Nirmatrelvir/ritonavir treatment and the risk of post-COVID condition over 180 days in Malaysia.

BACKGROUND: The effect of nirmatrelvir/ritonavir on preventing post-COVID condition (PCC) in the BA4, BA5, and XBB Omicron predominant periods is not well understood. The purpose of this study was to assess how nirmatrelvir/ritonavir treatment affected both PCC and health-related quality of life. METHODS: This retrospective cohort study enrolled 2,524 adults aged 18 years and older who were eligible for nirmatrelvir/ritonavir between July 14 to November 14, 2022. All outcomes were observed from the patient's first visit to the primary health clinic, 1 week, 1 month, 3 months, and 6 months after testing positive for COVID-19. The primary outcome was the presence of PCC. Secondary outcomes included the effects on health-related quality of life, such as walking, bathing and dressing, activities, cause adverse emotions or signs that prevent individuals from leading normal lives over a 180-day observation period. RESULTS: There were no significant differences observed between the nirmatrelvir/ritonavir and those not administered (control group) in terms of PCC symptoms at 3 months (OR 0.71 95% CI 0.31, 1.64) and 6 months (OR 1.30 95% CI 0.76, 2.21). At 3 months, the use of nirmatrelvir/ritonavir was associated with a 26% reduction in symptoms causing negative emotions (OR 0.74 95% CI 0.60, 0.92) and an increased likelihood of symptoms limiting walking (OR 1.58 95% CI 1.10, 2.27). However, there were no significant differences between the nirmatrelvir/ritonavir and the control group in terms of the impact of PCC on health-related quality of life at 6 months. CONCLUSIONS: Our study indicates that the administration of nirmatrelvir/ritonavir does not significantly reduce PCC after 3 months and 6 months in a population with high vaccination coverage.

Economic Evaluation of Nirmatrelvir/Ritonavir Among Adults Against Hospitalization During the Omicron Dominated Period in Malaysia: A Real-World Evidence Perspective.

BACKGROUND AND OBJECTIVES: Nirmatrelvir/ritonavir was administered orally to manage mild to moderate symptoms of COVID-19 in adult patients. The objectives of this study were to (i) evaluate the cost-effectiveness of prescribing nirmatrelvir/ritonavir within 5 days of a COVID-19 illness in order to avert hospitalization within a 30-day period in the Malaysia setting; (ii) determine how variations in pricing and hospitalization rates will affect the cost-effectiveness of nirmatrelvir/ritonavir. METHODS: The 30-day hospitalization related to COVID-19 was determined using 1 to 1 propensity score-matched real-world data in Malaysia from 14 July 2022 to 14 November 2022. To determine the total per-person costs related to COVID-19, we added the cost of drug (nirmatrelvir/ritonavir or control), clinic visits and inpatient care. Incremental cost-effectiveness ratio (ICER) per hospitalization averted was calculated. RESULTS: Our cohort included 31,487 patients. The rate of hospitalization within 30 days was found to be 0.35% for the group treated with nirmatrelvir/ritonavir, and 0.52% for the control group. The nirmatrelvir/ritonavir group cost an additional MYR 1,625.72 (USD 358.88) per patient. This treatment also resulted in a reduction of 0.17% risk for hospitalization, which corresponded to an ICER of MYR 946,801.26 (USD 209,006.90) per hospitalization averted. CONCLUSION: In Malaysia, where vaccination rates were high, nirmatrelvir/ritonavir has been shown to be beneficial in the outpatient treatment of adults with COVID-19 who have risk factors; however, it was only marginally cost effective against hospitalization for healthy adults during the Omicron period.

Real-world nirmatrelvir-ritonavir outpatient treatment in reducing hospitalization for high-risk patients with COVID-19 during Omicron BA.4, BA.5 and XBB subvariants dominance in Malaysia: A retrospective cohort study.

OBJECTIVE: To determine if nirmatrelvir-ritonavir 300mg/100mg treatment for 5 days in high-risk outpatients with mild to moderate COVID-19 symptoms was associated with a reduction in hospitalization, intensive care unit (ICU) admission, and death. METHODS: This 1:1 propensity score matched cohort study from 647 public health clinics in Malaysia included all patients with COVID-19 with positive tests aged 18 years and older, who were eligible for nirmatrelvir-ritonavir treatment within 5 days of illness from July 14, 2022, to November 14, 2022. The exposed group was patients with COVID-19 initiated with nirmatrelvir-ritonavir treatment, whereas those not initiated with the drug served as the control group. Data was analyzed from July 14, 2022 to December 31, 2022. RESULTS: A total of 20,966 COVID-19 high-risk outpatients (n = 10,483 for nirmatrelvir-ritonavir group and n = 10,483 for control group) were included in the study. Nirmatrelvir-ritonavir treatment was associated with a 36% reduction (adjusted hazard ratio 0.64 [95% CI 0.43, 0.94]) in hospitalization compared with those not given the drug. There was a single ICU admission for the control group and one death each was reported in the nirmatrelvir-ritonavir and control group, respectively. CONCLUSIONS: Nirmatrelvir-ritonavir treatment was associated with reduced hospitalization in high-risk patients with COVID-19 even in highly vaccinated populations.

Systematic comparison of plasma EBV DNA, anti-EBV antibodies and miRNA levels for early detection and prognosis of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is originated from the epithelial cells of nasopharynx, Epstein-Barr virus (EBV)-associated and has the highest incidence and mortality rates in Southeast Asia. Late presentation is a common issue and early detection could be the key to reduce the disease burden. Sensitivity of plasma EBV DNA, an established NPC biomarker, for Stage I NPC is controversial. Most newly reported NPC biomarkers have neither been externally validated nor compared to the established ones. This causes difficulty in planning for cost-effective early detection strategies. Our study systematically evaluated six established and four new biomarkers in NPC cases, population controls and hospital controls. We showed that BamHI-W 76 bp remains the most sensitive plasma biomarker, with 96.7% (29/30), 96.7% (58/60) and 97.4% (226/232) sensitivity to detect Stage I, early stage and all NPC, respectively. Its specificity was 94.2% (113/120) against population controls and 90.4% (113/125) against hospital controls. Diagnostic accuracy of BamHI-W 121 bp and ebv-miR-BART7-3p were validated. Hsa-miR-29a-3p and hsa-miR-103a-3p were not, possibly due to lower number of advanced stage NPC cases included in this subset. Decision tree modeling suggested that combination of BamHI-W 76 bp and VCA IgA or EA IgG may increase the specificity or sensitivity to detect NPC. EBNA1 99 bp could identify NPC patients with poor prognosis in early and advanced stage NPC. Our findings provided evidence for improvement in NPC screening strategies, covering considerations of opportunistic screening, combining biomarkers to increase sensitivity or specificity and testing biomarkers from single sampled specimen to avoid logistic problems of resampling.

Anti-inflammatory potential of ellagic acid, gallic acid and punicalagin A&B isolated from Punica granatum.

BACKGROUND: Punica granatum (pomegranate), an edible fruit originating in the Middle East, has been used as a traditional medicine for treatment of pain and inflammatory conditions such as peptic ulcer. The numerous risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs) for treatment of pain and inflammation give rise to using medicinal herbs as alternative therapies. This study aimed to evaluate the anti-inflammatory effect of isolated compounds from the ethyl acetate (EtOAc) fraction of P. granatum by determination of their inhibitory effects on lipopolysaccharide (LPS), stimulated nitric oxide (NO), prostaglandin E2 (PGE-2), interleukin-6 (IL-6) and cyclooxxgenase-2 (COX-2) release from RAW264.7 cells. METHODS: The compounds ellagic acid, gallic acid and punicalagin A&B were isolated from EtOAc by high performance liquid chromatography (HPLC) and further identified by mass spectrometry (MS). The inhibitory effect of ellagic acid, gallic acid and punicalagin A&B were evaluated on the production of LPS-induced NO by Griess reagent, PGE-2 and IL-6 by immunoassay kit and prostaglandin E2 competitive ELISA kit, and COX-2 by Western blotting. RESULTS: Ellagic acid, gallic acid and punicalagin A&B potentially inhibited LPS-induced NO, PGE-2 and IL-6 production. CONCLUSION: The results indicate that ellagic acid, gallic acid and punicalagin may be the compounds responsible for the anti-inflammatory potential of P. granatum.

Pigmentation and dermal conservative effects of the astonishing algae Sargassum polycystum and Padina tenuis on guinea pigs, human epidermal melanocytes (HEM) and Chang cells.

BACKGROUND: The preference for a fairer skin-tone has become a common trend among both men and women around the world. In this study, seaweeds Sargassum polycystum and Padina tenuis were investigated for their in vitro and in vivo potentials in working as skin whitening agents. Seaweed has been used as a revolutionary skin repairing agent in both traditional and modern preparations. The high antioxidant content is one of the prime reasons for its potent action. It has been employed in traditional Chinese and Japanese medicine. For centuries, most medical practitioners in the Asian cultures have known seaweed as an organic source of vitamins, minerals, fatty acids like omega-3 and omega-6 and antioxidants. The present objective of the study was to evaluate the potent dermal protective effect of the two seaweeds Sargassum polycystum and Padina tenuis on human cell lines and guinea pigs. MATERIAL AND METHODS: Seaweeds were extracted with ethanol and further fractionated with hexane, ethyl acetate and water. The extracts were tested for mushroom tyrosinase inhibitory activity, cytotoxicity in human epidermal melanocyte (HEM), and Chang cells. Extracts with potent melanocytotoxicity were formulated into cosmetic cream and tested on guinea pigs in dermal irritation tests and de-pigmentation assessments. RESULTS: Both Sargassum polycystum and Padina tenuis seaweeds showed significant inhibitory effect on mushroom tyrosinase in the concentration tested. SPEt showed most potent cytotoxicity on HEM (IC50 of 36µg/ml), followed by SPHF (65µg/ml), and PTHF (78.5µg/ml). SPHF and SPEt reduced melanin content in skin of guinea pigs when assessed histologically. CONCLUSION: SPEt, SPHF and PTHF were able to inhibit HEM proliferation in vitro, with SPHF being most potent and did not cause any dermal irritation in guinea pigs. The results obtained indicate that SPHF is a promising pharmacological or cosmetic agent.