Risk of major cardiovascular events in patients with psoriasis receiving biologic therapies: a prospective cohort study.

BACKGROUND: The cardiovascular safety profile of biologic therapies used for psoriasis is unclear. OBJECTIVES: To compare the risk of major cardiovascular events (CVEs; acute coronary syndrome, unstable angina, myocardial infarction and stroke) in patients with chronic plaque psoriasis treated with adalimumab, etanercept or ustekinumab in a large prospective cohort. METHODS: Prospective cohort study examining the comparative risk of major CVEs was conducted using the British Association of Dermatologists Biologics and Immunomodulators Register. The main analysis compared adults with chronic plaque psoriasis receiving ustekinumab with tumour necrosis-α inhibitors (TNFi: etanercept and adalimumab), whilst the secondary analyses compared ustekinumab, etanercept or methotrexate against adalimumab. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using overlap weights by propensity score to balance baseline covariates among comparison groups. RESULTS: We included 5468 biologic-naïve patients subsequently exposed (951 ustekinumab; 1313 etanercept; and 3204 adalimumab) in the main analysis. The secondary analyses also included 2189 patients receiving methotrexate. The median (p25-p75) follow-up times for patients using ustekinumab, TNFi, adalimumab, etanercept and methotrexate were as follows: 2.01 (1.16-3.21), 1.93 (1.05-3.34), 1.94 (1.09-3.32), 1.92 (0.93-3.45) and 1.43 (0.84-2.53) years, respectively. Ustekinumab, TNFi, adalimumab, etanercept and methotrexate groups had 7, 29, 23, 6 and 9 patients experiencing major CVEs, respectively. No differences in the risk of major CVEs were observed between biologic therapies [adjusted HR for ustekinumab vs. TNFi: 0.96 (95% CI 0.41-2.22); ustekinumab vs. adalimumab: 0.81 (0.30-2.17); etanercept vs. adalimumab: 0.81 (0.28-2.30)] and methotrexate against adalimumab [1.05 (0.34-3.28)]. CONCLUSIONS: In this large prospective cohort study, we found no significant differences in the risk of major CVEs between three different biologic therapies and methotrexate. Additional studies, with longer term follow-up, are needed to investigate the potential effects of biologic therapies on incidence of major CVEs.

Identification of factors that may influence the selection of first-line biological therapy for people with psoriasis: a prospective, multicentre cohort study.

BACKGROUND: The Psoriasis Stratification to Optimise Relevant Therapy (PSORT) consortium has a collective aim to develop a prescribing algorithm to help stratify eligible patients with psoriasis to the most appropriate biological treatment. To facilitate the adoption of a stratified approach, it is necessary to first understand the factors driving the choice of first-line biological therapy. OBJECTIVES: To identify and quantify factors that influence the selection of the first-line biological therapy for people with psoriasis. METHODS: Multinomial logistic regression was used to determine the factors that influenced the probability of treatment selection, using data from the British Association of Dermatologists Biologic Interventions Register from January 2012 to December 2015. Sensitivity analyses were performed to assess the robustness of the findings to key assumptions. RESULTS: The main analysis was based on a dataset comprising 3040 people with psoriasis. The identified factors affecting first-line biological selection within the available therapies were: presence of psoriatic arthritis; patient weight; employment status; country of registration; and baseline disease severity. Importantly, the analysis showed a general shift in prescribing behaviour over time. These results were robust to sensitivity analysis. CONCLUSIONS: This study offers important insights into the factors influencing current prescribing practice for first-line biological therapies for people with psoriasis. It provides baseline data to inform the evaluation of future potential changes that may affect prescribing behaviour, such as stratified medicine.

Iron Deficiency among Jamaican Adolescents.

OBJECTIVES: To raise awareness of significant iron deficiency anaemia occurring in Jamaican secondary school students. METHODS: Haematological screening of students in the fifth and sixth forms of 14 secondary schools in the parishes of Manchester and Clarendon, Jamaica, was done. Samples were subject to haemoglobin electrophoresis, examination of haematological indices, and haemoglobin, alpha 2 (HbA2) levels where indicated. RESULTS: Of 13 172 students with normal haemoglobin (AA) genotype aged 15-19 years, haemoglobin levels below 10 g/dL occurred in 0.36% of males and in 3.79% females. These subjects had low mean red cell volumes, low mean cell haemoglobin and high red cell distribution width, characteristic of iron deficiency, which was confirmed by dramatic increases in haemoglobin level following iron supplementation. Most revealed classic symptoms, histories of poor diets and pica, which generally resolved on iron supplementation. CONCLUSIONS: Iron deficiency, even in the absence of anaemia, is known to limit physical and mental functions and may impair intellectual performance in these high school students. Significant anaemia could be detected by incorporating a blood test into the school medical assessments performed on entry to secondary schools. There is a need for simple oral iron medications to be available at health centres.

Neuropsychological function and cerebral metabolites in HIV-infected youth.

The effects of HIV on brain metabolites and cognitive function are not well understood. Sixteen HIV+youths (15 vertical, 1 transfusion transmissions) receiving combination antiretroviral therapy and 14 age-matched HIV- youths (13-25 years of age) were evaluated with brain two-dimensional (2D) magnetic resonance spectroscopy (MRS) at 3 Tesla (T) and a neuropsychological battery that assessed three cognitive domains (attention/processing speed, psychomotor ability, and executive function). The relationship between brain metabolite ratios and cognitive performance was explored. Compared to HIV- controls, HIV+ subjects had higher sycllo-inositol (Scy)/total creatine (tCr) (+32%, p = 0.016) and higher Scy/total choline (tCho) (+31%, p = 0.018) on 2D-MRS in the right frontal lobe. HIV+ subjects also had higher glutamate (Glu)/tCr (+13%, p = 0.022) and higher Glu/tCho (+15%, p = 0.048) than controls. HIV+ subjects demonstrated poorer attention/processing speed (p = 0.011, d = 1.03) but similar psychomotor and executive function compared to HIV- controls. The attention/processing score also correlated negatively with the ratio of N-acetylaspartate (NAA) to tCr on 2D-MRS (r = -0.75, p = 0.0019) in the HIV- controls, but not in the HIV+ subjects (Fisher's r-z transformation, p < 0.05). Our results suggest that attention/processing speed is impacted by early HIV infection and is associated with right hemisphere NAA/tCr. Scy and Glu ratios are also potential markers of brain health in chronic, lifelong HIV infection in perinatally infected youths receiving antiretroviral therapy.

Iodine fortification is related to increased weight-for-age and birthweight in children in Asia.

Severe iodine deficiency causes stunting and mental retardation in utero, but the relation between mild deficiency and child growth is not well known. The use of iodated salt in relation to anthropometric data was examined from recent survey data. After potential confounding factors had been controlled for, significant associations were seen in Bangladesh, India, Nepal, and Sri Lanka. The use of iodated salt was related to increased weight-for-age and mid-upper-arm circumference, most strongly in the second year of life, mainly affecting soft tissue (thinness). The relation with weight-for-age was greater among children of mothers with lower body mass index. The use of iodated salt was related to birthweight in Sri Lanka and in the Philippines, where iodized oil capsules given during pregnancy had a negative effect when used with high levels of iodine in salt. The associations generally were concentrated in large geographic areas, possibly because of interactions with other environmental factors (e.g., selenium and arsenic). The apparent growth response to iodine may reflect functional effects of mild deficiency, which is widespread, possibly including effects on brain development.

Risk factors for symptomatic otic and sinus barotrauma in a multiplace hyperbaric chamber.

This retrospective study examines the relationship of multiplace chamber compression rates and the influence of several predisposing factors on the risk of symptomatic barotrauma. Data were reviewed from a 3-yr period for 111 patients who received 2,394 routine hyperbaric oxygen treatments. A total of 35 patients reported symptoms of barotrauma, with an overall rate of 3.05 cases per 100 treatments. Most symptoms occurred during a patient's initial three treatments and with minimal increased pressure. The most frequently affected area was the ears (95%) with objective findings noted in 18% of patients reporting fullness compared to 39% of patients reporting pain. Referral diagnosis was not related to the incidence of barotrauma. Although the overall risk of symptomatic barotrauma increased as the compression rate increased, it was not significant (RR = 1.57, CI0.95 = 0.65, 3.80). Female patients were at significantly increased risk (RR = 2.14, CI0.95 = 1.37, 3.34) compared to males, and patients less than age 40 were at higher risk than those age 40 and older (RR = 3.00, CI0.95 = 1.80, 5.03). Well-designed prospective studies are needed to more clearly define risk factors and identify compression rates with the least risk of barotrauma.

Expression of novel potassium channels in the chick basilar papilla.

Ionic currents are critical for the functioning of the inner ear auditory sensory epithelium. We set out to identify and molecularly clone the genes encoding the channels responsible for several currents in the chick basilar papilla. Here we describe an inward-rectifying K+ channel, cKir2.3, present in both hair cells and support cells in the apical end of the chick basilar papilla. The biophysical properties of the human ortholog, hKir2.3, are similar to those of an inward-rectifying channel found in the apical end of the chick basilar papilla, suggesting that this channel may contribute to the corresponding current. Additionally, we describe two new members of the Kv6 subfamily of putative regulatory voltage-gated K channels, cKv6.2 and cKv6.3. Both are expressed in hair cells in the apical end of the chick basilar papilla; cKv6.2 is also strongly expressed in support cells and in the brain.

Case-control study of the role of nutritional rickets in the risk of developing pneumonia in Ethiopian children.

BACKGROUND: Pneumonia is the most important cause of morbidity and mortality in children aged under 5 years worldwide. Studies in developing countries have suggested an association between nutritional rickets and pneumonia. Since both nutritional rickets and pneumonia are common in Ethiopia, we did a case-control study to determine the role of nutritional rickets in the development of pneumonia. METHODS: Cases were children younger than 5 years admitted to the Ethio-Swedish Children's Hospital during a 5-year period with a diagnosis of pneumonia (n = 521), but data were incomplete for 21 of these and they were not included. Controls (n = 500) were matched for admission within 3 months of cases and age within 3 months and had no evidence of pneumonia. Nutritional, demographic, and clinical and radiographic data for rickets and pneumonia were collected. Matched odd ratios and logistic regression were used to test the significance of the association of rickets and pneumonia. FINDINGS: Rickets was present in 210 of 500 cases compared with 20 of 500 controls (odds ratio 22.11). There were significant differences between cases and controls for family size, birth order, crowding, and months of exclusive breastfeeding (p < 0.05). After correction for these confounding factors by logistic regression, there was still a 13-fold higher incidence of rickets among children with pneumonia than among controls (13.37 [95% CI 8.08-24.22], p < 0.001). INTERPRETATION: Vitamin D or calcium deficiency may be important predisposing factors for pneumonia in children aged under 5 years in developing countries. Efforts to prevent vitamin D deficiency or calcium supplementation may result in significant reductions in morbidity and mortality from pneumonia in these children.

Effects of relaxation on anxiety in children: implications for coping with stress.

Although research shows that relaxation has the potential to reduce stress and anxiety in adults, there is little evidence to support this effect in children. This study examined the effects of relaxation on anxiety in 46 second-grade children in two classrooms. A nonequivalent control group design was strengthened by providing relaxation treatment to the control group after the second measure of anxiety. A third measure of anxiety was then given to both classes. The children were not significantly different with respect to sex, age, and initial anxiety. Although the main hypothesis was not supported (at p less than .05), a reduction in anxiety resulted for both classes after they completed the program. Subgroup analyses showed a significant treatment effect with the group receiving relaxation exhibiting less anxiety than the control group. This finding indicates that relaxation may be learned by children and may be beneficial in coping with stress.

A trial of folate supplementation in children with homozygous sickle cell disease.

A double blind controlled trial of supplementation with folic acid has been performed in 117 children with homozygous sickle cell (SS) disease aged 6 months to 4 years over a 1 year period. No megaloblastic change was observed in either group. At the end of the study period the folate supplemented group showed no significant differences in haemoglobin, growth characteristics, or in the proportion of children affected by major or minor infections, acute splenic sequestration, dactylitis or episodes of bone or abdominal pain. However, the folate supplemented group showed a significantly lower mean cell volume and the placebo group contained a significant excess of children experiencing multiple episodes of dactylitis. The results are compatible with mild folate deficiency in some patients in the placebo group but the absence of striking effects on haematology or growth suggest that the policy of regular folate supplementation in children with SS disease should be critically reviewed.

The first two decades of vitamin E.

This presentation reviews highlights of the first 20 years (1922-1942) of vitamin E. It begins with background information leading to identification of an antisterility factor for rats of both sexes and its acceptance into the vitamin family as vitamin E (1925). Research of the next 12 years revealed a multiplicity of deficiency manifestations: embryonic mortality, testis degeneration, encephalomalacia and exudative diathesis in the chick, and nutritional muscular dystrophy in avian and mammalian species. Toward the close of this period came the isolation of vitamin E from natural sources, determination of its empirical formula, and introduction of the designation alpha-tocopherol for vitamin E (1936). Within the next two years the structural formula of alpha-tocopherol was elucidated, its chemical synthesis accomplished, and its production from natural plant oils by molecular distillation was well established. The existence of other tocopherols with lesser degrees of biological activity became recognized. Also, the concurrent development of a chemical method for determining the vitamin E content of alpha-tocopherol in foods, body tissues and body fluids, which replaced the very laborious bioassay procedure, greatly facilitated later advances in knowledge of the distribution and nature of vitamin E.

Branched-chain amino acid substitutions in the biosynthesis of the antibiotic actinomycin.

Actinomycins normally contain N-methyl-l-valine and either d-valine, d-alloisoleucine or both amino acids in the molecule. During antibiotic formation in a medium supplemented with one of the four isoleucine stereoisomers, Streptomyces parvulus and S. chrysomallus form complex actinomycin mixtures (C(1), C(2), C(3), E(1), and E(2)-like compounds). Although chromatographic techniques suggested that single homogeneous components had been isolated, subsequent studies indicated that such chromatographic fractions probably consisted of multiple isomers of actinomycin. Amino acid analyses revealed the presence of N-methylvaline and/or N-methylalloisoleucine and, in addition, d-isoleucine, d-valine, and d-alloisoleucine were frequently found in a given fraction.