To assess the risk of new-onset type 1 diabetes mellitus (T1D) diagnosis following COVID-19 diagnosis and the impact of COVID-19 diagnosis on the risk of diabetic ketoacidosis (DKA) in patients with ...prior T1D diagnosis.
Retrospective data consisting of 27,292,879 patients from the Cerner Real-World Data were used. Odds ratios, overall and stratified by demographic predictors, were calculated to assess associations between COVID-19 and T1D. Odds ratios from multivariable logistic regression models, adjusted for demographic and clinical predictors, were calculated to assess adjusted associations between COVID-19 and DKA. Multiple imputation with multivariate imputation by chained equations (MICE) was used to account for missing data.
The odds of developing new-onset T1D significantly increased in patients with COVID-19 diagnosis (OR: 1.42, 95% CI: 1.38, 1.46) compared to those without COVID-19. Risk varied by demographic groups, with the largest risk among pediatric patients ages 0-1 years (OR: 6.84, 95% CI: 2.75, 17.02) American Indian/Alaskan Natives (OR: 2.30, 95% CI: 1.86, 2.82), Asian or Pacific Islanders (OR: 2.01, 95% CI: 1.61, 2.53), older adult patients ages 51-65 years (OR: 1.77, 95% CI: 1.66, 1.88), those living in the Northeast (OR: 1.71, 95% CI: 1.61, 1.81), those living in the West (OR: 1.65, 95% CI: 1.56, 1.74), and Black patients (OR: 1.59, 95% CI: 1.47, 1.71). Among patients with diagnosed T1D at baseline (n = 55,359), 26.7% (n = 14,759) were diagnosed with COVID-19 over the study period. The odds of developing DKA for those with COVID-19 were significantly higher (OR 2.26, 95% CI: 2.04, 2.50) than those without COVID-19, and the largest risk was among patients with higher Elixhauser Comorbidity Index.
COVID-19 diagnosis is associated with significantly increased risk of new-onset T1D, and American Indian/Alaskan Native, Asian/Pacific Islander, and Black populations are disproportionately at risk. In patients with pre-existing T1D, the risk of developing DKA is significantly increased following COVID-19 diagnosis.
Carrying orbital angular momentum per photon, the optical vortex has elicited widespread interest. Here, we demonstrate that dual coaxial longitudinal polarization vortices can appear upon a ...nonparaxial propagation of a tightly focused Pancharatnam-Berry tailored Laguerre-Gaussian beam. Most importantly, it is capable of accessing arbitrary independent topological charges for both vortices, as well as predesigned tunable spacing distances between them.
•Both speed-based texting and handheld texting impair driving performance.•Texting performance is also impaired when texting while driving.•Speech-based texting is less disruptive to driving than ...handheld texting.•Task duration is equated for a fair comparison of speech-based and handheld texting.
Research indicates that using a cell phone to talk or text while maneuvering a vehicle impairs driving performance. However, few published studies directly compare the distracting effects of texting using a hands-free (i.e., speech-based interface) versus handheld cell phone, which is an important issue for legislation, automotive interface design and driving safety training. This study compared the effect of speech-based versus handheld text entries on simulated driving performance by asking participants to perform a car following task while controlling the duration of a secondary text-entry task. Results showed that both speech-based and handheld text entries impaired driving performance relative to the drive-only condition by causing more variation in speed and lane position. Handheld text entry also increased the brake response time and increased variation in headway distance. Text entry using a speech-based cell phone was less detrimental to driving performance than handheld text entry. Nevertheless, the speech-based text entry task still significantly impaired driving compared to the drive-only condition. These results suggest that speech-based text entry disrupts driving, but reduces the level of performance interference compared to text entry with a handheld device. In addition, the difference in the distraction effect caused by speech-based and handheld text entry is not simply due to the difference in task duration.
AMPK is a central regulator of metabolism and autophagy. Here we show how lysosomal damage activates AMPK. This occurs via a hitherto unrecognized signal transduction system whereby cytoplasmic ...sentinel lectins detect membrane damage leading to ubiquitination responses. Absence of Galectin 9 (Gal9) or loss of its capacity to recognize lumenal glycans exposed during lysosomal membrane damage abrogate such ubiquitination responses. Proteomic analyses with APEX2-Gal9 have revealed global changes within the Gal9 interactome during lysosomal damage. Gal9 association with lysosomal glycoproteins increases whereas interactions with a newly identified Gal9 partner, deubiquitinase USP9X, diminishes upon lysosomal injury. In response to damage, Gal9 displaces USP9X from complexes with TAK1 and promotes K63 ubiquitination of TAK1 thus activating AMPK on damaged lysosomes. This triggers autophagy and contributes to autophagic control of membrane-damaging microbe Mycobacterium tuberculosis. Thus, galectin and ubiquitin systems converge to activate AMPK and autophagy during endomembrane homeostasis.
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•Lysosomal damage activates AMPK, autophagy, and metabolic and antimicrobial responses•Galectin 9 transduces damage signal to ubiquitin responses via USP9X and TAK1•TAK1 controls AMPK in the physiological context of lysosomal permeability changes•Anti-diabetic drug metformin causes mild lysosomal damage and downstream responses
Jia, Bissa, Brecht et al. show that AMPK is activated upon lysosomal damage caused by microbes, ligands such as TRAIL, and other agents including the anti-diabetes drug metformin, via a novel signal transduction system from galectins to ubiquitin and that this results in the activation of AMPK by TAK1.
Several novel biologics are available or in development for moderate‐to‐severe plaque psoriasis. These drugs may differ in time until Psoriasis Area and Severity Index (PASI) response is obtained. In ...this systematic review, we examined the time to onset of action for interleukin (IL)‐17 and IL‐23 agents in the treatment of psoriasis. The primary objective was the weighted mean time needed for 25% and 50% of patients with psoriasis to achieve PASI90. The medical databases PubMed, Web of Science and EMBASE were searched using the following terms: psoriasis AND (ixekizumab OR secukinumab OR brodalumab OR risankizumab OR guselkumab OR tildrakizumab). A total of 27 studies were included for data extraction and qualitative synthesis, and 26 of these were quantitatively analysed. The shortest time to 25% and 50% of patients to achieved PASI90 were seen with brodalumab 210 mg every 2 weeks (Q2W; 3.5 weeks and 6.2 weeks, respectively) followed by ixekizumab 80 mg Q2W (4.1 and 7.4 weeks, respectively) and ixekizumab 80 mg Q4W (4.6 and 8.1 weeks, respectively) dosages. In conclusion, clinical trials yielded shorter time to onset of action in studies assessing approved dosing ranges of IL‐17 inhibitors compared with studies assessing IL‐23 inhibitors.
Prophets serve as intermediaries between the human and divine worlds, granting them a special status in history across diverse religions and cultures. For Muslims, the Prophet Muhammad (570-632 CE) ...represents the culmination of the line of monotheistic prophets, including Abraham, Moses and Jesus. In his own lifetime, Muhammad overcame opposition and brought reforms, firmly establishing a thriving community of believers which would become a major world civilisation. Today, the Prophet's life and actions continue to inspire the Muslims worldwide.The Prophet Muhammad presents an illuminating portrait of Muhammad in his capacity as God's messenger and an exemplary figure to Muslims. Revealing the challenges and triumphs of prophecy, Stephen Burge examines how prophets have inspired faith communities' relationship with the Divine, and one another. In doing so, this engaging account elucidates the enduring influence of prophecy and the profound legacy of the Prophet Muhammad.
The two angels Hārūt and Mārūt are mentioned together with the prophet Solomon in the ‘magic pericope’ of Sūrat al-Baqara (Q. 2:101–103). Rashīd Riḍā and his mentor Muḥammad ῾Abduh rejected the ...folkloric, mythical legends that surrounded the two angels Hārūt and Mārūt and the image of Solomon as a magus-like figure, seeing it as a threat to the rational interpretation of the Qur’ān. In his exegesis, Tafsīr al-Manār, Riḍā includes a relatively substantial tract denouncing magic and its use, entitled Mabḥath al-siḥr wa-Hārūt wa-Mārūt. This article will provide an analysis of exegetical and homiletic features used in this section, focusing on four areas: (i) elements of homiletic antisemitism; (ii) the invocation of personal experience; (iii) the use of lexicology to demystify Qur’ānic references to magic; and (iv) the use of a variant reading to demythologize the story. The aim of this article is to explore the ways in which the rejection of magic is articulated and which homiletic and exegetic tools Riḍā uses to support his position. A final section will explore the modernist movement’s relationship with biblical studies and the influence that it may have had on the interpretation of myth in the Tafsīr al-Manār.
Summary
Background
Significantly more patients with moderate‐to‐severe plaque psoriasis treated with the interleukin (IL)‐17A inhibitor ixekizumab vs. the IL‐23p19 inhibitor guselkumab in the IXORA‐R ...head‐to‐head trial achieved 100% improvement in Psoriasis Area and Severity Index (PASI 100) at week 12.
Objectives
To compare skin and nail clearance and patient‐reported outcomes for ixekizumab vs. guselkumab, up to week 24.
Methods
IXORA‐R enrolled adults with moderate‐to‐severe plaque psoriasis, defined as static Physician’s Global Assessment ≥ 3, PASI ≥ 12 and involved body surface area ≥ 10%. Statistical comparisons were performed using the Cochran–Mantel–Haenszel test stratified by pooled site. Time‐to‐first‐event comparisons were performed using Kaplan–Meier analysis, and P‐values were generated using adjusted log‐rank tests stratified by treatment group. Cumulative days at clinical and patient‐reported responses were compared by ancova. The trial was registered with ClinicalTrials.gov (NCT03573323).
Results
Of the 1027 patients randomly assigned, 90% completed the trial (465 of 520 ixekizumab and 459 of 507 guselkumab). As early as week 2 and through week 16, more patients on ixekizumab achieved PASI 100 (P < 0·01). At week 24, ixekizumab was noninferior to guselkumab (50% vs. 52%, difference −2·3%), with no statistically significant difference in PASI 100 (P = 0·41). More patients receiving ixekizumab showed completely clear nails at week 24 (52% vs. 31%, P = 0·007). The median time to first PASI 50/75/90 and PASI 100 were 2 and 7·5 weeks shorter, respectively, for patients on ixekizumab vs. guselkumab (P < 0·001). Patients on ixekizumab also had a greater cumulative benefit, with more days at PASI 90 and 100, with Dermatology Life Quality Index of 0 or 1, and itch free (P < 0·05). The frequency of serious adverse events was 3% for each group, with no new safety signals.
Conclusions
Ixekizumab was noninferior to guselkumab in complete skin clearance and superior in clearing nails at week 24. Ixekizumab cleared skin more rapidly in patients with moderate‐to‐severe plaque psoriasis, with a greater cumulative benefit, than guselkumab. Overall, the safety findings were consistent with the known safety profile for ixekizumab.
What is already known about this topic?
Patients with plaque psoriasis desire both high levels of clearance and rapid onset of treatment effects.
Ixekizumab is a high‐affinity monoclonal antibody that selectively targets interleukin (IL)‐17A.
In the 12‐week report of the IXORA‐R study, ixekizumab demonstrated significantly higher efficacy at early timepoints than the IL‐23p19 inhibitor guselkumab, with more patients achieving 100% improvement in Psoriasis Area and Severity Index (PASI 100) and improved quality of life as early as week 4.
What does this study add?
Patients on ixekizumab vs. guselkumab achieved similar levels of skin clearance and superior efficacy in the resolution of nail psoriasis at week 24.
Patients on ixekizumab vs. guselkumab had a greater cumulative benefit, with more days at PASI 90 and 100, more days when psoriasis did not impact their quality of life, and more itch‐free days.
The safety profiles of both drugs were consistent with those in previous studies.
Linked Comment: Puig. Br J Dermatol 2021; 184:992–993.
掌跖脓疱病患者中的斑片状银屑病 Andersen, Y.M.F.; Augustin, M.; Petersen, J. ...
British journal of dermatology (1951),
November 2019, 20191101, Volume:
181, Issue:
5
Journal Article
Background
The clinical meaningfulness of improvements in the Work Productivity and Activity Impairment Questionnaire for Psoriasis (WPAI‐PsO) reported by patients with psoriasis in response to ...treatment is unknown due to the lack of any publications that report minimal clinically importance differences (MCID) for WPAI‐PsO outcomes.
Objective
To determine the MCIDs for the work productivity loss and activity impairment domains of the Work Productivity and Activity Impairment Questionnaire for Psoriasis (WPAI‐PsO) using results from three Phase 3 trials of ixekizumab.
Methods
MCIDs for WPAI‐PsO domains were derived using treatment agnostic data from patients participating in UNCOVER‐1/‐2/‐3. The analysis included patients randomized to placebo and two ixekizumab treatment groups (ixekizumab either every 2 weeks or 4 weeks) from the trials. WPAI‐PsO was administered at baseline and Week 12 for UNCOVER‐1/‐2/‐3 and at Weeks 24, 36, 52 and 60 in UNCOVER‐1/‐2. MCIDs for the WPAI‐PsO domains through Week 12 were derived using an anchor‐based method supplemented with the distribution‐based method. Anchors included 75%/90%/100% improvement in Psoriasis Area and Severity Index, Static Physicians Global Assessment (sPGA0 and sPGA0,1) and Dermatology Life Quality Index MCID). MCIDs were triangulated using receiver operating characteristics (ROC) and distribution‐based methods.
Results
The analyses included 3126 patients (Placebo: 792, Ixekizumab: 2334). All anchors were shown to be valid. Significant differences in the domains of WPAI‐PsO were observed between patients achieving clinically meaningful improvement in the validated anchors (all P‐values < 0.001). ROC analyses suggested a 20% improvement in the work productivity loss or activity impairment components best represented the benefit of meeting a clinical meaningful improvement in the validated anchors. The distribution‐based method supported the results of the anchor‐based method.
Conclusion
The MCIDs for both the work productivity loss and the activity impairment domains of WPAI‐PsO were estimated to be 20% in patients with PsO.
Linked article: This article is commented on S.M. John, pp. 257–258 in this issue. To view this article visit https://doi.org/10.1111/jdv.15418.
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