Anna G. Mattle

Introduction: Older patients with dementia or mild cognitive impairment (MCI) are particularly vulnerable to adverse effects from potentially inappropriate medications (PIMs). Previous studies demonstrated that pharmacist interventions may reduce PIMs, but the impact of pharmacists embedded in an outpatient memory care clinic has not been adequately studied.Objective: To determine the impact of pharmacist recommendations on PIM reduction in older adults with dementia or MCI.Methods: This prospective observational study within an outpatient neurology center included patients at least 65 years old diagnosed with dementia or MCI. Pharmacists utilized the American Geriatrics Society Beers Criteria, the Screening Tool of Older Persons' Potentially Inappropriate Prescriptions, and the Anticholinergic Burden Scale (ACB) to identify PIMs and reviewed patient charts to make pharmacologic and nonpharmacologic recommendations to prescribers when appropriate per clinical judgment. Primary outcomes included frequency and prevalence of PIMs before versus after pharmacist intervention and rate of acceptance of pharmacy recommendations. Additional outcomes included ACB scores before versus after intervention.Results: A total of 180 patients were included. Pharmacists made recommendations for 49% of patients, most commonly laboratory monitoring recommendations and medication discontinuations or substitutions. Out of 192 total pharmacist recommendations, 61 (32%) were accepted by providers within the memory clinic. After pharmacist intervention, the frequency and prevalence of PIMs were reduced from average 1.8 to 1.7 PIMs per patient and from 78% to 74% of patients with at least one PIM (p < 0.05). ACB scores were reduced from average 1.5 to 1.3 (p < 0.01).Conclusion: Pharmacist intervention resulted in a reduction in PIMs and ACB scores in patients with dementia or MCI. Future studies should incorporate a controlled prospective design with scheduled clinical outcomes assessments such as cognitive testing to examine the clinical benefit of pharmacist intervention and explore methods to improve multidisciplinary collaboration between pharmacists and prescribers.

Small therapeutic proteins are receiving increased interest as therapeutic drugs; however, their clinical success has been limited due to their rapid elimination. Here, we report a half-life extension strategy via strategy via red blood cell red blood cell (RBC) hitch-hiking. This manuscript details the development and characterization of novel anti-RBC single-domain antibodies (sdAbs), their genetic fusion to therapeutic antibody fragments (TAF) as bispecific fusion constructs, and their influence on TAF pharmacokinetics and biodistribution. Several sdAbs specific to the band 3 antigen were generated via phage-display technology. Binding affinity to RBCs was assessed via flow cytometry. Affinity maturation via random mutagenesis was carried out to improve the binding affinity of the sdAbs. Bi-specific constructs were generated by fusing the anti-RBC sdAbs with anti-tissue necrosis factor alpha (TNF-α) TAF via the use of a glycine-serine flexible linker, and assessments for binding were performed via enzyme-linked immunosorbent assay and flow cytometry. Pharmacokinetics of anti-RBC sdAbs and fusion constructs were evaluated following intravenous bolus dosing in mice at a 1 mg/kg dose. Two RBC-binding sdAbs, RB12 and RE8, were developed. These two clones showed high binding affinity to human RBC with an estimated K_D of 17.7 nM and 23.6 nM and low binding affinity to mouse RBC with an estimated K_D of 335 nM and 528 nM for RB12 and RE8, respectively. Two derivative sdAbs, RMA1, and RMC1, with higher affinities against mouse RBC, were generated via affinity maturation (K_D of 66.9 nM and 30.3 nM, respectively). Pharmacokinetic investigations in mice demonstrated prolonged circulation half-life of an anti-RBC-TNF-α bispecific construct (75 h) compared to a non-RBC binding control (1.3 h). In summary, the developed anti-RBC sdAbs and fusion constructs have demonstrated high affinity in vitro, and sufficient half-life extension in vivo.

BACKGROUND: Patients diagnosed as having multiple sclerosis (MS) experience a wide range of symptoms requiring pharmacologic management, and many do not achieve adequate symptom control. The purpose of this study was to evaluate the role of medical cannabis (MC) as part of a comprehensive treatment plan for patients with MS.METHODS: A retrospective medical record review of 141 patients with MS receiving MC for symptom management was conducted. Data were collected for up to 4 follow-up appointments after initiation of MC. Outcomes included changes in MS symptoms, medication changes, adverse events, and changes in cognition and mobility.RESULTS: Patients experienced extensive MS symptom improvement after initiation of MC, with alleviation of pain (72% of patients) and spasticity (48% of patients) and improvement in sleep (40% of patients) the most common. There was a significant reduction in concomitant opioid use after initiating MC as evidenced by a significant decrease in daily morphine milligram equivalents among patients prescribed opioid analgesics (P = .01). Decreases in muscle relaxant use and benzodiazepine use did not reach significance (P > .05). The most common adverse reaction to MC was fatigue (11% of patients).CONCLUSIONS: In many patients with MS, MC was well tolerated, eased pain and spasticity, improved sleep and other symptoms, and reduced use of concomitant opioid analgesics. Prospective studies are needed to further investigate the role of MC in the treatment of patients with MS.