Evaluation of rates of virologic suppression in HIV-positive patients with varying numbers of comorbidities.

PURPOSE: To evaluate the impact of the number of comorbidities on virologic suppression in HIV-positive patients. METHODS: This study included patients 18 years or older who were on antiretroviral therapy (ART) with at least 2 visits to an HIV primary care clinic in the past year. The primary outcome was the percentage of patients with an undetectable viral load (a blood HIV RNA level of <20 copies/mL) among groups of patients with 0, 1 or 2, 3 or 4, and 5 comorbidities, respectively. The secondary outcome was the percentage of patients with undetectable viral loads per each comorbidity, as listed above. The study was reviewed by an institutional review board and approved as exempt from full review. RESULTS: Among the 1,144 patients (median age of 52 years, 43% female, 74% Black) included in the study, 80% had an undetectable viral load, and the mean CD4 count was 638 cells/mm3. The majority of patients (48%) had 1 or 2 comorbidities, with only 2 patients having 5 comorbidities. For patients with 0, 1 or 2, 3 or 4, and 5 comorbidities, the percentages of patients with undetectable HIV viral loads were 76%, 81.7%, 87.9%, and 100%, respectively (P = 0.0009 in χ 2 test for trend). When looking at individual comorbidities, corresponding viral suppression rates were as follows: chronic kidney disease, 88.6%; hypertension, 85.8%; type 2 diabetes, 85.7%; clinical atherosclerotic cardiovascular disease, 83.1%; substance abuse, 76%; and psychiatric disorders, 75.2%. CONCLUSION: Improved viral suppression was seen among HIV-positive patients with an increased number of comorbidities. Patients with psychiatric disorders had the lowest viral suppression rates amongst all of the comorbidity subgroups.

Development and Validation of VM-PATHI: Vestibular Migraine Patient Assessment Tool and Handicap Inventory.

OBJECTIVE: The aim of this article is to develop and validate a disease-specific, patient-reported outcome measure for vestibular migraine. SETTING: Tertiary care vestibular center. PATIENTS: Adult patients with definite or probable vestibular migraine per Barany Society Criteria. STUDY DESIGN: This was a prospective cohort study. VM-PATHI (Vestibular Migraine Patient Assessment Tool and Handicap Inventory) was developed with expert input, literature review, and patient feedback. VM-PATHI scores were compared between those with vestibular migraine and controls, across several time points, and to other dizziness and quality of life (QoL) measures. RESULTS: A 25-item questionnaire was developed. Cronbach's α was high at 0.92. Test-retest reliability was excellent (r = 0.90, p < 0.001). Scores were much higher in patients with vestibular migraine (mean 42.5, SD = 16.1) than control patients (mean = 9.6, SD = 8.5). VM-PATHI scores were responsive to treatment (p = 0.01). Scores were well correlated with general QoL, depression, and anxiety scores. Scores were also correlated with the Dizziness Handicap Inventory (r = 0.69). An exploratory factor analysis was performed, which revealed 6 distinct factors that corresponded well to different aspects of disease-related symptomatology. CONCLUSION: VM-PATHI is a valid, reliable, and responsive measure of disease severity in vestibular migraine.

CGRP and Migraine: The Role of Blocking Calcitonin Gene-Related Peptide Ligand and Receptor in the Management of Migraine.

Migraine is a highly prevalent, complex neurological disorder. The burden of disease and the direct/indirect annual costs are enormous. Thus far, treatment options have been inadequate and mostly based on trial and error, leaving a significant unmet need for effective therapies. While the underlying pathophysiology of migraine is incompletely understood, blocking the calcitonin gene-related peptide (CGRP) using monoclonal antibodies targeting CGRP or its receptor and small molecule CGRP receptor antagonists (gepants) have emerged as a promising therapeutic opportunity for the management of migraine. In this review, we discuss new concepts in the pathophysiology of migraine and the role of CGRP, the current guidelines for treating migraine preventively, the medications that are being used, and their limitations. We then discuss small molecule CGRP receptor antagonists, monoclonal antibodies to CGRP ligand and receptor, as well as the detailed results of Phase II and III trials involving these novel treatments. We conclude with a discussion of the implications of blocking CGRP and its receptor.

Early implementation of QbD in biopharmaceutical development: a practical example.

In drug development, the "onus" of the low R&D efficiency has been put traditionally onto the drug discovery process (i.e., finding the right target or "binding" functionality). Here, we show that manufacturing is not only a central component of product success, but also that, by integrating manufacturing and discovery activities in a "holistic" interpretation of QbD methodologies, we could expect to increase the efficiency of the drug discovery process as a whole. In this new context, early risk assessment, using developability methodologies and computational methods in particular, can assist in reducing risks during development in a cost-effective way. We define specific areas of risk and how they can impact product quality in a broad sense, including essential aspects such as product efficacy and patient safety. Emerging industry practices around developability are introduced, including some specific examples of applications to biotherapeutics. Furthermore, we suggest some potential workflows to illustrate how developability strategies can be introduced in practical terms during early drug development in order to mitigate risks, reduce drug attrition and ultimately increase the robustness of the biopharmaceutical supply chain. Finally, we also discuss how the implementation of such methodologies could accelerate the access of new therapeutic treatments to patients in the clinic.