Clinical Unmet Needs and Treatment Patterns of Paediatric Psoriasis Patients: A Real-World Evidence Study in Spain. / [Artículo traducido] Necesidades clínicas no satisfechas y patrones de tratamiento de los pacientes pediátricos con psoriasis: estudio de evidencia en el mundo real en España.

BACKGROUND AND OBJECTIVE: Real-world evidence of paediatric psoriasis (PsO) is lacking in Spain. The purpose of this study was to identify physician-reported disease burden and current treatment patterns in a real-world paediatric PsO patient cohort in Spain. This will enhance our understanding of the disease and contribute to the development of regional guidelines. MATERIAL AND METHOD: This retrospective analysis of a cross-sectional market research survey assessed the clinical unmet needs and treatment patterns in patients with paediatric PsO in Spain, as reported by their primary care and specialist physicians, using data collected as part of the Adelphi Real World Paediatric PsO Disease-Specific Program (DSP™) between February and October 2020. RESULTS: Survey data from 57 treating physicians were included (71.9% [N = 41] dermatologists, 17.6% [N = 10] general practitioners/primary care physicians, and 10.5% [N = 6] paediatricians); the final analysis included 378 patients. At sampling, 84.1% (318/378) of patients had mild disease, 15.3% (58/378) had moderate disease and 0.5% (2/378) had severe disease. Retrospectively reported physician-judged severity at the time of PsO diagnosis recorded 41.8% (158/378) of patients with mild disease, 51.3% (194/378) with moderate disease and 6.9% (26/378) with severe disease. Overall, 89.3% (335/375) of patients were currently receiving topical PsO therapy, while 8.8% (33/375), 10.4% (39/375) and 14.9% (56/375) of patients were currently receiving phototherapy, conventional systemics and biologics, respectively. CONCLUSIONS: These real-world data reflect the current burden and treatment landscape of paediatric PsO in Spain. The management of patients with paediatric PsO could be improved by further educating healthcare professionals and developing regional guidelines.

Clinical Unmet Needs and Treatment Patterns of Paediatric Psoriasis Patients: A Real-World Evidence Study in Spain.

BACKGROUND AND OBJECTIVE: Real-world evidence of paediatric psoriasis (PsO) is lacking in Spain. The purpose of this study was to identify physician-reported disease burden and current treatment patterns in a real-world paediatric PsO patient cohort in Spain. This will enhance our understanding of the disease and contribute to the development of regional guidelines. MATERIAL AND METHOD: This retrospective analysis of a cross-sectional market research survey assessed the clinical unmet needs and treatment patterns in patients with paediatric PsO in Spain, as reported by their primary care and specialist physicians, using data collected as part of the Adelphi Real World Paediatric PsO Disease-Specific Program (DSP™) between February and October 2020. RESULTS: Survey data from 57 treating physicians were included (71.9% [N=41] dermatologists, 17.6% [N=10] general practitioners/primary care physicians, and 10.5% [N=6] paediatricians); the final analysis included 378 patients. At sampling, 84.1% (318/378) of patients had mild disease, 15.3% (58/378) had moderate disease and 0.5% (2/378) had severe disease. Retrospectively reported physician-judged severity at the time of PsO diagnosis recorded 41.8% (158/378) of patients with mild disease, 51.3% (194/378) with moderate disease and 6.9% (26/378) with severe disease. Overall, 89.3% (335/375) of patients were currently receiving topical PsO therapy, while 8.8% (33/375), 10.4% (39/375) and 14.9% (56/375) of patients were currently receiving phototherapy, conventional systemics and biologics, respectively. CONCLUSIONS: These real-world data reflect the current burden and treatment landscape of paediatric PsO in Spain. The management of patients with paediatric PsO could be improved by further educating healthcare professionals and developing regional guidelines.

A randomised controlled trial of bright light therapy and morning activity for adolescents and young adults with Delayed Sleep-Wake Phase Disorder.

A randomised controlled trial evaluated bright light therapy and morning activity for the treatment of Delayed Sleep-Wake Phase Disorder (DSWPD) in young people. 60 adolescents and young adults (range = 13-24 years, mean = 15.9 ± 2.2 y, 63% f) diagnosed with DSWPD were randomised to receive three weeks of post-awakening Green Bright Light Therapy (∼507 nm) and Sedentary Activity (sitting, watching TV), Green Bright Light Therapy and Morning Activity (standing, playing motion-sensing videogame), Red Light Therapy (∼643 nm) and Sedentary Activity or Red Light Therapy and Morning Activity. Sleep (ie sleep onset time, wake up time, sleep onset latency, total sleep time) and daytime functioning (ie morning alertness, daytime sleepiness, fatigue, functional impairment) were measured pre-treatment, post-treatment and at one and three month follow-up. Contrary to predictions, there were no significant differences in outcomes between treatment groups; and interaction effects between treatment group and time for all outcome variables were not statistically significant. However, adolescents and young adults in morning activity conditions did not meaningfully increase their objective activity (ie movement frequency). Overall, adolescents reported significantly improved sleep timing (d = 0.30-0.46), sleep onset latency (d = 0.32) and daytime functioning (d = 0.45-0.87) post-treatment. Improvements in sleep timing (d = 0.53-0.61), sleep onset latency (d = 0.57), total sleep time (d = 0.51), and daytime functioning (d = 0.52-1.02) were maintained, or improved upon, at the three month follow-up. However, relapse of symptomology was common and 38% of adolescents and young adults requested further treatment in addition to the three weeks of light therapy. Although there is convincing evidence for the short-term efficacy of chronobiological treatments for DSWPD, long-term treatment outcomes can be improved. To address this gap in our current knowledge, avenues for future research are discussed. CLINICAL TRIAL: Australian & New Zealand Clinical Trials Registry, https://www.anzctr.org.au, ACTRN12614000308695.

Cognitive performance in adolescents with Delayed Sleep-Wake Phase Disorder: Treatment effects and a comparison with good sleepers.

The present study aimed to investigate whether Australian adolescents with Delayed Sleep-Wake Phase Disorder have impaired cognitive performance and whether chronobiological treatment for Delayed Sleep-Wake Phase Disorder improves adolescents' sleep, daytime functioning and cognitive performance. Adolescents with Delayed Sleep-Wake Phase Disorder (mean = 15.68 ±â€¯2.1 y, 62% f) reported significantly later sleep timing (d = 1.03-1.45), less total sleep time (d = 0.82) and greater daytime sleepiness (d = 2.66), fatigue (d = 0.63) and impairment (d = 2.41), compared to good sleeping adolescents (mean = 15.9 ±â€¯2.4 y, 75% f). However, there were no significant between-group differences (all p > 0.05) in performance on the Operation Span (ηp2 = 0.043), Digit Span (forwards: ηp2 = 0.002, backwards: ηp2 = 0.003), Letter Number Sequencing (ηp2 < 0.001) (working memory) and Digit-Symbol Substitution Tasks (ηp2 = 0.010) (processing speed). Adolescents with Delayed Sleep-Wake Phase Disorder went on to receive 3 weeks of light therapy. At 3 months post-treatment, adolescents with Delayed Sleep-Wake Phase Disorder reported significantly advanced sleep timing (d = 0.56-0.65), greater total sleep time (d = 0.52) and improved daytime sleepiness (d = 1.33), fatigue (d = 0.84) and impairment (d = 0.78). Performance on the Operation Span (d = 0.46), Letter Number Sequencing (d = 0.45) and Digit-Symbol Substitution tasks (d = 0.57) also significantly improved.

Treatment for wound pruritus following burns.

OBJECTIVE: To review the current literature on the treatment of itching, or pruritus, in people with burn wounds. METHOD: A literature search using the databases PubMed, MEDLINE and Google Scholar was undertaken. Studies were included in the review if they discussed or evaluated different treatment options for pruritus in patients with burn wounds. RESULTS: A variety of treatments are available for the relief of pruritus in patients with burns wounds, ranging from antihistamines and topical emollients to psychological therapies, massage and dermatological treatments. Oral antihistamines are used most commonly, yet research indicates that these are not always effective. Few studies are methodologically robust. In recent years, there has been an attempt to design and implement treatment strategies and algorithms, however, there is currently no agreed and consistent management plan for the treatment of pruritus due to burn injury. CONCLUSION: Simple single therapies should be the first line therapy for the treatment of pruritus due to burns, however, if these are unsuccessful, combination therapy should be introduced early to try to reduce the onset of chronic itch. Current algorithms and treatment plans based on the stage of healing show promise but need further modification and testing before they can be recommended for common use.

Effects of dietary crude protein and supplemental urea levels on nitrogen and phosphorus utilization by feedlot cattle.

Three dietary CP concentrations (11.5, 13.0, and 14.5% of DM) and 3 supplemental urea levels (100, 50, and 0% of supplemental N) were used in a completely randomized block design experiment conducted at 2 locations to determine N and P balance and serum urea N (SUN) concentrations of feedlot cattle. Crossbred steers [British and British x Continental; initial BW = 315.0 +/- 3.2 kg at location 1 (n = 27) and initial BW = 353.2 +/- 8.4 kg at location 2 (n = 27)] were used in 3 nutrient balance sampling periods (SP) at the beginning, middle, and end of the feeding period (154 d in location 1 and 159 d in location 2). Fecal N (g/d; P = 0.03), urinary N (g/d; P < 0.01), urinary urea N (UUN; g/d; P < 0.01), apparent N absorption (g/d; P < 0.01), and SUN concentration (mg/dL; P < 0.01) increased linearly as dietary CP concentration increased. Nitrogen retention (g/d) was not affected (P = 0.61) by dietary CP concentration. Phosphorus intake (g/d; P = 0.02), fecal P (g/d; P = 0.04), and urinary P (g/d; P = 0.01) increased linearly as dietary CP increased, reflecting changes in diet composition with increasing CP concentrations. As dietary urea levels increased, urinary N (g/d; P = 0.04), UUN (g/d; P = 0.01), and apparent N absorption (g/d; P = 0.04) increased linearly, but P intake (g/d; P = 0.10) and urinary P (g/d; P = 0.02) decreased linearly. No interactions were observed between SP and dietary treatments for most variables. Evaluation of SP means, however, showed that as days on feed increased, fecal N (g/d; P = 0.01), urinary N (g/d; P < 0.01), UUN (g/d; P < 0.01), apparent absorption of N (g/d; P < 0.01), SUN (mg/dL; P < 0.01), and urinary P (g/d; P < 0.01) increased linearly, whereas retained N (g/d) decreased linearly (P < 0.01) with increasing days on feed. These data suggest that changes in dietary CP and urea levels, as well as stage of the feeding period, markedly alter N and P utilization by feedlot cattle.

Cyclooxygenase-2 protein levels are independent of epidermal growth factor receptor expression or activation in operable non-small cell lung cancer.

UNLABELLED: Both cyclooxygenase (COX)-2 and epidermal growth factor receptor (EGFR) are thought to play important roles in the pathogenesis of non-small cell lung cancer (NSCLC). A number of in vitro studies have postulated a link between EGFR activation and subsequent COX-2 upregulation. The relationship between these factors has not been established in patients with NSCLC. COX-2 and EGFR expression were studied in 172 NSCLC specimens using standard immunohistochemical techniques. Western blotting was used to determine COX-2 and EGFR levels in five NSCLC cell lines. The effect of treatment with EGF on COX-2 expression in A549 cells was assessed. RESULTS: Both EGFR and COX-2 are overexpressed in NSCLC. The predominant pattern of COX-2 and EGFR staining was cytoplasmic. Membranous EGFR staining was seen in 23.3% of cases. There was no relationship between COX-2 and EGFR expression and survival or any clinicopathological features. No correlation was seen between EGFR expression and COX-2 expression in the immunohistochemical series or in the cell lines. Treatment with EGF did not upregulate COX-2 levels in A549 cells, either in serum free or serum-supplemented conditions. CONCLUSIONS: Although COX-2 and EGFR are over-expressed in NSCLC neither was of prognostic significance in this series of cases. There is no correlation between these two factors in either tumour samples or cell lines. Although these factors show no correlation in NSCLC, they remain potential, though independent targets for treatment.

Epidermal growth factor receptors and cyclooxygenase-2 in the pathogenesis of non-small cell lung cancer: potential targets for chemoprevention and systemic therapy.

The epidermal growth factor receptor (EGFR) is part of a family of plasma membrane receptor tyrosine kinases that control many important cellular functions, from growth and proliferation to cell death. Cyclooxygenase (COX)-2 is an enzyme which catalyses the conversion of arachidonic acid to prostagladins and thromboxane. It is induced by various inflammatory stimuli, including the pro-inflammatory cytokines, Interleukin (IL)-1beta, Tumour Necrosis Factor (TNF)-alpha and IL-2. Both EGFR and COX-2 are over-expressed in non-small cell lung cancer (NSCLC) and have been implicated in the early stages of tumourigenesis. This paper considers their roles in the development and progression of lung cancer, their potential interactions, and reviews the recent progress in cancer therapies that are directed toward these targets. An increasing body of evidence suggests that selective inhibitors of both EGFR and COX-2 are potential therapeutic agents for the treatment of NSCLC, in the adjuvant, metastatic and chemopreventative settings.

Autologous blood donation and transfusion in Europe.

BACKGROUND AND OBJECTIVES: The aim of this study was to record practices in autologous blood transfusion in Europe in 1997. MATERIALS AND METHODS: A questionnaire mainly about predeposit was distributed to the National Representatives of all 41 member states of the Council of Europe's Committee of Experts on Blood Transfusion and Haematology. Replies were received from 29. RESULTS AND CONCLUSION: Autologous blood units collected in 1997 amounted to 4.2% of the allogeneic units, with wide variations between countries. Predeposit was used most frequently in Italy (8.9%), Germany (7.1%) and France (6.6%). Some countries, notably Scandinavia, do not encourage predeposit, chiefly on the grounds that it is not cost-effective, but others are promoting its use.

An iron-regulated ferric reductase associated with the absorption of dietary iron.

The ability of intestinal mucosa to absorb dietary ferric iron is attributed to the presence of a brush-border membrane reductase activity that displays adaptive responses to iron status. We have isolated a complementary DNA, Dcytb (for duodenal cytochrome b), which encoded a putative plasma membrane di-heme protein in mouse duodenal mucosa. Dcytb shared between 45 and 50% similarity to the cytochrome b561 family of plasma membrane reductases, was highly expressed in the brush-border membrane of duodenal enterocytes, and induced ferric reductase activity when expressed in Xenopus oocytes and cultured cells. Duodenal expression levels of Dcytb messenger RNA and protein were regulated by changes in physiological modulators of iron absorption. Thus, Dcytb provides an important element in the iron absorption pathway.

Soluble CD14 enriched in colostrum and milk induces B cell growth and differentiation.

Induction of resting B cell growth and differentiation requires a complex series of temporally coordinated signals that are initiated on contact with activated helper T cells. These signals complement one another, each rendering the B cell susceptible to factors supporting progressive activation. Here, we demonstrate that soluble CD14 (sCD14) bypasses the physiological sequelae of events that limit B cell activation. B cell growth and differentiation in vitro is induced by both native and recombinant forms of sCD14 at nanomolar concentrations. sCD14-mediated cellular activation does not require membrane CD14 expression, depends on a region of CD14 that is not involved in lipopolysaccharide binding, and requires functional Toll-like receptor 4. Consistent with biological activity of sCD14 in vitro, its administration to neonatal mice enhances Ig secretion. The results presented establish sCD14 as a naturally occurring soluble B cell mitogen of mammalian origin.

Contribution of dietary protein to sulfide production in the large intestine: an in vitro and a controlled feeding study in humans.

BACKGROUND: Hydrogen sulfide is a luminally acting, bacterially derived cell poison that has been implicated in ulcerative colitis. Sulfide generation in the colon is probably driven by dietary components such as sulfur-containing amino acids (SAAs) and inorganic sulfur (eg, sulfite). OBJECTIVE: We assessed the contribution of SAAs from meat to sulfide production by intestinal bacteria with use of both a model culture system in vitro and an in vivo human feeding study. DESIGN: Five healthy men were housed in a metabolic suite and fed a sequence of 5 diets for 10 d each. Meat intake ranged from 0 g/d with a vegetarian diet to 600 g/d with a high-meat diet. Fecal sulfide and urinary sulfate were measured in samples collected on days 9 and 10 of each diet period. Additionally, 5 or 10 g bovine serum albumin or casein/L was added to batch cultures inoculated with feces from 4 healthy volunteers. Concentrations of sulfide, ammonia, and Lowry-reactive substances were measured over 48 h. RESULTS: Mean (+/-SEM) fecal sulfide concentrations ranged from 0.22 +/- 0.02 mmol/kg with the 0-g/d diet to 3.38 +/- 0.31 mmol/kg with the 600-g/d diet and were significantly related to meat intake (P: < 0.001). Sulfide formation in fecal batch cultures supplemented with both bovine serum albumin and casein correlated with protein digestion, as measured by the disappearance of Lowry-reactive substances and the appearance of ammonia. CONCLUSION: Dietary protein from meat is an important substrate for sulfide generation by bacteria in the human large intestine.

Motor control problems in patients with spinal pain: a new direction for therapeutic exercise.

Recent research into muscle dysfunction in patients with low back pain has led to discoveries of impairments in deep muscles of the trunk and back. These muscles have a functional role in enhancing spinal segmental support and control. The muscle impairments are not those of strength but rather problems in motor control. These findings call for a different approach in therapeutic exercise, namely a motor learning exercise protocol. The specific exercise approach has an initial focus on retraining the cocontraction of the deep muscles (ie, the transversus abdominis and lumbar multi-fidus Initial clinical trials point to the effectiveness of the approach in patients with both acute and chronic low back pain in terms of reducing the neuromuscular impairment and in control of pain.

Oral transmission of human immunodeficiency virus by infected seminal fluid and milk: a novel mechanism.

Salivary transmission by the 30 million human immunodeficiency virus (HIV) carriers is rare, despite kissing, aerosolization, and dental treatment. The main protective mechanism of saliva is reported to be inactivation of HIV-transmitting leukocytes by its unique hypotonicity; however, the successful oral transmission of HIV by seminal fluid and milk is unexplained. Whether seminal fluid and milk successfully transmit HIV orally by overcoming the recipient's salivary hypotonic inactivation of HIV-transmitting leukocytes was tested. Isotonic salt solution and normal donor samples of milk, colostrum, seminal fluid, and blood were studied for their ability to overcome the salivary hypotonic inactivation. All samples, in physiologic volumes, prevented the hypotonic saliva from inactivating HIV-transmitting leukocytes by providing solutes and retarding diffusion. This indicates that successful oral transmission of HIV by seminal fluid, milk, and colostrum may be due to their isotonicity, which overcomes hypotonic salivary inactivation of HIV-transmitting leukocytes.

The neurosteroid pregnenolone sulphate enhances NMDA-induced phasic firing of vasopressin neurones in the rat supraoptic nucleus.

The effect of the neurosteroid pregnenolone sulphate (PS) on N-methyl-D-aspartate (NMDA)-induced phasic firing of supraoptic vasopressin (VP) neurones was studied in rat hypothalamic slices in vitro. In VP neurones which were induced to fire phasically by continuous perifusion with NMDA (9-30 microM), addition of 100 microM PS to the incubation medium significantly increased overall spike frequency, with a rise in both proportion of time active and intraburst firing rate. A similar effect was seen during picrotoxin block of GABAergic transmission. No significant change in NMDA-induced phasic firing was observed with 100 microM dehydroepiandrosterone sulphate. VP neurones became silent in the absence of NMDA, and under these conditions PS had no effect. In conclusion, PS increases NMDA-induced phasic firing in VP neurones, providing a mechanism whereby this neurosteroid may participate in the regulation of VP secretion.

A redrawn Vandenberg and Kuse mental rotations test: different versions and factors that affect performance.

The available versions of the Vandenberg and Kuse (1978) Mental Rotations Test (MRT) have physically deteriorated because only copies of copies are available. We report results from a redrawn version of the MRT and for alternate versions of the test. Males perform better than females, and students drawn from the physical sciences perform better than students drawn from the social sciences and humanities, confirming other reports with the original version of the MRT. Subjects find it very hard to perform the MRT when stimuli require rotation along both the top/bottom axis and the left/right axis. The magnitude of effect sizes for sex (which account, on average, for some 20% of the variance) does not increase with increasing difficulty of the task. Minimal strategy effects were observed and females did not perform differently during the menstrual period as opposed to the days between the menstrual periods. Practice effects are dramatic, confirming other reports with the original MRT, and can also be shown to be powerful in a transfer for practice paradigm, where test and retest involve different versions of the MRT. Main effects of handedness on MRT performance were not found.

Quality of light - is laser necessary for effective photobiostimulation?

Is true laser, with its unique qualities of coherence, collimation and monochromaticity, necessary for effective photobiostimulation, or is a simpler form of light sufficient? Doubt has been cast on the importance of coherence and collimation in influencing biostimulation. It is hypothesised that monochromaticity (or singularity of wavelength) is the only characteristic of laser necessary for photostimulation. If wavelength is the important factor in phototherapy, the clinician must consider which wavelengths are capable of producing specific effects within living tissues. In addition, it is important to distinguish the quality of light provided by a unit and whether it will give the desired results without a large financial outlay. This article reviews the unique properties of laser, discusses their contribution to photobiostimulation and looks at apparatus which provide these properties.

Factors affecting Low Level Laser Therapy.

Low Level Laser Therapy has been reported as causing many therapeutic reactions within living tissue, yet research studies have not been able to support conclusively the results which appear to occur clinically. If the physiotherapist accepts that light quality may have been a variable overlooked in previous studies, it is necessary to consider whether there are other factors which may have contributed to the variable and, at times, conflicting results. These factors include depth of penetration and resultant absorption. Factors such as power output, dose, pulse frequency and frequency of treatment will also influence the therapeutic action of laser. This review evaluates parameters common to most therapeutic lasers as well as other features including the multiple-diode probe. Issues which may help clinicians optimise their treatment when using Low Level Laser Therapy will be addressed.

Transferrin-gene expression in the rat mammary gland. Independence of maternal iron status.

Transferrin mRNA concentrations were measured in total RNA isolated from liver and mammary tissue of lactating rats at different stages of lactation. The mammary transferrin mRNA concentration varied in a biphasic manner, increasing up to parturition and then decreasing to undetectable levels at days 5 and 10 of lactation before increasing again markedly in late lactation. The values obtained at day 20 of lactation were double those found in livers of lactating rats. The concentrations of total RNA and mRNA for alpha-casein and alpha-lactalbumin did not change between days 5 and 20 of lactation. Transferrin concentrations were measured in milk from rats fed on an iron-free, a control and an iron-supplemented diet. Although there was a 5-fold difference in the transferrin concentration of samples taken between day 5 and day 20 of lactation, the dietary treatments did not result in significant changes. Maternal serum transferrin concentrations were, however, elevated, and pup haemoglobin concentrations were suppressed for the rats receiving the iron-free diet, indicating an alteration of the iron status of these rats.

DNA sequence analysis with a modified bacteriophage T7 DNA polymerase. Effect of pyrophosphorolysis and metal ions.

Pyrophosphorolysis by bacteriophage T7 DNA polymerase leads to the degradation of specific dideoxynucleotide-terminated fragments on DNA sequencing gels. This reaction can be prevented by pyrophosphatase. It is also inhibited by a high concentration of dNTPs; only the dNTP complementary to the next base in the template is an effective inhibitor, suggesting the formation of a stable polymerase-primer-template-nucleotide complex despite the absence of a 3' hydroxyl group on the primer. The use of pyrophosphatase, a genetically modified T7 DNA polymerase that lacks exonuclease activity, and Mn2+ rather than Mg2+ to eliminate discrimination between dideoxynucleotides and deoxynucleotides (Tabor, S., and Richardson, C. C. (1989) Proc. Nat. Acad. Sci. U. S. A. 86, 4076-4080) generates bands of uniform intensity on a DNA sequencing gel. Uniform band intensities simplify the analysis of a DNA sequence, particularly with automated procedures. For example, when genomic DNA is sequenced directly, heterozygotic sequences are readily detected because their bands have half the intensity of homozygotic sequences. A procedure for automated DNA sequencing is described that exploits the uniformity. A single reaction with a single labeled primer is carried out using four different ratios of dideoxynucleotides to deoxynucleotides; after gel electrophoresis in a single lane, the sequence is determined by the relative intensity of each band.