Therapy outcomes associated with prescription cannabidiol use at 12 months post-initiation.

OBJECTIVE: This study evaluated prescription cannabidiol (CBD) outcomes during the first 12 months of therapy. METHODS: A single-center, prospective cohort study was performed including patients prescribed CBD from January 2019 - April 2020, excluding clinical trial patients and those using external specialty pharmacy services. The primary outcome wasepilepsy-related emergency healthcare service (EHS) use within 12 months of initation. Secondary outcomes included prescription CBD discontinuation rate and reason and concomitant anti-seizure medication (ASM) use. A multiple logistic regression model evaluated the odds of EHS use, adjusting for initial concomitant ASM count, age, and insurance type. RESULTS: The 136 patients included were 85% white, 50% female, and 68% pediatric. EHS utilization occurred in 37% (n = 50) of patients; 29 patients (21%, n = 20 pediatric, n = 9 adult) had at least one emergency department (ED) visit, 9 patients (7%) had two or more; 30 patients (22%, n = 22 pediatric, n = 8 adult) had at least one hospitalizaion. Median time to first ED and hospitalization was 69 (IQR 31-196) and 104 (IQR 38-179) days, respectively. Prescription CBD was discontinued in 31 patients (23%, n = 18 pediatric, n = 13 adult), due to major side effects (n = 12, 39%), common side effects (n = 11, 36%), and unsatisfactory response (n = 11, 36%). There was no significant change in concomitant ASM use. CONCLUSION: Despite potential benefits of prescription CBD, many patients utilize EHSs in the first 12 months of treatment with minimal changes in concomitant ASM use.

Insurance Approval Delay of Biologic Therapy Dose Escalation Associated with Disease Activity in Patients with Inflammatory Bowel Disease.

BACKGROUND: Dose escalation of self-injectable biologic therapy for inflammatory bowel diseases may be required to counteract loss of response and/or low drug levels. Payors often require completion of a prior authorization (PA), which is a complex approval pathway before providing coverage. If the initial PA request is denied, clinic staff must complete a time and resource-intensive process to obtain medication approval. AIMS: This study measured time from decision to dose escalate to insurance approval and evaluated impact of approval time on disease activity. METHODS: This was a single-center retrospective analysis of adult patients with IBD prescribed an escalated dose of biologic therapy at an academic center with an integrated specialty pharmacy team from January to December 2018. Outcomes included time to insurance approval and the association between approval time and follow-up C-reactive protein (CRP) and Short Inflammatory Bowel Disease Questionnaire (SIBDQ) scores. Associations were tested using linear regression analyses. RESULTS: 220 patients were included, median age 39, 53% female, and 96% white. Overall median time from decision to dose escalate to insurance approval was 7 days [interquartile range (IQR) 1, 14]. Approval time was delayed when an appeal was required [median of 29 days (IQR 17, 43)]. Patients with a longer time to insurance approval were less likely to have CRP improvement (p = 0.019). Time to insurance approval did not significantly impact follow-up SIBDQ scores. CONCLUSION: Patients who had a longer time to insurance approval were less likely to have improvement in CRP, highlighting the negative clinical impact of a complex dose escalation process.

Public Preferences for Digital Health Data Sharing: Discrete Choice Experiment Study in 12 European Countries.

BACKGROUND: With new technologies, health data can be collected in a variety of different clinical, research, and public health contexts, and then can be used for a range of new purposes. Establishing the public's views about digital health data sharing is essential for policy makers to develop effective harmonization initiatives for digital health data governance at the European level. OBJECTIVE: This study investigated public preferences for digital health data sharing. METHODS: A discrete choice experiment survey was administered to a sample of European residents in 12 European countries (Austria, Denmark, France, Germany, Iceland, Ireland, Italy, the Netherlands, Norway, Spain, Sweden, and the United Kingdom) from August 2020 to August 2021. Respondents answered whether hypothetical situations of data sharing were acceptable for them. Each hypothetical scenario was defined by 5 attributes ("data collector," "data user," "reason for data use," "information on data sharing and consent," and "availability of review process"), which had 3 to 4 attribute levels each. A latent class model was run across the whole data set and separately for different European regions (Northern, Central, and Southern Europe). Attribute relative importance was calculated for each latent class's pooled and regional data sets. RESULTS: A total of 5015 completed surveys were analyzed. In general, the most important attribute for respondents was the availability of information and consent during health data sharing. In the latent class model, 4 classes of preference patterns were identified. While respondents in 2 classes strongly expressed their preferences for data sharing with opposing positions, respondents in the other 2 classes preferred not to share their data, but attribute levels of the situation could have had an impact on their preferences. Respondents generally found the following to be the most acceptable: a national authority or academic research project as the data user; being informed and asked to consent; and a review process for data transfer and use, or transfer only. On the other hand, collection of their data by a technological company and data use for commercial communication were the least acceptable. There was preference heterogeneity across Europe and within European regions. CONCLUSIONS: This study showed the importance of transparency in data use and oversight of health-related data sharing for European respondents. Regional and intraregional preference heterogeneity for "data collector," "data user," "reason," "type of consent," and "review" calls for governance solutions that would grant data subjects the ability to control their digital health data being shared within different contexts. These results suggest that the use of data without consent will demand weighty and exceptional reasons. An interactive and dynamic informed consent model combined with oversight mechanisms may be a solution for policy initiatives aiming to harmonize health data use across Europe.

Droxidopa management by an integrated health-system specialty pharmacy team.

BACKGROUND: Droxidopa, indicated for the treatment of symptomatic neurogenic orthostatic hypotension, can be challenging for patients to access owing to manufacturer and payer restrictions, and requires close monitoring to ensure safety and effectiveness. OBJECTIVE: This practice report describes the development and outcomes of an integrated neurology specialty pharmacy team for droxidopa management. PRACTICE DESCRIPTION: An integrated health-system specialty pharmacy (HSSP) connected to an academic institution with integrated specialty pharmacists working in collaboration with the providers in both the neurology and autonomic disfunction clinic. PRACTICE INNOVATION: In May 2017, the integrated HSSP developed droxidopa management services. Based on clinic-identified needs, the specialty pharmacy team completed droxidopa access requirements (insurance approval and affordability), provided comprehensive medication education at droxidopa initiation, and developed and executed droxidopa titration and monitoring plans in collaboration with providers. While patients were on droxidopa therapy, specialty pharmacist staff (pharmacists and technicians) monitored patients for safety and response to therapy and communicated with the health care team through the shared electronic health record. EVALUATION METHODS: We performed a retrospective cohort analysis of adult patients with at least 3 fills of droxidopa using the integrated specialty pharmacy services from May 2017 to April 2020. Outcomes included persistence (defined as lack of 60-day gap in treatment), adherence (calculated using pharmacy claims and proportion of days covered [PDC]), and number and type of pharmacist interventions after droxidopa initiation. RESULTS: Of the 83 patients reviewed, 60 patients (72%) were persistent on droxidopa therapy over the study period. The median PDC was 0.98 (interquartile range 0.90-1.00). Over 36 months, the specialty pharmacist performed 60 interventions after droxidopa initiation, most related to dose changes, drug-drug interaction management, and medication reconciliation. CONCLUSION: The development of integrated specialty pharmacy services for patients prescribed droxidopa resulted in high droxidopa persistence and adherence. Interventions from the specialty pharmacist ensured droxidopa remained safe and appropriate for patients.

Specialty pharmacy integration and the role of an advanced certified pharmacy technician in prescription cannabidiol access.

BACKGROUND: Insurance requirements that limit access to prescription cannabidiol (CBD), an adjunct therapy for uncontrolled seizure disorders, may lead to treatment initiation delays. Integrated health-system specialty pharmacies (IHSSPs) use pharmacists and advance certified pharmacy technicians (CPhTs) to help navigate prescription CBD access requirements. OBJECTIVE(S): Evaluate time from initial specialty pharmacy referral to prescription CBD shipment. METHODS: This was a single-center, retrospective analysis of patients prescribed CBD from January 2019 to April 2020 by the outpatient neurology clinic and dispensed by the center's IHSSP. The primary outcome was the time to prescription CBD access, defined as days between the specialty pharmacy completing an initial patient assessment and first medication shipment. Secondary outcomes were percentage of patients requiring financial assistance and days between key steps in the access pathway. Data were collected from electronic health records and the specialty pharmacy patient management database. The CPhT was responsible for completing most portions of the access pathway under supervision of the clinical pharmacist. RESULTS: After screening, 136 patients were included: 50% male, 85% white, 60% insured by Medicaid, and median age 14 years (interquartile range [IQR] 9-21). The most common indication was Lennox-Gastaut syndrome (n = 117, 86%). Of the 129 patients (95%) who required a prior authorization (PA), 92% were approved (n = 119). Median time from initial assessment to first shipment was 7 days (IQR 4-13). Of patients for whom the CPhT helped obtain financial assistance (n = 14, 10%), all had $0 costs after assistance. Median times for secondary outcomes led by the CPhT in days were as follows: initial assessment completion to benefits investigation (BI) = 0 (IQR 0-0), BI to PA submission = 0 (IQR 0-0), and PA denial to appeal submission = 4 (IQR 1-7). CONCLUSION: IHSSP teams, particularly advanced CPhT roles, helped patients afford and initiate prescription CBD quickly.

Primary medication nonadherence to oral oncology specialty medications.

BACKGROUND: Patients prescribed specialty oncology medications face logistical and financial challenges to medication procurement, leading to primary medication nonadherence (PMN). Limited research has evaluated rates and reasons for PMN within a specialty oncology population. Addressing PMN is essential to ensuring patient access and uptake and realizing benefits of these therapies. OBJECTIVES: The objectives of this study were to compute the rates of and reasons for PMN in patients prescribed oral oncology medications at an integrated health-system specialty pharmacy (IHSSP). METHODS: We performed a single-center, retrospective analysis of specialty oncology prescriptions electronically prescribed between January and December 2018. Data were extracted from electronic health record (EHR) and pharmacy claims databases. Prescriptions were PMN eligible if none of the following were met: fill of any cancer medication within the previous 180-day lookback window, duplicate prescription, cancellation within 30 days, rerouting to an external pharmacy within 30 days of prescribing, filled through alternate method, or nononcology or hematology condition. PMN was calculated by dividing eligible prescriptions unfilled during the study period by all eligible prescriptions. Reasons for a lack of prescription fulfillment were assessed via EHR review. Data were analyzed using descriptive statistics. RESULTS: We evaluated 4482 prescriptions from 1422 patients, resulting in 861 PMN-eligible prescriptions. Most PMN-eligible prescriptions (n = 668, 78%) were filled within 30 days, leaving 193 prescriptions as potential instances of PMN. After EHR review, 158 prescriptions met the exclusion criteria, resulting in a PMN rate of 4%. Of PMN prescriptions (n = 35), most were caused by clinical reasons (n = 22, 63%); however, 10 prescriptions were unfilled owing to patient decision, 2 owing to unaffordable treatment, and 1 owing to inability to reach the patient. Patients with PMN had a median age of 72 years and were mostly male (60%), with a median Charlson comorbidity index score of 7. CONCLUSION: Low rates of PMN to prescribed anticancer medications were found among electronic prescriptions intended to be filled at an IHSSP.

Hexametaphosphate cross-linked chitosan beads for the eco-efficient removal of organic dyes: Tackling water quality.

There is an increasing trend of developing various low-cost grafted natural amino polysaccharides for the biosorptive removal of noxious dye effluents like Malachite green (MG) and anionic Reactive Red-195 (RR-195) dyes from aqueous solution. Chemically cross-linked chitosan microsphere (CTS-HMP), a promising non-toxic biosorbent possessing high charge density and thermal stability was prepared by using hexametaphosphate as ionic cross-linker. Batch biosorption experiments were carried out under different temperatures (298, 308 and 318 K), pH (2.0-10.0), initial concentrations (25-250 mg L-1), adsorbent dosage (0.01-0.1 g) and contact times (0-180 min) to understand the optimum experimental conditions and simultaneously evaluate the adsorption isotherms and kinetics of CTS-HMP. Biosorption equilibrium was established in 120 and 60 min for MG and RR-195 removal process. The pseudo-equilibrium process was best described by the pseudo-second-order kinetic (R2 ≥ 0.98), Freundlich and Temkin isotherm model (R2 ≥ 0.90). The removal rate of MG and RR-195 gradually increased (69.40 and 148 mg g-1) at 250 mg L-1 of initial concentration till 100 and 50 min of contact period in a single contaminant system, though the removal efficiency of acid dye was ~2 times higher compared to basic dye under optimum conditions (p < 0.05; t-test). Thermodynamic parameters indicated exothermic (MG) and endothermic (RR-195) nature of spontaneous dye removal. The activation energy of sorption (Ea) was <50 kJ mol-1 which highlighted the importance of physical adsorption process. Therefore, the obtained results clearly validate the sustainable utilization of CTS-HMP as a promising functionalized chitosan microparticles/agent for removing dye effluents from the contaminated aqueous phase.

Intraspecific variation in testosterone-induced neuroplasticity in two canary strains.

Temperate zone songbird species, such as the canary (Serinus canaria), can serve as model systems to investigate adult seasonal plasticity in brain and behavior. An increase in day length, experienced by canaries in the early spring stimulates gonadal recrudescence and an associated increase in circulating testosterone concentrations. This increase in plasma testosterone results in marked morphological changes in well-defined neural circuitry regulating reproductive behaviors including birdsong as well as behavioral changes such as increases in song length and complexity. An obvious measure of plasticity in neural morphology can be assessed via changes in brain nuclei volume and testosterone actions on a number of cellular features including the integration and incorporation of new neurons in the adult canary brain. Previous work in our lab suggests that there may be systematic intraspecific variability within canaries in testosterone-induced adult neuroplasticity. For example, the song nucleus HVC increases in size in response to testosterone in male canaries but we found that males of the American Singer strain exhibited minimal and variable responses as compared to other canary strains such as the Border canary strain, which is thought to be closer to wild type canaries. In this study, we systematically compared the effects of testosterone on the volume of song nuclei and the number of new neurons as assessed with the neurogenesis marker doublecortin in American Singer and Border canaries. We found more pronounced testosterone-induced neuroplasticity in the Border strain than the American Singer. These data suggest that the process of selection for certain strain phenotypes is also associated with significant changes in hormone-regulated brain plasticity.

Development of a quality measures tool for the utilization of tyrosine kinase inhibitors in non-small cell lung cancer: An integrated specialty pharmacy initiative.

BACKGROUND: Tyrosine kinase inhibitors, commonly prescribed for non-small cell lung cancer, are efficacious but pose safety risks that can diminish quality of life. Quality measures to ensure appropriate utilization and monitoring of tyrosine kinase inhibitors are needed to reduce unnecessary healthcare costs and maximize therapeutic benefit. With integrated clinical and pharmaceutical care services, a health-system specialty pharmacy is the ideal setting for quality measures development. PURPOSE: The purpose of this initiative was to develop a tool to assess quality in the utilization of tyrosine kinase inhibitors in non-small cell lung cancer by engaging multiple key stakeholder perspectives to identify the fundamental elements of high-quality clinical and specialty pharmacy care. SUMMARY: Quality measures for the utilization of tyrosine kinase inhibitors in non-small cell lung cancer were developed by conducting package insert, guideline, and literature review followed by integrating feedback from key stakeholder groups through individual conversations and a structured assessment. The finalized guide assesses safety, efficacy, persistence, and patient-reported outcomes using defined clinical and specialty pharmacy measures. Most stakeholders agreed that the proposed measures were relevant as well as accurate and expressed support for implementation. CONCLUSIONS: The proposed tool provides a framework for specialty pharmacies to deliver quality care in the use of tyrosine kinase inhibitors for the treatment of non-small cell lung cancer. Further work is needed to implement and validate this tool.

Internal Amputation in Charcot Neuroarthropathy Complicated by Diabetic Foot Osteomyelitis.

Studies have demonstrated the importance of preserving plantar surface area, lever arm length, and plantar soft tissues in affording patients a plantigrade, stable, and functional limb. We describe a case of a patient who underwent internal pedal amputation that was amenable to functional bracing. The purpose of this case study is to present internal pedal amputation as a viable option to eradicate infection and produce a plantigrade, stable foot that is amenable to custom bracing.

Sharing data for future research-engaging participants' views about data governance beyond the original project: a DIRECT Study.

PURPOSE: Biomedical data governance strategies should ensure that data are collected, stored, and used ethically and lawfully. However, research participants' preferences for how data should be governed is least studied. The Diabetes Research on Patient Stratification (DIRECT) project collected substantial amounts of health and genetic information from patients at risk of, and with type II diabetes. We conducted a survey to understand participants' future data governance preferences. Results will inform the postproject data governance strategy. METHODS: A survey was distributed in Denmark, Sweden, The Netherlands, and the United Kingdom. RESULTS: In total 855 surveys were returned. Ninety-seven percent were supportive of sharing data postproject, and 90% were happy to share data with universities, and 56% with commercial companies. The top three priorities for data sharing were highly secure database, DIRECT researchers to monitor data used by other researchers, and researchers cannot identify participants. Respondents frequently suggested that a postproject Data Access Committee should involve a DIRECT researcher, diabetes clinician, patient representative, and a DIRECT participant. CONCLUSION: Preferences of how data should be governed, and what data could be shared and with whom varied between countries. Researchers are considered as key custodians of participant data. Engaging participants aids in designing governance to support their choices.

Adsorptive removal of nickel(II) ions from aqueous environment: A review.

Among various methods adsorption can be efficiently employed for the treatment of heavy metal ions contaminated wastewater. In this context the authors reviewed variety of adsorbents used by various researchers for the removal of nickel(II) ions from aqueous environment. One of the objectives of this review article is to assemble the scattered available enlightenment on a wide range of potentially effective adsorbents for nickel(II) ions removal. This work critically assessed existing knowledge and research on the uptake of nickel by various adsorbents such as activated carbon, non-conventional low-cost materials, nanomaterials, composites and nanocomposites. The system's performance is evaluated with respect to the overall metal removal and the adsorption capacity. In addition, the equilibrium adsorption isotherms, kinetics and thermodynamics data as well as various optimal experimental conditions (solution pH, equilibrium contact time and dosage of adsorbent) of different adsorbents towards Ni(II) ions were also analyzed. It is evident from a literature survey of more than 190 published articles that agricultural solid waste materials, natural materials and biosorbents have demonstrated outstanding adsorption capabilities for Ni(II) ions.

Adsorption of lead (II) ions onto novel cassava starch 5-choloromethyl-8-hydroxyquinoline polymer from an aqueous medium.

Adsorption of lead (II) ions onto cassava starch 5-choloromethyl-8-hydroxyquinoline polymer (CSCMQ) was investigated with the variation in the parameters of pH, contact time, lead (II) ions concentration, temperature and the adsorbent dose. The Langmuir and Freundlich models have been applied. CSCMQ was characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. Results showed that the adsorption process was better described by the Langmuir model. Adsorption kinetics data obtained for the metal ions sorption were investigated using pseudo-first-order, pseudo-second-order and intraparticle diffusion model. The maximum adsorption capacities (qm) were 46.512, 43.859 and 42.735 mg/g at 25, 35 and 45 °C, respectively. The dynamical data fit well with the second-order kinetics model. The results indicate that CSCMQ could be employed as low-cost material for the adsorption of Pb(II) ions from aqueous medium.

Adherence and discontinuation of prescription cannabidiol for the management of seizure disorders at an integrated care center.

OBJECTIVE: Evaluate adherence, discontinuation rates, and reasons for non-adherence and discontinuation of prescription CBD during the 12-months post-initiation period at an integrated care center. METHODS: This was a prospective study of patients prescribed CBD by a neurology clinic provider with initial prescription fulfillment through the center's specialty pharmacy from January 2019 through April 2020. Baseline demographics and reasons for non-adherence and/or discontinuation were collected from the electronic health record and pharmacy claims history was used to calculate adherence using proportion of days covered (PDC). Patients were included in the PDC analysis if they had at least 3 fills during the study period. Non-adherence was defined as a PDC < 0.8. Descriptive statistics were used to summarize data with categorical variables represented as frequencies and percentages and continuous variables as medians and interquartile ranges (IQRs). RESULTS: We included 136 patients with a median age of 14 years (IQR 9 - 21). Most patients were white (n = 115, 85%), with a diagnosis of intractable epilepsy (n = 100, 74%). Among the 128 patients with 3 or more fills, the median PDC was 0.99 (IQR 0.95 - 1.00) with non-adherence seen in 6% (n = 8) of patients. The most common reason for non-adherence was side effects (n = 2, 25%). Prescription CBD was discontinued by 23% (n = 31) of patients with a median time to discontinuation of 117 days (IQR 68 - 216). The most common reason for discontinuation was major side effects (n = 12, 39%). The most common side effects leading to discontinuation were agitation/irritability (n = 4), mood changes (n = 4), aggressive behavior (n = 3), and increased seizure frequency (n = 3). CONCLUSION: Adherence to prescription CBD at an integrated care center was high with approximately 94% of patients considered adherent. Providers and pharmacists may improve adherence and discontinuation rates by educating patients on the timeline of response, potential side effects, and potential for dose adjustments.

Moving beyond Technical Issues to Stakeholder Involvement: Key Areas for Consideration in the Development of Human-Centred and Trusted AI in Healthcare.

Discussion around the increasing use of AI in healthcare tends to focus on the technical aspects of the technology rather than the socio-technical issues associated with implementation. In this paper, we argue for the development of a sustained societal dialogue between stakeholders around the use of AI in healthcare. We contend that a more human-centred approach to AI implementation in healthcare is needed which is inclusive of the views of a range of stakeholders. We identify four key areas to support stakeholder involvement that would enhance the development, implementation, and evaluation of AI in healthcare leading to greater levels of trust. These are as follows: (1) aligning AI development practices with social values, (2) appropriate and proportionate involvement of stakeholders, (3) understanding the importance of building trust in AI, (4) embedding stakeholder-driven governance to support these activities.

IL-7R expression and IL-7 signaling confer a distinct phenotype on developing human B-lineage cells.

IL-7 is an important cytokine for lymphocyte differentiation. Similar to what occurs in vivo, human CD19⁺ cells developing in human/murine xenogeneic cultures show differential expression of the IL-7 receptor α (IL-7Rα) chain (CD127). We now describe the relationship between CD127 expression/signaling and Ig gene rearrangement. In the present study, < 10% of CD19⁺CD127⁺ and CD19⁺CD127⁻ populations had complete VDJ(H) rearrangements. IGH locus conformation measurements by 3D FISH revealed that CD127⁺ and CD127⁻ cells were less contracted than pediatric BM pro-B cells that actively rearrange the IGH locus. Complete IGH rearrangements in CD127⁺ and CD127⁻ cells had smaller CDR3 lengths and fewer N-nucleotide insertions than pediatric BM B-lineage cells. Despite the paucity of VDJ(H) rearrangements, microarray analysis indicated that CD127⁺ cells resembled large pre-B cells, which is consistent with their low level of Ig light-chain rearrangements. Unexpectedly, CD127⁻ cells showed extensive Ig light-chain rearrangements in the absence of IGH rearrangements and resembled small pre-B cells. Neutralization of IL-7 in xenogeneic cultures led to an increase in Ig light-chain rearrangements in CD127⁺ cells, but no change in complete IGH rearrangements. We conclude that IL-7-mediated suppression of premature Ig light-chain rearrangement is the most definitive function yet described for IL-7 in human B-cell development.

Uptake and predictors of anal cancer screening in men who have sex with men.

OBJECTIVES: We investigated attitudes about and acceptance of anal Papanicolaou (Pap) screening among men who have sex with men (MSM). METHODS: Free anal Pap screening (cytology) was offered to 1742 MSM in the Multicenter AIDS Cohort Study, who reported history of, attitudes about, and experience with screening. We explored predictors of declining screening with multivariate logistic regression. RESULTS: A history of anal Pap screening was uncommon among non-HIV-infected MSM, but more common among HIV-infected MSM (10% vs 39%; P < .001). Most participants expressed moderate or strong interest in screening (86%), no anxiety about screening (66%), and a strong belief in the utility of screening (65%). Acceptance of screening during this study was high (85%) across all 4 US sites. Among those screened, most reported it was "not a big deal" or "not as bad as expected," and 3% reported that it was "scary." Declining to have screening was associated with Black race, anxiety about screening, and low interest, but not age or HIV status. CONCLUSIONS: This study demonstrated high acceptance of anal Pap screening among both HIV-infected and non-HIV-infected MSM across 4 US sites.

Pharmacology and Therapeutic Potential of Benzothiazole Analogues for Cocaine Use Disorder.

Pharmacological targeting of the dopamine D4 receptor (D4R)─expressed in brain regions that control cognition, attention, and decision-making─could be useful for several neuropsychiatric disorders including substance use disorders (SUDs). This study focused on the synthesis and evaluation of a novel series of benzothiazole analogues designed to target D4R. We identified several compounds with high D4R binding affinity (Ki ≤ 6.9 nM) and >91-fold selectivity over other D2-like receptors (D2R, D3R) with diverse partial agonist and antagonist profiles. Novel analogue 16f is a potent low-efficacy D4R partial agonist, metabolically stable in rat and human liver microsomes, and has excellent brain penetration in rats (AUCbrain/plasma > 3). 16f (5-30 mg/kg, i.p.) dose-dependently decreased iv cocaine self-administration in rats, consistent with previous results produced by D4R-selective antagonists. Off-target antagonism of 5-HT2A or 5-HT2B may also contribute to these effects. Results with 16f support further efforts to target D4R in SUD treatment.

Prescription cannabidiol for seizure disorder management: Initial drug-drug interaction management by specialty pharmacists.

PURPOSE: To describe the presence, type, and management of drug-drug interactions (DDIs) at prescription cannabidiol (CBD) therapy initiation. METHODS: We conducted a single-center, retrospective study of patients prescribed CBD from a medical center's neurology clinic for seizure management from January 2019 through April 2020. Patients were excluded if they were enrolled in a CBD clinical trial or the insurance approval or medication fulfillment process was not completed by the center's specialty pharmacy. The primary outcomes were the numbers, types, and management of DDIs identified at the time of CBD prescribing. RESULTS: Of the 136 patients included, 109 (80%) had a DDI identified at baseline. Of the 260 DDIs, 71% (n = 184) were pharmacodynamic and 29% (n = 76) were pharmacokinetic in nature. Management of the 260 DDIs detected included counseling only (89% [n = 232 interactions]), discontinuation of the interacting agent [9% (n = 22 interactions]), and dosage change for the interacting agent [2% (n = 6 interactions]). Clobazam was the most commonly identified interacting medication (n = 63, 24%), while valproic acid accounted for 10% (n = 26) of the DDIs. The population was predominantly white (n = 115, 85%), 18 years of age or younger (n = 92, 68%), and had an indication for prescription CBD treatment of Lennox-Gastaut syndrome (n = 117, 86%). CONCLUSION: This study provides new information on the role that integrated specialty pharmacists can play in identifying and managing initial DDIs in patients starting prescription CBD.

A cross-sectional analysis of persistence to disease-modifying therapies in treatment naïve and experienced patients with relapsing multiple sclerosis at a health-system specialty pharmacy.

BACKGROUND: Patients with relapsing multiple sclerosis (RMS) are maintained on disease-modifying therapy (DMT) to prevent disease progression. Reported persistence rates to DMTs are varied and concerningly low. Limited data exists on long-term persistence rates and reasons for DMT discontinuation in patients with RMS. This study evaluated long-term DMT persistence, rates and reasons for DMT discontinuation or switch, specialty pharmacist involvement in DMT treatment transitions, and predictors associated with non-persistence in treatment naïve and experienced patients. METHODS: We performed a single-center retrospective, cross-sectional review of patients with RMS and ≥3 fills of DMT from a health-system specialty pharmacy (May-October 2017). Patients were followed for 3 years to determine DMT persistence, defined as the time a patient remained on index DMT. Descriptive statistics were used to summarize sample characteristics and outcomes. The Kaplan-Meier estimation method was used to estimate the probability of remaining persistent and we used the Cox proportional hazards regression model to analyze the primary outcome. Rates and reasons for DMT discontinuation were identified via pharmacy claims and confirmed via chart review of the electronic health record. RESULTS: The study included 540 patients, of which 41 (7.6%) were treatment naïve. Over 3 years, 193 (36%) patients remained on index DMT. The probability of remaining persistent for 3 years was 0.51 (95% confidence interval [CI] 0.47-0.56) and median time on index DMT was 642 days (interquartile range 317-1096). For the 347 patients that did not continue index DMT: 91 (26%) discontinued, 136 (39%) switched to a new DMT, 92 (27%) transferred care to a new specialty pharmacy or provider, 21 (6%) were lost to follow-up, and 7 (2%) died. Common reasons for DMT discontinuation or switch were insurance formulary change, side effects, clinical decline, and stable disease. Specialty pharmacists initiated 6 (7%) DMT discontinuations and 49 (36%) DMT switches. A strong non-linear relationship existed between age and risk of non-persistence (p = 0.003). Patients on an injectable index DMT were 1.5 times more likely to be non-persistent than those on an oral DMT (95% CI 1.1-2.1, p = 0.012) and patients with non-commercial insurance were 1.4 times more likely to be non-persistent (95% CI 1.02-2.0, p = 0.040). CONCLUSIONS: Long-term persistence to DMTs is low, with many patients switching or discontinuing DMT treatment. Specialty pharmacists identify the need for DMT discontinuation or switch and are uniquely positioned to assist during therapy transitions.