adherence-enhancing interventions have been tested in low-income and middle-income countries.Objectives: We aimed to assess whether a pharmacist-led intervention enhances medication adherence in patients with ACS and reduces mortality and hospital readmission.Methods: We conducted a randomized controlled trial in Vietnam. Patients with ACS were recruited, randomized to the intervention or usual care prior to discharge, and followed 3 months after discharge. Intervention patients received educational and behavioral interventions by a pharmacist. Primary outcome was the proportion of adherent patients 1 month after discharge. Adherence was a combined measure of self-reported adherence (the 8–item Morisky Medication Adherence Scale) and obtaining repeat prescriptions on time. Secondary outcomes were (1) the proportion of patients adherent to medication; (2) rates of mortality and hospital readmission; and (3) change in quality of life from baseline assessed with the European Quality of Life Questionnaire – 5 Dimensions – 3 Levels at 3 months after discharge. Logistic regression was used to analyze data. Registration: ClinicalTrials.gov (NCT02787941).Results: Overall, 166 patients (87 control, 79 intervention) were included (mean age 61.2 years, 73% male). In the analysis excluding patients from the intervention group who did not receive the intervention and excluding all patients who withdrew, were lost to follow-up, died or were readmitted to hospital, a greater proportion of patients were adherent in the intervention compared with the control at 1 month (90.0% vs. 76.5%; adjusted OR = 2.77; 95% CI, 1.01–7.62) and at 3 months after discharge (90.2% vs. 77.0%; adjusted OR = 3.68; 95% CI, 1.14–11.88). There was no significant difference in median change of EQ-5D-3L index values between intervention and control [0.000 (0.000; 0.275) vs. 0.234 (0.000; 0.379); p = 0.081]. Rates of mortality, readmission, or both were 0.8, 10.3, or 11.1%, respectively; with no significant differences between the 2 groups.Conclusion: Pharmacist-led interventions increased patient adherence to medication regimens by over 13% in the first 3 months after ACS hospital discharge, but not quality of life, mortality and readmission. These results are promising but should be tested in other settings prior to broader dissemination.
Streptococcus mutans is a major aetiological agent of dental caries. Formation of biofilms is a key virulence factor of S. mutans. Drugs that inhibit S. mutans biofilms may have therapeutic potential. Dihydrofolate reductase (DHFR) plays a critical role in regulating the metabolism of folate. DHFR inhibitors are thus potent drugs and have been explored as anticancer and antimicrobial agents. In this study, a library of analogues based on a DHFR inhibitor, trimetrexate (TMQ), an FDA-approved drug, was screened and three new analogues that selectively inhibited S. mutans were identified. The most potent inhibitor had a 50% inhibitory concentration (IC50) of 454.0 ± 10.2 nM for the biofilm and 8.7 ± 1.9 nM for DHFR of S. mutans. In contrast, the IC50 of this compound for human DHFR was ca. 1000 nM, a >100-fold decrease in its potency, demonstrating the high selectivity of the analogue. An analogue that exhibited the least potency for the S. mutans biofilm also had the lowest activity towards inhibiting S. mutans DHFR, further indicating that inhibition of biofilms is related to reduced DHFR activity. These data, along with docking of the potent analogue to the modelled DHFR structure, suggested that the TMQ analogues indeed selectively inhibited S. mutans through targeting DHFR. These potent and selective small molecules are thus promising lead compounds to develop new effective therapeutics to prevent and treat dental caries.
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