Sociodemographic and clinical characteristics associated with multiple biologic failure in psoriasis: A 2015-2022 prospective cohort analysis of the CorEvitas psoriasis registry.

BACKGROUND: Psoriasis patients with poor therapeutic response to multiple biologic agents are not well-characterized. OBJECTIVE: To describe the characteristics associated with development of multiple biologic failure (MBF) versus good clinical response (GR) to the first biologic. METHODS: This prospective cohort analysis evaluated patients in the multicenter CorEvitas Psoriasis Registry who initiated their first biologic between 2015 and 2020 and were followed for ≥24 months. Multivariable logistic regression identified sociodemographic, clinical, and patient-reported outcomes that differed between MBF (discontinued ≥2 biologics of different classes, each used for ≥90 days, due to inadequate efficacy) and GR (continued use of first biologic for ≥2 years) patients. RESULTS: One thousand thirty-nine patients were analyzed (490 GR [47.2%], 65 MBF [6.3%]). Female sex, shorter psoriasis duration, earlier year of biologic initiation, prior nonbiologic systemic therapy use, history of hyperlipidemia, and Medicaid insurance were significantly associated with MBF, though the latter 2 variables exhibited wider confidence intervals, indicating a lower level of support. The first-to-second biologic sequence most observed with MBF was Tumor necrosis factor-α inhibitor to IL-17 inhibitor use. LIMITATIONS: Biologic adherence between visits was not evaluated. CONCLUSION: Approximately 6% of psoriasis patients met MBF criteria. The results identify characteristics associated with MBF that may distinguish patients warranting more frequent follow-up.

Comparative Efficacy and Safety of Biological Agents in the Treatment of Lupus Nephritis: A Network Meta-Analysis.

BACKGROUND: To date, no studies have described randomized controlled trials (RCTs) evaluating the effectiveness and safety of various biological agents used in induction therapy for lupus nephritis. OBJECTIVES: We designed this study to assess the relative efficacy and safety of some of these biological agents in patients with lupus nephritis. METHOD: We collected data from RCTs that examined the efficacy and safety of any biological agents for lupus nephritis and then used these data to complete a Bayesian network meta-analysis to combine the direct and indirect evidence from these studies. RESULTS: We identified nine RCTs evaluating rituximab, abatacept, belimumab, anifrolumab, obinutuzumab, ocrelizumab, and low-dose interleukin-2 (IL-2) across 1,480 patients. Low-dose IL-2, obinutuzumab, rituximab, and belimumab achieved complete remission in a significant proportion of respondents when compared with that in the control. Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that low-dose IL-2 had the highest probability of achieving complete remission, followed by obinutuzumab, rituximab, belimumab, anifrolumab, abatacept, ocrelizumab, and the control. The risk of serious adverse events (SAE) tended to be lower for low-dose IL-2, rituximab, belimumab, and obinutuzumab than for the control. SUCRA-based ranking indicated that IL-2 had the highest probability of being safe, followed by rituximab, belimumab, obinutuzumab, control, anifrolumab, abatacept, and ocrelizumab. CONCLUSIONS: Low-dose IL-2 was the most effective induction treatment for patients with lupus nephritis and had the lowest potential for SAE. Higher complete remission rates and a more favorable safety profile suggest that low-dose IL-2, obinutuzumab, rituximab, and belimumab may be superior to the current control as treatments for lupus nephritis.

Perspectives on current and emerging therapies for immunoglobulin G4-related disease.

Understanding of the pathophysiology of immunoglobulin G4-related disease (IgG4-RD) over the last dozen years has opened the door to a variety of targeted treatment approaches. Glucocorticoids are an effective treatment for IgG4-RD if used at a sufficiently high dose, but disease flares are common during or after glucocorticoid tapers and these medications seldom lead to long-term, treatment-free remissions. Moreover, their long-term use in a disease that frequently affects middle-aged to elderly individuals and often causes major pancreatic damage leads to a narrow therapeutic index. Biological therapies offer the possibility of effective disease control with fewer treatment-associated side effects. Promising avenues of investigation include B-cell depletion, immunomodulation of B-cell subsets, interference with co-stimulation, Bruton's tyrosine kinase inhibition, and Signaling lymphocytic activation molecule F7-directed treatment.

Decontamination efficacy of common liquid disinfectants against non-spore-forming biological agents in soil matrices.

AIMS: The purpose of this study was to evaluate decontamination efficacy, within three soil types, against Yersinia pestis, Burkholderia pseudomallei, and the Venezuelan Equine Encephalitis virus (VEEV). METHODS AND RESULTS: One of three liquid disinfectants (dilute bleach, Virkon-S or Klozur One) was added to three soil types (sand, loam, or clay) and allowed contact for four pre-spike durations: 0, 15, 30 and 60 min. Y. pestis, B. pseudomallei, or VEEV was then spiked into the soil (10 microliters or approx. 1 × 107  CFU or PFU into 1 g soil) and decontamination efficacy assessed at post-spike contact times of 10 or 60 min at ambient environmental conditions. Across all soil types, sandy soil resulted in the least quenching to all three disinfectants tested as shown by sustained decontamination efficacy across all pre-spike and post-spike timepoints. Clay and loam soil types exhibited quenching effects on the hypochlorite and peroxygen based disinfectants (dilute bleach and Virkon S) and in general resulted in decreased efficacy with increased pre-spike contact time. The sodium persulfate (Klozur One) performance was the most consistent across all soil types and pre-spike contact times, resulting in greater efficacy with increased post-spike time. CONCLUSIONS: Liquid disinfectants can provide high levels of decontamination in soil for both viral and non-spore-forming bacterial select agents. Hypochlorite and peroxygen based disinfectants used in soils containing higher organic content (loam or clay) may require extended contact times or re-application of liquid disinfectant, in as little as 15 min of application, to achieve a 6-log reduction. SIGNIFICANCE AND IMPACT OF THE STUDY: These results provide information for the performance of three disinfectants in soil against non-spore-forming select agents. These data may aid response decision makers following a biological contamination incident by informing the selection of disinfectant as well as the re-application time to achieve effective site remediation.

Comprehensive risk analysis of postoperative complications in patients with rheumatoid arthritis for the 2020 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis.

OBJECTIVES: To examine the risk factors of surgical site infection (SSI), delayed wound healing, and death after orthopedic surgery in patients with rheumatoid arthritis (RA). METHODS: We identified articles indexed in the Cochrane Library, PubMed, and Japan Centra Revuo Medicina Web published from 2013 to 2019 and other articles. Articles fulfilling the predefined inclusion criteria were reviewed systematically and their quality was appraised according to the Grading of Recommendations Assessment, Development, and Evaluation system with some modifications. RESULTS: After inclusion and exclusion by full-text review, 29 articles were analyzed. Use of biological disease modifying antirheumatic drugs was a risk factor of SSI (risk ratio 1.66, 95% confidence interval 1.25-2.19), but not of delayed wound healing. RA itself was a risk factor of SSI, and oral glucocorticoid use was a risk factor of SSI in three of the four studies analyzed and of postoperative death. Age, male sex, comorbidities such as diabetes mellitus and chronic obstructive pulmonary disease, surgical factors such as foot/ankle and spine surgery and longer operative time were risk factors of those postoperative complications. CONCLUSION: Patients with those factors should be dealt with appropriate cautions to strike a risk-benefit balance of orthopedic surgeries.

Awareness of Complications of Dental Treatment in Patients Treated with Drugs Affecting the Immune System : A Nationwide Questionnaire Survey of Dental Practitioners in Japan.

The aim of this study was to investigate the awareness and experience, among dental practitioners, of adverse events resulting from dental treatment of patients undergoing therapy with drugs that affect the immune system [angiogenesis inhibitors, biological agents, immunosuppressants, and disease-modifying anti-rheumatic drugs (DMARDs)]. For this purpose, a nationwide questionnaire survey was conducted. Questionnaires were sent to 2,050 dentists, of which 206 (10.1%) were completed and returned. The results showed that most dentists were aware of complications associated with dental treatment of patients treated with drugs that affect the immune system, and about half had actually experienced such complications. Delayed wound healing, osteonecrosis of the jaw (ONJ), and postoperative infections were reported. Whereas approximately 50% of dentists did not discontinue the drugs during dental treatment, about 18% did. During temporary drug discontinuation, some patients experienced aggravation of the primary disease, such as worsening of rheumatism, growth of tumors, and rejection reactions of transplanted organs. As for medical cooperation, only less than half of the dentists were asked for oral hygiene management by a physician prior to starting the drug treatment. Prospective studies are needed because evidence for dental treatments in patients treated with these drugs remains limited.

Microbiome characterization and re-design by biologic agents for inflammatory bowel disease insights.

The therapeutic effect of inflammatory bowel disease has improved in the past decades, but most of patients cannot tolerate, do not respond to drugs, or relapse after treating with conventional therapy. Therefore, new and more effective treatment methods are still needed in treatment of IBD. In this review, we will discuss the relevant mechanisms and the latest research progress of biologics (anti-TNF treatments, interleukin inhibitors, integrin inhibitors, antisense oligonucleotide, and JAK inhibitors) for IBD, focus on the efficacy and safety of drugs for moderate-to-severe IBD, and summarize the clinical status and future development direction of biologics in IBD.

Bayesian optimization design for dose-finding based on toxicity and efficacy outcomes in phase I/II clinical trials.

In phase I trials, the main goal is to identify a maximum tolerated dose under an assumption of monotonicity in dose-response relationships. On the other hand, such monotonicity is no longer applied to biologic agents because a different mode of action from that of cytotoxic agents potentially draws unimodal or flat dose-efficacy curves. Therefore, biologic agents require an optimal dose that provides a sufficient efficacy rate under an acceptable toxicity rate instead of a maximum tolerated dose. Many trials incorporate both toxicity and efficacy data, and drugs with a variety of modes of actions are increasingly being developed; thus, optimal dose estimation designs have been receiving increased attention. Although numerous authors have introduced parametric model-based designs, it is not always appropriate to apply strong assumptions in dose-response relationships. We propose a new design based on a Bayesian optimization framework for identifying optimal doses for biologic agents in phase I/II trials. Our proposed design models dose-response relationships via nonparametric models utilizing a Gaussian process prior, and the uncertainty of estimates is considered in the dose selection process. We compared the operating characteristics of our proposed design against those of three other designs through simulation studies. These include an expansion of Bayesian optimal interval design, the parametric model-based EffTox design, and the isotonic design. In simulations, our proposed design performed well and provided results that were more stable than those from the other designs, in terms of the accuracy of optimal dose estimations and the percentage of correct recommendations.

Evaluation of altered environmental conditions as a decontamination approach for nonspore-forming biological agents.

AIMS: The purpose of this study was to evaluate the effects of altered environmental conditions on the persistence of Francisella tularensis bacteria and Venezuelan equine encephalitis virus (VEEV), on two material types. METHODS AND RESULTS: Francisella tularensis (F.t.) and VEEV were inoculated (c. 1 × 108 colony-forming units or PFU), dried onto porous and nonporous fomites (glass and paper), and exposed to combinations of altered environmental conditions ranging from 22 to 60°C and 30 to 75% relative humidity (RH). Viability of test organism was assessed after contact times ranging from 30 min to 10 days. Inactivation rates of F.t. and VEEV increased as both temperature and/or RH were increased. Greater efficacy was observed for paper as compared to glass for both test organisms. CONCLUSIONS: The use of elevated temperature and RH increased rate of inactivation for both organisms and greater than six log reduction was accomplished in as little as 6 h by elevating temperature to approximately 60°C. SIGNIFICANCE AND IMPACT OF THE STUDY: These results provide information for inactivation of nonspore-forming select agents using elevated temperature and humidity which may aid incident commanders following a biological contamination incident by providing alternative methods for remediation.

Microencapsulation of Bacillus megaterium NCT-2 and its effect on remediation of secondary salinization soil.

Aim: To prolong the shelf life of Bacillus megaterium NCT-2 by preparing microcapsules through spray drying, and evaluate their efficiency in secondary salinisation soil remediation.Methods: The wall material and spray drying conditions were optimised. Morphological characteristics of microcapsule were measured, and soil remediation effects were tested under field conditions.Results: A relatively higher survival rate of B. megaterium microcapsule was obtained with 1:1 of chitosan/maltodextrin (w/w) when spray drying was performed at 150.0 °C, with the feed flow rates of 800 mL h-1 and 1000 mL h-1, respectively. The span value of 0.93 ± 0.01 was obtained under above conditions. Microcapsule survival rate was 64.09 ± 0.12% after 6 months of storage. Moreover, microcapsule successfully decreased NO3- and EC value in strongly saline soil by 46.5 ± 1.48% and 45.2 ± 1.51%, respectively.Conclusion: Bacillus megaterium NCT-2 microcapsules have application potential in the remediation of secondary salinisation soil.

Frateuria defendens sp. nov., bacterium isolated from the yellows grapevine's disease vector Hyalesthes obsoletus.

A Dyella-like bacterium was previously isolated from the planthopper Hyalesthes obsoletus (Hemiptera). Based on its 16S rRNA gene sequence, strain DHoT was assigned to the family Rhodanobacteraceae with Dyella and Frateuria as its closest relatives. The closest 16S rRNA gene sequences were Frateuria aurantia DSM 6220T (98.2 %), Dyella thiooxydans ATSB10T (98 %), Dyella terrae JS14-6T (97.8 %) and Dyella marensis CS5-B2T (97.8 %). Strain DHoT is a Gram-negative, aerobic, motile, yellow-pigmented, rod-shaped bacterium. Strain DHoT cells grew well at 28-30 °C and at pH 6.5-7.5 on a nutrient agar plate. DNA-DNA hybridization showed that the relatedness between strain DHoT and D. jiangningensis strain SBZ3-12T, and F. aurantia DSM 6220T was 42.7 and 42.6 %, respectively. Ubiquinone Q-8 was the predominant respiratory quinone, and the major fatty acids (>10 %) were iso-C15 : 0, iso-C16 : 0 and iso-C17 : 0. In silico analysis based on phylogenetics and sequence identity at the nucleotide and protein levels suggests that Frateuria is the closest known relative of strain DHoT. Based on the phenotypic, chemotaxonomic and phylogenetic data, strain DHoT was designated as a novel species of the genus Frateuria, for which the name Frateuria defendens sp. nov. is proposed. The type strain is DHoT (=NCCB 100648T; =DLBT=DSM 106169T).

Changing biological disease modifying treatment for paediatric uveitis in the real world.

IMPORTANCE: Paediatric uveitis is a severe sight-threatening uveitis due to disease progression and treatment failure. Biological agents are a promising new treatment. This study provides real-world data on their use from Sydney, Australia. BACKGROUND: Traditionally corticosteroids and non-biological immunosuppressive agents were used to treat paediatric uveitis, often with poor outcomes. DESIGN: Retrospective, chart review over an 8-year period at a tertiary referral eye hospital. PARTICIPANTS: A total of 27 paediatric uveitis patients treated with biological agents. METHODS: Chart review of demographic data and treatment outcomes. MAIN OUTCOME MEASURES: Treatment efficacy (corticosteroid-sparing effect, topical steroid cessation/reduction, reduction in systemic-steroid sparing agents, change in intraocular inflammation, visual acuity and central macular thickness); treatment failure; and adverse events. Data were collected at biological initiation, 6 weeks, 6 months and 12 months. RESULTS: Biological therapy over 1 year was effective with prednisolone dose reduced to <5 mg/day in five of six patients (83%), number of systemic steroid-sparing agents was reduced to ≤1 in two of four patients (50%) and cessation of topical steroid achieved in 12/41 of eyes (29%). Improvement of anterior chamber cells by two grades occurred in 20/25 eyes (80%), improvement of logMAR to ≤0.3 occurred in 12/18 eyes (67%) and macular oedema decreased in 4/5 eyes (80%). Treatment failure occurred in six eyes (13.01%) and five patients (18.5%) developed an adverse reaction. CONCLUSIONS AND RELEVANCE: Biological therapy was effective in paediatric patients with uveitis. Intraocular inflammation improved with maintained visual acuity, systemic corticosteroid dose decreased and there was a low frequency of adverse events.

The Use of Platelet-Rich Plasma in Aesthetic and Regenerative Medicine: A Comprehensive Review.

INTRODUCTION: In recent years, platelet-rich plasma (PRP) has emerged as a promising autologous biological treatment modality for the use in aesthetic and regenerative medicine. PRP is a high concentration of platelets derived from whole blood which is isolated by centrifugation to separate and concentrate platelet-containing plasma from red blood cells. PRP comprises hundreds of bioactive proteins, including growth factors, peptides, and cytokines that stimulate healing of skin and soft tissues. Attractive features of PRP are the extended release of various growth and differentiation factors from activated platelets, tissue regenerative, and healing capabilities, as well as the lack of problems associated with immunogenicity. Because of the unique biological features of this whole blood-derived biological agent, multiple clinical uses for PRP exist for aesthetic and regenerative medicine. EVIDENCE ACQUISITIONS: A comprehensive review of the literature regarding the use of platelet-rich plasma in aesthetic and regenerative medicine was performed. EVIDENCE SYNTHESIS: Therapeutic applications of PRP including several methods for its clinical deployment in conditions related to aesthetic and regenerative medicine including wound healing, skin and facial rejuvenation, hair restoration, hand rejuvenation, breast augmentation, and musculoskeletal regeneration were reviewed. CONCLUSION: PRP treatment has shown itself as a bright future for a safe and efficient cosmetic intervention. However, more studies are needed to better our understanding of limitations and benefits in clinical phases associated with the aesthetic use of PRP. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

A review of the design and modification of lactoferricins and their derivatives.

Lactoferricin (Lfcin), a multifunction short peptide with a length of 25 residues, is derived from the whey protein lactoferrin by acidic pepsin hydrolysis. It has potent nutritional enhancement, antimicrobial, anticancer, antiviral, antiparasitic, and anti-inflammatory activities. This review describes the research advantages of the above biological functions, with attention to the molecular design and modification of Lfcin. In this examination of design and modification studies, research on the identification of Lfcin active derivatives and crucial amino acid residues is also reviewed. Many strategies for Lfcin optimization have been studied in recent decades, but we mainly introduce chemical modification, cyclization, chimera and polymerization of this peptide. Modifications such as incorporation of D-amino acids, acetylation and/or amidation could effectively improve the activity and stability of these compounds. Due to their wide array of bio-functions and applications, Lfcins have great potential to be developed as biological agents with multiple functions involved with nutritional enhancement, as well as disease preventive and therapeutic effects.

Inactivation of Burkholderia pseudomallei on environmental surfaces using spray-applied, common liquid disinfectants.

UNLABELLED: Five commercially available liquid antimicrobials were evaluated for their ability to decontaminate common environmental surface materials, contaminated with Burkholderia pseudomallei, using a spray-based disinfectant delivery procedure. Tests were conducted at both an ambient temperature (c. 20°C) and a lower temperature (c. 12°C) condition. Nonporous materials (glass and aluminium) were more easily decontaminated than porous materials (wood, concrete and carpet). Citric acid (1%) demonstrated poor efficacy in all test conditions. Bleach (pH-adjusted), ethanol (70%), quaternary ammonium and PineSol®, demonstrated high (>6 log10 reduction) efficacies on glass and aluminium at both temperatures, but achieved varying results for wood, carpet and concrete. Temperature had minimal effect on decontamination efficacy during these tests. SIGNIFICANCE AND IMPACT OF THE STUDY: Much of the antimicrobial efficacy data for pathogenic micro-organisms are generated with testing that utilizes hard nonporous surface materials. These data are not directly translatable for decontaminant selection following an incident whereby complex and porous environmental surfaces are contaminated. This study presents efficacy data for spray-applied antimicrobial liquids, when used to decontaminate common environmental surfaces contaminated with Burkholderia pseudomallei. These data can help responders develop effective remediation strategies following an environmental contamination incident involving B. pseudomallei.

Postoperative complications in patients with rheumatoid arthritis using a biological agent - A systematic review and meta-analysis.

OBJECTIVES: To evaluate, through a systematic review of the literature, the association between the use of biological disease-modifying antirheumatic drugs (bDMARDs) and surgical site infection (SSI) or wound healing delay after orthopedic surgery in patients with rheumatoid arthritis (RA). METHODS: A systematic review of articles indexed in the Cochrane Library, PubMed, and Web of Science from 1992 to 2012 was performed. The search aimed to identify studies describing SSI or wound healing delay in patients with RA treated with or without bDMARDs. Articles fulfilling the predefined inclusion criteria were reviewed systematically and their quality was appraised. RESULTS: There was no Cochrane review on this subject. We found 75 articles through specific searches of PubMed and Web of Science, and hand searching. After inclusion and exclusion by full-text review, 10 articles were found for SSI, and 5 articles for delayed wound healing. The use of bDMARDs appeared to increase the rate of SSI slightly, especially in large joint-replacement surgery. Delayed wound healing was not increased by the use of bDMARDs. However, the definitions of SSI and delayed wound healing varied between the reviewed articles. Most of the articles focused on tumor necrosis factor-α inhibitors. CONCLUSION: bDMARDs slightly increase the relative risk of SSI but not that of delayed wound healing after orthopedic surgery and should be used with appropriate caution.

Clinical features and predictors of clinical outcomes in Korean patients with Crohn's disease: a Korean association for the study of intestinal diseases multicenter study.

BACKGROUND AND AIM: Although differences in genetic susceptibility and the clinical features of Crohn's disease (CD) have been reported between Asian and Caucasian patients, the disease course and predictors of CD in Asians remains poorly defined. The study therefore aimed to investigate factors predictive of the clinical outcomes of patients with CD in a Korean population. METHODS: This retrospective multicenter cohort study included 728 Korean CD patients from 13 university hospitals. The first CD-related surgery or need for immunosuppressive or biological agents were regarded as the clinical outcomes of interest. RESULTS: A total of 126 (17.3%) CD patients underwent CD-related surgery, while 473 (65.0%) and 196 (26.9%) were prescribed thiopurine drugs and infliximab, respectively. Multivariate Cox regression analysis identified current (hazard ratio [HR] = 1.86; P = 0.018) and former smoking habits (HR = 1.78; P = 0.049), stricturing (HR = 2.24; P < 0.001), and penetrating disease behavior at diagnosis (HR = 3.07; P < 0.001) as independent predictors associated with the first CD-related surgery. With respect to immunosuppressive and biological agents, younger age (< 40 years) (HR = 2.17; P < 0.001 and HR = 2.10; P = 0.006, respectively), ileal involvement (HR = 1.36; P = 0.035 and HR = 2.17; P = 0.006, respectively), and perianal disease (HR = 1.42; P = 0.001 and HR = 1.38; P = 0.038, respectively) at diagnosis were significant predictors for the need of these medications. CONCLUSIONS: In Korean patients with CD, stricturing, penetrating disease behavior, and smoking habits at the time of diagnosis are independent predictors for CD-related surgery. It was also identified that younger age (< 40 years), ileal involvement, and perianal disease at diagnosis are predictive of a need for immunosuppressive or biological agents.

Efficacy of sporicidal wipes for inactivation of a Bacillus anthracis surrogate.

AIMS: To evaluate five commercially available sporicidal wipes and two disinfecting wipes for their ability to inactivate Bacillus atrophaeus spores deposited onto various material surfaces. METHODS AND RESULTS: Decontamination efficacy of the wipes was initially tested on glass Petri dishes (150 mm diameter). Following exposure for a specified time of contact, survival of the spores was assessed by quantification of the remaining viable spores, both on the coupon surface and on the towelette itself, with efficacy quantified in terms of mean log reduction. Based on these data, five wipes were down-selected for evaluation on a larger scale, using 36 × 36 cm coupons of five different material types. CONCLUSIONS: Results suggest that sodium hypochlorite-based sporicidal wipes were most effective, having completely inactivated the Bacillus spores on the glass Petri dish and several materials. Additionally, results demonstrate that the manufacturer-prescribed contact times for Clostridium difficile achieved a 6 log10 reduction of B. atrophaeus spores. Moreover, commercially available disinfecting wipes were not able to kill Bacillus spores as evaluated. SIGNIFICANCE AND IMPACT OF THE STUDY: These data show the potential of sporicidal wipes for decontamination of small, contained areas of biological contamination and may help on-scene coordinators develop remediation plans following a biological terrorism event.

Fumigation of a laboratory-scale HVAC system with hydrogen peroxide for decontamination following a biological contamination incident.

AIMS: To evaluate hydrogen peroxide vapour (H2 O2 ) for its ability to inactivate Bacillus spores within a laboratory-scale heating, ventilation and air-conditioning (HVAC) duct system. METHODS AND RESULTS: Experiments were conducted in a closed-loop duct system, constructed of either internally lined or unlined galvanized metal. Bacterial spores were aerosol-deposited onto 18-mm-diameter test material coupons and strategically placed at several locations within the duct environment. Various concentrations of H2 O2 and exposure times were evaluated to determine the sporicidal efficacy and minimum exposure needed for decontamination. For the unlined duct, high variability was observed in the recovery of spores between sample locations, likely due to complex, unpredictable flow patterns within the ducts. In comparison, the lined duct exhibited a significant desorption of the H2 O2 following the fumigant dwell period and thus resulted in complete decontamination at all sampling locations. CONCLUSIONS: These findings suggest that decontamination of Bacillus spore-contaminated unlined HVAC ducts by hydrogen peroxide fumigation may require more stringent conditions (higher concentrations, longer dwell duration) than internally insulated ductwork. SIGNIFICANCE AND IMPACT OF THE STUDY: These data may help emergency responders when developing remediation plans during building decontamination.

Efficacy of anti-interleukin-17A biological agents for palmoplantar psoriasis and palmoplantar pustulosis: A network meta-analysis.

BACKGROUND: The comparative efficacy of anti-IL (interleukin)-17A biological agents in palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP) are not well established. OBJECTIVE: To investigate the efficacy of different dosage regimens of anti-IL-17A biological agents compared with placebo in PP and PPP. METHODS: A literature search was conducted in PubMed, clinicaltrials.gov, and Embase. Meta-analysis was performed for all outcomes of randomized controlled trials, while network meta-analysis was only performed for the primary outcome. RESULTS: In total, 21 articles exploring the efficacy of 5 treatment options were included, 4 cohort studies were also reviewed. Meta-analysis demonstrated a statistically significant difference favoring anti-IL-17A biological agents versus placebo (OR = 6.84, 95 %[CI] [5.34, 8.76]). On-label secukinumab was identified as the most effective treatment option for patients with PP (OR = 33.50, 95 %[CI] [4.37,256.86]). PPP treated with secukinumab 300 mg showed benefit in terms of PPPASI 75 responses over 52 weeks. CONCLUSION: IL-17A biological agents had better PP disease clearance compared with placebo and on-label secukinumab was identified as the most effective treatment option for PP patients. Secukinumab 300 mg showed benefit for PPP patients.