One-Year Brolucizumab Outcomes in Neovascular Age-Related Macular Degeneration from a Large United States Cohort in the IRIS® Registry.

PURPOSE: To evaluate visual acuity (VA) and injection intervals in patients with neovascular age-related macular degeneration (nAMD) after 12 months of brolucizumab therapy in clinical practice. DESIGN: Retrospective cohort study. PARTICIPANTS: Adults in the United States-based IRIS® Registry (Intelligent Research in Sight) with nAMD who received brolucizumab exclusively for 12 months (2308 eyes of 2079 patients). METHODS: Observational study of eyes with a first injection of brolucizumab (index), followed by 2 or more brolucizumab injections over the following 12 months without switching to another anti-vascular endothelial growth factor (VEGF) agent. MAIN OUTCOME MEASURES: Primary outcomes were change in best recorded VA and, for eyes receiving prior anti-VEGF therapy (treatment-experienced eyes), the difference between the brolucizumab injection interval at 12 months and the anti-VEGF injection interval before switching. The interval before switching was defined as the time between the prior anti-VEGF and index brolucizumab injections; brolucizumab interval was the time between the closest injection to day 365 and the preceding injection. Secondary outcomes included incident adverse events. RESULTS: Overall VA at index was 61.6 ± 18.4 Early Treatment Diabetic Retinopathy Study letters; 83.7% of treatment-naive eyes (184/220) and 86.1% of treatment-experienced eyes (1797/2088) showed stable (< 10 letters gained or lost) or improved (≥ 10 letters gained) VA at 12 months. Among treatment-experienced eyes receiving a prior anti-VEGF injection within 365 days before index, 29.5% (594/2015) showed an interval before switching of 8 weeks or more (mean, 7.6 ± 5.5 weeks), whereas 83.1% (1734/2015) showed a brolucizumab injection interval at 12 months of 8 weeks or more (mean, 10.3 ± 4.0 weeks). In all, 77.1% of treatment-experienced eyes (1554/2015) showed an interval extension of 1 week or more; of these, 55.4% (861/1554) showed an extension of 4 weeks or more. CONCLUSIONS: In this community-based study, at 12 months, brolucizumab treatment prolonged the interval between anti-VEGF injections for most treatment-experienced eyes, particularly those with shorter intervals before switching, while maintaining or improving VA. With careful balancing of the benefits and risks, switching to brolucizumab treatment may offer the advantage of extending the treatment interval for patients with a high anti-VEGF therapy burden. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Factors Linked to Injection Interval Extension in Eyes with Wet Age-Related Macular Degeneration Switched to Brolucizumab.

PURPOSE: To evaluate factors associated with anti-vascular endothelial growth factor (VEGF) injection interval extension in patients with neovascular age-related macular degeneration (nAMD) switched to brolucizumab treatment. DESIGN: Retrospective, observational cohort study. PARTICIPANTS: Adults in the United States-based IRIS® Registry (Intelligent Research in Sight) with nAMD who switched from another anti-VEGF agent to brolucizumab-only treatment for ≥ 12 months from October 8, 2019, through November 26, 2021. METHODS: Univariable and multivariable analyses examined associations of demographic and clinical characteristics with the likelihood of interval extension after switching to brolucizumab therapy. MAIN OUTCOME MEASURES: Eyes were classified as either extenders or nonextenders at 12 months. Extenders were eyes that achieved (1) an extension of ≥ 2 weeks in the brolucizumab injection interval at 12 months versus the interval before switching (time between the last known prior anti-VEGF injection and first [index] brolucizumab injection) and (2) stable (< 10 letters gained or lost) or improved (≥ 10 letters gained) visual acuity (VA) at 12 months versus VA at index injection. RESULTS: Of 2015 eyes among 1890 patients who switched to brolucizumab treatment, 1186 (58.9%) were extenders. In univariable analyses, demographic and clinical characteristics were comparable between extenders and nonextenders, except that extenders had shorter intervals before switching versus nonextenders (mean, 5.9 ± 2.1 weeks vs. 10.1 ± 7.6 weeks, respectively). In multivariable logistic regression modeling, a shorter interval before switching was associated significantly and positively with interval extension with brolucizumab therapy (adjusted odds ratio, 5.6 for interval before switching of < 8 weeks versus ≥ 8 weeks; 95% confidence interval, 4.5-6.9; P < 0.001), and eyes with an index VA of 40 to 65 letters were significantly less likely to be extenders than eyes in the higher (better) index VA categories. CONCLUSIONS: Length of the treatment interval before switching was the characteristic associated most strongly with successful interval extension with brolucizumab. Treatment-experienced patients who required more frequent injections (i.e., shorter intervals before switching) showed the greatest extensions when switching to brolucizumab. With careful consideration of benefits and risks, brolucizumab may be a valuable option for patients with higher treatment burdens because of the need for frequent injections. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

The Treatment Patterns with Brolucizumab in Germany (REALIZE) Study: A Retrospective Cohort Study Based on Longitudinal Prescription Data.

INTRODUCTION: This study describes real-world treatment patterns in Germany for brolucizumab, an anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD). METHODS: This single-arm retrospective cohort study used German patient-level prescription data. Patients aged ≥ 50 years, who received ≥ 1 brolucizumab prescription in one eye only (unilateral) and had a minimum of 12 months follow-up were included. Three cohorts were defined from the overall population: anti-VEGF treatment-naive patients ("treatment-naive"); anti-VEGF treatment-experienced patients ("treatment-experienced"); and of the treatment-experienced cohort, patients persistent on brolucizumab for 12 months ("treatment-experienced persistent"), i.e. who received ≥ 2 brolucizumab injections and did not discontinue or use other anti-VEGF agents in that period. Descriptive statistics were used to analyse patient characteristics and injection intervals. RESULTS: A total of 2089 patients with at least 12 months follow-up and one brolucizumab injection were analysed. Most were female (58.1%), aged 80+ years (54.7%). A total of 539 (25.8%) were treatment-naive, 1550 (74.2%) treatment-experienced and, of those, 787 (50.8%) were persistent. Overall, the median (interquartile range, IQR) number of brolucizumab injections during the 12 months follow-up was 5.0 (3.0-8.0). In the treatment-naive and treatment-experienced sub-cohorts it was 5.0 (3.0-8.0) and 5.0 (3.0-9.0) injections, respectively. In the treatment-experienced persistent cohort the median (IQR) number of injections was 8.0 (5.0-10.0). In this same cohort, the median (IQR) treatment interval between anti-VEGF injections before switch to brolucizumab was 5.1 (4.0-8.0) weeks, whilst the brolucizumab interval at 12 months after switch was 8.0 (6.0-11.9) weeks. Of treatment-experienced patients, 67% extended their treatment interval and those with pre-switch intervals less than 6 weeks (< q6w), in particular, had meaningful treatment interval extensions. CONCLUSION: Patients who switched to brolucizumab had a median treatment interval extension of about 3 weeks at 12 months. These results show that treatment with brolucizumab has the potential to reduce treatment burden in patients with nAMD in routine clinical practice.

Efficacy and safety of brolucizumab in age-related macular degeneration: A systematic review of real-world studies.

Intravitreally injected anti-vascular endothelial growth factor (anti-VEGF) agents are first-line treatment for neovascular age-related macular degeneration (nAMD). Phase 3 trials demonstrated non-inferiority of anti-VEGF therapy with brolucizumab compared with aflibercept in best corrected visual acuity (BCVA) gains, with superior anatomical outcomes after brolucizumab. The purpose of the review was to summarize real-world efficacy and safety data on brolucizumab in patients with nAMD. The review protocol was registered with PROSPERO (ID: CRD42021290530). We conducted systematic searches in Embase, Medline and key ophthalmology congress websites (19 October 2021). Original reports of efficacy and/or safety in patients receiving brolucizumab to treat nAMD in clinical practice were eligible. The descriptive summary includes reports describing at least 10 brolucizumab-treated eyes. In total, 2907 brolucizumab-treated eyes from 26 studies were included. Outcomes were available for treatment-naive eyes (six studies), eyes switched to brolucizumab from other anti-VEGFs (16 studies), and/or treatment-naive and switch eyes combined (eight studies). Follow-up time points ranged from 4 weeks to 1 year post-brolucizumab initiation. For BCVA, significant improvements compared with brolucizumab initiation were reported in four of six studies in treatment-naive eyes (mean BCVA improvement, range: +3.7 to +11.9 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and in three of 12 studies in switch eyes (range: +9.0 to +15 ETDRS letters) (all p < 0.05); remaining studies reported no significant post-brolucizumab BCVA changes. For central subfield thickness (CST), improvements post-brolucizumab initiation were reported in all six studies in treatment-naive eyes (mean CST improvement, range: -113.4 to -150.1 µm) and in eight of 11 studies in switch eyes (range: -26 to -185.7 µm) (all p < 0.05). The 14 studies reporting on intraretinal, subretinal and/or total fluid observed improvements post-brolucizumab initiation. The four studies comparing treatment intervals observed extension of the interval between injections after switching to brolucizumab from other anti-VEGFs. Incidence of intraocular inflammation ranged from 0% to 19%. In conclusion, real-world efficacy and safety data concur with brolucizumab pivotal trials. Additionally, reduction of disease activity in anti-VEGF switch eyes was demonstrated by fluid reduction and/or visual acuity gain, along with prolongation of the interval between injections.

Comparative Efficacy of Brolucizumab in the Treatment of Neovascular Age-Related Macular Degeneration: A Systematic Literature Review and Network Meta-Analysis.

INTRODUCTION: A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy of brolucizumab relative to other anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) at 1 and 2 years, and overall safety and injection frequency of each treatment. METHODS: An SLR identifying randomized controlled trials (RCTs) published before June 2021 according to a pre-specified protocol was followed by a Bayesian NMA to compare brolucizumab (6 mg q12w/q8w) against sham and all relevant anti-VEGF regimens. Pooled mean injection frequency, serious adverse ocular events, and discontinuation rates were estimated for each treatment regimen. RESULTS: Nineteen RCTs were included in NMA base-case analysis. Brolucizumab (6 mg q12w/q8w) with loading-phase (LP) demonstrated superior best-corrected visual acuity (BCVA) gains to sham both at year 1 (mean difference 16.8 [95%CrI 13.3, 20.4]) and year 2 (mean difference 21.2 [95%CrI 17.4, 25.0]) and was comparable to other anti-VEGFs. Brolucizumab (6 mg q12w/q8w) also showed superior retinal thickness reduction to most comparators including ranibizumab (0.5 mg q4w; year 1 mean difference - 50.1 [95%CrI - 70.3, - 29.8]; year 2 mean difference - 49.5 [95%CrI - 70.8, - 28.6]), aflibercept (2 mg q8w; year 1 mean difference - 39.7 [95%CrI - 52.9, - 26.4]; year 2 mean difference - 35.0 [95%CrI - 49.1, - 21.4]), and faricimab (6 mg q16w/q8w; year 1 mean difference - 27.6 [95%CrI - 42.3, - 12.8]). Brolucizumab (6 mg q12w/q8w) showed similar rates of treatment discontinuation and serious and overall adverse events (both years). At year 2, pooled annualized injection frequency was lowest for brolucizumab (6 mg q12w/q8w) and highest for ranibizumab (0.5 mg q4w) at 5.7 and 11.5 injections annually, respectively. CONCLUSION: Among all licensed anti-VEGF treatments, brolucizumab showed superior reduction in retinal thickness and comparable BCVA gains and discontinuation rates, despite having the lowest injection frequency. The current study provides the most up-to-date, robust comparison of treatments for nAMD.

Risk of requiring a wheelchair in primary progressive multiple sclerosis: Data from the ORATORIO trial and the MSBase registry.

BACKGROUND AND PURPOSE: Reaching Expanded Disability Status Scale (EDSS) ≥7.0 represents the requirement for a wheelchair. Here we (i) assess the effect of ocrelizumab on time to EDSS ≥7.0 over the ORATORIO (NCT01194570) double-blind and extended controlled periods (DBP+ECP), (ii) quantify likely long-term benefits by extrapolating results, and (iii) assess the plausibility of extrapolations using an independent real-world cohort (MSBase registry; ACTRN12605000455662). METHODS: Post hoc analyses assessing time to 24-week confirmed EDSS ≥7.0 in two cohorts of patients with primary progressive multiple sclerosis (baseline EDSS 3.0-6.5) were investigated in ORATORIO and MSBase. RESULTS: In the ORATORIO DBP+ECP, ocrelizumab reduced the risk of 24-week confirmed EDSS ≥7.0 (hazard ratio = 0.54, 95% confidence interval [CI]: 0.31-0.92; p = 0.022). Extrapolated median time to 24-week confirmed EDSS ≥7.0 was 12.1 and 19.2 years for placebo and ocrelizumab, respectively (7.1-year delay [95% CI: -4.3 to 18.4]). In MSBase, the median time to 24-week confirmed EDSS ≥7.0 was 12.4 years. CONCLUSIONS: Compared with placebo, ocrelizumab significantly delayed time to 24-week confirmed wheelchair requirement in ORATORIO. The plausibility of the extrapolated median time to reach this milestone in the placebo group was supported by observed real-world data from MSBase. Extrapolated benefits for ocrelizumab over placebo could represent a truly meaningful delay in loss of ambulation and independence.

Ecological effects on female bill colour explain plastic sexual dichromatism in a mutually-ornamented bird.

Sex differences in ornamentation are common and, in species with conventional sex roles, are generally thought of as stable, due to stronger sexual selection on males. Yet, especially in gregarious species, ornaments can also have non-sexual social functions, raising the possibility that observed sex differences in ornamentation are plastic. For example, females may invest in costly ornamentation more plastically, to protect body and reproductive ability in more adverse ecological conditions. We tested this hypothesis with experimental work on the mutually-ornamented common waxbill (Estrilda astrild), supplementing their diets either with pigmentary (lutein, a carotenoid) or non-pigmentary (vitamin E) antioxidants, or alleviating winter cold temperature. We found that both lutein and vitamin E supplementation increased red bill colour saturation in females, reaching the same mean saturation as males, which supports the hypothesis that female bill colour is more sensitive to environmental or physiological conditions. The effect of vitamin E, a non-pigment antioxidant, suggests that carotenoids were released from their antioxidant functions. Alleviating winter cold did not increase bill colour saturation in either sex, but increased the stability of female bill colour over time, suggesting that female investment in bill colour is sensitive to cold-mediated stress. Together, results show that waxbill bill sexual dichromatism is not stable. Instead, sexual dichromatism can be modulated, and even disappear completely, due to ecology-mediated plastic adjustments in female bill colour.

Treatment Patterns in Patients with Incident Parkinson's Disease in the United States.

BACKGROUND: Treatment patterns in Parkinson's disease (PD) have not been extensively studied for nearly two decades. Insurance claims are appropriate for such analysis. OBJECTIVE: To understand the standard of care use of symptomatic treatments in new cases of PD and factors associated with treatment choice. METHODS: Retrospective cohort study using claims data from the United States between 2008 and 2016. We used Kaplan-Meier methodology to estimate time to treatment start and switch or add-on therapy and Cox proportional hazards models to identify predictors. RESULTS: We identified 68,532 patients eligible for treatment pattern analyses. Median time from diagnosis until first treatment was 37 days (95% confidence interval: 36-38). Two distinct patterns of treatment initiation were identified: fast initiators and patients with delayed treatment start (or no recorded treatment). Levodopa therapies were the most commonly prescribed treatment class (52.6%). Increased age was associated with shorter time to start of treatment with levodopa. Younger age was associated with shorter time to initiation of dopamine agonists and other symptomatic treatments. Patients that initiated treatment with levodopa/combinations had the fewest switches/add-ons [30.4%; median time 7.29 (6.71, 8.13) years]. Older patients had fewer switch/add-on therapies, but only in the group that started with levodopa/combination therapy. CONCLUSIONS: Time from diagnosis to treatment start was relatively short, suggesting that PD diagnosis, as reflected in the database, is closely linked to start of symptomatic treatment. Levodopa treatment remains the most common treatment, especially for older patients. Delayed treatment start was associated with increased age and comorbidity.

Violência conjugal lésbica: relatos de assistentes sociais que atendem mulheres na cidade de Niterói / Lesbian marital violence: reports of social workers attending women in the city of Niterói

Resumo: A violência contra as mulheres é fenômeno recorrente no contexto brasileiro e pode perpassar qualquer tipo de conjugalidade. Nesse sentido, este artigo aborda o tema da violência nas conjugalidades lésbicas e apresenta uma análise dos relatos de assistentes sociais que atendem mulheres em situação de violência na cidade de ­Niterói (RJ), a fim de verificar como a violência conjugal lésbica tem aparecido em seus cotidianos profissionais.

Abstract: Violence against women is a recurring phenomenon in the Brazilian context and can permeate any type of conjugality. In this sense, this article approaches the theme of violence in lesbian conjugalities, and presents an analysis of the reports of social workers attending women in a situation of violence in the city of Niterói, RJ, in order to verify of these professionals, how lesbian conjugal violence appears in their work actions.

Phylogenetic analysis of apicomplexan parasites infecting commercially valuable species from the North-East Atlantic reveals high levels of diversity and insights into the evolution of the group.

BACKGROUND: The Apicomplexa from aquatic environments are understudied relative to their terrestrial counterparts, and the seminal work assessing the phylogenetic relations of fish-infecting lineages is mostly based on freshwater hosts. The taxonomic uncertainty of some apicomplexan groups, such as the coccidia, is high and many genera were recently shown to be paraphyletic, questioning the value of strict morphological and ecological traits for parasite classification. Here, we surveyed the genetic diversity of the Apicomplexa in several commercially valuable vertebrates from the North-East Atlantic, including farmed fish. RESULTS: Most of the sequences retrieved were closely related to common fish coccidia of Eimeria, Goussia and Calyptospora. However, some lineages from the shark Scyliorhinus canicula were placed as sister taxa to the Isospora, Caryospora and Schellakia group. Additionally, others from Pagrus caeruleostictus and Solea senegalensis belonged to an unknown apicomplexan group previously found in the Caribbean Sea, where it was sequenced from the water column, corals, and fish. Four distinct parasite lineages were found infecting farmed Dicentrarchus labrax or Sparus aurata. One of the lineages from farmed D. labrax was also found infecting wild counterparts, and another was also recovered from farmed S. aurata and farm-associated Diplodus sargus. CONCLUSIONS: Our results show that marine fish apicomplexans are diverse, and we highlight the need for a more extensive assessment of parasite diversity in this phylum. Additionally, parasites recovered from S. canicula were recovered as basal to their piscine counterparts reflecting hosts phylogeny.

LONG-TERM OUTCOMES OF RANIBIZUMAB TREATMENT OF MYOPIC CHOROIDAL NEOVASCULARIZATION IN EAST-ASIAN PATIENTS FROM THE RADIANCE STUDY.

PURPOSE: To evaluate long-term efficacy and safety of ranibizumab for treatment of myopic choroidal neovascularization (mCNV) in clinical practice. METHODS: Noninterventional, retrospective cohort study of East-Asian patients previously treated with ranibizumab during the RADIANCE trial. Forty-one patients who completed the RADIANCE trial were followed-up for up to 48 months (post-RADIANCE observation period). Outcome measures were best-corrected visual acuity changes from baseline (assessed at RADIANCE trial initiation), mCNV recurrences, and ocular adverse events. RESULTS: Mean visual gain from baseline best-corrected visual acuity (56.5 ± 12.1 letters) (20/80) was significant at 12 months (+14.3 ± 11.4 letters, n = 40, P < 0.0001), 24 months (+10.4 ± 22.3 letters, n = 31, P = 0.0143), 30 months (+11.0 ± 22.4 letters, n = 29, P = 0.0134), 42 months (+12.9 ± 20.9 letters, n = 25, P = 0.0051), and 48 months (+16.3 ± 18.7, n = 16, P = 0.0034). Of the 16 patients who completed 48 months of follow-up, 63% gained ≥10 letters and 13% lost ≥10 letters. Over the post-RADIANCE observation period, 83% of patients required no further treatment for mCNV, 10% experienced mCNV recurrences, and 12% experienced a nonserious ocular adverse event. Patients who required additional treatment for mCNV received a mean of 5.0 (SD 5.9, range 1.0-18.0) ranibizumab injections. CONCLUSION: Best-corrected visual acuity gained at the end of the RADIANCE trial was sustained over additional 36 months of follow-up. Few patients required further treatment and no new safety concerns were observed.

A Systematic Review and Meta-Analysis of Prevalence Studies of Sporadic Inclusion Body Myositis.

BACKGROUND: Sporadic Inclusion Body Myositis (sIBM) is a rare and slowly progressive debilitating muscle disease with symptoms generally developing≥50 years of age. OBJECTIVE: To conduct a systematic review and meta-analysis of the prevalence of sIBM literature, including a methodological quality assessment of the selected papers. METHODS: A systematic search of Medline, Embase, Cochrane Database of Systematic Reviews and major Myositis and Neurological conferences was conducted. Articles reporting prevalence and published in English up to March 2017 were assessed for methodology quality using the Loney quality assessment, Downs & Black score, and the Methodological Evaluation of Observational Research checklists. Meta-analyses using random effects were completed on both general population and≥50 years prevalence estimates. RESULTS: 315 articles were retrieved and data were extracted from 10 relevant studies. One study was subsequently excluded due to methodological issues. The meta-prevalence estimate from 9 papers was 24.8/1,000,000 (95% CI: 20.0-29.6). The methodological quality results were consistent across assessment tools with four articles scoring 4 or 5 out of 8 in the Loney assessment. The meta-prevalence of these four articles was 45.6/ 1,000,000 (95% CI: 35.9-55.2). CONCLUSION: There was high variability in reported sIBM prevalence estimates and the quality of the studies conducted. Existing evidence suggests an increase of prevalence estimates over time, which may be explained by growing disease awareness, improvements in diagnostic criteria and study methodologies. Further high quality studies are needed to understand if prevalence varies across geographies or ethnicities.

Effect of MUC1/ß-catenin interaction on the tumorigenic capacity of pancreatic CD133+ cells.

Despite the fact that the biological function of cluster of differentiation (CD)133 remains unclear, this glycoprotein is currently used in the identification and isolation of tumor-initiating cells from certain malignant tumors, including pancreatic cancer. In the present study, the involvement of mucin 1 (MUC1) in the signaling pathways of a highly tumorigenic CD133+ cellular subpopulation sorted from the pancreatic cancer cell line HPAF-II was evaluated. The expression of MUC1-cytoplasmic domain (MUC1-CD) and oncogenic signaling transducers (epidermal growth factor receptor, protein kinase C delta, glycogen synthase kinase 3 beta and growth factor receptor-bound protein 2), as well as the association between MUC1 and ß-catenin, were characterized in HPAF-II CD133+ and CD133low cell subpopulations and in tumor xenografts generated from these cells. Compared with HPAF CD133low cells, HPAF-II CD133+ cancer cells exhibited increased tumorigenic potential in immunocompromised mice, which was associated with overexpression of MUC1 and with the accordingly altered expression profile of MUC1-associated signaling partners. Additionally, MUC1-CD/ß-catenin interactions were increased both in the HPAF-II CD133+ cell subpopulation and derived tumor xenografts compared with HPAF CD133low cells. These results suggest that, in comparison with HPAF CD133low cells, CD133+ cells exhibit higher expression of MUC1, which contributes to their tumorigenic phenotype through increased interaction between MUC1-CD and ß-catenin, which in turn modulates oncogenic signaling cascades.

Expanding the use of administrative claims databases in conducting clinical real-world evidence studies in multiple sclerosis.

OBJECTIVE: Administrative claims databases provide a wealth of data for assessing the effect of treatments in clinical practice. Our aim was to propose methodology for real-world studies in multiple sclerosis (MS) using these databases. RESEARCH DESIGN AND METHODS: In three large US administrative claims databases: MarketScan, PharMetrics Plus and Department of Defense (DoD), patients with MS were selected using an algorithm identified in the published literature and refined for accuracy. Algorithms for detecting newly diagnosed ('incident') MS cases were also refined and tested. Methodology based on resource and treatment use was developed to differentiate between relapses with and without hospitalization. RESULTS: When various patient selection criteria were applied to the MarketScan database, an algorithm requiring two MS diagnoses at least 30 days apart was identified as the preferred method of selecting patient cohorts. Attempts to detect incident MS cases were confounded by the limited continuous enrollment of patients in these databases. Relapse detection algorithms identified similar proportions of patients in the MarketScan and PharMetrics Plus databases experiencing relapses with (2% in both databases) and without (15-20%) hospitalization in the 1 year follow-up period, providing findings in the range of those in the published literature. LIMITATION: Additional validation of the algorithms proposed here would increase their credibility. CONCLUSIONS: The methods suggested in this study offer a good foundation for performing real-world research in MS using administrative claims databases, potentially allowing evidence from different studies to be compared and combined more systematically than in current research practice.

Estoques de C e de N e produtividade do milho sob sistemas de preparo e adubação nitrogenada em um Latossolo Vermelho-Amarelo do cerrado piauiense / C and N stocks and maize yield under tillage systems and nitrogen fertilization at Red Yellow Latosol in the savanna of the Piauí State

Os estoques totais de carbono orgânico (C) e nitrogênio (N) e a produção de culturas são influenciados pelo preparo do solo, pelo aporte de resíduos e pela fertilização nitrogenada. Este trabalho teve como objetivo avaliar o efeito de diferentes sistemas de preparo associados às doses de nitrogênio sobre a produtividade do milho e os estoques de C e N de um Latossolo Vermelho-Amarelo no cerrado piauiense. O experimento foi realizado no Município de Baixa Grande do Ribeiro, sudeste do Estado do Piauí. O delineamento experimental foi em blocos ao acaso, em esquema fatorial 2 x 5, (dois sistemas de preparo: (plantio direto (PD) e convencional (PC) e; cinco doses de nitrogênio (0, 60, 120, 180 e 240kg N ha-1)), com seis repetições. Foram avaliados a produtividade de grãos (PG), os aportes de C e N, provenientes da cultura do milho, e os estoques de C e N no solo, nas camadas de 0-5, 5-10, 10-20 e 20-40cm. As doses de N ocasionaram resposta quadrática na produtividade de grãos e no aporte e estoque de C e N, tanto no PC, quanto no PD. As maiores produtividades de grãos foram obtidas com as doses de 138 e 134kg N ha-1 para PC e PD, respectivamente. Os maiores aportes de C e N no PC foram observados nas doses de 140 e 175kg ha-1 de N e no PD, nas doses de 139 e 100kg ha-1 de N, respectivamente. A adubação nitrogenada aumentou os estoques de C no solo, no sistema PD, em comparação ao PC, nas camadas de 0-5 e 5-10cm. A adoção do sistema plantio direto em combinação com aplicação balanceada de fertilizante nitrogenado é importante para construção da matéria orgânica em solos do cerrado piauiense.

Total soil organic carbon (C) and nitrogen (N) stocks and crop yield are influenced by tillage, biomass input from crop and nitrogen fertilization. This research aimed to evaluate the effect of different tillage systems associated to nitrogen doses on corn yield and C and N stocks in the Red Yellow Latosol in savanna of Piauí state, Brazil. The experiment was carried out in Baixa Grande do Ribeiro, south of Piauí state. The treatments were distributed in a randomized complete blocks and factor arrange 2x5, two tillage systems (no-tillage (NT) and conventional (CT)) and five nitrogen doses (0, 60, 120,180 and 240kg ha-1 N), respectively, with six replications. The corn grain yield (GY) and C and N inputs were measured and C and N soil stocks were evaluated in the 0-5, 5-10, 10-20 and 20-40cm. N doses caused a quadratic response in the grain yield, C and N inputs from maize crop and soil C stocks in both tillage systems. Higher GY were obtained by 138 and 134kg N ha-1 to CT and NT, respectively. Higher C and N inputs were obtained by 140 and 175kg N ha-1, in the CT and by 139 and 100kg N ha-1 in the NT system, respectively. Nitrogen fertilization increased soil C stocks in the NT comparing to CT in the 0-5 and 5-10 depths. No tillage adoption combined with balanced nitrogen fertilization can be important to soil organic matter production in soils under cerrado of Piauí state.

[Do Capsicum spp. trichomes influence the biological aspects of the broad mite, Polyphagotarsonemus latus Banks (Acari: Tarsonemidae)?]. / Os tricomas de Capsicum spp. interferem nos aspectos biológicos do ácaro-branco, Polyphagotarsonemus latus Banks (Acari: Tarsonemidae)?

Plant morphology traits can affect the feeding preference, oviposition choice and the vulnerability of herbivores to natural enemies. At long term, these plant variations may influence herbivore population dynamics due to the interference on their development, survival and reproduction. In this paper, the development of the broad mite Polyphagotarsonemus latus (Banks) was evaluated on five species of Capsicum with different density of trichomes. We tested the hypothesis that P. latus population growth has a negative relationship with the increase trichome density on leaves. It was assessed a decrease in the intrinsic growth rate (r m) of P. latus with the increase of trichome density on the leaves tested. The lower r m was measured in leaves of C. praetermissum (r m = 0.46), which has the highest trichome density among the assessed Capsicum species. The highest values of r m were observed on Capsicum species with intermediate densities of trichomes on leaves such as Capsicum frutescens (r m = 0.77) and Capsicum chinense (r m = 0.76). Capsicum spp. trichomes acted as a limiting plant trait for the development of P. latus when they were in higher densities and better distributed on the leaf surface. We also discuss the role of morphologic and chemical plant defenses on P. latus development.

Os tricomas de Capsicum spp. interferem nos aspectos biológicos do ácaro-branco, Polyphagotarsonemus latus Banks (Acari: Tarsonemidae)? / Do Capsicum spp. trichomes Influence the biological aspects of the broad mite, Polyphagotarsonemus latus Banks (Acari: Tarsonemidae)?

Variações nas características morfológicas das plantas podem ter efeito imediato sobre a preferência alimentar, escolha de sítios de oviposição e vulnerabilidade de herbívoros a inimigos naturais. A longo prazo, podem ter consequências sobre a dinâmica populacional desses organismos, já que atuam sobre seu desenvolvimento, sobrevivência e reprodução. Neste trabalho, avaliou-se o desenvolvimento de Polyphagotarsonemus latus (Banks) em cinco espécies de Capsicum com diferentes densidades de tricomas. Testou-se a hipótese de que o crescimento populacional de P. latus nessas plantas apresenta relação negativa com o aumento da densidade de tricomas nas folhas. Observou-se um padrão decrescente na taxa intrínseca de crescimento (r m) de P. latus com o aumento da densidade de tricomas nas folhas. O menor r m foi obtido em folhas de C. praetermissum (r m = 0,46), que apresenta a maior densidade de tricomas entre as espécies de Capsicum avaliadas. Os maiores valores de r m foram observados em espécies de Capsicum com densidade intermediária de tricomas nas folhas, Capsicum frutescens (r m = 0,77) e Capsicum chinense (r m = 0,76). Os tricomas de Capsicum spp. atuaram como fator limitante ao desenvolvimento de P. latus à medida que se apresentaram em maiores densidades e mais bem distribuídos na superfície foliar. Foi discutido ainda o papel da defesa morfológica e química de plantas de Capsicum sobre o desenvolvimento de P. latus.

Plant morphology traits can affect the feeding preference, oviposition choice and the vulnerability of herbivores to natural enemies. At long term, these plant variations may influence herbivore population dynamics due to the interference on their development, survival and reproduction. In this paper, the development of the broad mite Polyphagotarsonemus latus (Banks) was evaluated on five species of Capsicum with different density of trichomes. We tested the hypothesis that P. latus population growth has a negative relationship with the increase trichome density on leaves. It was assessed a decrease in the intrinsic growth rate (r m) of P. latus with the increase of trichome density on the leaves tested. The lower r m was measured in leaves of C. praetermissum (r m = 0.46), which has the highest trichome density among the assessed Capsicum species. The highest values of r m were observed on Capsicum species with intermediate densities of trichomes on leaves such as Capsicum frutescens (r m = 0.77) and Capsicum chinense (r m = 0.76). Capsicum spp. trichomes acted as a limiting plant trait for the development of P. latus when they were in higher densities and better distributed on the leaf surface. We also discuss the role of morphologic and chemical plant defenses on P. latus development.

Domácias e seu papel na defesa das plantas / Domatia mediating plant defense

Domácias são pequenas estruturas presentes na face inferior das folhas de diversas plantas de importância agrícola e têm sido descritas por serem tipicamente habitadas por ácaros (predadores e fungívoros) que provêm benefícios às plantas. São estruturas extremamente complexas e não apresentam qualquer função fisiológica conhecida. Tem sido postulado que os ácaros se beneficiam das domácias pela obtenção de um local seguro para reprodução e proteção contra predadores e que as plantas também se beneficiam pela redução do ataque de herbívoros ou patógenos. Assim, ecologistas têm hipotetizado que as domácias mediam uma associação mutualística entre as plantas e os ácaros que protegem as folhas. Nesta revisão, é discutido o papel das domácias na defesa das plantas contra pequenos artrópodes.

Leaf domatia are small structures found on the underside of the leaves of many plants of agricultural importance. Domatia have been described to be typically inhabited by mites (predators and fungivorous) that provide benefits to the plant. The structures can be extremely complex and seem to have an unknown physiological function. It has been postulated that mites may get some benefit from leaf domatia by securing a safe place for reproduction and refuge from predators. Additionally, plants get benefits via reduced herbivory or pathogen attack. Hence, ecologists have hypothesized that domatia mediate a mutualistic association between plants and their bodyguard mites. In this review we discussed the pivotal role of the domatia in plant defenses against small arthropods.

Famílias e violência: Reflexões sobre as mães de Acari / Family and violence: Reflections on the mothers of Acary

Na década de 90 ganharam uma certa amplitude notícias que retratavam mulheres, especialmente mães, nas praças e ruas reivindicando justiça. O que uniria essas mulheres seria a maternidade e a violência que as tinham separado de seus filhos, mortos ou seqüestrados. Acredito que o fato de participar de movimentos tem levado as mulheres a redefinições e transformações em sua identidade de gênero, bem como tem possibilitado construir para a maternidade outras dimensões. Assim, a noção de experiência tornou-se central em meu estudo. Foi desse modo que pude perceber a construção de uma nova representação para a figura materna. Primeiro, a partir de jornais, depois, ao entrevistar essas mães. Minha análise se voltou para o protagonismo político da mulher das classes trabalhadoras a partir do lugar que tradicionalmente ocupam na família e que, em princípio, seria destituído de uma dimensão política. Dessa forma, este escrito visa resgatar a partir das falas e das imagens destacadas por essas mulheres, o modo como a violência é sentida ao se tornar parte de suas vidas. Utilizei, para tanto, as entrevistas e os recortes de jornais por elas mesmas selecionados para fazer parte de seus álbuns de recordação. A imagem de mulheres na luta, de mães em luta foi de onde parti; e busco, nesse texto, problematizar os impactos e contradições, as continuidades e rupturas, que essa representação traz em seu bojo(AU)

Famílias e violência: reflexöes sobre as mäes de Acari / Families and violence: reflections on the Mothers of \"Acary\"

Na década de 90 ganharam uma certa amplitude notícias que retratavam mulheres, especialmente mäes, nas praças e ruas reivindicando justiça. O que uniria essas mulheres seria a maternidade e a violência que as tinham separado de seus filhos, mortos ou seqüestrados. Acredito que o fato de participar de movimentos tem levado as mulheres a redefiniçöes e transformaçöes em sua identidade de gênero, bem como tem possibilitado construir para a maternidade outras dimensöes. Assim, a noçäo de experiência tornou-se central em meu estudo. Foi desse modo que pude perceber a construçäo de uma nova representaçäo para a figura materna. Primeiro, a partir de jornais, depois, ao entrevistar essas mäes. Minha análise se voltou para o protagonismo político da mulher das classes trabalhadoras a partir do lugar que tradicionalmente ocupam na família e que, em princípio, seria destituído de uma dimensäo política. Dessa forma, este escrito visa resgatar a partir das falas e das imagens destacadas por essas mulheres, o modo como a violência é sentida ao se tornar parte de suas vidas. Utilizei, para tanto, as entrevistas e os recortes de jornais por elas mesmas selecionados para fazer parte de seus álbuns de recordaçäo. A imagem de mulheres na luta, de mäes em luta foi de onde parti; e busco, nesse texto, problematizar os impactos e contradiçöes, as continuidades e rupturas, que essa representaçäo traz em seu bojo