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PURPOSE: Coats' disease can be difficult to differentiate from retinoblastoma. While MR imaging of retinoblastoma and Coats' disease have been examined for differentiating features such as eye size, vitreous seeding, and shape of retinal detachment, there is a lack of data on apparent diffusion coefficient (ADC). ADC is a measure of the diffusion (of water molecules) within tissue, and is commonly clinically calculated using MRI. DESIGN: Retrospective cross-sectional study. METHODS: Patient or study population: Children < 18 diagnosed with Coats disease or Retinoblastoma between January 1, 2018 and January 8, 2022 who had MRI imaging that was reviewable. MAIN OUTCOME MEASURE: Apparent diffusion coefficient (ADC) of the intraocular lesion. Retrospective brain MRIs were obtained from records of 5 eyes of 5 Coats' patients and 29 eyes of 23 patients with retinoblastoma. All MRIs were obtained prior to treatment. The eyedropper tool in Epic's default viewer (Ambra DICOM) was used to measure the ADC of five to eight randomly sampled points within the eye lesions seen on MRI. Average ADC was calculated for each affected eye. Internal reliability was confirmed by re-measuring mean ADC for a random sample of patients masked to their diagnosis and prior measurements. T-test was used to determine if ADC values differ between groups. RESULTS: The mean ADC for retinoblastoma patients (442 +/- 210 mm2/s) differed significantly from the mean for Coats' patients (1364 +/- 309 mm2/s), (P < .001). T-test between baseline and repeat measurements was not significantly different. Since ADC values can differ between different scanners and DW MRI pulse sequences, an ADC threshold may be difficult to generalize across institutes, in our data set a threshold of 900 mm2/s was useful in separating the two diagnoses with a high degree of accuracy. CONCLUSIONS: Clinical features of retinoblastoma and Coats' disease often resemble each other and can lead to misdiagnosis. Since ADCs are derived from diffusion-weighted MRI as an objective parameter, it has the potential to aid in establishing or confirming the diagnosis when retinoblastoma and/or Coats' disease are suspected.
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INTRODUCTION: Palmoplantar pustulosis (PPP) is a pruritic, painful, chronic dermatitis that greatly impacts functioning and quality of life and can be difficult to treat. Approved treatment options for PPP are limited, and many patients do not fully respond to current treatments. METHODS: This was a randomized, double-blind, placebo-controlled, phase 2 study in Japanese patients with moderate to severe PPP and inadequate response to topical treatment. Patients were randomized 1:1 to receive apremilast 30 mg twice daily or placebo for 16 weeks followed by an extension phase where all patients received apremilast through week 32. PPP Area and Severity Index (PPPASI), modified PPPASI (which evaluates pustules and vesicles separately), and Palmoplantar Severity Index (PPSI) total scores and subscores (erythema, pustules/vesicles, and desquamation/scales) were evaluated over 32 weeks of apremilast treatment. Achievement of ≥ 50% improvement in PPPASI (PPPASI-50) was evaluated at week 16 among baseline demographic and clinical characteristic subgroups. RESULTS: At week 16, improvements in total score and subscores for PPPASI, modified PPASI, and PPSI, as well as rates of PPPASI-50 were at least moderately greater with apremilast than placebo. Mean PPPASI total score decreased by - 68.3% from baseline to week 32 with continued apremilast treatment. At week 32, mean change from baseline in PPPASI/modified PPPASI subscores ranged from - 58.5% to - 77.0% with apremilast. At week 32, PPSI total score for physician and patient assessments decreased by - 51.3% and - 40.0%, respectively, with continued apremilast treatment. PPPASI-50 response at week 16 was greater with apremilast versus placebo in most demographic and baseline characteristic subgroups. CONCLUSIONS: Improvements in all PPPASI and PPSI total scores and subscores observed with apremilast over 16 weeks were maintained through 32 weeks in patients with moderate to severe PPP and inadequate response to topical treatment. Rates of PPPASI-50 response at week 16 were mostly consistent across patient subgroups. CLINICALTRIALS: GOV: NCT04057937.
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The bone-resorbing activity of osteoclasts plays a critical role in the life-long remodeling of our bones that is perturbed in many bone loss diseases. Multinucleated osteoclasts are formed by the fusion of precursor cells, and larger cells - generated by an increased number of cell fusion events - have higher resorptive activity. We find that osteoclast fusion and bone-resorption are promoted by reactive oxygen species (ROS) signaling and by an unconventional low molecular weight species of La protein, located at the osteoclast surface. Here, we develop the hypothesis that La's unique regulatory role in osteoclast multinucleation and function is controlled by a ROS switch in La trafficking. Using antibodies that recognize reduced or oxidized species of La, we find that differentiating osteoclasts enrich an oxidized species of La at the cell surface, which is distinct from the reduced La species conventionally localized within cell nuclei. ROS signaling triggers the shift from reduced to oxidized La species, its dephosphorylation and delivery to the surface of osteoclasts, where La promotes multinucleation and resorptive activity. Moreover, intracellular ROS signaling in differentiating osteoclasts oxidizes critical cysteine residues in the C-terminal half of La, producing this unconventional La species that promotes osteoclast fusion. Our findings suggest that redox signaling induces changes in the location and function of La and may represent a promising target for novel skeletal therapies.
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The impact of estrogen supplementation during the follicular/proliferative phase on the endometrial lining thickness (EMT) prior to intrauterine insemination (IUI) remains largely unstudied. Our study examined changes in EMT and rates of clinical pregnancy, miscarriage, and live birth for all patients who completed an IUI cycle at Stanford Fertility Center from 2017-2023 (n = 2281 cycles). Cycles with estradiol supplementation (n = 309) were compared to reference cycles without supplementation (n = 1972), with the reference cohort further categorized into cycles with a pre-ovulatory EMT of < 7 mm ("thin-lining", n = 536) and ≥ 7 mm ("normal-lining", n = 1436). The estradiol group had a statistically significant greater change in EMT from baseline to ovulation compared to the thin-lining reference groups (2.4 mm vs 1.9 mm, p < =0.0001). Similar rates of clinical pregnancy and live birth were observed. After adjusting for age, BMI, race/ethnicity, infertility diagnosis, and EMT at trigger, the estradiol cohort had a significantly increased odds of miscarriage versus the entire reference cohort (2.46, 95 % confidence interval [1.18, 5.14], p = 0.02). Thus, although estradiol supplementation had a statistically significant increase in EMT compared to IUI cycles with thin pre-ovulatory EMT (<7 mm), this change did not translate into improved IUI outcomes such as increased rates of clinical pregnancy and live birth or decreased rate of miscarriage. Our study suggests that supplemental estradiol does not appear to improve IUI outcomes.
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Endometrio , Estradiol , Inseminación Artificial , Índice de Embarazo , Humanos , Femenino , Estradiol/administración & dosificación , Embarazo , Adulto , Endometrio/efectos de los fármacos , Estudios Retrospectivos , Nacimiento VivoRESUMEN
The development of reductive electrosynthetic reactions is often enabled by the oxidation of a sacrificial metal anode, which charge-balances the reductive reaction of interest occurring at the cathode. The metal oxidation is frequently assumed to be straightforward and innocent relative to the chemistry of interest, but several processes can interfere with ideal sacrificial anode behavior, thereby limiting the success of reductive electrosynthetic reactions. These issues are compounded by a lack of reported observations and characterization of the anodes themselves, even when a failure at the anode is observed. Here, we weave lessons from electrochemistry, interfacial characterization, and organic synthesis to share strategies for overcoming issues related to sacrificial anodes in electrosynthesis. We highlight common but underexplored challenges with sacrificial anodes that cause reactions to fail, including detrimental side reactions between the anode or its cations and the components of the organic reaction, passivation of the anode surface by an insulating native surface film, accumulation of insulating byproducts at the anode surface during the reaction, and competitive reduction of sacrificial metal cations at the cathode. For each case, we propose experiments to diagnose and characterize the anode and explore troubleshooting strategies to overcome the challenge. We conclude by highlighting open questions in the field of sacrificial-anode-driven electrosynthesis and by indicating alternatives to traditional sacrificial anodes that could streamline reaction optimization.
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BACKGROUND: Approved systemic treatment options are limited for pediatric patients with moderate to severe plaque psoriasis. OBJECTIVE: To assess the efficacy and safety of apremilast over 16 weeks in pediatric patients with plaque psoriasis. METHODS: SPROUT (NCT03701763) was a phase 3, multicenter, randomized, double-blind, placebo-controlled study of apremilast in patients aged 6-17 years with moderate-to-severe psoriasis (Psoriasis Area and Severity Index [PASI] ≥12, body surface area ≥10%, static Physician Global Assessment [sPGA] ≥3) inadequately controlled by/inappropriate for topical therapy. Patients were stratified by age group and randomized (2:1) to apremilast (20 or 30 mg BID based on weight) or placebo for 16 weeks, followed by apremilast extension to 52 weeks. RESULTS: Of 245 patients randomized (apremilast: 163; placebo: 82), 221 (90%) completed the double-blind phase (apremilast: 149; placebo: 72). Significantly more patients achieved sPGA response and ≥75% reduction in PASI with apremilast than placebo, regardless of baseline age, weight, or disease severity. No new safety signals were observed. LIMITATIONS: Sample size of subgroup analyses. CONCLUSIONS: Improvements in global disease activity and skin involvement were significantly greater in pediatric patients treated with apremilast versus placebo. Adverse events were consistent with the known apremilast safety profile.
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Antiinflamatorios no Esteroideos , Psoriasis , Índice de Severidad de la Enfermedad , Talidomida , Humanos , Talidomida/análogos & derivados , Talidomida/uso terapéutico , Talidomida/efectos adversos , Talidomida/administración & dosificación , Psoriasis/tratamiento farmacológico , Adolescente , Niño , Método Doble Ciego , Masculino , Femenino , Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Resultado del Tratamiento , Inhibidores de Fosfodiesterasa 4/efectos adversos , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Inhibidores de Fosfodiesterasa 4/administración & dosificación , Relación Dosis-Respuesta a DrogaRESUMEN
One important decision in every event-related potential (ERP) experiment is which electrode site(s) to use in quantifying the ERP component of interest. A common approach is to measure the ERP from a single electrode site, typically the site where the ERP component is largest. Alternatively, two or more electrode sites in a given spatial region are averaged together, and the ERP is measured from the resulting multi-site cluster. The goal of the present study was to systematically compare these two measurement approaches across a range of outcome measures and ERP components to determine whether measuring from a single electrode site or an average of multiple sites yields consistently better results. We examined seven common ERP components from the open-source ERP CORE dataset that span a range of neurocognitive processes: N170, mismatch negativity (MMN), N2pc, N400, P3, lateralized readiness potential (LRP), and error-related negativity (ERN). For each component, we compared ERP amplitude, noise level, signal-to-noise ratio, and effect size at two single electrode sites and four multi-site clusters. We also used a Monte Carlo approach to simulate within-participant and between-groups experiments with known effect magnitudes to compare statistical power at single sites and multi-site clusters. Overall, measuring from a multi-site cluster produced results that were as good as or better than measuring from a single electrode site across analyses and components, indicating that the cluster-based measurement approach may be beneficial in quantifying ERPs from a range of neurocognitive domains.
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Electroencefalografía , Potenciales Evocados , Humanos , Masculino , Femenino , Relación Señal-RuidoRESUMEN
Trade in pangolins is illegal, and yet tons of their scales and products are seized at various ports. These large seizures are challenging to process and comprehensively genotype for upstream provenance tracing and species identification for prosecution. We implemented a scalable DNA barcoding pipeline in which rapid DNA extraction and MinION sequencing were used to genotype a substantial proportion of pangolin scales subsampled from 2 record shipments seized in Singapore in 2019 (37.5 t). We used reference sequences to match the scales to phylogeographical regions of origin. In total, we identified 2346 cytochrome b (cytb) barcodes of white-bellied (Phataginus tricuspis) (from 1091 scales), black-bellied (Phataginus tetradactyla) (227 scales), and giant (Smutsia gigantea) (1028 scales) pangolins. Haplotype diversity was higher for P. tricuspis scales (121 haplotypes, 66 novel) than that for P. tetradactyla (22 haplotypes, 15 novel) and S. gigantea (25 haplotypes, 21 novel) scales. Of the novel haplotypes, 74.2% were likely from western and west-central Africa, suggesting potential resurgence of poaching and newly exploited populations in these regions. Our results illustrate the utility of extensively subsampling large seizures and outline an efficient molecular approach for rapid genetic screening that should be accessible to most forensic laboratories and enforcement agencies.
Revelación de la magnitud de la caza furtiva del pangolín africano mediante el genotipo extenso de nanoporos de ADN de escamas incautadas Resumen Aunque el mercado de pangolines es ilegal, se incautan toneladas de sus escamas y productos derivados en varios puertos comerciales. Es un reto procesar estas magnas incautaciones y obtener el genotipo completo para usarlo en la trazabilidad logística ascendente e identificación de la especie y así imponer sanciones. Implementamos una canalización escalable del código de barras de ADN en el cual usamos la extracción rápida de ADN y la secuenciación MinION para obtener el genotipo de una proporción sustancial de las escamas de pangolín submuestreadas en dos cargamentos incautados en 2019 en Singapur (37.5 t). Usamos secuencias referenciales para emparejar las escamas con las regiones filogeográficas de origen. Identificamos en total 2,346 códigos de citocromo b (cytb) del pangolín de vientre blanco (Phataginus tricuspis) (de 1,091 escamas), de vientre negro (P. tetradactyla) (227 escamas) y del pangolín gigante (Smutsia gigantea) (1,028 escamas). La diversidad de haplotipos fue mayor en las escamas de P. tricuspis (121 haplotipos, 66 nuevos) que en las de P. tetradactyla (22 haplotipos, 15 nuevos) y S. gigantea (25 haplotipos, 21 nuevos). De los haplotipos nuevos, el 74.2% probablemente provenía del occidente y centrooccidente de África, lo que sugiere un resurgimiento potencial de la caza furtiva y poblaciones recién explotadas en estas regiones. Nuestros resultados demuestran la utilidad de submuestrear extensivamente las grandes incautaciones y esboza una estrategia molecular eficiente para un análisis genético rápido que debería ser accesible para la mayoría de los laboratorios forenses y las autoridades de aplicación.
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Nanoporos , Pangolines , Humanos , Animales , Genotipo , Conservación de los Recursos Naturales/métodos , ADN , ConvulsionesRESUMEN
PURPOSE: To describe contemporary management and outcomes in children with myocarditis who are admitted to a cardiac intensive care unit (CICU) and to identify the characteristics associated with mortality. METHODS: All patients in the Pediatric Cardiac Critical Care Consortium (PC4) registry between August 2014 and June 2021 who were diagnosed with myocarditis were included. Univariable analyses and multivariable logistic regression evaluated the factors associated with in-hospital mortality. RESULTS: There were 847 CICU admissions for myocarditis in 51 centers. The median age was 12 years (IQR 2.7-16). In-hospital mortality occurred in 53 patients (6.3%), and 60 (7.1%) had cardiac arrest during admission. Mechanical ventilation was required in 339 patients (40%), and mechanical circulatory support (MCS) in 177 (21%); extracorporeal membrane oxygenation (ECMO)-only in 142 (16.7%), ECMO-to-ventricular assist device (VAD) in 20 (2.4%), extracorporeal cardiac resuscitation in 43 (5%), and VAD-only in 15 (1.8%) patients. MCS was associated with in-hospital mortality; 20.3% receiving MCS died compared to 2.5% without MCS (P < 0.001). Mortality rates were similar in ECMO-only, ECMO-to-VAD and VAD-only groups. The median time from CICU admission to ECMO was 2.0 hours (IQR 0-9.4) and to VAD, it was 9.9 days (IQR 6.3-16.8). Time to MCS was not associated with mortality. In multivariable modeling of patients' characteristics, smaller body surface area (BSA) and low eGFR were independently associated with mortality, and after including critical therapies, mechanical ventilation and ECMO were independent predictors of mortality. CONCLUSION: This contemporary cohort of children admitted to CICUs with myocarditis commonly received high-resource therapies; however, most patients survived to hospital discharge and rarely received VAD. Smaller patient size, acute kidney injury and receipt of mechanical ventilation or ECMO were independently associated with mortality.
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Insuficiencia Cardíaca , Corazón Auxiliar , Miocarditis , Niño , Humanos , Miocarditis/diagnóstico , Miocarditis/terapia , Miocarditis/complicaciones , Insuficiencia Cardíaca/terapia , Enfermedad Crítica , Estudios Retrospectivos , CorazónRESUMEN
Al0 is widely used as a sacrificial anode in organic electrosynthesis. However, there remains a notable knowledge gap in the understanding of Al anode interface chemistry under electrolysis conditions. We hypothesize that Al interfacial chemistry plays a pivotal role in the discernible bias observed in solvent selections for reductive electrosynthesis. The majority of existing methodologies that employ an Al sacrificial anode use N,N-dimethylformamide (DMF) as the preferred solvent, with only isolated examples of ethereal solvents such as tetrahydrofuran (THF). Given the crucial role of the solvent in determining the efficiency and selectivity of an organic reaction, limitations on solvent choice could significantly hinder substrate reactivity and impede the desired transformations. In this study, we aim to understand the Al metal interfaces and manipulate them to improve the performance of an Al sacrificial anode in THF-based electrolytes. We have discovered that the presence of halide ions (Cl-, Br-, I-) in the electrolyte is crucial for efficient Al stripping. By incorporating halide additive, we achieve bulk Al stripping in THF-based electrolytes and successfully improve the cell potentials of electrochemically driven reductive methodologies. This study will encourage the use of ethereal solvents in systems using Al sacrificial anodes and guide future endeavors in optimizing electrolytes for reductive electrosynthesis.
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Deficits in emotion processing are core features of psychotic disorders. Electrophysiology research in schizophrenia suggests deficits in sustained engagement with emotional content (indexed by the late positive potential [LPP]) may contribute to emotion processing impairments. Despite similar behavioral emotion processing dysfunction in those at clinical high risk (CHR) for psychosis, limited research has examined neural mechanisms of impaired emotion processing in the high-risk period, where research can inform risk models. To examine mechanisms of emotion processing deficits in those at CHR for psychosis, the present study used a passive viewing task to elicit the LPP in response to emotionally engaging and neutral stimuli in 28 CHR and 32 control participants (60% female). Relative to controls, CHR participants showed reduced LPP amplitude when viewing unpleasant images (d = 0.75, p = .005) but similar LPP amplitude in response to both neutral (d = 0.35, p = .19) and pleasant images (d = 0.31, p = .24). This pattern suggests that individuals at CHR for psychosis exhibit a deficit in sustained engagement with unpleasant stimuli. Clinical and trait questionnaires were administered to examine potential exploratory explanations for group differences in LPP amplitude. Consistent with evidence suggesting LPP amplitude reflects engagement of approach/avoidance motivational systems, greater LPP amplitude was associated with greater trait-level behavioral avoidance in control participants (r = .42, p = .032) but not CHR participants (r = -.21, p = .40). Together, the present research is consistent with LPP studies in psychosis and implicates reduced sustained engagement with emotional content in the high-risk period. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Trastornos Psicóticos , Esquizofrenia , Humanos , Femenino , Masculino , Potenciales Evocados/fisiología , Electroencefalografía/métodos , Emociones/fisiologíaRESUMEN
The cross-electrophile dialkylation of alkenes enables the formation of two C(sp3)-C(sp3) bonds from readily available starting materials in a single transformation, thereby providing a modular and expedient approach to building structural complexity in organic synthesis. Herein, we exploit the disparate electronic and steric properties of alkyl halides with varying degrees of substitution to accomplish their selective activation and addition to alkenes under electrochemical conditions. This method enables regioselective dialkylation of alkenes without the use of a transition-metal catalyst and provides access to a diverse range of synthetically useful compounds.
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OBJECTIVE: To observe the characteristics of a new extracorporeal high intensity focused ultrasound transducer, titled Haifu system JCQ-B, and to compare its safety and efficacy for breast ablation with the standard Haifu system JC transducer. MATERIALS AND METHODS: Ox liver with pig skin and pork ribs were prepared in a semi-sphere shape, served as in vitro acoustic model. The udders of female goats were used as in vivo acoustic model. Both in vitro and in vivo models were ablated by either JCQ-B or JC transducer. The morphology of biological focal region (BFR), the coagulative necrosis volume, and the temperature increase were observed and compared. RESULTS: The BFR morphology of JCQ-B transducer was circular both in vitro and in vivo, with a length-width ratio close to one. Under the same sonication parameters (sonication power, time and depth in tissue), coagulation necrosis volume caused by JCQ-B transducer was larger than that caused by JC transducer both in vitro and in vivo. The increase in temperature in the near and far acoustic pathways with JCQ-B transducer was significantly lower than that of JC transducer in vitro. After receiving high sonication energy during in vivo experimentation, there were no complications observed after the ablation of JCQ-B transducer, while small skin damage was observed after the ablation of JC transducer. CONCLUSIONS: The JCQ-B transducer improved the safety and efficacy of treatment by optimizing BFR morphology and ablation efficiency, which could be applied in the treatment of breast tumor.
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Neoplasias de la Mama , Ultrasonido Enfocado de Alta Intensidad de Ablación , Femenino , Animales , Porcinos , Humanos , Hígado/cirugía , Necrosis , TransductoresRESUMEN
Mg0 is commonly used as a sacrificial anode in reductive electrosynthesis. While numerous methodologies using a Mg sacrificial anode have been successfully developed, the optimization of the electrochemistry at the anode, i.e., Mg stripping, remains empirical. In practice, electrolytes and organic substrates often passivate the Mg electrode surface, which leads to high overall cell potential causing poor energy efficiency and limiting reaction scale-up. In this study, we seek to understand and manipulate the Mg metal interfaces for a more effective counter electrode in tetrahydrofuran. Our results suggest that the ionic interactions between the cation and the anion of a supporting electrolyte can influence the electrical double layer, which impacts the Mg stripping efficiency. We find halide salt additives can prevent passivation on the Mg electrode by influencing the composition of the solid electrolyte interphase. This study demonstrates that, by tailoring the electrolyte composition, we can modify the Mg stripping process and enable a streamlined optimization process for the development of new electrosynthetic methodologies.
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Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including atherosclerosis. Long non-coding RNAs (lncRNAs) are a group of protein expression regulators; however, the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still unclear. The study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and atherogenesis. We identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with atherosclerosis. In cultured monocytes, Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage differentiation. The differentiation stimuli-induced monocyte-macrophage differentiation and the macrophage activity were inhibited by Morrbid knockdown. Moreover, overexpression of Morrbid alone was sufficient to elicit the monocyte-macrophage differentiation. The role of Morrbid in monocyte-macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout mice. We identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression, whereas s100a10 was involved in Morrbid-mediated effect on macrophage differentiation. To provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease, we applied an acute atherosclerosis model in mice. The results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in mice. The results suggest that Morrbid is a novel biomarker and a modulator of monocyte-macrophage phenotypes, which is involved in atherogenesis.
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Samarium diiodide (SmI2 ) is widely used as a strong one-electron reducing agent and is often employed to form C-C bonds in complex systems. Despite their utility, SmI2 and related salts suffer from several drawbacks that render the use of Sm reducing agents in large-scale synthesis impractical. Here, we report factors influencing the electrochemical reduction of Sm(III) to Sm(II), towards the goal of electrocatalytic Sm(III) reduction. We probe the effect of supporting electrolyte, electrode material, and Sm precursor on Sm(II)/(III) redox and on the reducing power of the Sm species. We find that the coordination strength of the counteranion of the Sm salt affects the reversibility and redox potential of the Sm(II)/(III) couple and establish that the counteranion primarily determines the reducibility of Sm(III). Electrochemically generated SmI2 performs similarly to commercial SmI2 solutions in a proof-of-concept reaction. The results will provide fundamental insight to facilitate the development of Sm-electrocatalytic reactions.
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BACKGROUND: Since US FDA approval in 2014, apremilast has consistently demonstrated a favorable benefit-risk profile in 706,585 patients (557,379 patient-years of exposure) worldwide across approved indications of plaque psoriasis, psoriatic arthritis, and Behçet's syndrome; however, long-term exposure across these indications has not been reported. OBJECTIVE: The aim of this study was to conduct a pooled analysis of apremilast data from 15 clinical studies with open-label extension phases, focusing on long-term safety. METHODS: We analyzed longer-term safety and tolerability of apremilast 30 mg twice daily across three indications for up to 5 years, focusing on adverse events of special interest, including thrombotic events, malignancies, major adverse cardiac events (MACE), serious infections, and depression. Data were pooled across 15 randomized, placebo-controlled studies and divided into placebo-controlled or all-apremilast-exposure groups. Treatment-emergent adverse events (TEAEs) were assessed. RESULTS: Overall, 4183 patients were exposed to apremilast (6788 patient-years). Most TEAEs were mild to moderate in the placebo-controlled period (96.6%) and throughout all apremilast exposure (91.6%). TEAE rates of special interest were similar between treatment groups in the placebo-controlled period and remained low throughout all apremilast exposure. Exposure-adjusted incidence rates per 100 patient-years during all apremilast exposure were MACE, 0.30; thrombotic events, 0.10; malignancies, 1.0; serious infections, 1.10; serious opportunistic infections, 0.21; and depression, 1.78. Safety findings were consistent across indications and regions. No new safety signals were identified. CONCLUSIONS: The incidence of serious TEAEs and TEAEs of special interest was low despite long-term exposure, further establishing apremilast as a safe oral option for long-term use across indications with a favorable benefit-risk profile. CLINICAL TRIAL REGISTRATION: NCT00773734, NCT01194219, NCT01232283, NCT01690299, NCT01988103, NCT02425826, NCT03123471, NCT03721172, NCT01172938, NCT01212757, NCT01212770, NCT01307423, NCT01925768, NCT00866359, NCT02307513.
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Artritis Psoriásica , Síndrome de Behçet , Neoplasias , Psoriasis , Humanos , Artritis Psoriásica/tratamiento farmacológico , Síndrome de Behçet/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Primary care providers in Prince George's County, Maryland reported inconsistencies in their ability to identify and refer patients with social care needs. This project aimed to improve health outcomes of Medicare beneficiaries by implementing social determinant of health (SDOH) screening to identify unmet needs and improve rates of referral to appropriate services. Buy-in was achieved from providers and frontline staff via stakeholder meetings at a private primary care group practice. The Health Leads questionnaire was modified and integrated into the electronic health record. Medical assistants (MA) were trained to conduct screening and initiate care plan referrals prior to visits with the medical provider. During implementation, 96.25% of patients (n = 231) agreed to screening. Of these, 13.42% (n = 31) screened positive for at least one SDOH need, and 48.39% (n = 15) reported multiple social needs. Top needs included social isolation (26.23%), literacy (16.39%), and financial concerns (14.75%). All patients screening positive for one or more social needs were provided referral resources. Patients who identified as being of Mixed or Other race had significantly higher rates of positive screens (p = 0.032) compared to Caucasians, African Americans, and Asians. Patients were more likely to report SDOH needs during in-person visits (17.22%) compared to telehealth visits (p = 0.020). Screening for SDOH needs is feasible and sustainable and can improve the identification of SDOH needs and resource referrals. A limitation of this project was the lack of follow-up to determine whether patients with positive SDOH screens had been successfully linked to resources after initial referral.
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COVID-19 , Determinantes Sociales de la Salud , Humanos , Anciano , Estados Unidos/epidemiología , Maryland/epidemiología , Pandemias , Medicare , COVID-19/epidemiología , Atención Primaria de SaludRESUMEN
BACKGROUND: Palmoplantar pustulosis (PPP) is a pruritic, painful, recurrent, and chronic dermatitis with limited therapeutic options. OBJECTIVE: To evaluate the efficacy and safety of apremilast for the treatment of Japanese patients with PPP and inadequate response to topical treatment. METHODS: This phase 2, randomized, double-blind, placebo-controlled study enrolled patients with Palmoplantar Pustulosis Area and Severity Index (PPPASI) total score ≥ 12 and moderate or severe pustules/vesicles on the palm or sole (PPPASI pustule/vesicle severity score ≥ 2) at screening and baseline with an inadequate response to topical treatment. Patients were randomized (1:1) to apremilast 30 mg twice daily or placebo for 16 weeks, followed by a 16-week extension phase during which all patients received apremilast. The primary endpoint was achievement of PPPASI-50 response (≥ 50% improvement from baseline in PPPASI). Key secondary endpoints included change from baseline in PPPASI total score, Palmoplantar Pustulosis Severity Index (PPSI), and patient's visual analog scale (VAS) for PPP symptoms (pruritus and discomfort/pain). RESULTS: A total of 90 patients were randomized (apremilast: 46; placebo: 44). A significantly greater proportion of patients achieved PPPASI-50 at week 16 with apremilast versus placebo (P = 0.0003). Patients receiving apremilast showed greater improvement in PPPASI at week 16 versus placebo (nominal P = 0.0013), as well as PPSI and patient-reported pruritus and discomfort/pain (nominal P ≤ 0.001 for all). Improvements were sustained through week 32 with apremilast treatment. The most common treatment-emergent adverse events included diarrhea, abdominal discomfort, headache, and nausea. CONCLUSIONS: Apremilast treatment demonstrated greater improvements in disease severity and patient-reported symptoms versus placebo at week 16 in Japanese patients with PPP with sustained improvements through week 32. No new safety signals were observed. CLINICALTRIALS: GOV: NCT04057937.