Statins in Chronic Liver Disease: Review of the Literature and Future Role.

Chronic liver disease (CLD) is a major contributor to global mortality, morbidity, and healthcare burden. Progress in pharmacotherapeutic for CLD management is lagging given its impact on the global population. While statins are indicated for the management of dyslipidemia and cardiovascular disease, their role in CLD prevention and treatment is emerging. Beyond their lipid-lowering effects, their liver-related mechanisms of action are multifactorial and include anti-inflammatory, antiproliferative, and immune-protective effects. In this review, we highlight what is known about the clinical benefits of statins in viral and nonviral etiologies of CLD and hepatocellular carcinoma (HCC), and explore key mechanisms and pathways targeted by statins. While their benefits may span the spectrum of CLD and potentially HCC treatment, their role in CLD chemoprevention is likely to have the largest impact. As emerging data suggest that genetic variants may impact their benefits, the role of statins in precision hepatology will need to be further explored.

Patient Characteristics, Outcomes, and Effects of Dapagliflozin According to the Duration of Heart Failure: A Prespecified Analysis of the DELIVER Trial.

BACKGROUND: How patient characteristics and outcomes vary according to the duration of heart failure (HF) is unknown in individuals with mildly reduced or preserved ejection fraction. We compared these, and the efficacy and safety of dapagliflozin, according to the time from diagnosis of HF in a prespecified analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure). METHODS: HF duration was categorized as ≤6 months, >6 to 12 months, >1 to 2 years, >2 to 5 years, or >5 years. The primary outcome was the composite of worsening HF or cardiovascular death. The effect of treatment was examined by HF duration category. RESULTS: The number of patients in each category was as follows: 1160 (≤6 months), 842 (>6 to 12 months), 995 (>1 to 2 years), 1569 (>2 to 5 years), and 1692 (>5 years). Patients with longer-duration HF were older and had more comorbidities with worse symptoms. The rate of the primary outcome (per 100 person-years) increased with HF duration: ≤6 months, 7.3 (95% CI, 6.3 to 8.4); >6 to 12 months, 7.1 (6.0 to 8.5); >1 to 2 years, 8.4 (7.2 to 9.7); >2 to 5 years, 8.9 (7.9 to 9.9); and >5 years, 10.6 (9.5 to 11.7). Similar trends were seen for other outcomes. The benefit of dapagliflozin was consistent across HF duration category: the hazard ratio for the primary outcome in the ≤6-month group was 0.67 (95% CI, 0.50 to 0.91); >6 to 12 months, 0.78 (0.55 to 1.12); >1 to 2 years, 0.81 (0.60 to 1.09); >2 to 5 years, 0.97 (0.77 to 1.22); and >5 years, 0.78 (0.64 to 0.96; Pinteraction=0.41). The absolute benefit was greatest in longest-duration HF; the number needed to treat for HF >5 years was 24 versus 32 for ≤6 months. CONCLUSIONS: Patients with longer-duration HF were older, had more comorbidities and symptoms, and had higher rates of worsening HF and death. The benefits of dapagliflozin were consistent across HF duration. Even patients with long-standing HF and generally mild symptoms are not stable, and it is not too late for such patients to benefit from a sodium-glucose cotransporter 2 inhibitor. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03619213.

Attitudes and beliefs towards medication burden and deprescribing in Parkinson disease.

BACKGROUND: Deprescribing of potentially inappropriate medications is recommended for older adults and may improve health outcomes and quality of life in persons living with Parkinson disease (PD). Patient attitudes, beliefs, and preferences play a crucial role in the success of deprescribing interventions. We aimed to examine the attitudes and beliefs about medication burden and deprescribing among persons living with PD. METHODS: We administered a survey to participants of Fox Insight, a prospective longitudinal study of persons living with PD. The survey included the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire and additional questions about adverse drug effects. We used logistic regression models to explore potential predictors of treatment dissatisfaction and willingness to deprescribe. RESULTS: Of the 4945 rPATD respondents, 31.6% were dissatisfied with their current medications, and 87.1% would be willing to deprescribe medications. Male sex was associated with a greater willingness to deprescribe (adjusted odds ratio [aOR] 1.62, 95% confidence interval [CI] 1.37-1.93). A greater belief that the medication burden was high or that some medications were inappropriate was associated with treatment dissatisfaction (aORs 3.74, 95% CI 3.26-4.29 and 5.61, 95% CI 4.85-6.50), and more willingness to deprescribe (aORs 1.74, 95% CI 1.47-2.06 and 2.87, 95% CI 2.41-3.42). Cognitive impairment was the adverse drug effect participants were most concerned about when prescribed new medications to treat nonmotor symptoms. CONCLUSIONS: Persons with PD are often dissatisfied with their overall medication load and are open to deprescribing. Medications that are associated with cognitive impairment might be prioritized targets for deprescribing interventions in this population.

Pachyonychia congenita: A father and son with a novel variant in the KRT16 gene.

This study underscores the significance of identifying the clinical manifestations of pachyonychia congenita (PC) and emphasizes the patterns of genetic inheritance. A 12-month-old boy presented with a "white hairy tongue" and, following a comprehensive evaluation, was diagnosed with PC. His father exhibited similar symptoms. Genetic testing revealed a KRT16 pathogenic variant (c.616 T > G) in both the patient and his father, marking it as a novel variant in the PC literature. This case contributes to a broader understanding of PC's genetic diversity and its clinical presentations.

Two New Benzoquinone Derivatives from Vietnamese Knema globularia Stems.

The chemical investigation of the stems of Knema globularia led to the isolation of two new benzoquinones derivatives, embenones A and B (1 and 2), along with three known compounds (3-5). The structures of the isolated compounds were determined using spectroscopic techniques, including HRESIMS, 1D and 2D NMR, in conjunction with comparison to existing literature data. Compounds 1 and 2 represent new carbon skeletons in nature. Furthermore, all isolated compounds were evaluated for their α-glucosidase inhibitory activity, with compounds 1-3 exhibiting superior potency relative to the positive control (acarbose, IC50 331 µM). Their IC50 values ranged from 1.40 to 96.1 µM.

Bio-Guided Isolation of Alpha-Glucosidase Inhibitory Compounds from Vietnamese Lichen Roccella Montagnei.

A bio-guided isolation was applied to the Vietnamese lichen Roccella montagnei based on alpha-glucosidase inhibition. Six compounds were isolated and structurally elucidated, including a new ortho depside, montagneside A (1), together with five known compounds, sekikaic acid (2), lanost-7-en-3ß-ol (3), ethyl orsellinate (4), D-montagnetol (5), and D-erythrin (6). Their chemical structures were identified by extensive 1D and 2D NMR analysis, high-resolution mass spectroscopy, and comparisons with those reported in the literature. D-Erythrin (6), a major component, was selected for further modification using Smiles rearrangement. Three erythritol derivatives 6a-6c were synthesized. Compounds 1-3, 6, and 6a-6c were evaluated for alpha-glucosidase inhibition. Compounds 2 and 6a-6c showed significant alpha-glucosidase inhibition with IC50 values ranging from 7.9 to 149 µM, respectively. Molecular docking was applied to the most active compound 6a to clarify the inhibitory mechanism.

Outbreak of Sexually Transmitted Nongroupable Neisseria meningitidis-Associated Urethritis, Vietnam.

We report on an outbreak of nongroupable Neisseria meningitidis-associated urethritis, primarily among men who have sex with men in southern Vietnam. Nearly 50% of N. meningitidis isolates were resistant to ciprofloxacin. This emerging pathogen should be considered in the differential diagnosis and management of urethritis.

Nanoparticles Targeted to Fibroblast Activation Protein Outperform PSMA for MRI Delineation of Primary Prostate Tumors.

Accurate delineation of gross tumor volumes remains a barrier to radiotherapy dose escalation and boost dosing in the treatment of solid tumors, such as prostate cancer. Magnetic resonance imaging (MRI) of tumor targets has the power to enable focal dose boosting, particularly when combined with technological advances such as MRI-linear accelerator. Fibroblast activation protein (FAP) is overexpressed in stromal components of >90% of epithelial carcinomas. Herein, the authors compare targeted MRI of prostate specific membrane antigen (PSMA) with FAP in the delineation of orthotopic prostate tumors. Control, FAP, and PSMA-targeting iron oxide nanoparticles were prepared with modification of a lymphotropic MRI agent (FerroTrace, Ferronova). Mice with orthotopic LNCaP tumors underwent MRI 24 h after intravenous injection of nanoparticles. FAP and PSMA nanoparticles produced contrast enhancement on MRI when compared to control nanoparticles. FAP-targeted MRI increased the proportion of tumor contrast-enhancing black pixels by 13%, compared to PSMA. Analysis of changes in R2 values between healthy prostates and LNCaP tumors indicated an increase in contrast-enhancing pixels in the tumor border of 15% when targeting FAP, compared to PSMA. This study demonstrates the preclinical feasibility of PSMA and FAP-targeted MRI which can enable targeted image-guided focal therapy of localized prostate cancer.

Clinical validation of a ctDNA-Based Assay for Multi-Cancer Detection: An Interim Report from a Vietnamese Longitudinal Prospective Cohort Study of 2795 Participants.

The SPOT-MAS assay "Screening for the Presence Of Tumor by Methylation And Size" detects the five most common cancers in Vietnam by evaluating circulating tumor DNA in the blood. Here, we validated its performance in a prospective multi-center clinical trial, K-DETEK. Our analysis of 2795 participants from 14 sites across Vietnam demonstrates its ability to detect cancers in asymptomatic individuals with a positive predictive value of 60%, with 83.3% accuracy in detecting tumor location. We present a case report to support further using SPOT-MAS as a complementary method to achieve early cancer detection and provide the opportunity for early treatment.

Vaccine acceptance, determinants, and attitudes toward vaccine among people experiencing homelessness: a systematic review and meta-analysis.

BACKGROUND: COVID-19 has caused millions of deaths globally, with vulnerable populations such as people experiencing homelessness (PEH) at higher risk. This systematic review and meta-analysis aims to identify the prevalence and key factors contributing to vaccine acceptance experienced by PEH. METHODS: The protocol of this study was registered in PROSPERO (CRD42023391659). We included studies that reported relevant information about vaccine acceptance or vaccine hesitant/refusal among PEH. Eight databases were systematically searched in January 2023. Meta-analysis was conducted for the prevalence of vaccine acceptance, vaccine uptake, and factors associated with vaccine acceptance. Attitudes toward vaccines were combined into bar charts. RESULT: A total of 29 papers were included in this systematic review and 19 papers were included for meta-analysis. The pooled prevalence of COVID-19 vaccine acceptance among PEH was 66% (95%CI: 58%-73%). Our meta-regression showed vaccine acceptance was significantly increased over time. Moreover, subgroup meta-analysis showed that PEH were more likely to accept the COVID-19 vaccine after June 2021 (78%, 95%CI: 65%-86%) compared with earlier period (56%, 95%CI: 54%-59%). Subgroup meta-analysis also revealed that women and participants without underlying medical condition (chronic diseases) were significantly less likely to accept the COVID-19 vaccine, compared to men and those with medical conditions, respectively. CONCLUSION: The study emphasizes the need for targeted public health interventions aimed at increasing vaccine acceptance among PEH, especially at the early stage of the pandemic, among females, those without underlying medical conditions, being Black (in Canada and the USA), and young people. These interventions should address the common concerns of vaccine safety, adverse effects, effectiveness, and distrust in health care systems. In addition to offering vaccinations in different areas convenient to them, education programs could be established to increase vaccine acceptance among PEH.

Preclinical evaluation of sentinel node localization in the stomach via mannose-labelled magnetic nanoparticles and indocyanine green.

BACKGROUND: Gastrectomy with extended (D2) lymphadenectomy is considered standard of care for gastric cancer to provide the best possible outcomes and pathologic staging. However, D2 gastrectomy is a technically demanding operation and reported to be associated with increased complications and mortality. Application of sentinel lymph node (SLN) concept in gastric cancer has the potential to reduce patient morbidity; however, SLN techniques are not established for gastrectomy, in part due to lack of practical tracers. An effective and convenient tracer with enhanced SLN accumulation is critically needed. METHODS: Mannose-labelled magnetic tracer 'FerroTrace' and fluorescent dye indocyanine green (ICG) were injected laparoscopically into the stomach submucosa of 8 healthy swine under general anaesthesia. Intraoperative fluorescence imaging was used to highlight draining lymphatic pathways containing ICG, while preoperative T2-weighted MRI and ex vivo magnetometer probe measurements were used to identify nodes containing FerroTrace. Lymphadenectomy was performed either robotically (n = 2) or via laparotomy (n = 6). RESULTS: Mixing ICG and FerroTrace ensured concurrence of fluorescent and magnetic signals in SLNs. An initial trial with robotic dissection removed all magnetic LNs (n = 4). In the subsequent laparotomy study that targeted all ICG-LNs based on intraoperative fluorescence imaging, dissection removed an average of 4.7 ± 1.2 fluorescent, and 2.0 ± 1.3 magnetic LNs per animal. Both MRI and magnetometer detected 100% of SLNs (n = 7). FerroTrace demonstrated high specificity to SLNs, which contained 76 ± 30% of total lymphotropic iron, and 88 ± 20 % of the overall magnetometer signal. CONCLUSIONS: Through utilisation of this dual tracer approach, SLNs were identified via preoperative MRI, visualised intraoperatively with fluorescence imaging, and confirmed with a magnetometer. This combination pairs the sensitivity of ICG with SLN-specific FerroTrace and can be used for reliable SLN detection in gastric cancer, with potential applications in neoadjuvant therapy.

Venous Thromboembolism After Abdominal and Minimally Invasive Large Specimen Hysterectomy.

STUDY OBJECTIVE: To investigate the incidence of venous thromboembolism (VTE) in patients undergoing large specimen hysterectomy for benign indications. To evaluate the impact of route of surgery and operative time in the development of VTE in this population. DESIGN: Retrospective cohort study (Canadian Task Force Classification II2) of targeted hysterectomy data prospectively collected from the American College of Surgeons National Surgical Quality Improvement Program involving over 500 hospitals across the United States. SETTING: National Surgical Quality Improvement Program Database. PATIENTS: Women aged 18 years or older undergoing hysterectomy for benign indications between 2014 and 2019. Patients were further classified into 4 groups according to uterine weight: <100 g, 100-249 g, 250 g-499 g, and specimens ≥500 g. INTERVENTIONS: Current Procedural Terminology codes were used to identify cases. Variables including age, ethnicity, body mass index, smoking status, diabetes, hypertension, blood transfusion, and American Society of Anesthesiologists classification system scores were collected. Cases were stratified by route of surgery, operative time, and uterine weight. MEASUREMENTS AND MAIN RESULTS: A total of 122,418 hysterectomies occurring between 2014 and 2019 were included in our study, of which 28,407 (23.2%) patients underwent abdominal, 75,490 (61.7%) laparoscopic, and 18,521 (15.1%) vaginal hysterectomy. The overall rate of VTE in patients with large specimen hysterectomies (≥500 g) was 0.64%. After multivariable adjustment, there was no significant difference in the odds of VTE between uterine weight groups. Only 30% of the surgeries with uterine weight above 500 g were performed with minimally invasive surgical routes. Patients who underwent minimally invasive hysterectomy had lower odds of VTE via laparoscopic (adjusted odds ratio [aOR] 0.62; confidence interval [CI]: 0.48-0.81) and vaginal (aOR 0.46; CI: 0.31-0.69) routes compared to laparotomy. Prolonged operative time (>120 min) was associated with increased odds of VTE (aOR 1.86; CI:1.51-2.29). CONCLUSION: The occurrence of VTE after a benign large specimen hysterectomy is rare. The odds of VTE is higher with longer operative times and lower with minimally invasive approaches, even for markedly enlarged uteri.

A New Carvotacetone Derivative from the Aerial Part of Sphaeranthus africanus.

Sphaeranthus africanus L. is native in Vietnam. Little is known about α-glucosidase inhibition of Sphaeranthus africanus and its isolated compounds. A bioactive-guided isolation was applied to the Vietnamese Sphaeranthus africanus to find α-glucosidase inhibitory components. Eight compounds were detected and structurally elucidated. They are 3-angeloyloxy-5-[2'',3''-epoxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[3''-chloro-2''-hydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2''R,3''R-dihydroxy-2''-methyl-butanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2''S,3''R-dihydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2''S,3''S-dihydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 5-angeloyloxy-7-hydroxy-3-tigloyloxycarvotacetone, 3-O-methylquercetin, and chrysosplenol D. Their chemical structures were elucidated by extensive 1D and 2D NMR analysis and high-resolution mass spectroscopy as well as comparisons in literature. 3-Angeloyloxy-5-[2''S,3''S-dihydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone is a new compound. Isolated compounds were evaluated for the α-glucosidase inhibition. Isolated compounds showed moderate activity with IC50 values ranging from 128.9-274.3 µM while others are weak. A molecular docking study was conducted, indicating that isolated compounds are potent α-glucosidase inhibitory compounds.

A New 3-Benzylphthalide from the Moss Erythrodontium julaceum.

From the moss Erythrodontium julaceum Paris growing in Vietnam, julacelide (1), a new 3-benzylphthalide, along with methyl orsellinate (2), ethyl orsellinate (3), 4-O-methylhaematommic acid (4), and zeorin (5), were isolated and structurally elucidated. Their chemical structures were elucidated through extensive 1D and 2D NMR analysis and high-resolution mass spectroscopy as well as through comparisons to the existing literature. Compound 4-O-methylhaematommic acid was a new natural product. The absolute configuration of julacelide was defined using time-dependent density functional theory (TDDFT) calculations. Julacelide was evaluated for α-glucosidase inhibition.

Extracorporeal membrane oxygenation support in refractory anaphylactic shock after bee stings: A case report.

An allergy to insect stings is one of the most frequent causes of anaphylactic reactions. Such reactions can be fatal, even on the first reaction, although it very rarely happens. The use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) in refractory anaphylactic shock was previously described. We report a case of a 31-year-old female who presented with refractory anaphylactic shock after bee stings without the presence of cutaneous manifestations other than the rashes in her neck. The toxic component of bee venom and systemic allergic response plays a vital role in pathophysiology. She did not respond to conventional advanced life support, but following urgent VA ECMO, she survived neurologically intact. Despite an uncommon indication for anaphylaxis, ECMO support may be possible and effective in patients with refractory shock.

Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF.

BACKGROUND: Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease that complicates pharmacological management and is associated with worse outcomes. We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure). We also examined the effect of dapagliflozin on kidney function after randomization. METHODS: Patients who have HFrEF with or without type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 mL·min-1·1.73 m-2 were enrolled in DAPA-HF. We calculated the incidence of the primary outcome (cardiovascular death or worsening heart failure) according to eGFR category at baseline (<60 and ≥60 mL·min-1·1.73 m-2) and used eGFR at baseline as a continuous measure, as well. Secondary cardiovascular outcomes and a prespecified composite renal outcome (≥50% sustained decline eGFR, end-stage renal disease, or renal death) were also examined, along with a decline in eGFR over time. RESULTS: Of 4742 patients with a baseline eGFR, 1926 (41%) had eGFR <60 mL·min-1·1.73 m-2. The effect of dapagliflozin on the primary and secondary outcomes did not differ by eGFR category or examining eGFR as a continuous measurement. The hazard ratio (95% CI) for the primary end point in patients with chronic kidney disease was 0.71 (0.59-0.86) versus 0.77 (0.64-0.93) in those with an eGFR ≥60 mL·min-1·1.73 m-2 (interaction P=0.54). The composite renal outcome was not reduced by dapagliflozin (hazard ratio=0.71 [95% CI, 0.44-1.16]; P=0.17) but the rate of decline in eGFR between day 14 and 720 was less with dapagliflozin, -1.09 (-1.40 to -0.77) versus placebo -2.85 (-3.17 to -2.53) mL·min-1·1.73 m-2 per year (P<0.001). This was observed in those with and without type 2 diabetes (P for interaction=0.92). CONCLUSIONS: Baseline kidney function did not modify the benefits of dapagliflozin on morbidity and mortality in HFrEF, and dapagliflozin slowed the rate of decline in eGFR, including in patients without diabetes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

Fluorescence-Shadowing Nanoparticle Clusters for Real-Time Monitoring of Tumor Progression.

Monitoring tumor progression is important for elucidating appropriate therapeutic strategies in response to anticancer therapeutics. To fluorescently monitor the in vivo levels of tumor-specific enzymes, we prepared matrix metalloprotease (MMP)-responsive gold nanoparticle (AuNP) clusters to sense tumor microenvironments. Specifically, AuNPs and quantum dots (QDs) were surface-engineered with two poly(ethylene glycol) [PEG] shells and cyclooctyne moieties, respectively, for the copper-free click reaction. Upon "peeling off" of the secondary shell from the double-PEGylated AuNPs under MMP-rich conditions, shielded azide moieties of the AuNPs were displayed toward the QD, and those two particles were clicked into nanoparticle clusters. This consequently resulted in a dramatic size increase and fluorescence quenching of QDs via fluorescence energy transfer (FRET) due to the molecular proximity of the particles. We observed that FRET efficiency was modulated via changes in MMP levels and exposure time. Cancer cell numbers exhibited a strong correlation with FRET efficiency, and in vivo studies that employed solid tumor models accordingly showed that FRET efficiency was dependent on the tumor size. Thus, we envision that this platform can be tailored and optimized for tumor monitoring based on MMP levels in solid tumors.

Perceived stigma and its correlates among Asian patients with advanced cancer: A multi-country APPROACH study.

OBJECTIVES: Perceived cancer-related stigma can affect mental health and potentially treatment choices for patients with cancer. Nevertheless, perceived stigma is not very well understood in Asia. This study investigated across six developing Asian countries: (1) the prevalence of perceived stigma among advanced cancer patients, (2) its risk factors, and (3) its association with patient treatment preferences. METHODS: This cross-sectional study recruited patients receiving oncology care across major hospitals in Bangladesh, China, India, Philippines, Sri Lanka and Vietnam. Participants (N = 1358) were adults diagnosed with stage IV metastatic solid cancer who completed self-reported surveys. Multi-variable logistic regression and ordered logit models examined the associations with perceived stigma and variables of interest. RESULTS: Across the countries, 35%, 95% CI [32%, 38%] of patients reported experiencing at least one facet of cancer-related stigma often or always, while 60% [57%, 63%] reported it occurring occasionally. Top-endorsed facets of perceived stigma across the Asian countries suggest a distinct pattern. Having knowingly engaged in health-risk behaviours (OR = 2.03-2.24, 95% CI [1.14-1.19, 3.43-4.41]), unemployment (2.64 [1.67, 4.19]) and body image change (1.57 [1.00, 2.45]) were associated with higher odds of perceived stigma, while time mitigated perceived stigma (0.49-0.65 [0.30-0.45, 0.76-0.92]). Perceived stigma was associated with lower odds of preference for life-extending treatments, although the associations did not hold up in the adjusted model. CONCLUSIONS: Perceived stigma is unique among Asian advanced cancer patients. Stigma is important to assess and address, taking into consideration the various sociodemographic, clinical and psychological factors of cancer patients.

Skeletal muscle relaxant drug-drug-drug interactions and unintentional traumatic injury: Screening to detect three-way drug interaction signals.

AIM: The aim of this study was to identify skeletal muscle relaxant (SMR) drug-drug-drug interaction (3DI) signals associated with increased rates of unintentional traumatic injury. METHODS: We conducted automated high-throughput pharmacoepidemiologic screening of 2000-2019 healthcare data for members of United States commercial and Medicare Advantage health plans. We performed a self-controlled case series study for each drug triad consisting of an SMR base-pair (i.e., concomitant use of an SMR with another medication), and a co-dispensed medication (i.e., candidate interacting precipitant) taken during ongoing use of the base-pair. We included patients aged ≥16 years with an injury occurring during base-pair-exposed observation time. We used conditional Poisson regression to calculate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for injury with each SMR base-pair + candidate interacting precipitant (i.e., triad) versus the SMR-containing base-pair alone. RESULTS: Among 58 478 triads, 29 were significantly positively associated with injury; confounder-adjusted RRs ranged from 1.39 (95% CI = 1.01-1.91) for tizanidine + omeprazole with gabapentin to 2.23 (95% CI = 1.02-4.87) for tizanidine + diclofenac with alprazolam. Most identified 3DI signals are new and have not been formally investigated. CONCLUSION: We identified 29 SMR 3DI signals associated with increased rates of injury. Future aetiologic studies should confirm or refute these SMR 3DI signals.

New onset of psoriasis following COVID-19 vaccination.

The cutaneous side effects of COVID-19 vaccines are being studied and their immunogenicity is most likely linked to the pathophysiology of psoriasis. Although uncommon, several cases of exacerbation and new onset of psoriasis have been reported globally after vaccination. To contribute to the literature on this intriguing topic, we present three cases of de novo psoriasis in adult patients following COVID-19 vaccination. Our observations and a literature review show that this occurrence is independent of the type and brand of vaccines.