The Personalized Acne Treatment Tool - Recommendations to facilitate a patient-centered approach to acne management from the Personalizing Acne: Consensus of Experts

BACKGROUND: Acne, a commonly treated skin disease, requires patient-centered management due to its varying presentations, chronicity, and impact on health-related quality of life. Despite this, evidence-based clinical guidelines focus primarily on clinical severity of facial acne, omitting important patient- and disease-related factors, including ongoing management. OBJECTIVES: To generate recommendations to support patient-centered acne management, which incorporate priority and prognostic factors beyond conventional clinical severity, traditionally defined by grading the appearance and extent of visible lesions. METHODS: The Personalizing Acne: Consensus of Experts consisted of 17 dermatologists who used a modified Delphi approach to reach consensus on statements regarding patient- and treatment-related factors pertaining to patient-centered acne management. Consensus was defined as ≥75% voting agree or strongly agree. RESULTS: Recommendations based on factors such as acne sequelae, location of acne, high burden of disease, and individual patient features were generated and incorporated into the Personalized Acne Treatment Tool. LIMITATIONS: Recommendations are based on expert opinion, which may differ from patients\u27 perspectives. Regional variations in healthcare systems may not be represented. CONCLUSIONS: The Personalizing Acne: Consensus of Experts panel provided practical recommendations to facilitate individualized management of acne, based on patient features, which can be implemented to improve treatment outcomes, adherence, and patient satisfaction

Air quality and error quantity: pollution and performance in a high-skilled, quality-focused occupation

We provide the first evidence that short-term exposure to air pollution affects the work performance of a group of highly-skilled, quality-focused employees. We repeatedly observe the decision-making of individual professional baseball umpires, quasi-randomly assigned to varying air quality across time and space. Unique characteristics of this setting combined with high-frequency data disentangle effects of multiple pollutants and identify previously under-explored acute effects. We find a 1 ppm increase in 3-hour CO causes an 11.5% increase in the propensity of umpires to make incorrect calls and a 10 mg/m3 increase in 12-hour PM2.5 causes a 2.6% increase. We control carefully for a variety of potential confounders and results are supported by robustness and falsification checks

Drug Discovery Using Chemical Systems Biology: Identification of the Protein-Ligand Binding Network To Explain the Side Effects of CETP Inhibitors

Systematic identification of protein-drug interaction networks is crucial to correlate complex modes of drug action to clinical indications. We introduce a novel computational strategy to identify protein-ligand binding profiles on a genome-wide scale and apply it to elucidating the molecular mechanisms associated with the adverse drug effects of Cholesteryl Ester Transfer Protein (CETP) inhibitors. CETP inhibitors are a new class of preventive therapies for the treatment of cardiovascular disease. However, clinical studies indicated that one CETP inhibitor, Torcetrapib, has deadly off-target effects as a result of hypertension, and hence it has been withdrawn from phase III clinical trials. We have identified a panel of off-targets for Torcetrapib and other CETP inhibitors from the human structural genome and map those targets to biological pathways via the literature. The predicted protein-ligand network is consistent with experimental results from multiple sources and reveals that the side-effect of CETP inhibitors is modulated through the combinatorial control of multiple interconnected pathways. Given that combinatorial control is a common phenomenon observed in many biological processes, our findings suggest that adverse drug effects might be minimized by fine-tuning multiple off-target interactions using single or multiple therapies. This work extends the scope of chemogenomics approaches and exemplifies the role that systems biology has in the future of drug discovery

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Colliding Worlds: Asteroid research and the legitimization of war in space

Accepted versio

Comparison of review articles published in peer-reviewed and throwaway journals.

CONTEXT: To compare the quality, presentation, readability, and clinical relevance of review articles published in peer-reviewed and throwaway journals. METHODS: We reviewed articles that focused on the diagnosis or treatment of a medical condition published between January 1 and December 31, 1998, in the 5 leading peer-reviewed general medical journals and high-circulation throwaway journals. Reviewers independently assessed the methodologic and reporting quality, and evaluated each article\u27s presentation and readability. Clinical relevance was evaluated independently by 6 physicians. RESULTS: Of the 394 articles in our sample, 16 (4.1%) were peer-reviewed systematic reviews, 135 (34.3%) were peer-reviewed nonsystematic reviews, and 243 (61.7%) were nonsystematic reviews published in throwaway journals. The mean (SD) quality scores were highest for peer-reviewed articles (0.94 [0.09] for systematic reviews and 0.30 [0.19] for nonsystematic reviews) compared with throwaway journal articles (0.23 [0.03], F(2,391) = 280.8, P\u3c.001). Throwaway journal articles used more tables (P =.02), figures (P =.01), photographs (P\u3c.001), color (P\u3c.001), and larger font sizes (P\u3c.001) compared with peer-reviewed articles. Readability scores were more often in the college or higher range for peer-reviewed journals compared with the throwaway journal articles (104 [77.0%] vs 156 [64.2%]; P =.01). Peer-reviewed article titles were judged less relevant to clinical practice than throwaway journal article titles (P\u3c.001). CONCLUSIONS: Although lower in methodologic and reporting quality, review articles published in throwaway journals have characteristics that appeal to physician readers

33463 Pooled efficacy and safety results from the DERMIS-1 and DERMIS-2 phase 3 trials of once-daily roflumilast cream 0.3% by baseline body surface area

Roflumilast cream 0.3% is a selective and potent phosphodiesterase-4 inhibitor under investigation as a once-daily treatment for psoriasis. Here we describe pooled efficacy and safety results from 2 identical phase 3 randomized controlled trials of roflumilast cream (DERMIS-1: NCT04211363 and DERMIS-2: NCT04211389) analyzed by baseline body surface area (BSA) affected ( 10%). Patients (≥2 years) with psoriasis involving 2-20% BSA were randomized to roflumilast (n = 576) or vehicle (n = 305) for 8 weeks. Overall, significantly more roflumilast- vs. vehicle-treated patients achieved the primary efficacy endpoint of Investigator Global Assessment (IGA) Success (Clear or Almost Clear IGA status plus ≥2-grade improvement from baseline) at Week 8 (39.9% vs. 6.5%; P \u3c.0001). More roflumilast-treated patients achieved IGA Success at Week 8 with generally consistent rates (36.5%-46.7% with roflumilast vs. 1.8%-8.5% with vehicle) across all BSA categories (P \u3c.0001 for all). Differences favoring roflumilast were also observed for percentages achieving 75% reduction in Psoriasis Area Severity Index (38.1%-47.8% with roflumilast vs. 1.8%-9.4% with vehicle) across all BSA categories. Percentages with baseline Worst Itch-Numeric Rating Scale ≥4 achieving a 4-point reduction favored roflumilast (P ≤.0001 for all BSA subgroups). Overall incidence of treatment-emergent adverse events (TEAE), serious adverse events, and TEAEs leading to discontinuation were low with similar rates between roflumilast and vehicle. Local tolerability was highly favorable on patient and investigator assessments. Once-daily roflumilast cream 0.3% provided superior improvement across multiple efficacy endpoints and favorable safety and tolerability in patients with psoriasis in 2 phase 3 trials regardless of BSA affected