Targeting the High-Density Lipoprotein Proteome for the Treatment of Post-Acute Sequelae of SARS-CoV-2.

Here, we target the high-density lipoprotein (HDL) proteome in a case series of 16 patients with post-COVID-19 symptoms treated with HMG-Co-A reductase inhibitors (statin) plus angiotensin II type 1 receptor blockers (ARBs) for 6 weeks. Patients suffering from persistent symptoms (post-acute sequelae) after serologically confirmed SARS-CoV-2 infection (post-COVID-19 syndrome, PCS, n = 8) or following SARS-CoV-2 vaccination (PVS, n = 8) were included. Asymptomatic subjects with corresponding serological findings served as healthy controls (n = 8/8). HDL was isolated using dextran sulfate precipitation and the HDL proteome of all study participants was analyzed quantitatively by mass spectrometry. Clinical symptoms were assessed using questionnaires before and after therapy. The inflammatory potential of the patients' HDL proteome was addressed in human endothelial cells. The HDL proteome of patients with PCS and PVS showed no significant differences; however, compared to controls, the HDL from PVS/PCS patients displayed significant alterations involving hemoglobin, cytoskeletal proteins (MYL6, TLN1, PARVB, TPM4, FLNA), and amyloid precursor protein. Gene Ontology Biological Process (GOBP) enrichment analysis identified hemostasis, peptidase, and lipoprotein regulation pathways to be involved. Treatment of PVS/PCS patients with statins plus ARBs improved the patients' clinical symptoms. After therapy, three proteins were significantly increased (FAM3C, AT6AP2, ADAM10; FDR < 0.05) in the HDL proteome from patients with PVS/PCS. Exposure of human endothelial cells with the HDL proteome from treated PVS/PCS patients revealed reduced inflammatory cytokine and adhesion molecule expression. Thus, HDL proteome analysis from PVS/PCS patients enables a deeper insight into the underlying disease mechanisms, pointing to significant involvement in metabolic and signaling disturbances. Treatment with statins plus ARBs improved clinical symptoms and reduced the inflammatory potential of the HDL proteome. These observations may guide future therapeutic strategies for PVS/PCS patients.

The JAPAN-FORTA (Fit fOR The Aged) list: Consensus validation of a clinical tool to improve drug therapy in older adults.

PURPOSE: Multimorbidity and subsequent polypharmacy are highly prevalent in older people. To improve inappropriate drug treatment, listing approaches such as the Beers or FORTA lists have been developed. Latter is the only clinically validated drug list issuing both positive (FORTA labels A, B) and negative (FORTA labels C, D) recommendations. Several country-specific FORTA lists have been developed to acknowledge national prescription habits, drug availabilities, and expert opinions. Here, this approach was applied to Japan. METHODS: 13 Japanese experts in geriatric pharmacotherapy participated as raters in a 2-step Delphi consensus validation of the FORTA list. The proposal of FORTA labels was based on the EURO-FORTA List and raters were asked to add, delete or re-evaluate medications, add relevant diagnoses and comments. RESULTS: The final JAPAN-FORTA list contains 210 items aligned to 24 main indication groups. 15 items were added to the proposal and the 71 items either not used/approved in Japan or not evaluated by any rater (oncological drugs) were removed. Excluding latter, the JAPAN-FORTA list differs from the EURO-FORTA list by 23 %. Removals mainly concerned psychotropic drugs. A maximum of one label was changed per indication. The majority (96.9 percent) of the proposed FORTA labels were confirmed, only 6 labels had to be changed. CONCLUSION: The new JAPAN-FORTA list addresses the appropriateness of drug treatment in older people in Japan. This unique listing approach issuing both positive and negative medication recommendations has been shown to improve of drug therapy in older adults and its country-specific version is now available for Japan.

The U.S.-FORTA (Fit fOR The Aged) List: Consensus Validation of a Clinical Tool to Improve Drug Therapy in Older Adults.

BACKGROUND/OBJECTIVES: Polypharmacy and multimorbidity is a threat to older people; hence, listing approaches should support physicians to optimize medication. The FORTA (Fit fOR The Aged) classification of drug appropriateness for older people provides positive or negative labels: A (A-bsolutely), B (B-eneficial), C (C-areful), and D (D-on't). Based on these categories, FORTA-labeled drug lists were developed in 7 European countries or regions; the same approach was used to develop a U.S.-FORTA List reflecting the country-specific availability and usage of drugs. DESIGN/SETTING: A 2-step Delphi-type approach was employed to add, remove, or relabel drugs from the listing proposal and to add or remove new indications. The proposal utilized the European (EURO)-FORTA list as template. PARTICIPANTS: Eight US-based geriatricians/pharmacists served as raters. MEASUREMENTS: Raters gave recommendations and comments on the list items. RESULTS: The first U.S.-FORTA List contains 273 items aligned to 27 main indication groups; 30 drugs and drug groups were added, and 23 removed as being unavailable in the United States. The highest percentage of changes in FORTA labels as compared to the EURO-FORTA List occurred for sleep disorders associated with dementia (40%). In 8 indications, the labels for 11 items were different from the proposal. Thus, for the majority of the items (n = 232, 95.5%), the proposals were accepted by the US raters. Only 16 (6.6%) of the proposed items (n = 243) had to be re-evaluated in the second round as a result of inconsistent rating in the first round. CONCLUSIONS AND IMPLICATIONS: The U.S.-FORTA List addresses the appropriateness of drugs for older people in the United States reflecting country-specific availability, usage, and expert rating. As shown for the FORTA list in Europe, this listing approach is among the few that are clinically validated and improve well-being and geriatric outcomes. The U.S.-FORTA List now largely enhances the global availability of this approach.