Clinical Evidence for Improved Outcomes with Histamine Antagonists and Aspirin in 22,560 COVID-19 Patients

COVID-19 has spurred much interest in the therapeutic potential of repurposed drugs. A family of acid-reducing drugs, known as histamine H2 receptor antagonists (H2RA), competitively bind the H2R and block its stimulation by histamine; examples of such drugs are famotidine (e.g., Pepcid) and ranitidine (e.g., Zantac). A dense web of functionalities between histamine and H2RAs, on the one hand, and downstream cellular pathways, on the other hand, links disparate physiological pathways in gastrointestinal contexts (e.g., acid reduction) to the dysregulated inflammatory cas-cades (cytokine storm) underlying the pathophysiology of COVID-19. Is famotidine beneficial in treating COVID-19? This question remains unresolved, though not for lack of effort: over 10 studies have examined the potential therapeutic value of famotidine in COVID-19, but have found conflicting results (pro-famotidine, anti-famotidine, and neutral). Given the contradictory reports, we have undertaken the new analysis reported herein. Notably, studies published thus far rest upon substantially smaller datasets than drawn upon in the present work. We analyzed a cohort of 22,560 COVID-19 patients taking H1/H2 receptor antagonists, focusing on 1,379 severe cases requiring respiratory support. We analyzed outcomes for treatment with the H1RAs loratadine (e.g., Claritin) and cetirizine (e.g., Zyrtec), the H2RA famotidine, aspirin, and a famotidine & aspirin combination. For cases that reached the point of respiratory support, we found a significantly reduced fatality risk for famotidine treatment. We did not detect a benefit from dual-histamine receptor blockade (concurrently targeting H1 and H2 receptors). Notably, famotidine combined with aspirin did exhibit a significant synergistic survival benefit (odds ratio of 0.55). The relative risk for death decreased by 32.5%--an immense benefit, given the more than 2.6 million COVID-19-related deaths thus far. We found lower levels of serum markers for severe disease (e.g., C-reactive protein) in famotidine users, consistent with prior findings by others and with a role for famotidine in attenuating cytokine release. The large, international, multi-center retrospective study reported here, sampling over 250,000 COVID-19 cases, hopefully helps clarify the possible value of clinically-approved histamine antagonists such as famotidine. Given these findings, alongside the cost-effectiveness and mild side-effects of popular drugs like famotidine and aspirin, we suggest that further prospective clinical trials, perhaps utilizing the aspirin combination reported here, are advisable.

Evidence for treatment with estradiol for women with SARS-CoV-2 infection

BackgroundGiven that an individuals age and gender are strongly predictive of COVID-19 outcomes, do such factors imply anything about preferable therapeutic options? MethodsAn analysis of electronic health records for a large (68,466-case), international COVID-19 cohort, in five-year age strata, revealed age-dependent sex differences. In particular, we surveyed the effects of systemic hormone administration in women. The primary outcome for estradiol therapy was death. Odds Ratios (ORs) and Kaplan-Meier survival curves were analyzed for 37,086 COVID-19 women in two age groups: pre- (15-49 years) and post-menopausal (>50 years). ResultsThe incidence of SARS-CoV-2 infection is higher in women than men (about +15%) and, in contrast, the fatality rate is higher in men (about +50%). Interestingly, the relationships between these quantities are also linked to age. Pre-adolescent girls had the same risk of infection and fatality rate as boys. Adult premenopausal women had a significantly higher risk of infection than men in the same five-year age stratum (about 16,000 vs. 12,000 cases). This ratio changed again in postmenopausal women, with infection susceptibility converging with men. While fatality rates increased continuously with age for both sexes, at 50 years there was a steeper increase for men. Thus far, these types of intricacies have been largely neglected. Because the hormone 17{beta}-estradiol has a positive effect on expression of the human ACE2 protein--which plays an essential role for SARS-CoV-2 cellular entry--propensity score matching was performed for the womens sub-cohort, comparing users versus non-users of estradiol. This retrospective study of hormone therapy in female COVID-19 patients shows that the fatality risk for women >50 yrs receiving estradiol therapy (user group) is reduced by more than 50%; the OR was 0.33, 95 % CI [0.18, 0.62] and the Hazard Ratio was 0.29, 95% CI[0.11,0.76]. For younger, pre-menopausal women (15-49 yrs), the risk of COVID-19 fatality is the same irrespective of estradiol treatment, probably because of higher endogenous estradiol levels. ConclusionsAs of this writing, still no effective drug treatment is available for COVID-19; since estradiol shows such a strong improvement regarding fatality in COVID-19, we suggest prospective studies on the potentially more broadly protective roles of this naturally occurring hormone.

Clinical outcome after orbital floor fracture reduction with special regard to patient's satisfaction / 中华创伤杂志(英文版)

PURPOSE@#Primary reconstruction via transconjunctival approach is a standardized treatment option for orbital floor fractures. The aim of this study was to compare the findings of specific ophthalmologic assessment with the patient's complaints after fracture reduction.@*METHODS@#A retrospective medical chart analysis was performed on patients who had undergone transconjunctival orbital floor fracture reduction for fracture therapy with resorbable foil (ethisorb sheet or polydioxanone foil). A follow-up assessment including ophthalmological evaluation regarding visual acuity (eye chart projector), binocular visual field screening (Bagolini striated glasses test) and diplopia (cover test, Hess screen test) was conducted. Additionally, a questionnaire was performed to assess patients' satisfaction.@*RESULTS@#A total of 53 patients with a mean follow-up of 23 months (ranging from 11 to 72) after surgical therapy were included. Diplopia was present preoperatively in 23 (43.4%) and reduced in follow-up examination (n = 12, 22.6%). Limitations in ocular motility reduced from 37.7% to 7.5%. The questionnaire about the patient's satisfaction revealed excellent outcomes in relation to the functional and esthetical parameters.@*CONCLUSION@#Transconjunctival approach is a safe approach for orbital fracture therapy. Postoperative diplopia is nearly never perceptible for the individual and differs to pathologic findings in the ophthalmic assessment.

The feasibility of immediately loading dental implants in edentulous jaws

PURPOSE: Immediate loading of dental implants has been proved to be feasible in partially edentulous jaws. The purpose of this retrospective investigation was to assess the feasibility of immediately loading dental implants in fully edentulous jaws. METHODS: A total of 24 patients aged between 53 and 89 years received a total of 154 implants in their edentulous maxillae or mandibles. Among the implants, 45 were set in fresh extracted sockets and 109 in consolidated alveolar bones. The implants were provisionally managed with chair-side made provisional resin bridges and exposed to immediate loading. Implants were followed up for 1–8 years, including radiographic imaging. Marginal bone levels were evaluated based on radiographic imaging. RESULTS: A total of 148 out of the 154 implants survived over the follow-up period of 1 to 8 years, giving a survival rate of 96%. The time or region of the implantation, the pre-implant augmentation, and the length and diameter of the implants had no statistically significant influence on the survival or the success rate. The marginal bone level remained stable with only minimal loss of 0.3 mm after 60 months of loading. CONCLUSIONS: Within the limitations of this study, immediate loading is feasible for dental implants in edentulous jaws.