Cognitive profile, neuroimaging and fluid biomarkers in post-acute COVID-19 syndrome.

We aimed to characterize the cognitive profile of post-acute COVID-19 syndrome (PACS) patients with cognitive complaints, exploring the influence of biological and psychological factors. Participants with confirmed SARS-CoV-2 infection and cognitive complaints ≥ 8 weeks post-acute phase were included. A comprehensive neuropsychological battery (NPS) and health questionnaires were administered at inclusion and at 1, 3 and 6 months. Blood samples were collected at each visit, MRI scan at baseline and at 6 months, and, optionally, cerebrospinal fluid. Cognitive features were analyzed in relation to clinical, neuroimaging, and biochemical markers at inclusion and follow-up. Forty-nine participants, with a mean time from symptom onset of 10.4 months, showed attention-executive function (69%) and verbal memory (39%) impairment. Apathy (64%), moderate-severe anxiety (57%), and severe fatigue (35%) were prevalent. Visual memory (8%) correlated with total gray matter (GM) and subcortical GM volume. Neuronal damage and inflammation markers were within normal limits. Over time, cognitive test scores, depression, apathy, anxiety scores, MRI indexes, and fluid biomarkers remained stable, although fewer participants (50% vs. 75.5%; p = 0.012) exhibited abnormal cognitive evaluations at follow-up. Altered attention/executive and verbal memory, common in PACS, persisted in most subjects without association with structural abnormalities, elevated cytokines, or neuronal damage markers.

Health state utility estimates for value assessments of novel treatments in Huntington's disease: a systematic literature review.

BACKGROUND: Huntington's disease (HD) is a progressive neurodegenerative disease with a devastating impact on patients and their families. Quantifying how treatments affect patient outcomes is critical for informing reimbursement decisions. Many countries mandate a formal value assessment in which the treatment benefit is measured as quality-adjusted life-years, calculated with the use of utility estimates that reflect respondents' preferences for health states. OBJECTIVE: To summarize published health state utility data in HD and identify gaps and uncertainties in the data available that could be used to inform value assessments. METHODS: We conducted a systematic literature review of studies that used preference-based instruments (e.g., EQ-5D and SF-6D) to estimate utility values for people with HD. The studies were published between January 2012 and December 2022. RESULTS: Of 383 articles screened, 16 articles reported utility values estimated in 11 distinct studies. The utility measure most frequently reported was EQ-5D (9/11 studies). Two studies reported SF-6D data; one used time trade-off methods to value health state descriptions (vignettes). Although utility scores generally worsened to a lower value with increased HD severity, the estimates varied considerably across studies. The EQ-5D index range was 0.89 - 0.72 for mild/prodromal HD and 0.71 - 0.37 for severe/late-stage disease. CONCLUSIONS: This study uncovered high variability in published utility estimates, indicating substantial uncertainty in existing data. Further research is needed to better understand preferences and valuation across all stages and domains of HD symptoms and the degree to which generic utility measures capture the impact of cognitive changes on quality of life.

The role of implementing instructional design principles on learner experience with training in current good manufacturing practices (cGMP).

INTRODUCTION: The objective of the study was to assess if improvement of the learner experience could be achieved through the use of instructional design strategies in current Good Manufacturing Practices (cGMP) training. This is a novel application in a topic that is known to be boring but is critical to ensuring patient safety. METHODS: An experimental randomized controlled repeated measures cross-over design was utilized in a sample of pharmacy students to determine the effect of an intervention training strategy (which utilized a mix of strategies including weeding, signaling, use of multimedia, and optimized space and type) on the learner experience (Evaluation, Overall Satisfaction, Perceived Knowledge, and Future Recommendation) compared with a control. RESULTS: The sample of 52 pharmacy students that participated evaluated the intervention training strategy with higher scores than the control, with better overall satisfaction, perceived knowledge, and future recommendation scores than the control training strategy. Thus, an apparent effect which resulted from the use of instructional design strategies was seen for all learner experience variables (p < .01). CONCLUSION: Improvement in the learner experience can be achieved by using instructional design strategies in cGMP training. This indicates that similar results could be obtained in other topics where such techniques have not yet been applied.

Number needed to treat and cost per responder of Janus kinase inhibitors approved for the treatment of moderate-to-severe rheumatoid arthritis in Japan.

OBJECTIVE: This study evaluated the effectiveness and cost-effectiveness of baricitinib, tofacitinib, and upadacitinib regimens, compared to conventional synthetic disease-modifying antirheumatic drug (csDMARD) alone, among Japanese patients with moderate-to-severe rheumatoid arthritis (RA) inadequately responsive to csDMARD, measured in terms of number needed to treat (NNT) and cost per responder (CPR). METHODS: Efficacy data were derived from two recent network meta-analyses among global and Japanese population. The cost perspective was that of the Japanese Health Service. Both NNT and CPR were based on disease activity score for 28 joints with C-reactive protein (DAS28-CRP) remission and American College of Rheumatology (ACR) 20/50/70 at 12 and 24 weeks. RESULTS: Over 12 weeks, the median NNT and the median CPR to achieve DAS28-CRP remission were 4.3 and JPY 1,799,696 [USD 16,361], respectively, for upadacitinib 15 mg + csDMARD. The equivalent results were 6.0 and JPY 2,691,684 [USD 24,470] for baricitinib 4 mg + csDMARD and 5.6 and JPY 2,507,152 [USD 22,792] for tofacitinib 5 mg + csDMARD. Similar rankings were observed at 24 weeks and for other outcomes. CONCLUSIONS: Upadacitinib 15 mg was associated with the lowest NNT and CPR among the three Janus kinase inhibitors used in treatment regimens for Japanese patients with moderate-to-severe RA inadequately responsive to csDMARD.

Value of Remission in Patients with Rheumatoid Arthritis: A Targeted Review.

The treat-to-target strategy, which defines clinical remission as the primary therapeutic goal for rheumatoid arthritis (RA), is a widely recommended treatment approach in clinical guidelines. Achieving remission has been associated with improved clinical outcomes, quality of life, and productivity. These benefits are likely to translate to reduced economic burden in terms of lower healthcare costs and resource utilization. As such, a literature review was conducted to better understand the economic value of remission. Despite the large heterogeneity found in RA-related economic outcomes across studies, patients in remission consistently had lower direct medical and indirect costs, less healthcare resource utilization, and greater productivity compared to those without remission. Remission was associated with 19-52% savings in direct medical costs and 37-75% savings in indirect costs. The economic value of remission should thus be considered in economic analyses of RA therapies to inform treatment and reimbursement decisions.

Healthcare Costs of Not Achieving Remission in Patients with Rheumatoid Arthritis in the United States: A Retrospective Cohort Study.

INTRODUCTION: To compare all-cause and rheumatoid arthritis (RA)-related healthcare costs and resource use in patients with RA who do not achieve remission versus those who achieve remission, using clinical practice data. METHODS: Data were derived from Optum electronic health records linked to claims from commercial and Medicare Advantage health plans. Two cohorts were created: remission and non-remission. Remission was defined as Disease Activity Score 28-joint count with the C-reactive protein level or erythrocyte sedimentation rate (DAS28-CRP/ESR) < 2.6 or Routine Assessment of Patient Index Data 3 (RAPID3 ≤ 3.0). Outcomes were all-cause and RA-related costs and resource use during a 1-year follow-up period. A weighted generalized linear regression and negative binomial regression were used to estimate adjusted annual costs and resource use, respectively, controlling for confounding factors, including patient and socio-demographic characteristics. RESULTS: Data from 335 patients (remission: 125; non-remission: 210) were analyzed. Annual all-cause total costs were significantly less in the remission versus non-remission cohort ($30,427 vs. $38,645, respectively; cost ratio [CR] = 0.79; 95% CI 0.63, 0.99). All-cause resource use (mean number of visits) was less in the remission versus non-remission cohort: inpatient (0.23 vs. 0.63; visit ratio [VR] = 0.36; 95% CI 0.19, 0.70), emergency department (0.36 vs. 0.77; VR = 0.47; 95% CI 0.30, 0.74), and outpatient visits (20.7 vs. 28.5; VR = 0.73; 95% CI 0.62, 0.86). Annual RA-related total costs were similar in both cohorts; however, RA-related medical costs were numerically lower in the remission versus non-remission cohort ($8,594 vs. $10,002, respectively; CR = 0.86; 95% CI 0.59, 1.25). RA-related resource use was less in the remission versus non-remission cohort. CONCLUSIONS: Significant economic burden was associated with patients who did not achieve remission compared with those who did achieve remission.

A Matching-Adjusted Indirect Comparison of Upadacitinib Versus Tofacitinib in Adults with Moderate-to-Severe Rheumatoid Arthritis.

INTRODUCTION: Upadacitinib and tofacitinib are Janus kinase inhibitors approved for moderate-to-severe rheumatoid arthritis (RA). In the absence of head-to-head trials comparing their effectiveness, this study assessed the efficacy of upadacitinib 15 mg once-daily monotherapy/combination therapy against tofacitinib 5 mg twice-daily combination therapy among patients with RA using matching-adjusted indirect comparisons (MAICs). METHODS: The first of two MAICs used individual patient data (IPD) from the 14-week SELECT-MONOTHERAPY trial (upadacitinib [n = 217] vs. methotrexate [n = 216]) and published data from the ORAL Standard trial (tofacitinib + methotrexate [n = 204] vs. methotrexate [n = 108]). The second MAIC used IPD from the 26-week SELECT-COMPARE trial (upadacitinib + methotrexate [n = 647] vs. adalimumab + methotrexate [n = 324]) and published data from ORAL Strategy (tofacitinib + methotrexate [n = 376] vs. adalimumab + methotrexate [n = 386]). Data from patients in the upadacitinib trials were re-weighted based on age, sex, race, swollen joint count 66/28, tender joint count 68/28, C-reactive protein (CRP), and patients' global assessments to match the patient characteristics in tofacitinib trials. After matching, ACR20/50/70 and clinical remission (SDAI[CRP] ≤ 3.3, CDAI ≤ 2.8, DAS28-ESR/CRP < 2.6) were compared for upadacitinib vs. tofacitinib + methotrexate at month 3 and upadacitinib + methotrexate vs. tofacitinib + methotrexate at months 3 and 6 using Wald tests. RESULTS: At month 3, upadacitinib monotherapy patients experienced significantly larger improvement in ACR70 compared to tofacitinib + methotrexate (mean difference in difference [DID]: 9.9%; p = 0.019), while upadacitinib + methotrexate was associated with higher ACR50 compared to tofacitinib + methotrexate (DID: 12.9%; p = 0.011). At month 6, upadacitinib + methotrexate patients experienced significantly larger improvement in SDAI/CDAI/DAS28-ESR clinical remission compared to tofacitinib + methotrexate, with DIDs of 9.1% (p = 0.011), 7.5% (p = 0.038), and 11.3% (p = 0.002), respectively. CONCLUSIONS: Compared to tofacitinib combination therapy, treatment with upadacitinib monotherapy and combination therapy were associated with improved outcomes at 3/6 months (monotherapy: ACR70; combination: ACR50, SDAI, CDAI, and DAS28-ESR remission).

Comparative Efficacy of JAK Inhibitors for Moderate-To-Severe Rheumatoid Arthritis: A Network Meta-Analysis.

INTRODUCTION: Janus kinase (JAK) inhibitors are a class of targeted therapies for rheumatoid arthritis (RA) with established clinical efficacy. However, little is known about their efficacy compared with each other. This network meta-analysis (NMA) estimated the comparative efficacy of JAK inhibitors currently approved for RA. METHODS: A targeted literature review was conducted for phase III randomized controlled trials (RCTs) evaluating the efficacy of three approved JAK inhibitors (tofacitinib, baricitinib, and upadacitinib) as monotherapy or combination therapy among patients with moderate-to-severe RA who had inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR). Using Bayesian NMA, American College of Rheumatology (ACR) 20/50/70 responses and clinical remission (defined as DAS28-CRP < 2.6) were evaluated separately at 12 and 24 weeks. RESULTS: Eleven RCTs were identified and included in the NMA. All JAK inhibitors demonstrated significantly better efficacy than csDMARD. Among combination therapies, upadacitinib 15 mg had the highest 12-week ACR50 responses (median [95% credible interval]: 43.4% [33.4%, 54.5%]), followed by tofacitinib 5 mg (38.7% [28.6%, 49.8%]), baricitinib 2 mg (37.1% [25.0%, 50.6%]), and baricitinib 4 mg (36.7%, [27.2%, 47.0%]). Similar results were observed for ACR20/70 and at week 24. Upadacitinib 15 mg + csDMARD was also found to have the highest clinical remission rates at week 12 (29.8% [16.9%, 47.0%]), followed by tofacitinib 5 mg (24.3%, [12.7%, 40.2%]), baricitinib 4 mg (22.8%, [11.8%, 37.5%]), and baricitinib 2 mg (20.1%, [8.6%, 37.4%]). Similar results were seen at week 24. Among monotherapies, upadacitinib had a higher ACR50 response (38.5% [25.3%, 53.2%]) than tofacitinib (30.4% [18.3%, 45.5%]). The differences in efficacy measures were not statistically significant between the JAK inhibitors. CONCLUSIONS: The NMA found that upadacitinib 15 mg once daily had numerically higher efficacy in terms of ACR response and clinical remission among approved JAK combination therapies and monotherapies for csDMARD-IR patients with RA.

Predictors of on-site interview selection and admission for a doctor of pharmacy program using the pharmacy college application service (PharmCAS) variables.

INTRODUCTION: The study aimed to identify predictors of selection for on-site interview and admission into the doctor of pharmacy (PharmD) program using variables from the Pharmacy College Application Service (PharmCAS). METHODS: Admission data (de-identified) was obtained from University of Houston's College of Pharmacy for the years 2015 and 2016. The data consisted of relevant variables from the PharmCAS application system for all applicants during 2015 and 2016 admission cycles. Primary dependent variables were the admission committee decisions of (i) selection for on-site interview and (ii) admission into PharmD program. Descriptive frequency distributions, bivariate and multivariable logistic regression analyses were conducted to identify the predictors of admission decisions. RESULTS: A total of 968 completed application records were obtained out of which 651 were selected for on-site interview and 413 were offered admission into the PharmD program. The logistic regression analyses indicated that as compared to pre-pharmacy grade-point-average (GPA) score of <3.2, applicants with a score of 3.2-3.49 (C.I 2.52-9.66) and ≥3.5 (C.I. 2.49-12.42) were more likely to be selected for interview. Applicants with pharmacy college admissions test (PCAT) score of 70-79 (C.I. 3.37-13.96) and ≥80 (C.I. 7.73-33.83) were more likely to be selected for interview as compared to those with PCAT < 70. With respect to admissions, female gender (C.I. 1.01-2.12), pre-pharmacy GPA ≥ 3.5 (C.I. 1.62-4.82), PCAT ≥ 80 (C.I. 2.33-6.61), letters of reference score ≥ 3.7 (C.I. 1.04-2.29) and at least one known additional language (C.I. 0.47-0.99) influenced the likelihood of being admitted into the PharmD program. CONCLUSION: The study findings can be used to optimize the applicant review process by assigning more weightage to the significant predictors in decision making towards admission into PharmD programs. Future studies evaluating the influence of the predictors on academic performance are warranted.

Communicating risk of medication side-effects: role of communication format on risk perception.

BACKGROUND: Medication side-effects often arouse fear in the minds of consumers and therefore need to be communicated in a manner such that the intended message is clearly understood, without causing undue fear. OBJECTIVES: Considering the message format and contextual factors that influence perceptions of risk, this study aimed at assessing the interaction effects of message format and contextual factors (rate of occurrence and severity) on risk perception of medication side-effects. METHODS: Using Rhormann's risk communication process model, a 2 (message format: words-only vs. words + numeric) X 2 (rate of occurrence: high vs low) X 2 (severity: mild vs severe) experimental factorial study was designed. Participants were presented with four of eight possible combinations of the three factors and were asked to indicate the risk perception with the associated side-effects. Repeated measures analysis was conducted while adjusting for control variables. RESULTS: A total of 196 completed surveys were collected. Communication format did not have significant main effect on risk perception (P=0.4237) but demonstrated a significant interaction with rate of occurrence (P=0.0001). As compared to words-only format, least square means for words + numeric format were lower among low-rate side-effects but were higher among high-rate side-effects. Rate of occurrence (P<0.0001) and severity (P<0.0001) had significant main effects on risk perception as well as interaction effect with each other (P<0.0001). CONCLUSIONS: The results indicated that effect of communication format on risk perception of side-effect is dependent on the underlying rate of occurrence of side-effect. Healthcare providers should therefore carefully construct risk communication messages for effective communication with patients.

Communicating risk of medication side-effects: role of communication format on risk perception

Background: Medication side-effects often arouse fear in the minds of consumers and therefore need to be communicated in a manner such that the intended message is clearly understood, without causing undue fear. Objectives: Considering the message format and contextual factors that influence perceptions of risk, this study aimed at assessing the interaction effects of message format and contextual factors (rate of occurrence and severity) on risk perception of medication side-effects. Methods: Using Rhormann's risk communication process model, a 2 (message format: words-only vs. words + numeric) X 2 (rate of occurrence: high vs low) X 2 (severity: mild vs severe) experimental factorial study was designed. Participants were presented with four of eight possible combinations of the three factors and were asked to indicate the risk perception with the associated side-effects. Repeated measures analysis was conducted while adjusting for control variables. Results: A total of 196 completed surveys were collected. Communication format did not have significant main effect on risk perception (P=0.4237) but demonstrated a significant interaction with rate of occurrence (P=0.0001). As compared to words-only format, least square means for words + numeric format were lower among low-rate side-effects but were higher among high-rate side-effects. Rate of occurrence (P<0.0001) and severity (P<0.0001) had significant main effects on risk perception as well as interaction effect with each other (P<0.0001). Conclusions: The results indicated that effect of communication format on risk perception of side-effect is dependent on the underlying rate of occurrence of side-effect. Healthcare providers should therefore carefully construct risk communication messages for effective communication with patients

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Predicting pharmacy students' intention to apply for a residency: A systematic theory of planned behavior approach.

OBJECTIVE: The current literature has identified many motivating factors and barriers influencing pharmacy students' decision to apply for residency training. Despite a growing need for residency trained pharmacists to advance the profession, it is not clear why only about one in four pharmacy students decide to pursue a residency, and which of these factors have the most influence on student decision-making. The study examines the factors associated with pharmacy students' intention to apply for a postgraduate residency using the theory of planned behavior (TPB) framework. METHODS: Second and third-year students from four Texas pharmacy schools were surveyed using an online questionnaire based on the TPB. Descriptive statistics and multiple linear regression analyses were utilized to assess the study objectives. RESULTS: A total of 251 completed responses were received. Attitude, subjective norms (SN), and perceived behavioral control (PBC) were significant predictors of intention to apply for a pharmacy residency (ß = 0.32, 0.58, and 0.36, respectively, p < 0.001). Attending ASHP's midyear meeting or other residency showcase was a significant predictor of intention (ß = 0.71, p = 0.006). Additional significant predictors of intention include believing a residency would increase confidence in practicing pharmacy (ß = 0.36, p < 0.001) and help achieve career goals (ß = 0.16, p < 0.02); the social influence of faculty members (ß = 0.10, p = 0.003) and family (ß = 0.08, p = 0.02); believing financial obligations (ß = 0.20, p = 0.006), feeling afraid of the competition and/or not matching (ß = 0.24, p < 0.001), needing to relocate (ß = 0.09, p = 0.04), and the lengthy application and/or interview process (ß = 0.12, p = 0.04) would make it more difficult to apply for a residency. CONCLUSIONS: The TPB model was useful in predicting pharmacy students' intention to apply for a residency, and all TPB constructs were significant predictors. Therefore, interventions that target students' attitude, SN, and PBC may be valuable to increase their intention, especially the specific beliefs identified to significantly predict intention. Future research into methods in which these motivating factors can be encouraged and perceived barriers can be addressed by pharmacy stakeholders will increase interest and participation in residency training.

Physicians' intention to prescribe hydrocodone combination products after rescheduling: A theory of reasoned action approach.

BACKGROUND: The U.S. Drug Enforcement Administration (DEA) rescheduled hydrocodone combination products (HCPs) in an attempt to mitigate the prescription opioid epidemic. Many in the medical and pharmacy community expressed concerns of unintended consequences as a result of rescheduling. OBJECTIVES: This study examined physicians' intentions to prescribe HCPs after rescheduling using the framework of the theory of reasoned action (TRA). METHODS: A cover letter containing a link to the online questionnaire was sent to physicians of the Texas Medical Association who were likely to prescribe opioids. The questionnaire assessed physicians' intentions to prescribe HCPs after rescheduling. Predictor variables included attitude toward rescheduling, subjective norm toward HCP prescribing, and past prescribing behavior of schedule II prescriptions. All variables were measured on a 7-point, Likert-type scale. Intention to prescribe as a dependent variable was regressed over TRA variables and respondent characteristics. RESULTS: A total of 1176 usable responses were obtained, yielding a response rate of 13.3%. Mean (M) age was 53.07 ± 11 and most respondents were male (70%) and Caucasian (75%). Physicians held a moderately positive intention to prescribe HCPs (M = 4.36 ± 2.08), held a moderately negative attitude towards rescheduling, M = 4.68 ± 1.51 (reverse coded). Subjective norm was moderately low, M = 3.06 ± 1.78, and past prescribing behavior M = 2.43 ± 1.21. The linear regression analysis indicated that attitude (ß = 0.10; P = 0.006), subjective norm (ß = 0.35; P < 0.0001) and past prescribing behavior (ß = 0.59; P < 0.0001) were significant predictors of intention to prescribe HCPs after rescheduling. CONCLUSIONS: TRA was shown to be a predictive model of physicians' intentions to prescribe HCPs after rescheduling. Overall, physicians held a moderately positive intention to prescribe HCPs. Past behavior concerning schedule II prescribing was found to be the most significant predictor of intention. Understanding the impact of federal rule changes on pain management care and patient satisfaction is necessary to determine whether this change has produced the intended consequences without harming patients in need of HCPs.

Effect of Communication Style on Perceptions of Medication Side Effect Risk among Pharmacy Students.

Objective. To assess the effect of communication style, and frequency and severity of medication side-effects, on pharmacy students' perception of risk of experiencing side effects. Methods. One hundred responses from pharmacy students were obtained using an online survey. Participants were presented with a drug information box containing drug name, drug usage, and one side-effect associated with the drug. Information on side-effect for each drug was presented in one of eight experimental conditions, in a 2 (side-effect frequency: low, high), X2 (side-effect severity: mild, severe) X2 (communication style: verbal, verbal + natural frequency) factorial design. Risk perception of experiencing side effects was measured. Results. Communication style was found to have a significant impact on risk perception depending on the context of frequency and severity associated with the side effect. Conclusion. Communication style plays a significant role in formulating risk perceptions of medication side effects. Training in pharmaceutical counseling should include special emphasis on effective language use.