Comparing the efficacy and tolerability of biologic therapies in psoriasis: an updated network meta-analysis.

BACKGROUND: The rapid expansion of psoriasis biologics has led to an urgent need to understand their relative efficacy and tolerability to inform treatment decisions better and, specifically, to inform guideline development. OBJECTIVES: To update a 2017 meta-analysis on the comparative efficacy and tolerability of biologic treatments for psoriasis. METHODS: We searched the MEDLINE, PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs), published up to 7 September 2018, of 11 licensed, NICE-approved biologics targeting tumour necrosis factor (adalimumab, etanercept, infliximab, certolizumab pegol), interleukin (IL)-12/IL-23p40 (ustekinumab), IL-17A (secukinumab, ixekizumab), IL-17RA (brodalumab) and IL-23p19 (guselkumab, tildrakizumab, risankizumab). A frequentist network meta-analysis ascertained direct or indirect evidence comparing biologics with one another, methotrexate or placebo. This was combined with hierarchical cluster analyses to consider efficacy (≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) or Physician's Global Assessment 0 or 1; PASI 75; Dermatology Life Quality Index improvement) and tolerability (drug withdrawal due to adverse events) outcomes at 10-16 weeks, followed by assessments of study quality, heterogeneity and inconsistency. RESULTS: We identified 62 RCTs presenting data on direct comparisons (31 899 participants). All biologics were efficacious compared with placebo or methotrexate at 10-16 weeks. Hierarchical cluster analyses revealed that adalimumab, brodalumab, certolizumab pegol, guselkumab, risankizumab, secukinumab, tildrakizumab and ustekinumab were comparable with respect to high short-term efficacy and tolerability. Infliximab and ixekizumab clustered together, with high short-term efficacy but relatively lower tolerability than the other agents, although the number of drug withdrawal events across the network was low, so these findings should be treated with caution. CONCLUSIONS: Using our methodology we found that most biologics cluster together with respect to short-term efficacy and tolerability, and we did not identify any single agent as 'best'. These data need to be interpreted in the context of longer-term efficacy, effectiveness data, safety, posology and drug acquisition costs when making treatment decisions.

Farmers' actions toward sustainability: a typology of dairy farms according to sustainability indicators.

Milk production is an important economic and social activity in Brazil. Failure to meet institutional and market demands for quality and sustainability has led farmers, particularly small-scale farmers, to leave agriculture. The aim of this study was to assess and compare the sustainability of dairy farms in Paraná, Brazil. A semi-structured questionnaire was administered to 75 dairy farm operators. Sustainability indicators were generated on the basis of economic, environmental and social data using exploratory factor analysis. Factor scores were subjected to hierarchical clustering, which resulted in the formation of three groups of dairy farms. Groups 1, 2 and 3 had high, intermediate and low levels of sustainability, respectively. Group 1 comprised large-scale dairy farms with high productivity. Dairy farms with intermediate sustainability (group 2) had medium production capacity, and farms with low sustainability (group 1) had the smallest production scale and capacity. Large-scale dairy farms have greater economic, environmental and social sustainability and are, therefore, more likely to survive in the medium and long term.

Cost comparison of pressure ulcer preventive dressings: hydrocolloid dressing versus transparent polyurethane film.

OBJECTIVE: To evaluate and compare the costs of using a transparent polyurethane film (PF) and hydrocolloid dressing (HD) in the prevention of pressure ulcers (PUs). METHOD: This descriptive, observational, longitudinal, comparative study was conducted in the intensive care units, coronary care unit and medical clinic of a charity hospital in Brazil. Data were collected during a 30-day study period, consisting of physical examination, assessment of risk factors for PU development and application of the Braden scale, which were performed at inclusion in the study and once daily during hospitalisation. Either PF or HD was applied bilaterally in the sacral and trochanteric regions for prevention of PUs in patients at a moderate to high risk of PUs according to the Braden scale, and costs of using PU preventive dressings were estimated. RESULTS: The mean total costs per dressing change per patient when using the HD and PF to prevent PUs were 413.60 BRL and 74.04 BRL, respectively. There were significant between-group differences in mean costs for all variables, except for saline solution and nurse-technician services. CONCLUSION: Results showed that the mean cost per dressing change per patient was lower when using the transparent PF than when using the HD.

Impact of surgical wound dehiscence on health-related quality of life and mental health.

OBJECTIVE: To assess the impact of surgical wound dehiscence on health-related quality of life and mental health. Dehiscence of surgical wounds is a serious postoperative complication associated with high morbidity and mortality. METHOD: Sixty-one adult patients, who had undergone neurological, general, colorectal, orthopaedic, gynaecological, plastic, cardiovascular, urological or neurological surgery in a university hospital in Brazil, were assessed between 30 and 180 days after surgery. Twenty participants who achieved complete wound healing were allocated to the control group and 41 participants who developed surgical wound dehiscence were allocated to the dehiscence group. Patients unable to complete the questionnaires because of cognitive impairment and those who declined to participate or died were excluded from the study. Data were collected using a questionnaire assessing sociodemographic and clinical characteristics of participants; the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36); and the Beck Depression Inventory (BDI). RESULTS: Surgical wound dehiscences were 0.5-30 cm in length, 0.5-7 cm in depth, and located in the arms, legs or trunk. There were significant between-group differences in mean scores on the physical functioning (p<0.01), role physical (p<0.01), social functioning (p=0.01), and bodily pain (p=0.01) dimensions of the SF-36. Participants with wound dehiscence reported significantly higher BDI scores (more depressive symptoms) than controls (p=0.01). CONCLUSION: Surgical wound dehiscence had a negative impact on the physical functioning, role physical, social functioning, and bodily pain dimensions of health-related quality of life and on mental health. DECLARATION OF INTEREST: No conflict of interest to declare.

Routine cognitive screening in older patients admitted to acute medicine: abbreviated mental test score (AMTS) and subjective memory complaint versus Montreal Cognitive Assessment and IQCODE.

INTRODUCTION: Routine cognitive screening for in-patients aged ≥75 years is recommended, but there is uncertainty around how this should be operationalised. We therefore determined the feasibility and reliability of the Abbreviated mental test score (AMTS/10) and its relationship to subjective memory complaint, Montreal Cognitive Assessment (MoCA/30) and informant report in unselected older admissions. METHODS: Consecutive acute general medicine patients aged ≥75 years admitted over 10 weeks (March-May 2013) had AMTS and a question regarding subjective memory complaint (if no known dementia/delirium). At ≥72 h, the 30-point Montreal Cognitive Assessment (MoCA) and Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) were done. Cognitive impairment was defined as AMTS < 9 or MoCA < 26 (mild impairment) and MoCA < 20 (moderate/severe impairment) or IQCODE ≥ 3.6. RESULTS: Among 264 patients (mean age/SD = 84.3/5.6 years, 117 (44%) male), 228 (86%) were testable with AMTS. 49/50 (98%) testable patients with dementia/delirium had low AMTS compared with 79/199 (44%) of those without (P < 0.001). Subjective memory complaint agreed poorly with objective cognitive deficit (39% denying a memory problem had AMTS < 9 (kappa = 0.134, P = 0.086)) as did informant report (kappa = 0.18, P = 0.15). In contrast, correlation between AMTS and MoCA was strong (R2 = 0.59, P < 0.001) with good agreement between AMTS < 9 and MoCA < 20 (kappa = 0.50, P < 0.01), although 85% of patients with normal AMTS had MoCA < 26. CONCLUSIONS: The AMTS was feasible and valid in older acute medicine patients agreeing well with the MoCA albeit with a ceiling effect. Objective cognitive deficits were prevalent in patients without known dementia or delirium but were not reliably identified by subjective cognitive complaint or informant report.

Using transparent polyurethane film and hydrocolloid dressings to prevent pressure ulcers.

OBJECTIVE: To compare the performance and effectiveness of a hydrocolloid dressing (HD) and a transparent polyurethane film (PF) in preventing pressure ulcer (PU) development. METHOD: The study was conducted in the intensive care unit, coronary care unit and medical clinic of the Holy House of Mercy of Passos, Brazil. Data were collected 48 hours after admission and during hospitalisation. The Braden scale was used for PU risk assessment. Consecutive eligible patients without PUs were randomly assigned by lottery to the two groups, either the HD or PF group. RESULTS: Of the 160 eligible patients, significant between-group differences were found in the mean total number of dressing changes (HD, 6.09±1.655 changes; PF, 5.59±2.036 changes; p=0.010), and mean number of dressing changes in the sacral region (HD, 2.50±0.871; PF, 2.05±0.825; p=0.001), with the PF group requiring significantly fewer changes than the HD group. The most common reasons for changing dressings in both groups were moisture (PF 51.1%; HD 47.9%) and shear (HD 43%; PF 38.9%), with a significant difference in shear between groups. The incidence of PUs was significantly lower (p=0.038) in the PF group (8.7%) compared with that in the HD group (15%). CONCLUSION: The results suggest that the transparent polyurethane film had a better performance and was more effective than the hydrocolloid dressing in preventing PU development.

Impact of compression therapy using Unna's boot on the self-esteem of patients with venous leg ulcers.

OBJECTIVE: To assess self-esteem in patients with venous leg ulcers treated with Unna's boot. • METHOD: A descriptive, analytic, clinical study was conducted from June 2010 to May 2011 in an outpatient wound care clinic in São Paulo, Brazil. Patients of both sexes, aged ≥18 years, who had had a venous leg ulcer for more than one year and a Doppler ankle brachial index ranging from 0.8-1.0 were consecutively selected for inclusion. Patients were treated with wound dressings and Unna's boot. Self-esteem was assessed using the Brazilian version of the Rosenberg Self-Esteem Scale (RSE) at inclusion (baseline) and after 4, 8, and 12 months of compression therapy using Unna's boot. The scale is reverse-scored; thus lower scores indicate higher levels of self-esteem. • RESULTS: The patients showed a slight but significant improvement in self-esteem after 4 months of treatment (mean RSE score=17.12) compared with baseline (mean RSE score=24.90). However, a marked and significant improvement in self-esteem was observed after 8 months (mean RSE score=7.40) and 12 months (mean RSE score=2.10) of compression therapy using Unna's boot. • CONCLUSION: Patients with venous leg ulcers treated with Unna's boot for 12 months showed a significant improvement in self-esteem • DECLARATION OF INTEREST: All authors declare that no competing financial interests exist. There was no external funding for this study.

Altered plasma glutathione levels in bipolar disorder indicates higher oxidative stress; a possible risk factor for illness onset despite normal brain-derived neurotrophic factor (BDNF) levels.

BACKGROUND: Oxidative stress and neurotrophic factors have been implicated in the pathophysiology of bipolar disorder. Our objective was to determine whether plasma glutathione or brain-derived neurotrophic factor (BDNF) levels were abnormal in bipolar disorder and therefore useful as possible biomarkers. METHOD: Blood samples were collected from subsyndromal, medicated bipolar I patients (n = 50), recruited from OXTEXT, University of Oxford, and from 50 matched healthy controls. Total and oxidized glutathione levels were measured using an enzymatic recycling method and used to calculate reduced, percentage oxidized, ratio of reduced:oxidized and redox state. BDNF was measured using an enzyme-linked immunoassay. Self-monitored mood scores for the bipolar group were available (Quick Inventory of Depressive Symptomatology and the Altman Self-Rating Mania Scale) over an 8-week period. RESULTS: Compared with controls, bipolar patients had significantly lower levels of total glutathione and it was more oxidized. BDNF levels were not different. Age of illness onset but not current mood state correlated with total glutathione levels and its oxidation status, so that lower levels of total and reduced glutathione were associated with later onset of disease, not length of illness. CONCLUSIONS: Plasma glutathione levels and redox state detect oxidative stress even in subsyndromal patients with normal BDNF. It may relate to the onset and development of bipolar disorder. Plasma glutathione appears to be a suitable biomarker for detecting underlying oxidative stress and for evaluating the efficacy of antioxidant intervention studies.

Analysis of follicular events in owl monkeys (Aotus azarai infulatus) using B-mode and Doppler ultrasound.

Ultrasound (B-mode) was used to analyze follicular events in 12 trained female owl monkeys (Aotus azarai infulatus). The animals were examined every 48 hours for over 90 days to measure and map follicular growth in both ovaries and to measure (using Doppler velocimetry) local hemodynamic changes during the peri-ovulatory stage. There were 44 follicular growth events, each with two or three follicular waves, and a mean ± SEM interval between events of 17 ± 1.13 days. There were various hemodynamic changes during follicular growth; both vascular resistance index and pulsatility index decreased during the time when the follicle diameter peaked. Thus, both B-mode and Doppler ultrasound were useful for monitoring ovarian follicular events in owl monkeys.

Antigenic fractions of Leishmania (Viannia) braziliensis: the immune response characterization of patients at the initial phase of disease.

American cutaneous leishmaniasis (ACL) has different clinical manifestations and these manifestations are dependent on the immunological status of the host. As CD4(+) and CD8(+) T cells and their mediators play a fundamental role in the host response to Leishmania and there is also a search for antigenic molecules to be used as future vaccines and tools for prognostic tests, this study characterized ACL patients' immune response after stimulation with soluble and insoluble fractions of L. (V.) braziliensis. We demonstrated a prevailing production of the Th2 cytokines, IL-4 and IL-10 and a specific production of IFN-γ and TNF-α in patients before treatment. There was also a predominance of CD4(+) T cells and a small percentage CD8(+) T cells. The insoluble antigenic fraction primarily stimulated CD4(+) T cells, while the soluble antigenic fraction showed a mixed profile, with CD4(+) T cells being the main responsible for Th2 cytokines and CD8(+) T cells for Th1 cytokines. Therefore, our results showed that a down-modulation of the Th1 type of response occurs in the initial phase of L. braziliensis disease, being the antigenic fractions capable of stimulating a specific immune response.

Adenosine A(2A) receptors in portal hypertension: their role in the abnormal response to adenosine of the cranial mesenteric artery in rabbits.

1. Adenosine is a regulator of mesenteric vasodilation involved in auto-regulation and post-prandial hyperemia, but the adenosine receptor subtype involved in this relaxant effect is poorly characterized. We have now pharmacologically characterized this receptor in rabbit mesenteric arteries and investigated how this adenosine receptor response changes in portal hypertensive animals since the adenosine response is decreased. 2. The closest non-metabolisable adenosine analogue, 2-chloroadenosine (CADO), the mixed A(1)/A(2) receptor agonist, 5'-ethylcarboxamidoadenosine (NECA), and the selective A(2A) receptor agonist, 2-[4-(2-p-carbonyethyl)phenylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680) (1 pM -- 1 mM) relaxed noradrenaline pre-contracted arteries with a rank order of potency of CGS 21680 (EC(50)=20 nM) > or = NECA (60 nM)>>CADO (640 nM). 3. The selective A(2A) receptor antagonist, 4-(2-[7-amino-2-(2-furyl)-[1,2,4]-triazolo[2,3-a][1,3,5]-triazin-5-ylamino]ethyl)phenol (ZM 241385, 100 nM), shifted to the right the CADO concentration-response curve. 4. In portal hypertensive animals, there was mainly a decreased potency but also a decreased efficacy of all tested adenosine agonists compared to normal animals. Concomitantly, there was a decreased adenosine plasma level and a decreased binding density of [(3)H]-CGS 21680 and [(3)H]-ZM 241385 to mesenteric artery membranes from portal hypertensive compared to normal rabbits. 5. These results indicate that A(2A) receptor activation is required for the adenosine-induced mesenteric relaxation and that the decreased density of A(2A) receptors may contribute to the decreased relaxation induced by adenosine of mesenteric arteries in portal hypertensive animals.

Dot enzyme-linked immunosorbent assay (dot-ELISA) for schistosomiasis diagnosis using dacron as solid-phase.

Dacron and nitrocellulose were evaluated as matrices for the dot enzyme linked immunosorbent assay (dot-ELISA) for schistosomiasis and compared to indirect immunofluorescence (IMF). Titration of sera from 18 schistosomiasis patients against soluble worm antigen preparation (SWAP) was carried out and sera from healthy individuals from non-endemic areas were used as controls. The IMF was less sensitive than the dot-ELISAs, although the difference was not statistically significant (p > 0.05). The dot-ELISA based on nitrocellulose was as sensitive as that using dacron. Stability did not differ between nitrocellulose and dacron. Specificity was lower when dacron was used than when nitrocellulose was used, although the difference was not statistically significant (p > 0.05). In conclusion, this work showed that nitrocellulose and dacron performed similarly in dot-ELISA, suggesting that they may be used alternatively in population surveillance in endemic areas.