Cardioprotective Effects of PARP Inhibitors: A Re-Analysis of a Meta-Analysis and a Real-Word Data Analysis Using the FAERS Database.

Objective: This study aimed to assess the potential of PARP inhibitors to prevent cardiotoxicity. Methods: First, a re-analysis and update of a previously published study was conducted. Additional searches were conducted of the PubMed and Cochrane Central Register of Controlled Trials databases on 2 June 2023. After the selection process, the pooled odds ratio (OR) for cardiac adverse events (AEs) was calculated. Second, the FAERS database was examined for 10 frequently co-administered anticancer agents. The reporting odds ratio (ROR) was calculated based on the occurrence of cardiac AEs depending on the co-administration of PARP inhibitors. Results: Seven studies were selected for the meta-analysis. Although not statistically significant, co-administration of PARP inhibitors with chemotherapy/bevacizumab decreased the risk of cardiac AEs (Peto OR = 0.61; p = 0.36), while co-administration with antiandrogens increased the risk of cardiac AEs (Peto OR = 1.83; p = 0.18). A total of 19 cases of cardiac AEs were reported with co-administration of PARP inhibitors in the FAERS database. Co-administration of PARP inhibitors with chemotherapy/bevacizumab significantly decreased the risk of cardiac AEs (ROR = 0.352; 95% confidence interval (CI), 0.194-0.637). On the other hand, for antiandrogens co-administered with PARP inhibitors, the ROR was 3.496 (95% CI, 1.539-7.942). The ROR for immune checkpoint inhibitors co-administered with PARP inhibitors was 0.606 (95% CI, 0.151-2.432), indicating a non-significant effect on cardiac AEs. Conclusion: This study reports that PARP inhibitors show cardioprotective effects when used with conventional anticancer agents.

Hepatitis Risk in Diabetes Compared to Non-Diabetes and Relevant Factors: A Cross-Sectional Study with National Health and Nutrition Examination Survey (NHANES), 2013-2018.

This study aimed to identify the development of hepatitis B or C infection in diabetes patients compared to those without and to elucidate factors associated with the prevalence of hepatitis B or C infection in diabetes. We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2013-2018. As evaluation factors, we included variables such as age, race, illicit drug use, and poverty. The diabetic group had a significantly higher prevalence of hepatitis B or C infection than the non-diabetic group (odds ratio (OR) = 1.73; 95% confidence interval (CI), 1.36-2.21, p < 0.01). In multivariate Cox regression, non-poverty and non-illicit drug use were lower risk factors contributing to hepatitis development in diabetes (hazard ratio (HR) = 0.50; 95% CI, 0.32-0.79, p < 0.01, and HR = 0.05; 95% CI, 0.03-0.08, p < 0.01, respectively). Logistic regression also showed that these factors were significant contributors to hepatitis development in the diabetic group (p < 0.01). In patients with diabetes, the development of hepatitis was higher than that in those without, and hepatitis development was influenced by poverty and illicit drug use. This may provide supporting evidence of response strategies for diabetes to care for hepatitis development in advance.

Comparative impact of repositioned anticancer therapies on non-cancer COVID-19 patient treatment: A systematic review and network meta-analysis of randomized controlled trials.

PURPOSE: Coronavirus disease 2019 (COVID-19) has emerged as a serious threat to public health; anticancer-repositioning treatment strategy has been formulated to treat the disease. However, evidence supporting the efficacy and safety of repositioned anticancer treatment in treating COVID-19-infected non-cancer patients (CINPs) is limited. Therefore, this study analyzed published randomized controlled trials (RCTs) evaluating the impact of anticancer drugs compared to current standards of care (SOCs) on CINP treatment. MATERIALS AND METHODS: The PubMed and Embase databases were searched to identify eligible RCTs. Outcome measures included mortality, the use of mechanical ventilation (MV), and serious adverse events (SAEs). RESULTS: 25 RCTs were reviewed in our study. Compared to SOCs, repositioned anticancer therapy for treating CINPs was associated with mortality reduction (odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.65 - 0.94, p = 0.01). Using the repositioned anticancer treatment exhibited statistically significant reduction, in both the number of CINPs using MV (OR = 0.67, 95% CI = 0.51 - 0.88, p = 0.004) and experiencing SAEs (OR = 0.79, 95% CI = 0.69 - 0.91, p = 0.0009). CONCLUSION: Conclusively, repositioned anticancer treatment was shown significant differences from SOCs in treating CINPs, which appears to be more associated with mortality, MV use, and SAE development reduction in CINPs.

A Theory of Planned Behavior informed factorial survey of New York community pharmacists to determine their intentions to monitor antihypertensive medication adherence among older adults.

BACKGROUND: Older adults with uncontrolled hypertension can benefit from pharmacist-led interventions as they regularly access community pharmacies. However, several barriers to adherence interventions in a community pharmacy setting exist, and few studies have evaluated the feasibility of medication adherence monitoring within the community pharmacy workflow in the United States. OBJECTIVES: To undertake a factorial survey to determine medication adherence monitoring attitudes of pharmacists and the factors that facilitate or impede adherence counseling by pharmacists within a U.S. community pharmacy setting for antihypertensives in older adults. METHODS: The study was a Theory of Planned Behavior informed factorial survey of New York community pharmacists. The survey had (1) a factorial vignette, to determine how pharmacists make real-life decisions in response to complex situations; (2) questionnaires on medication monitoring attitudes, behavioral beliefs, normative beliefs, and perceived behavioral control regarding medication adherence monitoring, and (3) respondent and workplace characteristics. In response to vignettes, the adherence monitoring tasks were (1) examining patients dispensing records to assess adherence, (2) asking patients about their adherence behavior, and (3) exploring patient beliefs about their antihypertensives. RESULTS: From the 350 completed responses, more than the vignette characteristics, it was the pharmacist characteristics that explained the major variance in the 3 medication monitoring tasks. The respondents demonstrated modestly positive attitudes to medication monitoring, were less positive about their external perception of medication monitoring, and reported difficulty to perform the medication monitoring tasks. In factorial vignette analysis, these attitudes and beliefs significantly impacted adherence monitoring tasks as did situational factors such as time pressures, medication beliefs of patients, the relationship developed with patients, and staffing in the pharmacy, and respondent factors such as pharmacy type and location. CONCLUSION: Future community pharmacist-led adherence interventions should be designed to address pharmacist attitudes and beliefs and certain workplace characteristics to enable successful implementation.

Comparative Impact of Pharmacological Therapies on Cluster Headache Management: A Systematic Review and Network Meta-Analysis.

It is important to find effective and safe pharmacological options for managing cluster headache (CH) because there is limited evidence from studies supporting the general efficacy and safety of pharmacological therapies. This systematic review and network meta-analysis (NMA) analyzed published randomized controlled trials (RCTs) to evaluate the efficacy and safety of pharmacological treatments in patients with CH. The PubMed and Embase databases were searched to identify RCTs that evaluated the efficacy and safety of pharmacological treatments for CH. Efficacy outcomes included frequency and duration of attacks, pain-free rate, and the use of rescue agents. Safety outcomes were evaluated based on the number of patients who experienced adverse events. A total of 23 studies were included in the analysis. The frequency of attacks was reduced (mean difference (MD) = −1.05, 95% confidence interval (CI) = −1.62 to −0.47; p = 0.0004), and the pain-free rate was increased (odds ratio (OR) = 3.89, 95% CI = 2.76−5.48; p < 0.00001) in the pharmacological treatment group, with a lower frequency of rescue agent use than the placebo group. Preventive, acute, and triptan or non-triptan therapies did not show significant differences in efficacy (p > 0.05). In the NMA, different results were shown among the interventions; for example, zolmitriptan 5 mg was more effective than zolmitriptan 10 mg in the pain-free outcome (OR = 0.40, 95% CI = 0.19−0.82; p < 0.05). Pharmacological treatment was shown to be more effective than placebo to manage CH with differences among types of therapies and individual interventions, and it was consistently shown to be associated with the development of adverse events. Thus, individualized therapy approaches should be applied to treat CH in real-world practice.

The Positive Association between Proton Pump Inhibitors and Clostridium Difficile Infection.

BACKGROUND: Proton pump inhibitors (PPIs) are among the most commonly used medications by patients due to its availability over the counter and frequent prescribing by physicians to treat and alleviate symptoms of gastroesophageal reflux disease. Recently, the FDA issued a warning with respect to the utilization of PPIs and risk of developing Clostridium difficile infections (CDI). The most commonly known medications to cause CDI are antibiotics. However, available studies suggest an association and increase in risk for CDI with PPI use as well. OBJECTIVE: The purpose of this research is to review and summarize data currently available on the association between PPIs and CDI. METHODS: To search for eligible studies, EBSCO engines were investigated using proton pump inhibitors or PPIs and Clostridium difficile or C. diff. as search terms. Meta analyses and systematic reviews published between 2000 and 2020 on adult patients were considered. RESULTS: Eight meta-analyses and systematic reviews met the inclusion criteria. They included studies conducted in the US, Europe, Asia and Canada on inpatient and outpatient adults. The final result for all 8 studies showed a statistically significant association between PPIs and CDI ranging from mild to high risk. CONCLUSION: Currently available data suggest a positive association between PPIs and CDI.

Pre-Exposure Prophylaxis (PrEP) in the Prevention of HIV: Strategies, Target Populations and Upcoming Treatments.

Pre-exposure prophylaxis (PrEP) against HIV infection with tenofovir/emtricitabine is proven to be effective yet uptake of this preventive measure has been difficult due to several barriers such as cost, access, and misinformation. Certain subpopulations are disproportionately affected by this problem. Several methods have been developed to close the gap in care. New antiretroviral treatment strategies are being investigated for safety and efficacy in preventing HIV infection.

Medication adherence among chronic condition patients in the Medicaid coverage gap.

BACKGROUND: People with incomes below the Federal Poverty Level (FPL) do not qualify for health insurance subsidies and may not be eligible for Medicaid. Patients in this Medicaid Coverage Gap may have difficulty paying for their medications. OBJECTIVE: To estimate medication adherence and the prevalence of underinsurance among chronic condition patients in the Medicaid Coverage Gap. METHODS: A retrospective cohort study was conducted using 2014-2016 data extracted from the Medical Expenditure Panel Survey. The sample included non-elderly patients with prescription fills (≥2) for at least one of five chronic conditions (hypertension, hyperlipidemia, diabetes, depression and anxiety disorder) and income below the FPL. Medication adherence was measured using Medication Possession Ratio (MPR), and adjusted using patient demographics, health conditions, and health care utilization. The prevalence of underinsurance also was examined. RESULTS: Of the 316 patients, 60.4% were female, with an average age of 50, and an average of 3 health conditions. The weighted MPR was 72.0% and 44.6% had an adjusted MRP ≥80%. Nearly 80% of the patients were either continuously uninsured (21.6%) or underinsured (59.0%). CONCLUSIONS: A significant proportion of chronic condition patients in Medicaid Coverage Gap were underinsured and less than half were adherent to their medications.

Shared Decision-Making and Women's Adherence to Breast and Cervical Cancer Screenings.

We examined the effect of shared decision-making (SDM) on women's adherence to breast and cervical cancer screenings and estimated the prevalence and adherence rate of screenings. The study used a descriptive cross-sectional design using the 2017 Health Information National Trends Survey (HINTS) data collected by the National Cancer Institute. Adherence was defined based on the guidelines from the American Cancer Society and the composite measure of shared decision-making was constructed using three items in the data. Multivariable logistic regression was performed to examine the association between the SDM and adherence, controlling for cancer beliefs and socio-demographic variables. The analysis included 742 responses. Weighted to represent the U.S. population, 68.1% adhered to both breast and cervical cancer screening guidelines. The composite measure of SDM was reliable (α = 0.85), and a higher SDM score was associated with women's screening adherence (b = 0.17; p = 0.009). There were still women who did not receive cancer screenings as recommended. The results suggest that the use of the SDM approach for healthcare professionals' communication with patients can improve screening adherence.

Variability of assister availability in health insurance marketplace in the U.S.

BACKGROUND: The Affordable Care Act (ACA) established the health insurance marketplaces to provide people the opportunity to obtain healthcare coverage. Assisters have worked with people who may have difficulty understanding the new system and selecting the right plan. This study aims to describe the local availability of assister programs, and examine the factors influencing assister provision. METHODS: The 2016 Small Area Health Insurance Estimates data and a database of assister programs constructed using healthcare.gov were analyzed at the county level. Bivariate analysis by assister provision was performed to determine the differences between the two groups, and the hierarchical generalized linear model was used to examine the factors predicting assister availability. RESULTS: The study analyzed 2260 counties nested within 35 states. Assister availability largely varied across counties and states. About half of the counties did not provide assisters at all, and the assister provision rate at state level ranged between 19 - 100%. Counties in metropolitan areas were more likely to provide assister programs than rural areas, and so were counties with higher adult uninsured rate or higher uninsured rate among the people with incomes between 138 - 400% of federal poverty level (FPL). CONCLUSIONS: Despite the important role of in-person assistance in plan enrollment, no previous study has examined the local variability of assister program. Our study found a large geographical variation in assister availability, raising concerns about the disparity in access to assister service.

Perceived Value of Health Insurance and Enrollment Decision among Low-Income Population.

The individual mandate is one of the key features of the Affordable Care Act (ACA) and has contributed to a substantial decrease in the overall uninsured rate. We examined the relationship between the individual's insurance status and his/her attitude towards risk and uncertainty among the nonelderly adults, without employer-sponsored insurance (ESI) sources and who are most likely to benefit from the ACA. A descriptive, cross-sectional study was conducted using the 2014 full-year consolidated data file from the Household Component of the Medical Expenditure Panel Survey-Household Component (MEPS-HC). This study included 4,848 individuals, aged 18-64 years, with incomes between 138-400 % of the Federal Poverty Level (FPL), and without access to public coverage or ESI. We examined the factors associated with the likelihood of being uninsured using a logit model. We found that the proportion of the uninsured among the low-income nonelderly adults without ESI (31.1%) was much higher than the one among the nonelderly adults (14.3%). The uninsured adults were likely to have lower demand for insurance and perceived value of insurance and were less likely to visit a doctor or to fill prescription drugs. More rigorous outreach efforts focusing on increasing perceived value of health insurance could contribute to an increased insurance coverage among low-income populations.

Medicare Part D Beneficiaries' Plan Switching Decisions and Information Processing.

Medicare Part D beneficiaries tend not to switch plans despite the government's efforts to engage beneficiaries in the plan switching process. Understanding current and alternative plan features is a necessary step to make informed plan switching decisions. This study explored beneficiaries' plan switching using a mixed-methods approach, with a focus on the concept of information processing. We found large variation in beneficiary comprehension of plan information among both switchers and nonswitchers. Knowledge about alternative plans was especially poor, with only about half of switchers and 2 in 10 nonswitchers being well informed about plans other than their current plan. We also found that helpers had a prominent role in plan decision making-nearly twice as many switchers as nonswitchers worked with helpers for their plan selection. Our study suggests that easier access to helpers as well as helpers' extensive involvement in the decision-making process promote informed plan switching decisions.

Cost-Effectiveness of a Physician-Pharmacist Collaboration Intervention to Improve Blood Pressure Control.

Previous studies have demonstrated the cost-effectiveness of physician-pharmacist collaborations to improve hypertension control. However, most studies have limited generalizability, lacking minority and low-income populations. The Collaboration Among Pharmacist and Physicians to Improve Blood Pressure Now (CAPTION) trial randomized 625 patients from 32 medical offices in 15 states. Each office had an existing clinical pharmacist on staff. Pharmacists in intervention offices communicated with patients and made recommendations to physicians about changes in therapy. Demographic information, blood pressure (BP), medications, and physician visits were recorded. In addition, pharmacists tracked time spent with each patient. Costs were assigned to medications and pharmacist and physician time. Cost-effectiveness ratios were calculated based on changes in BP measurements and hypertension control rates. Thirty-eight percent of patients were black, 14% were Hispanic, and 49% had annual income <$25 000. At 9 months, average systolic BP was 6.1 mm Hg lower (±3.5), diastolic was 2.9 mm Hg lower (±1.9), and the percentage of patients with controlled hypertension was 43% in the intervention group and 34% in the control group. Total costs for the intervention group were $1462.87 (±132.51) and $1259.94 (±183.30) for the control group, a difference of $202.93. The cost to lower BP by 1 mm Hg was $33.27 for systolic BP and $69.98 for diastolic BP. The cost to increase the rate of hypertension control by 1 percentage point in the study population was $22.55. Our results highlight the cost-effectiveness of a clinical pharmacy intervention for hypertension control in primary care settings.

The role of satisfaction and switching costs in Medicare Part D choices.

BACKGROUND: Most U.S. states had over 50 Medicare Prescription Drug Plans (PDPs) in 2007. Medicare beneficiaries are expected to switch Part D plans based on their health and financial needs; however, the switching rate has been low. Such consumer inertia potentially has negative effects on both beneficiaries and the insurance market, resulting in a critical need to investigate its cause. OBJECTIVES: To 1) describe how Medicare beneficiaries who were satisfied with their current Part D plan differed from those who were not satisfied; 2) examine the effect of switching costs on consideration of switching among Medicare beneficiaries who were dissatisfied with their current Part D plan. METHODS: Data from the 2007 Prescription Drug Study supplement to the Health and Retirement Study (HRS) survey were used in this study. The satisfied and dissatisfied groups were compared in terms of cost variables, switching costs, and perception of Part D complexity. Structural equation modeling was used to examine relationships among switching costs, Part D complexity, cost variables, and consideration of switching for beneficiaries who were dissatisfied with their current Part D coverage. RESULTS: Out of 467 participants, a total of 255 (54.6%) were satisfied with their current Part D plan. The satisfied group paid lower out-of-pocket costs ($50.63 vs. $114.60) and premiums ($30.88 vs. $40.77) than the dissatisfied group. They also had lower switching costs. Only 11.3% of the dissatisfied beneficiaries switched plans. Among respondents who were dissatisfied with their current plan, those who perceived Part D as complex had high switching costs and were less likely to consider switching plans. Out-of-pocket cost did not have a statistically significant association with consideration of switching. CONCLUSIONS: Medicare beneficiaries who were satisfied with their current Part D plans had lower out-of-pocket costs and premiums as well as higher switching costs. Among beneficiaries who were dissatisfied with their current Part D plan, those who had higher switching costs were less likely to consider switching Part D plans.

Synthesis and antifungal activity of 2/3-arylthio- and 2,3-bis(arylthio)-5-hydroxy-/5-methoxy-1,4-naphthoquinones.

2/3-Arylthio- and 2,3-bis(arylthio)-5-hydroxy-/5-methoxy-1,4-naphthoquinones 5-9 were synthesized and tested for in vitro antifungal activity against Candida species and Aspergillus niger. The synthesized compounds 5-9 generally showed good activities against Candida albicans and C. tropicalis. The results suggest that the 1,4-naphthoquinones 5-9 would be potent antifungal agents.

Synthesis and antifungal activity of 5-arylamino-4,7-dioxobenzo[b]thiophenes.

5-Arylamino-4,7-dioxobenzo[b]thiophenes 3-6 were synthesized and tested for in vitro antifungal activity against Candida and Aspergillus species. 5-Arylamino-6-chloro-2-(methoxycarbonyl)-4,7-dioxobenzo[b]thiophenes 5 showed, in general, more potent antifungal activity against Candida species than the other 4,7-dioxobenzo[b]thiophenes 3, 4 and 6. The results suggest that 5-arylamino-4,7-dioxobenzo[b]thiophenes would be potent antifungal agents.

Synthesis and antifungal activity of noble 5-arylamino- and 6-arylthio-4,7-dioxobenzoselenazoles.

5-Arylamino- and 6-arylthio-4,7-dioxobenzoselenazoles 4 and 5 were synthesized and tested for in vitro antifungal activity against Candida and Aspergillus species. 5-Arylamino-4,7-dioxobenzoselenazoles 4 showed, in general, more potent antifungal activity than 6-arylthio-4,7-dioxobenzoselenazoles 5. The results suggest that 5-arylamino-4,7-dioxobenzoselenazoles 4 would be potent antifungal agents.

Synthesis and antifungal activity of 5,8-quinazolinedione derivatives modified at positions 6 and 7.

5,8-Quinazolinediones modified at positions 6 and 7 were synthesized and tested for in vitro antifungal activities against Candida species and Aspergillus niger. Most of 5,8-quinazolinediones 3-5 generally exhibited potent antifungal activity. 6-Arylamino-7-chloro-5,8-quinazolinediones (3) generally showed more potent antifungal activity than 7-arylthio-5,8-quinzolinediones (4) and 6,7-bis-(arylthio)-5,8-quinazolinediones (5).

Synthesis and biological evaluation of benzimidazole-4,7-diones that inhibit vascular smooth muscle cell proliferation.

A series of 6-arylamino-5-chloro-benzimidazole-4,7-diones were synthesized and tested for their inhibitory activity on the rat aortic smooth muscle cell (RAoSMC) proliferation. Among them, 6-arylamino-5-chloro-2-methyl-benzimidazole-4,7-diones exhibited potent antiproliferative activity. Benzimidazole-4,7-dione 2c activated SAPK/JNK signaling pathway in the RAoSMCs.