Would plain packaging and health warning labels reduce smoking in the presence of informal markets? A choice experiment in Colombia.

BACKGROUND: Despite progress made by many countries on the adoption of plain tobacco packaging laws over the last years, low- and middle-income countries, with a large supply of loose cigarettes via informal vendors, remain far behind. AIM: To study the potential effectiveness of plain tobacco packaging and dissuasive cigarette sticks, via willingness-to-pay estimates, when illicit cigarette options are available. METHODS: We conducted a discrete choice experiment (DCE) in which respondents chose licit and illicit products with three attributes: packaging (standard vs. plain packaging), stick design (branded stick vs. stick with warning), and price level. The sample, collected on 12/2021, consisted of 1761 respondents from an internet panel involving smokers and nonsmokers. Conditional logit and latent class models were used to estimate the willingness-to-pay (WTP) to avoid restrictive packaging elements. RESULTS: Nonsmokers are willing to pay USD $5.63 for a pack of cigarettes to avoid plain packaging, which is higher than the actual commercial price of illicit cigarettes (USD $2.40). The WTP increases to USD $12.14 in the presence of illicit alternatives. Smokers are also willing to pay to avoid illicit options, which they also deem riskier, and the presence of such options increases the WTP to avoid plain packaging. However, nonsmokers do not perceive the illicit option as riskier. The dissuasive stick (stick with warning) does not affect perceptions of risk and plays a small role in terms of choice for both smokers and nonsmokers. CONCLUSIONS: Even in the presence of illicit tobacco alternatives, plain packaging seems to be as effective in reducing the attractiveness of tobacco products in Colombia as in other countries that have already adopted it. Given conflicting results on the case for dissuasive sticks, there is a need for more research.

Outcome clusters and their stability over 1 year in patients with SLE: self-reported and performance-based cognitive function, disease activity, mood and health-related quality of life.

OBJECTIVE: To determine if self-reported fatigue, anxiety, depression, cognitive difficulties, health-related quality of life, disease activity scores and neuropsychological battery (NB) cluster into distinct groups in patients with SLE based on symptom intensity and if they change at 1-year follow-up. METHODS: This is a retrospective analysis of consecutive consenting patients, followed at a single centre. Patients completed a comprehensive NB, the Beck Anxiety Inventory, Beck Depression Inventory, Fatigue Severity Scale, Short-Form Health Survey Physical Component Summary and Mental Component Summary scores and the Perceived Deficits Questionnaire. Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index 2000. Ward's method was used for clustering and principal component analysis was used to visualise the number of clusters. Stability at 1 year was assessed with kappa statistic. RESULTS: Among 142 patients, three clusters were found: cluster 1 had mild symptom intensity, cluster 2 had moderate symptom intensity and cluster 3 had severe symptom intensity. At 1-year follow-up, 49% of patients remained in their baseline cluster. The mild cluster had the highest stability (77% of patients stayed in the same cluster), followed by the severe cluster (51%), and moderate cluster had the lowest stability (3%). A minority of patients from mild cluster moved to severe cluster (19%). In severe cluster, a larger number moved to moderate cluster (40%) and fewer to mild cluster (9%). CONCLUSION: Three distinct clusters of symptom intensity were documented in patients with SLE in association with cognitive function. There was a lower tendency for patients in the mild and severe clusters to move but not moderate cluster over the course of a year. This may demonstrate an opportunity for intervention to have moderate cluster patients move to mild cluster instead of moving to severe cluster. Further studies are necessary to assess factors that affect movement into moderate cluster.

Thoracodorsal to long thoracic nerve transfer in a patient with traumatic injury: A case report.

Background: Traumatic injury to the long thoracic nerve causes paralysis of the serratus muscle, clinically expressed as winged scapula and functional impairment of the shoulder girdle. Treatment varies according to the severity of the injury, with a focus on early intervention for best results; however, the therapeutic approach remains a challenge at present. Case Description: We present the case of a 32-year-old male patient, athlete, right-handed, presented with bilateral paresis predominantly in the right arm, associated with paresthesia and changes in the coloring of the upper limbs. After being diagnosed with Thoracic Outlet Syndrome and undergoing surgery, vascular symptoms persisted with a significant loss of strength in the right shoulder. Winged scapula was observed and structural lesions were excluded on magnetic resonance imaging. Electromyographic studies confirmed the presumption of traumatic nerve involvement of the long thoracic nerve. Notwithstanding 6 months of physical therapy, there was no improvement, so a nerve transfer from the thoracodorsal nerve to the right long thoracic nerve was chosen. At 12 months, complete resolution of the winged scapula and functional recovery were observed. The patient also experienced a decrease in preoperative pain from 5/10 to 2/10 on the visual analog scale. Conclusion: Nerve transfer from the thoracodorsal nerve to the long thoracic nerve is a safe and effective technique to treat winged scapula due to long thoracic nerve injury.

Performance Evaluation of QT-RR Adaptation Time Lag Estimation in Exercise Stress Testing.

BACKGROUND: Slower adaptation of the QT interval to sudden changes in heart rate has been identified as a risk marker of ventricular arrhythmia. The gradual changes observed in exercise stress testing facilitates the estimation of the QT-RR adaptation time lag. METHODS: The time lag estimation is based on the delay between the observed QT intervals and the QT intervals derived from the observed RR intervals using a memoryless transformation. Assuming that the two types of QT interval are corrupted with either Gaussian or Laplacian noise, the respective maximum likelihood time lag estimators are derived. Estimation performance is evaluated using an ECG simulator which models change in RR and QT intervals with a known time lag, muscle noise level, respiratory rate, and more. The accuracy of T-wave end delineation and the influence of the learning window positioning for model parameter estimation are also investigated. RESULTS: Using simulated datasets, the results show that the proposed approach to estimation can be applied to any changes in heart rate trend as long as the frequency content of the trend is below a certain frequency. Moreover, using a proper position of the learning window for exercise so that data compensation reduces the effect of nonstationarity, a lower mean estimation error results for a wide range of time lags. Using a clinical dataset, the Laplacian-based estimator shows a better discrimination between patients grouped according to the risk of suffering from coronary artery disease. CONCLUSIONS: Using simulated ECGs, the performance evaluation of the proposed method shows that the estimated time lag agrees well with the true time lag.

3D printed needleless injector based on thermocavitation: analysis of impact and penetration depth in skin phantoms in a repetitive regime.

A global issue that requires attention is the duality between the shortage of needles for regular vaccination campaigns and the exponential increase in syringe and needle waste from such campaigns, which has been exacerbated by the COVID-19 pandemic. In response to this problem, this study presents a 3D printed needleless injector based on thermocavitation. The work focused on investigating the interaction of the resulting liquid jets with skin phantoms at different concentrations (1-2%), emphasizing their impact and penetration depth in a repetitive regime. The injector was designed and fabricated from a semi-transparent polymer using a high-resolution 3D printer, allowing the ejection of liquid jets with velocities up to ~ 73 m/s. The impact of these jets on skin phantoms was evaluated using a high-speed camera. After 6 consecutive liquid jets (1% concentration), a maximum penetration depth of ~ 2.5 mm was achieved, delivering approximately 4.7 µL. For the highest concentration (2.0%) and the same number of shots, the penetration depth was reduced to ~ 0.6 mm with a delivered volume of ~ 0.7 µL. An important finding of this study is that the liquid jet with the highest pressure does not cause the maximum penetration depth, but is the result of a series of successive shots. In addition, the velocity and shape of the ejected jet are determined by the amount of solution and the meniscus formed inside the injector. These findings advance the development of precise and efficient thermocavitation-based injectors with broad potential applications in medical and pharmaceutical fields.

T-wave Peak-to-End Changes Quantified by Time-Warping Predicts Ventricular Fibrillation in a Porcine Myocardial Infarction Model.

BACKGROUND: The T-peak-to-T-end ( Tpe) interval has shown potential in predicting ventricular arrhythmic risk. It is an appealing index to be measured during ischemia since it is less influenced by ST-segment changes than the early part of the T wave. A time-warping-based index, derived from a spatially transformed PCA lead, [Formula: see text], quantifying changes in the Tpe morphology, has previously demonstrated utility in tracking repolarization changes induced by a 5-minute ischemia model in humans. The value of [Formula: see text] as a predictor of ventricular fibrillation (VF) episodes is assessed in a porcine model of myocardial ischemia with ischemia maintained for 40 minutes. METHODS: From 32 pigs undergoing a coronary occlusion, pre-occlusion and occlusion ECG recordings from 10 pigs suffering a VF episode after 10 min of occlusion (Delayed VF) and 16 that did not had any episode during the recording were analyzed. The [Formula: see text] series was measured by comparing Tpe morphologies at different stages of the occlusion relative to the peak-to-end morphology of a baseline T-wave. RESULTS: During baseline, [Formula: see text] remained stationary with an intra-recording median [IQR] value of 1.60 [1.33] ms. During artery occlusion, [Formula: see text] followed a well-marked gradual increasing trend as ischemia progressed, reaching a median of 14.58 [17.72] ms. [Formula: see text] averages were significantly higher ( ) in the VF group than in the Non-VF group at time intervals 0-5, 5-10, 10-15, 15-20, 20-25 min after occlusion onset and at 10-15, 5-10 and 5-0 minutes prior to VF episode, with median values of 12.5, 18.8, 26.8, 24.0, 31.0, 18.6, 25.0 and 28.8 vs 6.3, 7.6, 8.0, 7.8, 7.8, 8.5, 7.2 and 6.0 ms, respectively. The [Formula: see text] interval was also significantly higher in the VF group at all analyzed time periods, but with a lower significance level. Pigs with maximum [Formula: see text] ≥ 20.0 ms and [Formula: see text] ≥ 85.4 ms had significantly higher risk for VF occurring in the early 5-10 minutes interval, with 90.0%/75.0% and 80.0%/69.0% sensitivity/specificity, respectively. Univariate Cox analysis yielded hazard ratios of 12.5 for [Formula: see text] vs 5.5 for [Formula: see text]. CONCLUSIONS AND SIGNIFICANCE: The time-warping-based index, [Formula: see text], is a stronger VF predictor than [Formula: see text] during ischemia in a porcine model, advising for further clinical exploration studies in humans.

Argentophilic Interactions, Flexibility, and Dynamics of Pyrrole Cages Encapsulating Silver(I) Clusters.

Recently, pyrrole cages have been synthesized that encapsulate ion pairs and silver(I) clusters to form intricate supramolecular capsules. We report here a computational analysis of these structures using density functional theory combined with a semiempirical tight-binding approach. We find that for neutral pyrrole cages, the Gibbs free energies of formation provide reliable predictions for the ratio of bound ions. For charged pyrrole cages, we find strong argentophilic interactions between Ag ions on the basis of the calculated bond indices and molecular orbitals. For the cage with the Ag4 cluster, we find two minimum-geometry conformations that differ by only 6.5 kcal/mol, with an energy barrier <1 kcal/mol, suggesting a very flexible structure as indicated by molecular dynamics. The predicted energies of formation of [Agn⊂1]n-3+ (n = 1-5) cryptands provide low energy barriers of formation of 5-20 kcal/mol for all cases, which is consistent with the experimental data. Furthermore, we also examined the structural variability of mixed-valence silver clusters to test whether additional geometrical conformations inside the organic cage are thermodynamically accessible. In this context, we show that the time-dependent density functional theory UV-vis spectra may potentially serve as a diagnostic probe to characterize mixed-valence and geometrical configurations of silver clusters encapsulated into cryptands.

Different Reaction Modes Operating in ansa-Half-Sandwich Magnesium Catalysts.

Magnesium-based catalysts are becoming popular for hydroelementation reactions specially using p-block reagents. Based on the seminal report from Schäfer's group (ChemCatChem 2022, 14, e202201007), our study demonstrates that the reaction mechanisms exhibit a far greater degree of complexity than originally presumed. Magnesium has a variety of coordination modes (and access to different hybridizations) which allows this electron-deficient centre to modulate its catalytic power depending on the σ-donor properties of the reagent. DFT calculations demonstrate several reaction channels closely operating in these versatile catalysts. In addition, variations in limiting energy barriers resulting from catalyst modifications were examined as a function of the Hammett constant, thereby predicting enhanced efficiency in reaction conversions.

Extending the age criteria of lung transplant donors to 70+ years old does not significantly affect recipient survival.

OBJECTIVES: To determine the impact of older donor age (70+ years) on long-term survival and freedom from chronic lung allograft dysfunction in lung transplant (LTx) recipients. METHODS: A retrospective single-center study was performed on all LTx recipients from 2002 to 2017 and a modern subgroup from 2013 to 2017. Recipients were stratified into 4 groups based on donor lung age (<18, 18-55, 56-69, ≥70 years). Donor and recipient characteristics were compared using χ2 tests for differences in proportions and analysis of variance for differences in means. Univariable and multivariable Cox regression was used to describe differences in long-term survival and freedom from chronic lung allograft dysfunction. RESULTS: Between 2002 and 2017, 1600 LTx were performed, 98 of which were performed from donors aged 70 years or older. Recipients of 70+ years donor lungs were significantly older with a mean age of 55.5 ± 12.9 years old (P = .001) and had more Status 3 (urgent) recipients (37.4%, P = .002). After multivariable regression, there were no significant differences in survival or freedom from chronic lung allograft dysfunction between the 4 strata of recipients. CONCLUSIONS: Lung transplantation using donors 70 years old or older can be considered when all other parameters suggest excellent donor lung function without compromising short- or long-term outcomes.

Bioassay-guided identification of antithrombotic compounds from Cnidoscolus aconitifolius (Mill.) I. M. Jhonst.: molecular docking, bioavailability, and toxicity prediction.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Conventional antithrombotic therapy has reported hemorrhagic accidents. Ethnobotanical and scientific reports point to Cnidoscolus aconitifolius as an antithrombotic adjuvant. Previously, C. aconitifolius leaves ethanolic extract displayed antiplatelet, anticoagulant, and fibrinolytic activities. This work aimed to identify compounds from C. aconitifolius with in vitro antithrombotic activity through a bioassay-guided study. Antiplatelet, anticoagulant, and fibrinolytic tests guided the fractionation. Ethanolic extract was subjected to a liquid-liquid partitioning, followed by vacuum liquid, and size exclusion chromatography to obtain the bioactive JP10B fraction. The compounds were identified through UHPLC-QTOF-MS, and their molecular docking, bioavailability, and toxicological parameters were determined computationally. Kaempferol-3-O-glucorhamnoside and 15(S)-HPETE were identified; both showed affinity for antithrombotic targets, low absorption, and safety for human consumption. Further in vitro and in vivo evaluations will better understand their antithrombotic mechanism. This bioassay-guided fractionation demonstrated that C. aconitifolius ethanolic extract has antithrombotic compounds.Communicated by Ramaswamy H. Sarma.

Conduct and reporting of multivariate network meta-analyses: a scoping review.

OBJECTIVES: Combining multivariate and network meta-analysis methods simultaneously in a multivariate network meta-analysis (MVNMA) provides the methodological framework to analyze the largest amount of evidence relevant to decision-makers (i.e., from indirect evidence and correlated outcomes). The objectives of this scoping review were to summarize the characteristics of MVNMAs published in the health sciences literature and map the methodological guidance available for MVNMA. STUDY DESIGN AND SETTING: We searched MEDLINE, Embase, and the Cumulative Index to Nursing and Allied Health Literature from inception to 28 August 2023, along with citations of included studies, for quantitative evidence syntheses that applied MVNMA and articles addressing MVNMA methods. Pairs of reviewers independently screened potentially eligible studies. Collected data included bibliographic, methodological, and analytical characteristics of included studies. We reported results as total numbers, frequencies, and percentages for categorical variables and medians and interquartile ranges for continuous variables that were not normally distributed. RESULTS: After screening 1,075 titles and abstracts, and 112 full texts, we included 38 unique studies, of which, 10 were quantitative evidence syntheses that applied MVNMA and 28 were articles addressing MVNMA methods. Among the 10 MVNMAs, the first was published in 2013, four used studies identified from already published systematic reviews, and eight addressed pharmacological interventions, which were the most common interventions. They evaluated interventions for metastatic melanoma, colorectal cancer, prostate cancer, oral hygiene, disruptive behavior disorders, rheumatoid arthritis, narcolepsy, type 2 diabetes, and overactive bladder syndrome. Five MVNMAs analyzed two outcomes simultaneously, and four MVNMAs analyzed three outcomes simultaneously. Among the articles addressing MVNMA methods, the first was published in 2007 and the majority provided methodological frameworks for conducting MVNMAs (26/28, 93%). One study proposed criteria to standardize reporting of MVNMAs and two proposed items relevant to the quality assessment of MVNMAs. Study authors used data from 18 different illnesses to provide illustrative examples within their methodological guidance. CONCLUSIONS: The application of MVNMA in the health sciences literature is uncommon. Many methodological frameworks are published; however, standardization and specific criteria to guide reporting and quality assessment are lacking. This overview of the current landscape may help inform future conduct of MVNMAs and research on MVNMA methods.

Iminopyrrole-Based Self-Assembly: A Route to Intrinsically Flexible Molecular Links and Knots.

The use of 2,5-diformylpyrrole in self-assembly reactions with diamines and Zn(II)/Cd(II) salts allowed the preparation of [2]catenane, trefoil knot, and Borromean rings. The intrinsically dynamic nature of the diiminopyrrole motif rendered all of the formed assemblies intramolecularly flexible. The presence of diiminopyrrole revealed new coordination motifs and influenced the host-guest chemistry of the systems, as illustrated by hexafluorophosphate encapsulation by Borromean rings.

Model-based Estimators of QT Series Time Delay in Following Heart-Rate Changes.

Sudden cardiac death is the leading cause of death among cardiovascular diseases. Markers for patient risk stratification focusing on QT-interval dynamics in response to heart-rate (HR) changes can be characterized in terms of parametric QT to RR dependence and QT/RR hysteresis. The QT/RR hysteresis can be quantified by the time delay the QT interval takes to accommodate for the HR changes. The exercise stress test has been proposed as a proper test, with large HR dynamics, to evaluate the QT/RR hysteresis. The present study aims at evaluating several time-delay estimators based on noise statistic (Gaussian or Laplacian) and HR changes profile at stress test (gradual transition change). The estimator's performance was assessed on a simulated QT transition contaminated by noise and in a clinical study including patients affected by coronary arteries disease (CAD). As expected, the Laplacian and Gaussian estimators yield the best results when noise follows the respective distribution. Further, the Laplacian estimator showed greater discriminative power in classifying different levels of cardiac risk in CAD patients, suggesting that real data fit better the Laplacian distribution than the Gaussian one. The Laplacian estimator appears to be the choice for time-delay estimation of QT/RR hysteresis lag in response to HR changes in stress test.Clinical Relevance-The proposed time-delay estimator of QT/RR hysteresis lag improves its significance as biomarkers for coronary artery diseases risk stratification.

Intra- and inter-specific reproductive barriers in the tomato clade.

Tomato (Solanum lycopersicum L.) domestication and later introduction into Europe resulted in a genetic bottleneck that reduced genetic variation. Crosses with other wild tomato species from the Lycopersicon clade can be used to increase genetic diversity and improve important agronomic traits such as stress tolerance. However, many species in the Lycopersicon clade have intraspecific and interspecific incompatibility, such as gametophytic self-incompatibility and unilateral incompatibility. In this review, we provide an overview of the known incompatibility barriers in Lycopersicon. We begin by addressing the general mechanisms self-incompatibility, as well as more specific mechanisms in the Rosaceae, Papaveraceae, and Solanaceae. Incompatibility in the Lycopersicon clade is discussed, including loss of self-incompatibility, species exhibiting only self-incompatibility and species presenting both self-compatibility and self-incompatibility. We summarize unilateral incompatibility in general and specifically in Lycopersicon, with details on the 'self-compatible x self-incompatible' rule, implications of self-incompatibility in unilateral incompatibility and self-incompatibility-independent pathways of unilateral incompatibility. Finally, we discuss advances in the understanding of compatibility barriers and their implications for tomato breeding.

Inhibition of the Decomposition Pathways of Ruthenium Olefin Metathesis Catalysts: Development of Highly Efficient Catalysts for Ethenolysis.

Ruthenium-based Hoveyda-type olefin metathesis catalysts bearing novel rigid spirocyclic alkyl amino carbenes (CAACs) have been developed. They are characterized by exceptional stability toward decomposition through ß-elimination and bimolecular pathways, thus enabling unprecedented efficiency in the cross-metathesis of seed oil-derived fatty acid esters with ethylene (ethenolysis). Catalyst loading as low as 100 ppb was applied to the ethenolysis of the model substrate methyl oleate, leading to a remarkable turnover number (TON) of 2.6 million, significantly higher than previously reported (TON 340 000 at 1 ppm and 744 000 at 0.5 ppm catalyst loading). Ethenolysis of methyl esters derived from high oleic sunflower oil and rapeseed oil, readily available on an industrial scale, inexpensive, and renewable feedstocks, was for the first time effectively carried out with 0.5 ppm catalyst loading with TON as high as 964 000.

An Anthracene-Thiolate-Ligated Ruthenium Complex: Computational Insights into Z-Stereoselective Cross Metathesis.

Stereoselective control of the cross metathesis of olefins is a crucial aspect of synthetic procedures. In this study, we utilized density functional theory methods to calculate thermodynamic and kinetic descriptors to explore the stereoselectivity of cross metathesis between allylbenzene and 2-butene-1,4-diyl diacetate. A ruthenium-based complex, characterized primarily by an anthracene-9-thiolate ligand, was designed in silico to completely restrict the E conformation of olefins through a bottom-bound mechanism. Our investigation of the kinetics of all feasible propagation routes demonstrated that Z-stereoisomers of metathesis products can be synthesized with an energy cost of only 13 kcal/mol. As a result, we encourage further research into the synthetic strategies outlined in this work.

Chia mucilage carrier systems: A review of emulsion, encapsulation, and coating and film strategies.

The use of carrier systems for the protection and delivery of bioactive compounds in the agri-food industry is an area of opportunity that requires the design of new systems and sources of materials for their structure. Chia seeds (Salvia hispanica L.) produce mucilage with functional qualities that allow their application in diverse areas of the food industry. These qualities have been used to form very stable carrier systems, such as capsules, emulsions, coatings, and films that can protect and prolong the functionalities of loaded compounds (e.g., antimicrobial and antioxidant capabilities). This paper presents a review of chia mucilage-based carrier systems and their applications in food products (micro-and nanoparticles, emulsions, coatings, and films for food packaging), as well as the current technological prospects of these systems. The use of chia mucilage in coatings and films shows a high potential for use in biodegradable, edible, and organic packaging. Although many studies have been conducted on chia mucilage encapsulation systems, there is still a gap in the application of capsules and particles in food.

Topical treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Atopic dermatitis (AD) is a common skin condition with multiple topical treatment options, but uncertain comparative effects. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD prescription topical treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, CINAHL, LILACS, ICTRP, and GREAT databases to September 5, 2022, for randomized trials addressing AD topical treatments. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. We classified topical corticosteroids (TCS) using 7 groups-group 1 being most potent. This review is registered in the Open Science Framework (https://osf.io/q5m6s). RESULTS: The 219 included trials (43,123 patients) evaluated 68 interventions. With high-certainty evidence, pimecrolimus improved 6 of 7 outcomes-among the best for 2; high-dose tacrolimus (0.1%) improved 5-among the best for 2; low-dose tacrolimus (0.03%) improved 5-among the best for 1. With moderate- to high-certainty evidence, group 5 TCS improved 6-among the best for 3; group 4 TCS and delgocitinib improved 4-among the best for 2; ruxolitinib improved 4-among the best for 1; group 1 TCS improved 3-among the best for 2. These interventions did not increase harm. Crisaborole and difamilast were intermediately effective, but with uncertain harm. Topical antibiotics alone or in combination may be among the least effective. To maintain AD control, group 5 TCS were among the most effective, followed by tacrolimus and pimecrolimus. CONCLUSIONS: For individuals with AD, pimecrolimus, tacrolimus, and moderate-potency TCS are among the most effective in improving and maintaining multiple AD outcomes. Topical antibiotics may be among the least effective.

Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD systemic treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna). RESULTS: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. CONCLUSIONS: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.

Time-Warping Analysis of the T-Wave Peak-to-End Interval to Quantify Ventricular Repolarization Dispersion During Ischemia.

Variations in the dispersion of ventricular repolarization can be quantified by T-wave time-warping based index, dw. However, the early phase of the T-wave can be affected by ST-segment changes during ischemia. We hypothesized that restricting dw to the T-wave peak-to-end ( Tpe) would circumvent this limitation while still quantifying variations in repolarization dispersion. A total of 101 ECG recordings from patients undergoing coronary occlusion, together with their control recordings, were analyzed. A series of dw values was calculated by quantifying the Tpe morphological variations between the T-waves at different occlusion stages and a baseline T-wave. We introduced a normalized version of dw, Rd, reflecting variations of dw during occlusion relative to control recordings ( Rd = 1 corresponds to the same level of variation). The dw series followed a gradually increasing trend with occlusion time, reaching median [range] Rd values of 9.44 [1.01, 80.74] at the occlusion end. Rd at occlusion end was significantly higher than threshold values of 1, 2, 5, and 10 in 94.1%, 85.11%, 64.4% and 48.5% of patients, respectively. The spatial lead-wise analysis of dw showed distinct distributions depending on the occluded artery, suggesting a relation with the ischemia location. The relative variation R with ischemia of index dw (9.4) is greater than that of the T-wave amplitude (7.7), Tpe interval (2.7) and T-wave width (3.0). In conclusion, dw tracks ischemic-induced variations in repolarization dispersion in a more robust manner than classical indexes, avoiding the impact of ST segment elevation/depression or early T-wave distortions, thus warranting further clinical studies.