Genome-Wide Association Analysis of Neonatal White Matter Microstructure.

A better understanding of genetic influences on early white matter development could significantly advance our understanding of neurological and psychiatric conditions characterized by altered integrity of axonal pathways. We conducted a genome-wide association study (GWAS) of diffusion tensor imaging (DTI) phenotypes in 471 neonates. We used a hierarchical functional principal regression model (HFPRM) to perform joint analysis of 44 fiber bundles. HFPRM revealed a latent measure of white matter microstructure that explained approximately 50% of variation in our tractography-based measures and accounted for a large proportion of heritable variation in each individual bundle. An intronic SNP in PSMF1 on chromosome 20 exceeded the conventional GWAS threshold of 5 x 10-8 (p = 4.61 x 10-8). Additional loci nearing genome-wide significance were located near genes with known roles in axon growth and guidance, fasciculation, and myelination.

Reducing greenhouse gas emissions through genetic selection in the Australian dairy industry.

This research explores possible options to reduce greenhouse gas (GHG) emissions in the Australian dairy industry by (1) including an environmental component in the national breeding program and (2) estimating the economic and environmental impacts of implementation of the subsequent indexes. A total of 12 possible selection indexes were considered. These indexes were developed to predict changes in gross per-animal methane production (using 3 scenarios depending on availability and efficacy of a direct methane trait breeding value prediction) with 4 different carbon prices, integrating them into an augmentation of the current conventional national selection index. Although some economic response is lost with inclusion of the GHG subindexes in the Balanced Performance Index, options do exist where this loss is marginal and, even in scenarios where all selection pressure is based on the environmental weighting, economic progress is still made in all cases. When including environmental traits within an index, if a relatively low percentage of economic gain or index progression is sacrificed, then approximately 40 to 50% of the maximum possible reductions in emissions may be achieved. This concurrent selection of estimated breeding values that have a correlated favorable response in emissions in addition to direct selection on a residual methane trait allows a high level of methane reduction to be achieved with a realized cost to farmers that is far lower than the economic value placed on carbon. By implementing a GHG subindex in the national breeding program, we can achieve up to a 7.9% decrease in residual methane and 9 times the reduction in gross emissions in 10 yr, compared with the current breeding program, with little to no cost to farmers. By 2050, selection based on one of the more moderate index scenarios at a carbon price of AUD$250/t (AUD$1 = US$0.71), or opportunity cost to farmers of AUD$87.22, will reduce gross emissions by 8.23% and emissions intensity by 21.25%, therefore offering a mitigation strategy that will be effective at reducing emissions with little compromise to profit.

A head-to-head comparison of ixekizumab vs. guselkumab in patients with moderate-to-severe plaque psoriasis: 24-week efficacy and safety results from a randomized, double-blinded trial.

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.

Theoretical and experimental study of peroxy and alkoxy radicals in the NO3-initiated oxidation of isoprene.

The initial stages of the nitrate radical (NO3) initiated oxidation of isoprene, in particular the fate of the peroxy (RO2) and alkoxy (RO) radicals, are examined by an extensive set of quantum chemical and theoretical kinetic calculations. It is shown that the oxidation mechanism is highly complex, and bears similarities to its OH-initiated oxidation mechanism as studied intensively over the last decade. The nascent nitrated RO2 radicals can interconvert by successive O2 addition/elimination reactions, and potentially have access to a wide range of unimolecular reactions with rate coefficients as high as 35 s-1; the contribution of this chemistry could not be ascertained experimentally. The chemistry of the alkoxy radicals derived from these peroxy radicals is affected by the nitrate moiety, and can lead to the formation of nitrated epoxy peroxy radicals in competition with isomerisation and decomposition channels that terminate the organic radical chain by NO2 elimination. The theoretical predictions are implemented in the FZJ-NO3-isoprene mechanism for NO3-initiated atmospheric oxidation of isoprene. The model predictions are compared against peroxy radical (RO2) and methyl vinyl ketone (MVK) measurements in a set of experiments on the isoprene + NO3 reaction system performed in the SAPHIR environmental chamber (IsopNO3 campaign). It is shown that the formation of NO2 from the peroxy radicals can prevent a large fraction of the peroxy radicals from being measured by the laser-induced fluorescence (ROxLIF) technique that relies on a quantitative conversion of peroxy radicals to hydroxyl radicals. Accounting for the relative conversion efficiency of RO2 species in the experiments, the agreement between observations and the theory-based FZJ-NO3-isoprene model predictions improves significantly. In addition, MVK formation in the NO3-initiated oxidation was found to be suppressed by the epoxidation of the unsaturated RO radical intermediates, allowing the model-predicted MVK concentrations to be in good agreement with the measurements. The FZJ-NO3-isoprene mechanism is compared against the MCM v3.3.1 and Wennberg et al. (2018) mechanisms.

Altered Brain Structure in Infants with Turner Syndrome.

Turner syndrome (TS) is a genetic disorder affecting approximately 1:2000 live-born females. It results from partial or complete X monosomy and is associated with a range of clinical issues including a unique cognitive profile and increased risk for certain behavioral problems. Structural neuroimaging studies in adolescents, adults, and older children with TS have revealed altered neuroanatomy but are unable to identify when in development differences arise. In addition, older children and adults have often been exposed to years of growth hormone and/or exogenous estrogen therapy with potential implications for neurodevelopment. The study presented here is the first to test whether brain structure is altered in infants with TS. Twenty-six infants with TS received high-resolution structural MRI scans of the brain at 1 year of age and were compared to 47 typically developing female and 39 typically developing male infants. Results indicate that the typical neuroanatomical profile seen in older individuals with TS, characterized by decreased gray matter volumes in premotor, somatosensory, and parietal-occipital cortex, is already present at 1 year of age, suggesting a stable phenotype with origins in the prenatal or early postnatal period.

The Lumbricals Are Not the Workhorse of Digital Extension and Do Not Relax Their Own Antagonist.

That the lumbrical muscles are the workhorse of digital extension and that they can relax their own antagonist have been time-honored principles. However, we believe this dogma is incorrect and an oversimplification. We base our assertion on anatomy, innervation, and the notion that muscle architecture is the most important determinant of muscle function. Wang and colleagues proposed the lumbrical to be a sophisticated tension monitoring device. We elaborate on their well-supported thesis, further proposing that the lumbricals also function as a constant tension spring within the closed loop composed of the digital flexors and the extensor mechanism.

Facial Rejuvenation With Fat Grafting and Fillers.

Facial rejuvenation requires a multi-modality approach to address the sun damage, volume loss, and thinning of skin that occurs with aging. With age, the collagen fibrils that provide strength become fragmented and fibroblasts connections become weak, leading to skin laxity and loss of youthful skin. Fillers can lead to a more youthful appearance by providing volumetric support. Synthetic fillers such as hyaluronic acid products, calcium hydroxyapatite, polylactic acid, and polymethylmethacralate have bio-stimulatory affects, ranging from small effects on fibroblast production to prolonged stimulatory effects on dermal thickness and blood supply. Fat grafting is also an ideal technique for facial rejuvenation because it is readily available, natural, and has regenerative effects. This review describes a new technique of fat grafting for the face called Injectable Tissue Replacement and Regeneration that specifically addresses the different anatomic compartments of the face with volume loss. With this brief review, we aim to evaluate the currents trends of fat grafting and fillers in the management of facial rejuvenation, including the cellular changes that occur with facial aging, the bio-stimulatory effects of fillers, and the anatomic replacement of tissue with fat grafting. >Level of Evidence: 4.

Baseline patient-reported outcomes from UNITE: an observational, international, multicentre registry to evaluate hidradenitis suppurativa in clinical practice.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory, skin condition associated with many comorbidities and often has a substantial impact on patients' lives. OBJECTIVES: To evaluate symptom burden and health-related quality of life (HRQoL) at baseline in patients with HS in an observational, real-world, clinical setting using several tools including a validated HS-specific instrument. METHODS: This study evaluated HRQoL data from the international UNITE HS disease registry. Administration of patient-reported outcome (PRO) instruments and collection of data were executed per local regulations. All data were assessed using descriptive statistical methods. RESULTS: PRO data from 529 adults and 65 adolescents were evaluated. Most adults (64.5%) and adolescents (73.8%) were classified as Hurley Stage II with substantial disease burden at baseline. HS had a large effect (mean DLQI = 12.6) and moderate effect (mean CDLQI = 6.9) on the lives of adults and adolescents, respectively. Approximately 58% of adults and 41% of adolescents had anxiety scores beyond the normal range; 30% of adults and 16% of adolescents exhibited symptoms of depression. Based on HSSA and HSIA scores, approximately 30% of adults reported a substantial burden of multiple HS clinical symptoms and more than 45% reported a significant emotional impact of HS that adversely affected their intimate relationships. Only 60% of adults were employed and of those, 64% reported at least some degree of impairment while working because of HS. CONCLUSIONS: Based on PROs collected from patients enrolled in the UNITE registry, a real-world, clinical setting, HS has a significant negative impact on the everyday lives of patients affected by this disease.

Improvements in Clinical Outcomes in Children with Cystic Fibrosis aged Six and 16 years.

Aims Our aim was to assess if outcomes for cystic fibrosis (CF) patients at six & sixteen years of age have improved in the last 17 years looking at FEV1, BMI and death. Methods A retrospective observational study using a prospectively maintained database of CF patients at Cork University Hospital. Results 84 patients were included in the 16-year-old data and 89 patients were included in the six-year-old data. The mean FEV1 and BMI (16 years) for the 2002-2007 group was 72.9±21.0% and 18.9±2.53 respectively, 2008-2013 group was 75.4±27.2% and 19.8±2.7 and for the 2014-2018 group was 95.2±16.0% and 22.9±4.1. The percentage of patients (16 years) with chronic pseudomonas status was 37.9% (11/30) in the 2002-2007 group, 51.6 % (16/31) in the 2008-2013 group and 4.2% (1/24) in the 2014-2018 group. The relationship between FEV1 and FVC with BMI remained significant in multivariate analysis (P <0.001). The mean FEV1 (six years) for the 2002-2007 group was 90.7±16.1%, 2008-2013 group was 99.3±17.9% and for the 2014-2018 group was 100.9±15.8%. Conclusions Improvements in FEV1 and BMI aged six and 16 years are notable as well as a significant decline in the number of patients with chronic pseudomonas.

Improved ethical guidance for the return of results from psychiatric genomics research.

There is an emerging consensus that genomic researchers should, at a minimum, offer to return to individual participants clinically valid, medically important and medically actionable genomic findings (for example, pathogenic variants in BRCA1) identified in the course of research. However, this is not a common practice in psychiatric genetics research. Furthermore, psychiatry researchers often generate findings that do not meet all of these criteria, yet there may be ethically compelling arguments to offer selected results. Here, we review the return of results debate in genomics research and propose that, as for genomic studies of other medical conditions, psychiatric genomics researchers should offer findings that meet the minimum criteria stated above. Additionally, if resources allow, psychiatry researchers could consider offering to return pre-specified 'clinically valuable' findings even if not medically actionable-for instance, findings that help corroborate a psychiatric diagnosis, and findings that indicate important health risks. Similarly, we propose offering 'likely clinically valuable' findings, specifically, variants of uncertain significance potentially related to a participant's symptoms. The goal of this Perspective is to initiate a discussion that can help identify optimal ways of managing the return of results from psychiatric genomics research.

A total-population multigenerational family clustering study of autoimmune diseases in obsessive-compulsive disorder and Tourette's/chronic tic disorders.

The association between obsessive-compulsive disorder (OCD) and Tourette's/chronic tic disorders (TD/CTD) with autoimmune diseases (ADs) is uncertain. In this nationwide study, we sought to clarify the patterns of comorbidity and familial clustering of a broad range of ADs in individuals with OCD, individuals with TD/CTD and their biological relatives. From a birth cohort of 7 465 455 individuals born in Sweden between 1940 and 2007, we identified 30 082 OCD and 7279 TD/CTD cases in the National Patient Register and followed them up to 31 December 2013. The risk of 40 ADs was evaluated in individuals with OCD, individuals with TD/CTD and their first- (siblings, mothers, fathers), second- (half siblings) and third-degree (cousins) relatives, compared with population controls. Individuals with OCD and TD/CTD had increased comorbidity with any AD (43% and 36%, respectively) and many individual ADs. The risk of any AD and several individual ADs was consistently higher among first-degree relatives than among second- and third-degree relatives of OCD and TD/CTD probands. The risk of ADs was very similar in mothers, fathers and siblings of OCD probands, whereas it tended to be higher in mothers and fathers of TD/CTD probands (compared with siblings). The results suggest a familial link between ADs in general (that is, not limited to Streptococcus-related conditions) and both OCD and TD/CTD. Additional mother-specific factors, such as the placental transmission of antibodies, cannot be fully ruled out, particularly in TD/CTD.

Comparative genomic evidence for the involvement of schizophrenia risk genes in antipsychotic effects.

Genome-wide association studies (GWAS) for schizophrenia have identified over 100 loci encoding >500 genes. It is unclear whether any of these genes, other than dopamine receptor D2, are immediately relevant to antipsychotic effects or represent novel antipsychotic targets. We applied an in vivo molecular approach to this question by performing RNA sequencing of brain tissue from mice chronically treated with the antipsychotic haloperidol or vehicle. We observed significant enrichments of haloperidol-regulated genes in schizophrenia GWAS loci and in schizophrenia-associated biological pathways. Our findings provide empirical support for overlap between genetic variation underlying the pathophysiology of schizophrenia and the molecular effects of a prototypical antipsychotic.

Safety of selective IL-23p19 inhibitors for the treatment of psoriasis.

Psoriasis is a chronic disease that requires long-term treatment. Consequently, understanding the safety and tolerability of any potential treatment over time is critical to effective prescribing. The biologic agents currently available for the treatment of psoriasis target a number of different inflammatory cytokines involved in psoriasis disease pathogenesis. The monoclonal antibodies tildrakizumab, guselkumab and risankizumab target the p19 subunit that is specific to interleukin (IL)-23. This article reviews published data on the safety of these IL-23p19 inhibitors in patients with psoriasis compared with other currently available biologic therapies. Data from randomized, placebo- and active-controlled phase 3 clinical trials show tildrakizumab, guselkumab and risankizumab to have a favourable risk-benefit profile in patients with moderate to severe psoriasis. No significant safety concerns have been observed for any of these IL-23p19 inhibitors in the data published to date. The most commonly reported adverse events (AEs) associated with these agents in phase 3 studies were upper respiratory tract infections. No increase was seen in rates of serious infections, malignancies or major adverse cardiovascular events, with no signals suggestive of an elevated risk of opportunistic infections, active tuberculosis or reactivation of latent tuberculosis infection, mucocutaneous Candida infections, triggering or worsening of inflammatory bowel disease, demyelinating disorders or suicidal ideation. Selectively targeting IL-23p19 may help avoid AEs that have been associated with biologic agents with other mechanisms of action. Data from long-term extension studies and patient registries will further establish the safety profile of IL-23p19 inhibitors for the treatment of moderate to severe psoriasis in routine practice.

Adalimumab for nail psoriasis: efficacy and safety over 52 weeks from a phase-3, randomized, placebo-controlled trial.

BACKGROUND: Few clinical trials have evaluated long-term treatment of nail psoriasis with biologics. OBJECTIVE: Safety and efficacy of adalimumab [ADA; Humira AbbVie Inc, North Chicago, IL, USA)] long-term treatment (52 weeks) was evaluated in a phase-3, randomized trial in patients with moderate-to-severe plaque psoriasis and concomitant moderate-to-severe fingernail psoriasis. Results from the first 26 weeks (Period A) have been reported. METHODS: Patients receiving 40 mg ADA every other week or placebo in Period A, continued with or switched to 40 mg ADA every-other-week treatment in the subsequent 26-week open-label extension (OLE) period. Main efficacy evaluations were ≥75% improvement in total-fingernail modified Nail Psoriasis Severity Index (mNAPSI 75) and achievement of Physician's Global Assessment for Fingernail Psoriasis of clear or minimal disease (PGA-F 0/1) with a ≥2-grade improvement from baseline, across the trial for patients who continued ADA from Period A through the OLE (Continuous-ADA Population). Safety was evaluated during the OLE and for patients receiving ADA at any time during the study (All-ADA Population). RESULTS: Of the 217 patients initially randomized in Period A, 188 (86.6%; 94 in each treatment group) entered the OLE after completion of or early escape from Period A. For the Continuous-ADA Population (N = 109), endpoint achievement rates improved from OLE entry (Week 26) to Week 52, including total-fingernail mNAPSI 75 (47.4-54.5%); PGA-F 0/1 (51.1-55.6%) and total-fingernail mNAPSI = 0 (6.6-17.9%). Serious adverse event and serious infection rates for the All-ADA Population (N = 203) were 6.9% and 3.4%, respectively. CONCLUSIONS: In this population of psoriasis patients with concomitant, moderate-to-severe nail psoriasis, long-term efficacy and improvement in signs and symptoms of nail disease were demonstrated after every-other-week ADA treatment, including incremental improvements in rate of total clearance of nail disease. No new safety risks were identified for patients receiving at least one ADA dose across 52 weeks.

Absolute and relative-rate measurement of the rate coefficient for reaction of perfluoro ethyl vinyl ether (C2F5OCF[double bond, length as m-dash]CF2) with OH.

The rate coefficient (k1) for the reaction of OH radicals with perfluoro ethyl vinyl ether (PEVE, C2F5OCF[double bond, length as m-dash]CF2) has been measured as a function of temperature (T = 207-300 K) using the technique of pulsed laser photolysis with detection of OH by laser-induced fluorescence (PLP-LIF) at pressures of 50 or 100 Torr N2 bath gas. In addition, the rate coefficient was measured at 298 K and in one atmosphere of air by the relative-rate technique with loss of PEVE and reference reactant monitored in situ by IR absorption spectroscopy. The rate coefficient has a negative temperature dependence which can be parameterized as: k1(T) = 6.0 × 10-13 exp[(480 ± 38/T)] cm3 molecule-1 s-1 and a room temperature value of k1 (298 K) = (3.0 ± 0.3) × 10-12 cm3 molecule-1 s-1. Highly accurate rate coefficients from the PLP-LIF experiments were achieved by optical on-line measurements of PEVE and by performing the measurements at two different apparatuses. The large rate coefficient and the temperature dependence indicate that the reaction proceeds via OH addition to the C[double bond, length as m-dash]C double bond, the high pressure limit already being reached at 50 Torr N2. Based on the rate coefficient and average OH levels, the atmospheric lifetime of PEVE was estimated to be a few days.

Products and mechanism of the OH-initiated photo-oxidation of perfluoro ethyl vinyl ether, C2F5OCF[double bond, length as m-dash]CF2.

The OH-initiated photo-oxidation of perfluoro ethyl vinyl ether (C2F5OCF[double bond, length as m-dash]CF2, PEVE) in air (298 K, 50 and 750 Torr total pressure) was studied in a photochemical reactor using in situ detection of PEVE and its products by Fourier transform IR absorption spectroscopy. The relative rate technique was used to derive the rate coefficient, k1, for the reaction of PEVE with OH as k1 = (2.8 ± 0.3) × 10-12 cm3 molecule-1 s-1. The photo-oxidation of PEVE in the presence of NOx at 1 bar results in formation of C2F5OCFO, FC(O)C(O)F and CF2O in molar yields of 0.50 ± 0.07, 0.46 ± 0.07 and 1.50 ± 0.22, respectively. FC(O)C(O)F and CF2O are formed partially in secondary, most likely heterogeneous processes. At a reduced pressure of 50 Torr, the product distribution is shifted towards formation of FC(O)C(O)F, indicating the important role of collisional quenching of initially formed association complexes, and enabling details of the reaction mechanism to be elucidated. An atmospheric photo-oxidation mechanism for PEVE is presented and the environmental implications of PEVE release and degradation are discussed.

Biosimilars: what the dermatologist should know.

Biosimilars are highly similar versions of approved branded biologics. In contrast to generics, which are identical copies of the originator medicines, biosimilars are considered unique but related molecules that differ from the originator reference product as well as from each other. Owing to the complexity of biologic medicines, such as therapeutic monoclonal antibodies, minor differences between biosimilars and the reference products are acceptable provided these differences do not result in any clinically meaningful differences in safety or efficacy. In addition, minor changes in structure and function may occur over time in originator biologic products as a result of alterations in production materials (e.g. cell lines), processes or conditions. The developmental process for biosimilars focuses on a 'totality of evidence' approach that emphasizes a stepwise investigational process, including comprehensive structural, functional, pharmacologic and clinical assessment for similarity. The goal of the phase 3 clinical development programme for a biosimilar is not to establish efficacy, per se, but to demonstrate that there are no clinically meaningful differences between the proposed biosimilar and the reference product. The requirement to show clinical similarity informs biosimilar study design, including the selection of the patient population, disease state (indication), study endpoints and statistical methods. Based on the clinical trial results in a representative patient population, results may be extrapolated to other indications provided scientific justification is demonstrated based on, among other things, similar mechanism of action in the extrapolated indications. This review presents the current state of knowledge with respect to biosimilars. We aim to provide the practising clinician with a working knowledge of biosimilars as well as provide some practical guidance on their use and potential benefits in treating dermatologic diseases.

Systematic review of the real-world evidence of adalimumab safety in psoriasis registries.

Long-term safety of adalimumab in psoriasis clinical studies has been established. The objective of this research was to review real-world evidence of adalimumab safety from registries of adult patients with psoriasis treated in clinical practice. Databases (BIOSIS Previews, Current Contents Search, Derwent Drug File, EMBASE, EMBASE Alert, EMCare, MEDLINE, SciSearch) were searched for psoriasis registries with adalimumab safety data. Eligible papers were English language manuscripts (conference abstracts excluded) from psoriasis registries presenting safety data for adult patients with psoriasis receiving adalimumab. The incidence and rate (events/100 patient-years [PY]) of adverse events (AEs), serious AEs (SAEs) and AEs of special interest are reported. Abstracts of 425 publications were screened, and 401 publications excluded (208 conference abstracts; 193 papers). Remaining manuscripts were fully screened; 14 were excluded (no adalimumab data, n = 10; no safety data, n = 2; no on-treatment data, n = 1; not English, n = 1), and 10 selected. Overall rates of AEs (4273 [22.2/100PY]) and SAEs (827 [4.3/100PY]) were reported in the ESPRIT registry (N = 6059). Rates of infections (7.7-14.7/100PY) and serious infections (<0.6-2.0/100PY) were reported in four studies. Cardiovascular-related events were reported in three studies: ≤0.1/100PY per major cardiac event in ESPRIT, <0.5/100PY major cardiac events in PsoBest and serious cardiovascular events in two patients (<1%) in DERMBIO. Malignancies were reported in three studies (any malignancy, 0.9/100PY; malignancies excluding non-melanoma skin cancer [NMSC], <0.6/100PY; NMSC, 0.6-<0.5/100PY). These findings suggest that real-world safety of adalimumab is consistent across different psoriasis registries, which supports the existing long-term safety profile of adalimumab from clinical studies.

Post-training Beliefs, Intentions, and Use of Prolonged Exposure Therapy by Clinicians in the Veterans Health Administration.

To examine how changes in beliefs during the training process predict adoption of prolonged exposure therapy (PE) by veterans health administration clinicians who received intensive training in this evidence-based treatment. Participants completed a 4-day PE workshop and received expert consultation as they used PE with two or more training cases. Participants were surveyed prior to the workshop, after the workshop, after case consultation (n = 1.034), and 6 months after training (n = 810). Hierarchical regression was used to assess how pre-training factors, and changes in beliefs during different stages of training incrementally predicted post-training intent to use PE and how many patients clinicians were treating with PE 6 months after training. Post-training intent to use PE was high (mean = 6.2, SD = 0.81 on a 1-7 scale), yet most participants treated only 1 or 2 patients at a time with PE. Pre-training factors predicted intent to use and actual use of PE. Changes in beliefs during the workshop had statistically significant yet modest effects on intent and use of PE. Changes in beliefs during case consultation had substantial effects on intent and actual use of PE. Pre-training factors and changes in beliefs during training (especially during case consultation) influence clinicians' adoption of PE. Use of PE was influenced not only by its perceived clinical advantages/disadvantages, but also by contextual factors (working in a PTSD specialty clinic, perceived control over one's schedule, and ability to promote PE to patients and colleagues).