Risk of myocarditis and pericarditis after the COVID-19 mRNA vaccination in the USA: a cohort study in claims databases.

BACKGROUND: Several passive surveillance systems reported increased risks of myocarditis or pericarditis, or both, after COVID-19 mRNA vaccination, especially in young men. We used active surveillance from large health-care databases to quantify and enable the direct comparison of the risk of myocarditis or pericarditis, or both, after mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) vaccinations. METHODS: We conducted a retrospective cohort study, examining the primary outcome of myocarditis or pericarditis, or both, identified using the International Classification of Diseases diagnosis codes, occurring 1-7 days post-vaccination, evaluated in COVID-19 mRNA vaccinees aged 18-64 years using health plan claims databases in the USA. Observed (O) incidence rates were compared with expected (E) incidence rates estimated from historical cohorts by each database. We used multivariate Poisson regression to estimate the adjusted incidence rates, specific to each brand of vaccine, and incidence rate ratios (IRRs) comparing mRNA-1273 and BNT162b2. We used meta-analyses to pool the adjusted incidence rates and IRRs across databases. FINDINGS: A total of 411 myocarditis or pericarditis, or both, events were observed among 15 148 369 people aged 18-64 years who received 16 912 716 doses of BNT162b2 and 10 631 554 doses of mRNA-1273. Among men aged 18-25 years, the pooled incidence rate was highest after the second dose, at 1·71 (95% CI 1·31 to 2·23) per 100 000 person-days for BNT162b2 and 2·17 (1·55 to 3·04) per 100 000 person-days for mRNA-1273. The pooled IRR in the head-to-head comparison of the two mRNA vaccines was 1·43 (95% CI 0·88 to 2·34), with an excess risk of 27·80 per million doses (-21·88 to 77·48) in mRNA-1273 recipients compared with BNT162b2. INTERPRETATION: An increased risk of myocarditis or pericarditis was observed after COVID-19 mRNA vaccination and was highest in men aged 18-25 years after a second dose of the vaccine. However, the incidence was rare. These results do not indicate a statistically significant risk difference between mRNA-1273 and BNT162b2, but it should not be ruled out that a difference might exist. Our study results, along with the benefit-risk profile, continue to support vaccination using either of the two mRNA vaccines. FUNDING: US Food and Drug Administration.

Thermal Air Oxidation-Mediated Synchronous Coordination and Carbonation of Lanthanum on Biochar toward Phosphorus Adsorption from Wastewater.

Biochar has attracted increasing attention as the sustainable and structure-tunable carrier for lanthanum (La) species for diverse applications. Carbonated La species possesses a higher biocompatibility and a lower leaching potential than other commonly used La species, while less attention is paid on the application of carbonated La in phosphorus (P) adsorption. Herein, thermal air oxidation (TAO) was applied as a novel strategy for synchronously tuning the coordination environment and chemical species of La on biochar surface. The results demonstrated that TAO induced the coordination of La with oxidation-generated oxygenated functional groups (OFGs) and carbonation of La species by the oxidation-generated CO2 on the biochar surface. The batch adsorption results showed that the Qm of resultant biochar remarkably increased from 68.92 to 132.49 mg/g at 1 g/L dosage. It also showed a robust adsorption stability in pH 2-6, a strong resistance to the co-existing Cl-, SO42-, NO3-, CO32-, or HCO3-, a stable adsorption recyclability, and an ultralow La leaching potential. The P adsorption was dominated by ligand exchange-induced inner-sphere complexation. In practical swine wastewater, the resultant biochar composite (1 g/L) removed 99.87% of P from 92.3 to 0.12 mg/L at a practical pH of 7.12. The density functional theory calculation further revealed the significant role of the binding of carbonated La by the biochar surface OFGs in reducing the P adsorption energies, indicating the synergism between the oxygenated biochar carrier and the carbonated La in P adsorption. Finally, this study provided a novel route to synchronously tune the coordination environment and chemical species of La on biochar via a facile TAO process for high-efficient P adsorption from wastewater.

A critical review on the development of lanthanum-engineered biochar for environmental applications.

Biochar and lanthanum (La) have been widely used in environment. However, there is a lack of knowledge and perspective on the development of La-engineered biochar (LEB) for environmental applications. This review shows that LEBs with a variety of La species via pre-/post-doping routes are developed for environmental applications. Specifically, precipitation, gelation, and calcination are the common sub-processes involved in the pre-/post-doping of La on the resultant LEB. The dominant La species for LEBs is La(OH)3, which is formed through precipitation of La ions with various bases. Various La carbonates, e.g., LaOHCO3, La2(CO3)3, La2CO5, and NaLa(CO3)2, are also involved in the preparation of LEBs. The LEBs are high-efficient in the adsorption of phosphate, arsenic, antimonate and fluoride ions, attributed to the strong affinity of La to oxyanions and Lewis hard base. Lanthanum is also favorable for co-doping with transition metal species to further enhance the performances in adsorption or catalysis. This review also analyzes the prospects and future challenges for the preparation and application of LEBs in environment. Finally, this review is beneficial to inspire new breakthroughs on the preparation and environmental application of LEBs.

Converting a Non-Porous Rare-Earth Metal-Organic Framework into a Porous Yttrium-Based NH2UiO-66 Network via a Linker Exchange Approach.

The solvent-assisted linker exchange (SALE) method was used to produce amino-functionalized yttrium-based UiO-66 [NH2UiO-66(Y)], which is not obtainable via a direct synthetic method. Remarkably, SALE not only produced relatively highly porous NH2UiO-66(Y) from completely non-porous 3,3-bpdc-Y but also changed the network topology from 8-connected bcu in 3,3-bpdc-Y to 12-connected fcu in NH2UiO-66(Y). Based on our knowledge, this is one of the rare cases where SALE changes the whole network topology of the resulting metal-organic framework. NH2UiO-66(Y) also showed promising ability for selective detection of Cu2+ at a low concentration.

In Situ Transformation of Metal-Organic Frameworks into Hollow Nickel-Cobalt Double Hydroxide Arrays for Efficient Water Oxidation.

Developing earth-abundant electrocatalysts for efficient oxygen evolution reaction (OER) is of paramount significance for electrochemical water splitting. Herein, an efficient in situ etching-deposition growth strategy is employed to transform pristine two-dimensional (2D) Co-metal-organic frameworks into hollow Ni/Co double hydroxide arrays (denoted as Ni/Co-DH), which not only yields a larger surface area and exposes more active sites but also decreases the activation energy to the OER. With structural and compositional benefits, the Ni/Co-DH exhibits high performance with an overpotential of 229 mV at 10 mA cm-2 and exceptional long-term stability of over 90 h in 1 M KOH medium for OER, comparable to most non-noble oxygen evolution catalysts reported so far. In addition, a two-electrode Ni/Co-DH∥Pt/C electrolyzer also requires a considerably low voltage of 1.58 V at 10 mA cm-2 for overall water splitting. This study affords a rational strategy to develop water-alkali electrolyzers with great complexity for large-scale water-splitting systems.

Drug Delivery Using Hydrophilic Metal-Organic Frameworks (MOFs): Effect of Structure Properties of MOFs on Biological Behavior of Carriers.

To study the influence of pore structural properties of metal-organic frameworks (MOFs) on drug adsorption and delivery, we synthesized two MOF termed TMU-6(RL1) {[Zn(oba)(RL1)0.5]n·(DMF)1.5} and TMU-21(RL2) {[Zn(oba)(RL2)0.5]n·(DMF)1.5} with amine basic N-donor pillars containing phenyl or naphthyl cores with various hydrophilic properties around the main center of the reaction. TG, IR, XPS, and PXRD analyses were used to extensively characterize the MOFs. The synthesized carriers showed high adsorption efficiency, stability, and controlled release. As an anticancer drug, Nimesulide (Nim) was adsorbed to MOFs using multiple adsorption mechanisms, such as Hostπ-πGuest interaction and HostN-H···OGuest hydrogen bonds. Moreover, Hirshfeld surface analysis showed when the benzene core was replaced with the naphthalene core, the percentage of intermolecular interactions of π···π and N···H by amine sites in TMU-21(RL2) decreased compared with TMU-6(RL1), while the percentage of these interactions with guest molecules increased. The results showed that changes in the hydrophobicity/hydrophilicity properties of MOFs would alter their ability to adsorb Nim in the pore of the frameworks. In vitro anticancer studies also showed that the cytotoxicity of Nim in MOFs@Nim composites against human cervical cancer cell line (HeLa cells) and human colon cancer cell line (HT-29 cells) is much higher than that of free Nim. Generally, based on the results, it can be said that the biological behavior of carriers can be regulated by adjusting the structure properties of MOFs.

Results of the osteochondral autologous transplantation for treatment of osteochondral lesions of the talus with harvesting from the ipsilateral talar articular facets.

PURPOSE: There are few studies on the clinical outcomes of osteochondral autologous transplantation (OAT) harvesting from local talar non-weight-bearing articular facets for the treatment of osteochondral lesions of the talus (OLTs). The purpose of this study was to review the short- to midterm outcomes of our patients who were treated with OAT harvesting from ipsilateral talar articular facets for OLTs. METHODS: Between December 2010 and November 2018, 24 patients were enrolled in this study. There were 16 males and eight females with an average age of 39.1 years and a follow-up period of 50.9 months. The clinical results were evaluated according to the American Orthopedic Foot & Ankle Society (AOFAS) ankle-hindfoot score and the visual analogue scale (VAS) score. Pre-operative plain radiographs and magnetic resonance imaging (MRI) scans, post-operative radiographs, and X-ray and computed tomography (CT) scans at the last follow-up were observed. RESULTS: There was a significant improvement in the AOFAS score from 61.3 ± 19.0 pre-operatively to 84.9 ± 9.2 post-operatively (P < 0.001). The VAS score improved from 6.1 ± 2.3 to 2.0 ± 1.4 at the last follow-up (P < 0.001). Twenty-one patients (87.5%) were satisfied with their clinical results. By the last follow-up CT scan, there was bone cyst formation at the donor sites in three patients, at the recipient sites in five patients and at both sites in five patients. Two patients (8.3%) underwent re-operation with arthroscopic debridement because of medial gutter hypertrophic soft tissue impingement. CONCLUSION: OAT harvesting from the ipsilateral talar articular facet showed satisfactory results. The mean post-operative VAS score and AOFAS ankle-hindfoot score improved significantly. Post-operative impingement around the osteotomy site was the main complication and reason for re-operation after the index procedure. In addition, bone cysts at the recipient and/or donor site(s) were found with a large percentage under CT. Therefore, longer follow-up is necessary to determine the long-term clinical results for this technique.

Natural History of Coronavirus Disease 2019: Risk Factors for Hospitalizations and Deaths Among >26 Million US Medicare Beneficiaries.

BACKGROUND: The current study was performed to evaluate risk factors for severe coronavirus disease 2019 (COVID-19) outcomes among Medicare beneficiaries during the pandemic's early phase. METHODS: In a retrospective cohort study covering Medicare fee-for-service beneficiaries, we separated out elderly residents in nursing homes (NHs) and those with end-stage renal disease (ESRD) from the primary study population of individuals age ≥65 years. Outcomes included COVID-19 hospital encounters and COVID-19-associated deaths. We estimated adjusted odds ratios (ORs) using logistic regression. RESULTS: We analyzed 25 333 329 elderly non-NH beneficiaries without ESRD, 653 966 elderly NH residents, and 292 302 patients with ESRD. COVID-related death rates (per 10 000) were much higher among elderly NH residents (275.7) and patients with ESRD (60.8) than in the primary study population (5.0). Regression-adjusted clinical predictors of death among the primary population included immunocompromised status (OR, 1.43), frailty index conditions such as cognitive impairment (3.16), and other comorbid conditions, including congestive heart failure (1.30). Demographic-related risk factors included male sex (OR, 1.77), older age (3.09 for 80- vs 65-year-olds), Medicaid dual-eligibility status (2.17), and racial/ethnic minority. Compared with whites, ORs were higher for blacks (2.47), Hispanics (3.11), and Native Americans (5.82). Results for COVID-19 hospital encounters were consistent. CONCLUSIONS: Frailty, comorbid conditions, and race/ethnicity were strong risk factors for COVID-19 hospitalization and death among the US elderly.

Guillain-Barré Syndrome After High-Dose Influenza Vaccine Administration in the United States, 2018-2019 Season.

BACKGROUND: The Vaccine Safety Datalink (VSD) identified a statistical signal for an increased risk of Guillain-Barré syndrome (GBS) in days 1-42 after 2018-2019 high-dose influenza vaccine (IIV3-HD) administration. We evaluated the signal using Medicare. METHODS: We conducted early- and end-of-season claims-based self-controlled risk interval analyses among Medicare beneficiaries ages ≥65 years, using days 8-21 and 1-42 postvaccination as risk windows and days 43-84 as control window. The VSD conducted chart-confirmed analyses. RESULTS: Among 7 453 690 IIV3-HD vaccinations, we did not detect a statistically significant increased GBS risk for either the 8- to 21-day (odds ratio [OR], 1.85; 95% confidence interval [CI], 0.99-3.44) or 1- to 42-day (OR, 1.31; 95% CI, 0.78-2.18) risk windows. The findings from the end-of-season analyses were fully consistent with the early-season analyses for both the 8- to 21-day (OR, 1.64; 95% CI, 0.92-2.91) and 1- to 42-day (OR, 1.12; 95% CI, 0.70-1.79) risk windows. The VSD's chart-confirmed analysis, involving 646 996 IIV3-HD vaccinations, with 1 case each in the risk and control windows, yielded a relative risk of 1.00 (95% CI, 0.06-15.99). CONCLUSIONS: The Medicare analyses did not exclude an association between IIV3-HD and GBS, but it determined that, if such a risk existed, it was similar in magnitude to prior seasons. Chart-confirmed VSD results did not confirm an increased risk of GBS.

[Research progress on camptothecin and its derivative nano-prodrugs based on tumor microenvironment response].

Nano-prodrug, one of the most widely used nano-formulation at present, has excellent efficacies in tumor treatment with high potential and clinical value. Camptothecin and its derivatives have broad prospects in the preparation of prodrugs for the treatment of tumors. Given the special microenvironment of tumors, including partial acidity, high concentration of reactive oxygen species, high concentration of glutathione and enzyme concentration, a large number of tumor microenvironment-responsive camptothecin and its derivative prodrugs were prepared. This paper classified them from the microenvironment response types and drug release characteristics, reviewed the research progress of camptothecin and its derivative prodrugs based on safety and clinical trials, and analyzed the existing problems and deficiencies, hoping to provide references for the development of camptothecin and its derivatives.

Highly Sensitive Colorimetric Naked-Eye Detection of HgII Using a Sacrificial Metal-Organic Framework.

This study has developed a specific, easy, and novel approach to designing a sacrificial metal-organic framework (MOF) that can detect and measure the amount of Hg2+ in aqueous and nonaqueous solutions using the naked eye. The functionalized [Zn(oba)(RL3)0.5]n·1.5DMF (TMU-59) provides the ability of simple visual assessment or colorimetric readout without sophisticated analytical equipment. Because of the special interaction with Hg2+, degradation of the structure of this unique MOF causes the solution to change color from colorless to a pink that is easily recognizable to the naked eye. The presence of a methyl group plays a major role in naked-eye detection by a qualitative sensor. Furthermore, this qualitative sensor data for the production of a simple, instant, and portable red, green, and blue (RGB)-based quantitative sensor were used to determine the concentration of Hg2+ in different specimens. As a turn-off fluorescence sensor, this unique structure is also capable of detecting Hg2+ at very low concentrations (the limit of detection is 0.16 ppb). To the best of our knowledge, TMU-59 is the first MOF-based naked-eye sensor that can successfully and specifically display the presence of Hg2+ through a major color change.

New 3D Porous Silver Nanopolycluster as a Highly Effective Supercapacitor Electrode: Synthesis and Study of the Optical and Electrochemical Properties.

A high-nucleus silver nanopolycluster as a new type of silver-based polymer supercapacitor (SSc) by a simple and single-step synthesis process was designed and synthesized. The structural, optical, and electrochemical properties of SSc-2 were determined. This highly stable conductive 3D nanopolycluster shows great cycling stability, large capacity, and high energy density without any modification or doping process and so acts as an excellent SSc (412 F g-1 at 1.5 A g-1). In addition, there was a stable cycling performance (94% capacitance) following 7000 cycles at 3 A g-1 current density. The presence of fluorinated groups, 3D expansion of high-nucleus metallic clusters, and porosity are the advantages of SSc-2 that lead to stability, conductivity, and high capacity, respectively. These results lead to the development of a novel kind of SSc by overcoming the low conductivity and limited capacity challenges without any modification.

All-Carboxylate-Protected Superatomic Silver Nanocluster with an Unprecedented Rhombohedral Ag8 Core.

We report the synthesis and structure of the first all-carboxylate-protected superatomic silver nanocluster. It was prepared by heating a dimethylformamide solution of perfluoroglutaric acid and AgNO3 under alkaline conditions, yielding a single crystal of [(CH3)2NH2]6[Ag8(pfga)6]. The [Ag8(pfga)6]6- cluster has a rhombohedral Ag86+ core, with each of its faces protected by one dianionic perfluoroglutarate (pfga) ligand. Electronic-structure analysis from density functional theory confirms the stability of this two-electron cluster due to the shell closing of the superatomic orbital in the (1S)2 configuration and explains the optical absorption of the cluster in the visible region as the transition from 1S to 1P orbital. The [Ag8(pfga)6]6- cluster emits bright green-yellow light in THF solution and bright orange light in the solid state. This work opens the door to using the widely available carboxylic acids to synthesize atomically precise Ag clusters of attractive properties.

Comparative Study of the Supercapacitive Performance of Three Ferrocene-Based Structures: Targeted Design of a Conductive Ferrocene-Functionalized Coordination Polymer as a Supercapacitor Electrode.

As redox-active based supercapacitors are known as highly desirable next-generation supercapacitor electrodes, the targeted design of two ferrocene-functionalized (Fc(COOH)2 ) clusters based on coinage metals, [(PPh3 )2 AgO2 CFcCO2 Ag(PPh3 )2 ]2 ⋅7 CH3 OH (SC1 : super capacitor) and [(PPh3 )3 CuO2 CFcCO2 Cu(PPh3 )3 ]⋅3 CH3 OH (SC2 ), is reported. Both structures are fully characterized by various techniques. The structures are utilized as energy storage electrode materials, giving 130 F g-1 and 210 F g-1 specific capacitance at 1.5 A g-1 in Na2 SO4 electrolyte, respectively. The obtained results show that the presence of CuI instead of AgI improves the supercapacitive performance of the cluster. Further, to improve the conductivity, the PSC2 ([(PPh3 )2 CuO2 CFcCO2 ]∞ ), a polymeric structure of SC2 , was synthesized and used as an energy storage electrode. PSC2 displays high conductivity and gives 455 F g-1 capacitance at 3 A g-1 . The PSC2 as a supercapacitor electrode presents a high power density (2416 W kg-1 ), high energy density (161 Wh kg-1 ), and long cycle life over 4000 cycles (93 %). These results could lead to the amplification of high-performance supercapacitors in new areas to develop real applications and stimulate the use of the targeted design of coordination polymers without hybridization or compositions with additive materials.

Size-Selective Urea-Containing Metal-Organic Frameworks as Receptors for Anions.

Anion recognition by neutral hosts that function in aqueous solution is an emerging area of interest in supramolecular chemistry. The design of neutral architectures for anion recognition still remains a challenge. Among neutral anion receptor systems, urea and its derivatives are considered as "privileged groups" in supramolecular anion recognition, since they have two proximate polarized N-H bonds exploitable for anion recognition. Despite promising advancements in urea-based structures, the strong hydrogen bond drives detrimental self-association. Therefore, immobilizing urea fragments onto the rigid structures of a metal-organic framework (MOF) would prevent this self-association and promote hydrogen-bond-accepting substrate recognition. With this aim, we have synthesized two new urea-containing metal-organic frameworks, namely [Zn(bpdc)(L2)]n·nDMF (TMU-67) and [Zn2(bdc)2(L2)2]n·2nDMF (TMU-68) (bpdc = biphenyl-4,4'-dicarboxylate; bdc = terephthalate; L2 = 1,3-bis(pyridin-4-yl)urea), and we have assessed their recognition ability toward different anions in water. The two MOFs show good water stability and anion affinity, with a particular selectivity toward dihydrogen arsenate for TMU-67 and toward fluoride for TMU-68. Crystal structure characterizations reveal 3-fold and 2-fold interpenetrated 3D networks for TMU-67 and TMU-68, respectively, where all single interpenetrated networks are hydrogen bonded to each other in both cases. Despite the absence of self-quenching, the N-H urea bonds are tightly hydrogen bonded to the oxygen atoms of the dicarboxylate ligands and cannot be directly involved in the recognition process. The good performance in anion sensing and selectivity of the two MOFs can be ascribed to the network interpenetration that, shaping the void, creates monodimensional channels, decorated by exposed oxygen atom sites selective for arsenate sensing in TMU-67 and isolated cavities, covered by phenyl groups selective for fluoride recognition in TMU-68.

Hexavalent Octahedral Template: A Neutral High-Nucleus Silver Alkynyl Nanocluster Emitting Infrared Light.

The first silver nanocluster with an octahedral template of TeO66- was synthesized as a neutral 36-nucleus nanocluster, and its structure was demonstrated using single-crystal X-ray diffraction, Fourier transform infrared spectroscopy, electrospray ionization mass spectrometry, and X-ray photoelectron spectroscopy. The peripheral ligands of the cagelike skeleton of the nanocluster are CF3COO- and tBuC≡C-. During the synthesis, the TeO66- template arranged the nanocluster, and a 36-nucleus nanocluster was formed. The effect of the template nature was displayed on the structural features of the nanocluster in comparison with an 8-nucleus cluster, with the same synthesis conditions. The photoluminescence and UV-vis absorption analyses of the nanocluster were also investigated. The nanocluster displayed near-infrared luminescence emission at 690 nm.

Investigation of the Effect of a Mixed-Ligand on the Accommodation of a Templating Molecule into the Structure of High-Nucleus Silver Clusters.

Advancement of the synthesis and control of the self-assembly process of new high-nucleus silver clusters with desired structures is important for both the material sciences and the many applications. Herein, three new silver clusters, 20-, 22-, and 8-nucleus, based on alkynyl ligands were constructed and their structures were confirmed by single-crystal X-ray diffraction, powder X-ray diffraction, elemental analyses, and Fourier-transform infrared spectroscopy (FT-IR). For the first time, the trivalent tetrahedron anion of AsO43-, as a template, and the surface ligand of Ph2PO2H, with new coordination modes, were employed in preparation of the silver clusters. The role of surface ligands and template anions in the size and structure of the clusters was investigated. The presence of the template in the structure of the clusters led to the formation of the high-nucleus clusters. Also, in this report, it was shown that the participation of the template in the assembly of a cluster can be controlled by the surface ligands. UV-vis absorption and luminescent properties of the clusters and the thermal stability of the 8-nucleus cluster were also studied.

Comparison of propensity score methods for pre-specified subgroup analysis with survival data.

Examining medical products' benefits and risks in different population subsets is often necessary for informing public health decisions. In observational cohort studies, safety analyses by pre-specified subgroup can be powered, and are informative about different population subsets' risks if the study designs or analyses adequately control for confounding. However, few guidelines exist on how to simultaneously control for confounding and conduct subgroup analyses. In this simulation study, we evaluated the performance, in terms of bias, efficiency and coverage, of six propensity score methods in 24 scenarios by estimating subgroup-specific hazard ratios of average treatment effect in the treated with Cox regression models. The subgroup analysis methods control for confounding either by propensity score matching or by inverse probability treatment weighting. These methods vary as to whether they subset information or borrow it across subgroups to estimate the propensity score. Simulation scenarios varied by size of subgroup, strength of association of subgroup with exposure, strength of association of subgroup with outcome (simulated survival), and outcome incidence. Results indicated that subsetting the data by the subgrouping variable, to estimate the propensity score and hazard ratio, has the smallest bias, far exceeding any penalty in precision. Moreover, weighting methods pay a heavier price in bias than do matching methods when the propensity score model is misspecified and the subgrouping variable is a strong confounder.

Trivalent Tetrahedral Anion Template: A 26-Nucleus Silver Alkynyl Cluster Encapsulating Vanadate.

In order to study the charge effect on the formation of an anion-templated silver cluster, a trivalent tetrahedral anion was incorporated into the silver assembly. A 26-nuclear silver cluster was prepared, and its structure was confirmed by single-crystal X-ray diffraction. Also, the resulting structure was characterized by powder X-ray diffraction data. Its light absorption and photoluminescent properties were studied by solid-state UV diffuse-reflectance and fluorescence spectroscopy. Compared with the other reported silver clusters with tetrahedral anion templates, the more negative VO43- anion led to the formation of a bigger silver cluster. Also, the supramolecular motif O-H(CH3OH)···O(trifluoroacetate) was confirmed on the cluster surface for the first time.

A simulation study of the statistical power and signaling characteristics of an early season sequential test for influenza vaccine safety.

PURPOSE: The US Food and Drug Administration monitors the risk of Guillain-Barré syndrome (GBS) following influenza vaccination using several data sources including Medicare. In the 2017 to 2018 season, we transitioned our near real-time surveillance in Medicare to more effectively detect large GBS risk increases early in the season while avoiding false positives. METHODS: We conducted a simulation study examining the ability of the updating sequential probability ratio test (USPRT) to detect substantially elevated GBS risk in the 8- to 21-day postvaccination versus 5× to 30× the historical rate. We varied the first testing week (weeks 5-8) and the null rate (1×-3×) and evaluated power. We estimated signal probability and the risk ratio (RR) after signaling when high-risk seasons were rare. RESULTS: Applying fixed alternatives, we found >80% power to detect a risk 30× the historical rate in week 5 for the 1× null and in week 6 for the 1.5× to 3× nulls. Nearly all testing schedules had >80% power for a 5× risk by week 11. To test the robustness of USPRT, we further simulated seasons where 1% were true high-risk seasons. Using a 1× null led to 10% of seasons signaling by week 11 (median RR approximately 1.4), which decreased to approximately 1% with the ≥2.5× null (median RR approximately 16.0). CONCLUSIONS: On the basis of the results from this simulation and subsequent consultations with experts and stakeholders, we specified USPRT to test continuously from weeks 7 to 11 using the null hypothesis that the observed GBS rate was 2.5× the historical rate. This helped improve the ability of USPRT to provide early detection of GBS risk following influenza vaccination as part of a multilayered system of surveillance.