Immunomodulator adherence in multiple myeloma patients with lower socioeconomic status: a retrospective study.

OBJECTIVE: Poor adherence to oral chemotherapy adversely impacts clinical outcomes and escalates overall healthcare costs. Despite barriers to medication adherence, a significant gap remains in assessing adherence to oral chemotherapy among multiple myeloma (MM) patients with lower socioeconomic status. Hence, our study aims to evaluate immunomodulator adherence in MM patients at a county hospital, primarily serving underrepresented and indigent individuals with low socioeconomic status across the greater Houston area. METHODS: Inclusion criteria composed of patients diagnosed with MM, aged at least 18 years, and treated with lenalidomide or pomalidomide-two widely used immunomodulators-for a minimum of 2 months or having two or more records of dispensation between May 2019 and May 2021. Adherence was gauged using an adjusted version of the medication possession ratio (MPR). RESULTS: Sixty-two patients were enrolled, yielding a mean MPR value of 88% (SD, ± 18.9). Of these, 43 patients (69.3%) demonstrated adherence with an MPR of ≥ 0.90. A significant difference was found in treatment duration between the adherent (mean 8.8 months; SD, ± 7.2) and non-adherent (mean 13.4 months; SD, ± 7.9) groups (p = 0.027). Notably, race/ethnicity demonstrated a significant difference (p = 0.048), driven by disparities in African American and Hispanic representation across adherence levels. CONCLUSION: In summary, our findings highlight race and treatment duration to be predictors of immunomodulator adherence among MM patients with lower socioeconomic status. Further research is imperative to devise and test innovative interventions aimed at enhancing medication adherence, thereby contributing to improved survival and healthcare quality in this population.

Predictors of adherence to direct oral anticoagulants after cardiovascular or bleeding events in Medicare Advantage Plan enrollees with atrial fibrillation.

BACKGROUND: Direct oral anticoagulants (DOACs) are recommended for patients with atrial fibrillation (AF) given their improved safety profile. Suboptimal adherence to DOACs remains a significant concern among individuals with AF. However, the extent of adherence to DOACs following a cardiovascular or bleeding event has not been fully evaluated. OBJECTIVE: To evaluate the pattern of adherence trajectories of DOACs after a cardiovascular or bleeding event and to investigate the sociodemographic and clinical predictors associated with each adherence trajectory by using claims-based data. METHODS: This retrospective study was conducted among patients with AF prescribed with DOACs (dabigatran/apixaban/rivaroxaban) between July 2016 and December 2017 and who were continuously enrolled in the Texas-based Medicare Advantage Plan. Patients who experienced a cardiovascular or bleeding event while using the DOACs were further included in the analysis. The sample was limited to patients who experienced a clinical event such as a cardiovascular or bleeding event while using the DOACs. The clinical events considered in this study were cardiovascular (stroke, congestive heart failure, myocardial infarction, systemic embolism) and bleeding events. To assess adherence patterns, each patient with a DOAC prescription was followed up for a year after experiencing a clinical event. The monthly adherence to DOACs after these events was evaluated using the proportion of days covered (PDC). A group-based trajectory model incorporated the monthly PDC to classify groups of patients based on their distinct patterns of adherence. Predictors associated with each trajectory were assessed using a multinomial logistic regression model, with the adherent trajectory serving as the reference group in the outcome variable. RESULTS: Among the 694 patients with AF who experienced clinical events after the initiation of DOACs, 3 distinct adherence trajectories were identified: intermediate nonadherent (30.50%), adherent (37.7%), and low adherent (31.8%); the mean PDC was 0.47 for the intermediate nonadherent trajectory, 0.93 for the adherent trajectory, and 0.01 for low adherent trajectory. The low-income subsidy was significantly associated with lower adherence trajectories (odds ratio [OR] = 4.81; 95% CI = 3.07-7.51) and with intermediate nonadherent trajectories (OR = 1.57; 95% CI = 1.06-2.34). Also, nonsteroidal anti-inflammatory drug use was significantly associated with lower adherence trajectories (OR = 5.10; 95% CI = 1.95-13.36) and intermediate nonadherent trajectories (OR = 3.17; 95% CI = 1.26-7.93). Other predictors significantly associated with both nonadherent trajectories are type of DOACs (OR = 0.53; 95% CI = 0.35-0.79), presence of coronary artery disease (OR = 1.89; 95% CI = 1.01-3.55), and having 2 or more clinical events (OR = 1.65; 95% CI = 1.09-2.50). CONCLUSIONS: Predictors identified provide valuable insights into the suboptimal adherence of DOACs among Medicare Advantage Plan enrollees with AF, which can guide the development of targeted interventions to enhance adherence in this high-risk patient population.

Integrated curriculum in the United States pharmacy programs.

INTRODUCTION: In the last decade, significant changes in pharmaceutical sciences have influenced the delivery of pharmacy education in Pharmacy programs. Integrated curriculum is one such method considered. We aimed to describe the perceived level of integrated curriculum among PharmD programs in the US. METHODS: From October 26th, 2021, until January 18th, 2022, faculty administrators across 138 US pharmacy colleges were surveyed. Data was collected regarding each program's perceived curriculum integration and assessment integration. Characteristics of each college, including region and the type of school (public/private), were obtained from the PharmCAS website. Programs were categorized into high-integration and low-integration groups for analysis purposes. Descriptive and comparative analysis by the level of curriculum integration was performed. RESULTS: Overall, 60 colleges completed surveys (participation rate = 43.48%). Most schools were from the South region (38.33%) and public colleges (53.33%). The average perceived curriculum integration was 45% (SD = 23.69), while the average perceived assessment integration was 36% (SD = 25.52). Pharmacy practice [clinical sciences] (76.67%) was the most common discipline considered for integration, and the social and administrative sciences (21.67%) was the discipline least commonly considered for integration. Case-based learning (95%) was the most common pedagogy strategy to integrate knowledge from different disciplines. CONCLUSIONS: Integrated curriculum implementation in the US PharmD programs varied across colleges. While most programs integrated their clinical practice courses, social and administrative sciences was the course least commonly integrated. Very limited progress in assessment integration was perceived.

Regional Variation in Opioid-Related Emergency Medical Services Transfers During the COVID-19 Pandemic: An Interrupted Time Series Analysis.

BACKGROUND: The COVID-19 pandemic has impacted public infrastructure and healthcare utilization. However, regional variation in opioid-related harm secondary to COVID-19 remains poorly understood. This study aimed to measure the regional variation in the association between stay-at-home orders (SAHOs) and nonfatal opioid-related emergency medical services (EMS) transfers in the United States. METHODS: In this interrupted time series design, counts of nonfatal opioid overdoses were identified in each week between July 29, 2019 and December 27, 2020 from the National Emergency Medical Services Information System Dataset. A longitudinal, interrupted time series model was used to compare the change in the number of nonfatal opioid overdose transfers between the pre-pandemic period (July 29, 2019-January 6, 2020) and the pandemic period (June 1, 2020-December 27, 2020). The time period between January 7, 2020 and May 31, 2020 was treated as a washout period to account for state-level variation in the timing of SAHO implementation. RESULTS: We identified 277 141 adult nonfatal opioid-related overdose EMS transfers in the United States across all census regions. After implementation of the SAHO, EMS transfers significantly increased in all regions, with an increase most notable in the Southern United States (2161, 95% CI: 1699-2623 transfers per week). In the post-SAHO period between June 1 and December 27, 2020, EMS transfers declined from this regional peak in the Southern, Midwestern, and Northeastern United States. No change in trend was observed in the Western United States. CONCLUSION: These findings underscore the importance of tailoring public health policies regionally. While most regions saw a modest decline in opioid-related EMS transfers after an initial increase, the COVID-19 pandemic led to notable increases in opioid-related EMS transfers nationwide. Future research should focus on identifying public health strategies to counteract the deleterious effects of the COVID-19 pandemic on opioid-related morbidity.

Trajectories of adherence to ACEI/ARB medications following a motivational interviewing intervention among Medicare Advantage beneficiaries in Texas.

OBJECTIVES: To assess the impact of student telephone motivational interviewing intervention on angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEI/ARBs) adherence trajectories and identify predictors of each trajectory. METHODS: The intervention group included continuously enrolled Medicare Advantage Plan patients non-adherent to ACEI/ARBs vs the control group (1:2 ratio). The intervention was tailored by pre-intervention trajectories and included an initial and five follow-up calls. Adherence was measured 6 months after initial calls using the proportion of days covered (PDC). Monthly PDCs were integrated into a group-based trajectory model and categorized patients into 4-groups. A multinomial logistic regression model was used to evaluate trajectory predictors. RESULTS: The study comprised 240 intervention patients and 480 controls with four trajectories: adherent trajectory 44.2%, gradual improvement in adherence 13.4%, slow decline in adherence 24.1%, and discontinuation 18.3%. Patients with the intervention were less likely to experience a slow decline in adherence than controls (OR: 0.627 [0.401-0.981]). Patients with specialty prescribers' visits, ≥ 1 previous hospitalization, rapid decline in adherence as pre-intervention trajectory, and higher CMS risk score were associated with discontinuation trajectory. CONCLUSION: Intervention patients vs controls had a lower likelihood of following a slow decline in adherence pattern. PRACTICE IMPLICATIONS: This study underscores the importance of individualized interventions and the association between past adherence patterns and post-intervention trajectories.

Systematic Review of Polyherbal Combinations Used in Metabolic Syndrome.

Background: Metabolic syndrome (MetS) is a multifactorial disease, whose main stay of prevention and management is life-style modification which is difficult to attain. Combination of herbs have proven more efficacious in multi-targeted diseases, as compared to individual herbs owing to the "effect enhancing and side-effect neutralizing" properties of herbs, which forms the basis of polyherbal therapies This led us to review literature on the efficacy of herbal combinations in MetS. Methods: Electronic search of literature was conducted by using Cinnahl, Pubmed central, Cochrane and Web of Science, whereas, Google scholar was used as secondary search tool. The key words used were "metabolic syndrome, herbal/poly herbal," metabolic syndrome, clinical trial" and the timings were limited between 2005-2020. Results: After filtering and removing duplications by using PRISMA guidelines, search results were limited to 41 studies, out of which 24 studies were evaluated for combinations used in animal models and 15 in clinical trials related to metabolic syndrome. SPICE and SPIDER models were used to assess the clinical trials, whereas, a checklist and a qualitative and a semi-quantitative questionnaire was formulated to report the findings for animal based studies. Taxonomic classification of Poly herbal combinations used in animal and clinical studies was designed. Conclusion: With this study we have identified the potential polyherbal combinations along with a proposed method to validate animal studies through systematic qualitative and quantitative review. This will help researchers to study various herbal combinations in MetS, in the drug development process and will give a future direction to research on prevention and management of MetS through polyherbal combinations.

Production, purification and physicochemical characterization of D-xylose/glucose isomerase from Escherichia coli strain BL21.

Cell lysate of Escherichia coli strain BL21 showed significant D-glucose isomerase activity. The rate of glucose conversion was increased up to 40% when cells were induced with 1% D-xylose. E. coli BL21 xylose isomerase (ECXI-BL21) was purified to homogeneity, up to 1.9-fold with overall 10.88% enzyme yield by heat shock, salting out and electro-elution. The molecular mass of ECXI-BL21 was estimated as 43.9 kDa on SDS-PAGE. pHopt. and Topt. of the enzyme were calculated as 7.0 and 50 °C, respectively. Activation energy (E a) of ECXI-BL21 was 45 kJ/mol. Enzyme was stable from 30 to 55 °C and at pH range 6.0-8.0. ECXI-BL21(holo) was activated by 10 mM magnesium (35%), 0.5 mM cobalt (20%) and manganese (25%), and 0.5/10 mM Mn2+/Mg2+ (50%) and Co2+/Mg2+ (30%) as compared to ECXI-BL21(apo). Catalytic affinity (K m) of ECXI-BL21 for D-glucose was calculated as 0.82 mM, while maximum velocity (V max) of the reaction D-glucose(aldo) ⇌ D-fructose(keto) was 108 µmol/mg/min. D-fructose formed was identified on silica gel plate. This thermophilic enzyme, T m = 75 °C, has great potential for high fructose syrup production used in food and soft drink industries.

A quantitative insight of the interactions of prescribers with pharmaceutical organization's representatives in clinical settings of Karachi.

Objectives: The study was conducted with the aim to evaluate the prescribers' approach of interaction with medical representatives for drug promotion. Methods: An explanatory, cross-sectional design was used to evaluate prescribers' interactions with the medical sales representatives (MSRs) through an anonymous, self-filled questionnaire from June to December 2017. Data presented as means±SEM or as percentages and statistically analyzed by one way ANOVA, using significance level of 0.05. Results: A response rate of 82.8% was achieved. More than 70% agreed that knowledge obtained from MSRs is reliable and useful. A large proportion of respondents acknowledged that MSRs are a key link between pharmaceutical companies and health care professionals, and their interactions are beneficial as MSRs perform an important teaching function. More than 45% agreed that gifts are influential; however, physicians cannot be compromised with very expensive gifts. The majority of the respondents (76%) considered that promotional items are ethically appropriate; however, 66.21% thought that promotional items influence the practice of prescribing. More than half (52.18%) deemed a promotional material more reliable than a printed advertisement. More than 80% of the respondents opined that medication samples are considered appropriate; however, they should only be given to those patients who cannot financially afford them. Around 69% thought that company-sponsored meetings promote their own drugs under the disguise of CME programs. Conclusion: The present study emphasizes the importance of employing scientifically sound prescribing decision by prescribers in their day to day practice without being influenced by pharmaceutical company's promotional activities. There is a need for restricting unprincipled practices by the concerned regulatory authorities to evade preventable harm to the patient's well-being.

Cloning, purification, and characterization of xylose isomerase from Thermotoga naphthophila RKU-10.

A 1.3 kb xyl-A gene encoding xylose isomerase from a hyperthermophilic eubacterium Thermotoga naphthophila RKU-10 (TnapXI) was cloned and over-expressed in Escherichia coli to produce the enzyme in mesophilic conditions that work at high temperature. The enzyme was concentrated by lyophilization and purified by heat treatment, fractional precipitation, and UNOsphere Q anion-exchange column chromatography to homogeneity level. The apparent molecular mass was estimated by SDS-PAGE to be 49.5 kDa. The active enzyme showed a clear zone on Native-PAGE when stained with 2, 3, 5-triphenyltetrazolium chloride. The optimum temperature and pH for D-glucose to D-fructose isomerization were 98 °C and 7.0, respectively. Xylose isomerase retains 85% of its activity at 50 °C (t1/2 1732 min) for 4 h and 32.5% at 90 °C (t1/2 58 min) for 2 h. It retains 90-95% of its activity at pH 6.5-7.5 for 30 min. The enzyme was highly activated (350%) with the addition of 0.5 mM Co(2+) and to a lesser extent about 180 and 80% with the addition of 5 and 10 mM Mn(2+) and Mg(2+) , respectively but it was inhibited (54-90%) in the presence of 0.5-10 mM Ca(2+) with respect to apo-enzyme. D-glucose isomerization product was also analyzed by Thin Layer Chromatography (Rf 0.65). The enzyme was very stable at neutral pH and sufficiently high temperature and required only a trace amount of Co(2+) for its optimal activity and stability. Overall, 52.2% conversion of D-glucose to D-fructose was achieved by TnapXI. Thus, it has a great potential for industrial applications.

Kinetics of improved 1,4-alpha-D-glucan glucohydrolase biosynthesis from a newly isolated Aspergillus oryzae IIB-6 and parameter significance analysis by 2-factorial design.

Sixteen different mould cultures viz. Aspergillus, Alternaria, Arthroderma, Trichoderma, Fusarium, Penicillium, Rhizopus and Chochliobolus were isolated from the soil samples of Qatar by serial dilution method. The preliminary screening of isolates was done by selecting initial colonies showing relatively bigger zones of starch hydrolysis on nutrient agar plates. The isolates were then subjected to secondary screening by submerged fermentation (SmF). The 1,4-α-D-glucan glucohydrolase (GGH) activity ranged from 1.906-12.675 U/ml/min. The product yield was analysed in dependence of mycelial morphology, biomass level and protein content. The isolate Aspergillus oryzae llB-6 which gave maximum enzyme production was incubated in M3 medium containing 20 g/l starch, 10 g/l lactose, 8.5 g/l yeast extract, 6 g/l corn steep liquor (CSL), 1.2 g/l MgSO4.7H2O, 1.3 g/l NH4Cl, 0.6 g/l CaCl2.2H2O, pH 5 at 30±2°C and 200 rpm. On the basis of kinetic variables, notably Qp (0.058±0.01(a) U/g/h), Yp/s (0.308±0.03(ab) U/g) and qp (0.210±0.032(abc) U/g fungal biomass/h), A. oryzae IIB-6 was found to be a hyper producer of GGH (LSD 0.0345) compared to A. kawachii IIB-2. A noticeable enhancement in enzyme activity of over 30% was observed (13.917±1.01 U/ml/min) when the process parameters viz. cultural conditions (pH 5, incubation period 72 h) and nutritional requirements (6 g/l CSL, 9.5 g/l yeast extract, 10 g/l starch, 20 g/l lactose) were further optimized using a 2-factorial Plackett-Burman design. The model terms were found to be highly significant (HS, p≤0.05), indicating the potential utility of the culture (dof~3).