Determination of carbamazepine in fingerprints: a feasibility study to evaluate adherence in epilepsy patients.

Background: Fingerprint drug concentrations can be used as a noninvasive and convenient alternative to evaluate adherence to pharmacotherapy. Methods: Fingerprints were applied over glass slides, extracted and analyzed by ultra-high performance LC-MS/MS. The assay and drug adherence questionnaires were applied to 30 epilepsy patients. Results: The assay had linearity in the range 0.05-10 ng fingerprint-1, with precision of 2.16-7.9% and accuracy of 95.0-102.8%. Carbamazepine (CBZ) levels in fingerprints were stable at 45°C for 15 days. Concentrations in patient samples were 0.06-9.28 ng fingerprint-1. A significant difference (p = 0.003) was found between CBZ concentrations in fingerprints between patient groups divided as low and medium/high adherence. Conclusion: This method can potentially be applied to the identification of epilepsy patients with low adherence to CBZ pharmacotherapy.

Proposal of a screening instrument for autism spectrum disorder in children (Mini-TEA Scale).

BACKGROUND: Autism spectrum disorder (ASD) requires trained professionals for its adequate diagnosis. There is a shortage of such professionals in Brazil. Screening tools could identify priority cases. The only instrument for that in Brazilian Portuguese is employed for toddlers up to 2.5 years old. OBJECTIVE: The Mini-TEA scale was conceived and tested as a screening for children from 2.5 to 12 years old. METHODS: After local ethics committee's approval, this study was conducted from December 2022 to April 2023 in the Associação de Pais e Amigos dos Excepcionais, Passo Fundo/RS, of invitations to children's parents/relatives who were under evaluation for ASD and by local advertisement. Inclusion criteria were age from 2.5 to 12 years old; consent from the child's legal guardians. 75 children's parents/relatives were interviewed using the 15-item Mini-TEA scale. After that, children were evaluated for the diagnosis of ASD by a pediatric neurologist. Sensibility and specificity for ASD diagnosis along the Mini-TEA scores were measured. Experts and target population evaluated the validity/reliability of the Mini-TEA scale. The reproducibility of the scores was assessed about 40 days later. RESULTS: From the 75 participants, 28 received a diagnosis of ASD. Scores ≥ 10 on the Mini-TEA scale require further evaluation of the children (sensitivity 100%; specificity 68%). Content validity coefficient (CVC) rendered values > 0.80 (acceptable). Test-retest analyzes with the intraclass correlation coefficient (ICC) indicated excellent reliability (> 0.90). The time spent for applying the screening was about 10 minutes. CONCLUSION: The Mini-TEA scale presents as an easy tool for screening ASD among children.

ANTECEDENTES: O transtorno do espectro autista (TEA) requer profissionais treinados para o diagnóstico, escassos no Brasil. Instrumentos de triagem poderiam identificar casos prioritários para avaliação. O único em português brasileiro é empregado para crianças até 30 meses de idade. OBJETIVO: A escala Mini-TEA foi concebida e testada como triagem para crianças entre 2,5 e 12 anos. MéTODOS: Estudo foi conduzido de dezembro de 2022 a abril de 2023 na Associação de Pais e Amigos dos Excepcionais (APAE) de Passo Fundo/RS, após a aprovação bioética local. O recrutamento consistiu em convite aos familiares de crianças que estavam sendo avaliadas para TEA e por divulgação local. Os critérios de inclusão foram idade entre 2,5 e 12 anos e consentimento do guardião legal. Familiares de 75 crianças foram entrevistados com a escala Mini-TEA (15 itens). Depois, as crianças foram avaliadas para o diagnóstico de TEA por neuropediatra. A sensibilidade e a especificidade do diagnóstico de TEA com os escores da Mini-TEA foram mensuradas. A validade e a confiabilidade da escala Mini-TEA foram avaliadas por experts e pela população alvo. A reprodutibilidade dos escores foi medida após ± 40 dias. RESULTADOS: Dos 75 participantes, 28 receberam diagnóstico de TEA. Escores ≥ 10 na escala Mini-TEA requerem avaliação das crianças (sensibilidade 100%; especificidade 68%). O coeficiente de validação de conteúdo (CVC) rendeu valores > 0,80 (aceitável). Análises de teste-reteste com coeficiente de correlação intraclasse (ICC) indicou excelente confiabilidade (> 0,90). O tempo gasto para a triagem foi cerca de 10 minutos. CONCLUSãO: A escala Mini-TEA constitui ferramenta breve e fácil para triagem de TEA em crianças.

Spirulina Platensis Attenuates Rebound Dyspeptic Symptoms After Proton Pump Inhibitors' Discontinuation: Phase 2 Placebo-controlled Trial.

Context: Rebound acid hypersecretion after cessation of proton pump inhibitors (PPIs) can provoke dyspeptic symptoms. The search for alternatives to minimize the dyspeptic rebound symptoms after PPI discontinuation is warranted. Spirulina platensis, a dietary supplement made from blue-green algae, might be an alternative. Objective: The study intended to assess whether Spirulina platensis, through its anti-inflammatory and analgesic properties, can minimize rebound symptoms after PPI withdrawal. Design: The research team performed a randomized, phase 2, double-blinded, placebo-controlled clinical trial. Setting: The study took place at São Vicente de Paulo Hospital (trial registry number NCT04988347) in Passo Fundo, Brazil. Participants: Participants were 45 Brazilian patients in the clinical practice of two of the research team's member between November 2010 and February 2012, who were using PPIs regularly. Interventions: Participants underwent clinical and endoscopic evaluations after a 28-day run-in phase of 40 mg/day of pantoprazole. In the absence of a large hiatal hernia, peptic ulcer, or severe reflux esophagitis, participants stopped using PPIs, and the research team randomly assigned them to receive either 1.6g/day of spirulina or of a placebo for two months, followed by clinical and endoscopic reevaluations. Outcome measures: Using an intention-to-treat analysis, the primary outcomes postintervention were dyspepsia and typical reflux symptoms, either the appearance or maintenance of symptoms of >50% from baseline. Results: The median time of continuous PPI use was 32 months. The research team excluded two participants due to large hiatal hernias. Among the remaining 43 participants, 18 received spirulina (42%), and 25 used a placebo (58%). Two months later, 12 participants who had received spirulina (67%) and 18 who had received the placebo (72%) completed the study (P = .968). Rebound dyspepsia occurred in 10 out of 18 patients treated with spirulina (55.56%) and in 22 out of 25 patients treated with placebo (88%), with relative risk=0.63, CI95% (0.41-0.98), and P = .039. Reflux symptoms postintervention occurred in 72% and 76%, with the relative risk=0.95, CI95% (0.66-1.36), and P > .05, respectively. No significant side effects occurred in either group. The findings from endoscopy and gastric histology didn't differ between groups. Conclusions: A two-month course of Spirulina platensis was able to attenuate rebound dyspepsia but not reflux symptoms after PPI discontinuation. Considering its good safety profile, spirulina might be useful to relieve dyspeptic symptoms after PPI discontinuation.

Prevalence of fibromyalgia in a Brazilian series of patients with multiple sclerosis.

BACKGROUND: The prevalence of pain in patients with multiple sclerosis is remarkable. Fibromyalgia has been considered as one of the forms of chronic pain encompassed in multiple sclerosis, but data are restricted to studies from Europe and North America. OBJECTIVE: To assess the prevalence of fibromyalgia in a series of Brazilian patients with multiple sclerosis and the characteristics of this comorbidity. METHODS: The present cross-sectional study included 60 consecutive adult patients with multiple sclerosis. Upon consent, participants underwent a thorough evaluation for disability, fatigue, quality of life, presence of fibromyalgia, depression, and anxiety. RESULTS: The prevalence of fibromyalgia was 11.7%, a figure similar to that observed in previous studies. Patients with the comorbidity exhibited worse scores on fatigue (median and interquartile range [IQR]: 68 [48-70] versus 39 [16.5-49]; p < 0.001), quality of life (mean ± standard deviation [SD]: 96.5 ± 35.9 versus 124.8 ± 28.8; p = 0.021), anxiety (mean ± SD: 22.7 ± 15.1 versus 13.8 ± 8.4; p = 0.021), and depression (median and IQR: 23 [6-28] versus 6 [3-12.5]; p = 0.034) indices than patients without fibromyalgia. There was a strong positive correlation between depression and anxiety scores with fatigue (r = 0.773 and r = 0.773, respectively; p < 0.001). Conversely, a moderate negative correlation appeared between the Expanded Disability Status Scale (EDSS), fatigue, and depression scores with quality of life (r= -0.587, r= -0.551, r= -0.502, respectively; p < 0.001). CONCLUSION: Fibromyalgia is a comorbidity of multiple sclerosis that can enhance fatigue and decrease quality of life, although depression, anxiety, and disability are factors that can potentiate the impact of the comorbidity.

ANTECEDENTES: A prevalência de dor em pacientes com esclerose múltipla é significativa. A fibromialgia é considerada uma forma de dor crônica encontrada na esclerose múltipla, mas os dados são restritos a estudos europeus e da América do Norte. OBJETIVO: Avaliar a prevalência de fibromialgia em uma série de pacientes com esclerose múltipla e as características desta comorbidade. MéTODOS: O presente estudo transversal incluiu consecutivamente 60 pacientes adultos com esclerose múltipla. Após o consentimento, os participantes foram submetidos à avaliação para determinação de incapacidade, fadiga, qualidade de vida, presença de fibromialgia, depressão e ansiedade. RESULTADOS: A prevalência de fibromialgia foi de 11,7%, similar ao observado em estudos prévios. Pacientes com a comorbidade apresentaram piores escores de fadiga (mediana e intervalo interquartil [IIQ]: 68 [48­70] versus 39 [16,5­49]; p < 0,001], qualidade de vida (média ± desvio padrão [DP]: 96,5 ± 35,9 versus 124,8 ± 28,8; p = 0,021), ansiedade (média ± DP: 22,7 ± 15,1 versus 13,8 ± 8,4; p = 0,021) e depressão (mediana e IIQ: 23 (6­28) versus 6 (3­12,5); p = 0,034] do que pacientes sem fibromialgia. Houve correlação positiva forte dos escores de depressão e de ansiedade com a fadiga (r = 0,773 e r = 0,773, respectivamente; p < 0,001). Concomitantemente, houve correlação negativa moderada entre os escores de escala de estado de incapacidade expandida, fadiga e depressão com a qualidade de vida (r = - 0,587, r = - 0,551, r = - 0,502, respectivamente; p < 0,001). CONCLUSãO: A fibromialgia é uma comorbidade de esclerose múltipla que pode aumentar a fadiga e diminuir a qualidade de vida, embora depressão, ansiedade e incapacidade sejam fatores potencializadores dessa morbidade associada.

The brain-esophagus axis in subjects with and without obesity assessed by esophageal acid perfusion and functional brain imaging.

Background: Gastroesophageal reflux disease (GERD) has a complex pathophysiology and a heterogeneous symptom profile. The brain-esophageal axis in GERD has been studied with functional brain imaging during the last decades, but data from obese patients was just recently reported. A comparison of such a group with non-obese subjects is lacking in the literature. This study aimed to evaluate heartburn perception and brain connectivity responses during esophageal acid stimulation in subjects with and without obesity, controlling for the presence of typical reflux symptoms. Methods: In this cross-sectional study, 25 patients with obesity (body mass index ≥30 kg/m2) and 46 subjects without obesity underwent functional magnetic resonance imaging (fMRI) of the brain with esophageal water and acid perfusion. The fMRI paradigm and connectivity were assessed. Results: About two-thirds of the participants had reflux symptoms. Heartburn perception during fMRI did not differ between subjects with and without obesity. The presence of reflux symptoms was associated with lower activation in frontal brain regions during acid perfusion compared to water perfusion. Compared to subjects without obesity, patients with obesity presented significantly lower connectivity within the anterior salience network. Corrected clusters included left caudate, left putamen and left anterior cingulate gyrus. Conclusions: The brain-esophagus axis showed differences between subjects with and without obesity. Even without symptomatic differences following esophageal acid perfusion, patients with reflux symptoms showed less brain activation in frontal areas, while obese individuals presented lower connectivity within the anterior salience network.

Prevalence of fibromyalgia in a Brazilian series of patients with multiple sclerosis / Prevalência de fibromialgia em uma série brasileira de pacientes com esclerose múltipla

Abstract Background The prevalence of pain in patients with multiple sclerosis is remarkable. Fibromyalgia has been considered as one of the forms of chronic pain encompassed in multiple sclerosis, but data are restricted to studies from Europe and North America. Objective To assess the prevalence of fibromyalgia in a series of Brazilian patients with multiple sclerosis and the characteristics of this comorbidity. Methods The present cross-sectional study included 60 consecutive adult patients with multiple sclerosis. Upon consent, participants underwent a thorough evaluation for disability, fatigue, quality of life, presence of fibromyalgia, depression, and anxiety. Results The prevalence of fibromyalgia was 11.7%, a figure similar to that observed in previous studies. Patients with the comorbidity exhibited worse scores on fatigue (median and interquartile range [IQR]: 68 [48-70] versus 39 [16.5-49]; p < 0.001), quality of life (mean ± standard deviation [SD]: 96.5 ± 35.9 versus 124.8 ± 28.8; p = 0.021), anxiety (mean ± SD: 22.7 ± 15.1 versus 13.8 ± 8.4; p = 0.021), and depression (median and IQR: 23 [6-28] versus 6 [3-12.5]; p = 0.034) indices than patients without fibromyalgia. There was a strong positive correlation between depression and anxiety scores with fatigue (r = 0.773 and r = 0.773, respectively; p < 0.001). Conversely, a moderate negative correlation appeared between the Expanded Disability Status Scale (EDSS), fatigue, and depression scores with quality of life (r= −0.587, r= −0.551, r= −0.502, respectively; p < 0.001). Conclusion Fibromyalgia is a comorbidity of multiple sclerosis that can enhance fatigue and decrease quality of life, although depression, anxiety, and disability are factors that can potentiate the impact of the comorbidity.

Resumo Antecedentes A prevalência de dor em pacientes com esclerose múltipla é significativa. A fibromialgia é considerada uma forma de dor crônica encontrada na esclerose múltipla, mas os dados são restritos a estudos europeus e da América do Norte. Objetivo Avaliar a prevalência de fibromialgia em uma série de pacientes com esclerose múltipla e as características desta comorbidade. Métodos O presente estudo transversal incluiu consecutivamente 60 pacientes adultos com esclerose múltipla. Após o consentimento, os participantes foram submetidos à avaliação para determinação de incapacidade, fadiga, qualidade de vida, presença de fibromialgia, depressão e ansiedade. Resultados A prevalência de fibromialgia foi de 11,7%, similar ao observado em estudos prévios. Pacientes com a comorbidade apresentaram piores escores de fadiga (mediana e intervalo interquartil [IIQ]: 68 [48-70] versus 39 [16,5-49]; p < 0,001], qualidade de vida (média ± desvio padrão [DP]: 96,5 ± 35,9 versus 124,8 ± 28,8; p = 0,021), ansiedade (média ± DP: 22,7 ± 15,1 versus 13,8 ± 8,4; p = 0,021) e depressão (mediana e IIQ: 23 (6-28) versus 6 (3-12,5); p = 0,034] do que pacientes sem fibromialgia. Houve correlação positiva forte dos escores de depressão e de ansiedade com a fadiga (r = 0,773 e r = 0,773, respectivamente; p < 0,001). Concomitantemente, houve correlação negativa moderada entre os escores de escala de estado de incapacidade expandida, fadiga e depressão com a qualidade de vida (r = - 0,587, r = - 0,551, r = - 0,502, respectivamente; p < 0,001). Conclusão A fibromialgia é uma comorbidade de esclerose múltipla que pode aumentar a fadiga e diminuir a qualidade de vida, embora depressão, ansiedade e incapacidade sejam fatores potencializadores dessa morbidade associada.

Seizure occurring with retinal laser therapy: a report of the first case with frequency-doubled Nd-YAG / Convulsão durante laserterapia retiniana: relato do primeiro caso com o Nd-YAG de frequência dobrada

ABSTRACT Laser photocoagulation is a safe method for the treatment of retinal disorders. We present a case of a 21-year-old woman with high myopia, retinal detachment in the right eye, and bilateral lattice degeneration. She underwent surgical repair in the right eye followed by bilateral retinal laser therapy. During laser photocoagulation of the left eye, she experienced a generalized tonic-clonic seizure for the first time in her life. She had a positive family history of epilepsy. Neurological examination and brain magnetic resonance imaging findings were normal, but an electroencephalogram revealed epileptogenic discharges, more frequent during photostimulation. She avoided flickering lights during the 2-year follow-up, without seizure recurrence. Approximately 5% of patients with epilepsy have photosensitive epilepsy, of whom a considerable proportion will experience seizures only during exposition to flashing lights. Laser photocoagulation was already successfully employed in an animal model of photosensitive epilepsy. Personal or family history of photosensitivity warrants a neurological consultation before retinal treatment with laser therapy.

RESUMO Fotocoagulação a laser é método seguro para tratamento de retinopatias. Apresentamos o caso de uma mulher de 21 anos com alta miopia e degeneração lattice bilateral que sofreu descolamento de retina no olho direito e foi submetida a tratamento cirúrgico e ulterior laserterapia. Durante a fotocoagulação no olho esquerdo, ela teve uma convulsão tônico-clônica generalizada, a primeira em sua vida. Havia história familiar de epilepsia. O exame neurológico e a ressonância magnética de en céfalo foram normais, mas o electroencefalograma revelou descargas epileptogênicas, mais frequentes durante a fotoesti mulação. Ela evitou luzes piscantes durante os 2 anos subsequentes, sem recorrência de convulsões. Cerca de 5% dos pacientes com epilepsia têm fotossensibilidade. Proporção considerável deles terá convulsões somente durante exposição à luz piscante. Fotocoagulação a laser já foi empregada como modelo animal de sucesso para epilepsia fotossensível. Presença de fotossensibilidade na história pessoal ou familiar deve merecer avaliação neurológica antes do tratamento retiniano.

Boston Carpal Tunnel Questionnaire and Severity of Carpal Tunnel Syndrome.

OBJECTIVES: Carpal tunnel syndrome (CTS) is a common compressive neuropathy linked to disability in severe cases. Tools capable of distinguishing the severity spectrum median nerve entrapment in clinical practice are desirable. METHODS: This cross-sectional study included 58 CTS patients assisted in a Brazilian neurologic clinic. Participants were naive of surgical interventions and answered to Boston Carpal Tunnel Questionnaire (BCTQ). CTS was classified as mild, moderate, and severe according to electrodiagnostic testing. RESULTS: There was no significant difference in BCTQ scores across the severity spectrum of median nerve entrapment, not even comparing mild cases with the group moderate/severe. Mild cases were younger (mean ± SD: 46.5 ± 9.2 years) than severe ones (60.0 ± 13.5, P = 0.04) and the group moderate/severe (55.5 ± 14.5, P = 0.01). CONCLUSIONS: Results suggest that BCTQ is not adequate to assess the interpatient severity of median nerve entrapment on clinical practice.

Disruption of the brain-esophagus axis in obese patients with heartburn.

Obesity is a risk factor for gastroesophageal reflux disease. Studies addressing the brain-esophagus axis in obese are lacking. In obese with and without heartburn, we assessed: (i) the brain responses to esophageal acid perfusion during functional brain imaging; (ii) esophageal impedance baseline before and after acid perfusion; and (iii) abdominal fat distribution. In this exploratory study, 26 obese underwent functional magnetic resonance imaging (fMRI) of the brain combined with esophageal acid perfusion. Esophageal impedance baseline was determined before and after fMRI, followed by tomographic quantification of the abdominal fat. Among 26 obese (54% men, 39.7 years old, 33.5 kg/m2), there were 17 with heartburn and 9 without heartburn. Before fMRI, the esophageal impedance baseline was lower in obese with heartburn than without heartburn (median 1187 vs. 1890 Ω; P = 0.025). After acid perfusion, impedance baseline decreased in obese with heartburn (from 1187 to 899 Ω; P = 0.011) and was lower in this group than in obese without heartburn (899 vs. 1614 Ω; P = 0.001). fMRI task-residual analysis showed that obese with heartburn presented higher functional connectivity in several brain regions than obese without heartburn. Abdominal fat area did not differ between obese with and without heartburn either for total (72.8 ± 4.4% vs. 70.3 ± 6.0%; P = 0.280), subcutaneous (42.2 ± 9.0% vs. 37.4 ± 9.0%; P = 0.226), or visceral (30.6 ± 7.9% vs. 33.0 ± 7.8%; P = 0.484). In subjects with obesity, the brain-esophagus axis is disrupted centrally with higher functional brain connectivity and peripherally with decreased esophageal mucosa integrity in the presence of heartburn.

Seizure occurring with retinal laser therapy: a report of the first case with frequency-doubled Nd-YAG.

Laser photocoagulation is a safe method for the treatment of retinal disorders. We present a case of a 21-year-old woman with high myopia, retinal detachment in the right eye, and bilateral lattice degeneration. She underwent surgical repair in the right eye followed by bilateral retinal laser therapy. During laser photocoagulation of the left eye, she experienced a generalized tonic-clonic seizure for the first time in her life. She had a positive family history of epilepsy. Neurological examination and brain magnetic resonance imaging findings were normal, but an electroencephalogram revealed epileptogenic discharges, more frequent during photostimulation. She avoided flickering lights during the 2-year follow-up, without seizure recurrence. Approximately 5% of patients with epilepsy have photosensitive epilepsy, of whom a considerable proportion will experience seizures only during exposition to flashing lights. Laser photocoagulation was already successfully employed in an animal model of photosensitive epilepsy. Personal or family history of photosensitivity warrants a neurological consultation before retinal treatment with laser therapy.

Clock drawing test: comparison between the Pfizer and the Shulman systems / Teste do desenho do relógio: comparação dos sistemas de Pfizer e de Shulman

ABSTRACT Cognitive decline can be screened by the clock drawing test (CDT), which has several versions. Objective: This survey aimed to analyze the correlation between two simple methods for scoring the CDT. Methods: This cross-sectional study was nested in the Elo-Creati cohort from Passo Fundo, Brazil and comprised 404 subjects. Two raters underwent previous training and scored the subjects' CDT according to both the Pfizer and Shulman systems. The inter-observer and intra-observer concordance within each method was analyzed with the Spearman's rank correlation coefficient, as well as the concordance of the scores between the two methods. Age and scholarity were also correlated with the scores. Results: Most of the participants were women (93.8%) and Caucasian (84.6%), with a mean age of 66.9 (±7.8) years and a scholarity of 10.9 years (±5.6). There was significant inter-observer (Pfizer: r=0.739, p£0.001; Shulman: r=0.727, p£0.001) and intra-observer correlation (Pfizer: rater 1, r=0.628, p≤0.001; rater 2, r=0.821, p≤0.001; Shulman: rater 1, r=0.843, p≤0.001; rater 2: r=0.819; p≤0.001). Intra-observer correlation was also observed comparing Pfizer and Shulman methods (rater 1: r=0.744; p≤0.001; rater 2: r=0.702; p≤0.001). There was weak correlation of the scores with scholarity (Pfizer: r=0.283, p£0.001; Shulman: r=0.244, p£0.001) and age (Pfizer: r=-0.174, p£0.001; Shulman: r=-0.170, p£0.001). More participants were classified with decreased cognition through the Pfizer system (rater 1: 44.3 vs. 26.5%; rater 2: 42.1 vs. 16.3%; p≤0.001). Conclusions: For this population, our results suggest that the Pfizer system of scoring CDT is more suitable for screening cognitive decline.

RESUMO O déficit cognitivo pode ser triado pelo teste do desenho do relógio (TDR), que tem várias versões. Objetivo: Esta pesquisa visou avaliar a concordância entre dois métodos simples de TDR. Métodos: Estudo transversal, aninhado na coorte Elo-Creati de Passo Fundo, Brasil, que incluiu 404 sujeitos. Dois avaliadores previamente treinados analisaram o TDR dos participantes de acordo com os sistemas de Pfizer e de Shulman. A concordância inter e intraobservador foi analisada com o teste de coeficiente de correlação de postos de Spearman, assim como a concordância pela estatística kappa dos escores entre os métodos. Idade e escolaridade também foram correlacionados com os escores. Resultados: A maioria dos participantes era de mulheres (93,8%) e caucasianos (84,6%), com média de idade de 66,9±7,8 anos e de escolaridade de 10,9±5,6 anos. Houve significativa correlação interobservador (Pfizer: r=0,739, p£0,001; Shulman: r=0,727, p£0,001) e intraobservador (Pfizer: avaliador 1, r=0,628, p≤0,001; avaliador 2, r=0,821, p≤0,001; Shulman: avaliador 1, r=0,843, p≤0,001; avaliador 2: r=0,819; p≤0,001). Correlação intraobservador significativa também foi evidenciada comparando-se os sistemas de Pfizer e Shulman (avaliador 1: r=0,744; p≤0,001; avaliador 2: r=0,702; p≤0,001). Houve fraca correlação dos escores com escolaridade (Pfizer: r=0,283, p£0,001; Shulman: r=0,244, p£0,001) e idade (Pfizer: r=-0,174, p£0,001; Shulman: r=-0,170, p£0,001). Mais participantes foram classificados com declínio cognitivo com o sistema de Pfizer (avaliador 1: 44,3 vs. 26,5%; avaliador 2: 42,1 vs. 16,3%; p≤0,001). Conclusões: Nossos resultados sugerem que, para essa população, o sistema de Pfizer para avaliar o TDR é mais adequado para a triagem cognitiva.

Thioredoxin reductase-1 levels are associated with NRF2 pathway activation and tumor recurrence in non-small cell lung cancer.

Activating mutations in the KEAP1/NRF2 pathway characterize a subset of non-small cell lung cancer (NSCLC) associated with chemoresistance and poor prognosis. We herein evaluated the relationship between 64 oxidative stress-related genes and overall survival data from 35 lung cancer datasets. Thioredoxin reductase-1 (TXNRD1) stood out as the most significant predictor of poor outcome. In a cohort of NSCLC patients, high TXNRD1 protein levels correlated with shorter disease-free survival and distal metastasis-free survival post-surgery, including a subset of individuals treated with platinum-based adjuvant chemotherapy. Bioinformatics analysis revealed that NSCLC tumors harboring genetic alterations in the NRF2 pathway (KEAP1, NFE2L2 and CUL3 mutations, and NFE2L2 amplification) overexpress TXNRD1, while no association with EGFR, KRAS, TP53 and PIK3CA mutations was found. In addition, nuclear accumulation of NRF2 overlapped with upregulated TXNRD1 protein in NSCLC tumors. Functional cell assays and gene dependency analysis revealed that NRF2, but not TXNRD1, has a pivotal role in KEAP1 mutant cells' survival. KEAP1 mutants overexpress TXNRD1 and are less susceptible to the cytotoxic effects of the TXNRD1 inhibitor auranofin when compared to wild-type cell lines. Inhibition of NRF2 with siRNA or ML-385, and glutathione depletion with buthionine-sulfoximine, sensitized KEAP1 mutant A549 cells to auranofin. NRF2 knockdown and GSH depletion also augmented cisplatin cytotoxicity in A549 cells, whereas auranofin had no effect. In summary, these findings suggest that TXNRD1 is not a key determinant of malignant phenotypes in KEAP1 mutant cells, although this protein can be a surrogate marker of NRF2 pathway activation, predicting tumor recurrence and possibly other aggressive phenotypes associated with NRF2 hyperactivation in NSCLC.

Clock drawing test: comparison between the Pfizer and the Shulman systems.

Cognitive decline can be screened by the clock drawing test (CDT), which has several versions. Objective: This survey aimed to analyze the correlation between two simple methods for scoring the CDT. Methods: This cross-sectional study was nested in the Elo-Creati cohort from Passo Fundo, Brazil and comprised 404 subjects. Two raters underwent previous training and scored the subjects' CDT according to both the Pfizer and Shulman systems. The inter-observer and intra-observer concordance within each method was analyzed with the Spearman's rank correlation coefficient, as well as the concordance of the scores between the two methods. Age and scholarity were also correlated with the scores. Results: Most of the participants were women (93.8%) and Caucasian (84.6%), with a mean age of 66.9 (±7.8) years and a scholarity of 10.9 years (±5.6). There was significant inter-observer (Pfizer: r=0.739, p£0.001; Shulman: r=0.727, p£0.001) and intra-observer correlation (Pfizer: rater 1, r=0.628, p≤0.001; rater 2, r=0.821, p≤0.001; Shulman: rater 1, r=0.843, p≤0.001; rater 2: r=0.819; p≤0.001). Intra-observer correlation was also observed comparing Pfizer and Shulman methods (rater 1: r=0.744; p≤0.001; rater 2: r=0.702; p≤0.001). There was weak correlation of the scores with scholarity (Pfizer: r=0.283, p£0.001; Shulman: r=0.244, p£0.001) and age (Pfizer: r=-0.174, p£0.001; Shulman: r=-0.170, p£0.001). More participants were classified with decreased cognition through the Pfizer system (rater 1: 44.3 vs. 26.5%; rater 2: 42.1 vs. 16.3%; p≤0.001). Conclusions: For this population, our results suggest that the Pfizer system of scoring CDT is more suitable for screening cognitive decline.

O déficit cognitivo pode ser triado pelo teste do desenho do relógio (TDR), que tem várias versões. Objetivo: Esta pesquisa visou avaliar a concordância entre dois métodos simples de TDR. Métodos: Estudo transversal, aninhado na coorte Elo-Creati de Passo Fundo, Brasil, que incluiu 404 sujeitos. Dois avaliadores previamente treinados analisaram o TDR dos participantes de acordo com os sistemas de Pfizer e de Shulman. A concordância inter e intraobservador foi analisada com o teste de coeficiente de correlação de postos de Spearman, assim como a concordância pela estatística kappa dos escores entre os métodos. Idade e escolaridade também foram correlacionados com os escores. Resultados: A maioria dos participantes era de mulheres (93,8%) e caucasianos (84,6%), com média de idade de 66,9±7,8 anos e de escolaridade de 10,9±5,6 anos. Houve significativa correlação interobservador (Pfizer: r=0,739, p£0,001; Shulman: r=0,727, p£0,001) e intraobservador (Pfizer: avaliador 1, r=0,628, p≤0,001; avaliador 2, r=0,821, p≤0,001; Shulman: avaliador 1, r=0,843, p≤0,001; avaliador 2: r=0,819; p≤0,001). Correlação intraobservador significativa também foi evidenciada comparando-se os sistemas de Pfizer e Shulman (avaliador 1: r=0,744; p≤0,001; avaliador 2: r=0,702; p≤0,001). Houve fraca correlação dos escores com escolaridade (Pfizer: r=0,283, p£0,001; Shulman: r=0,244, p£0,001) e idade (Pfizer: r=-0,174, p£0,001; Shulman: r=-0,170, p£0,001). Mais participantes foram classificados com declínio cognitivo com o sistema de Pfizer (avaliador 1: 44,3 vs. 26,5%; avaliador 2: 42,1 vs. 16,3%; p≤0,001). Conclusões: Nossos resultados sugerem que, para essa população, o sistema de Pfizer para avaliar o TDR é mais adequado para a triagem cognitiva.

The influence of allergic rhinoconjunctivitis on migraine disability in children.

OBJECTIVE: Migraine is a common condition in the pediatric population and causes a significant impact on the quality of life. Atopic disorders are some of the migraine comorbidities. We hypothesized that allergic rhinitis could aggravate migraine in the pediatric population. METHODS: This cross-sectional study consecutively evaluated 90 pediatric outpatients (46 children 6-12 years of age; 44 adolescents up to 18 years of age) who sought medical assistance because of migraine at a general neurology clinic in Passo Fundo, RS, Brazil. They, and their parents, were given three questionnaires, to evaluate the diagnosis of current allergic rhinitis, allergic rhinoconjunctivitis and seasonal allergic rhinitis, as well as the disability caused by headache (ISAAC - International Study of Asthma and Allergies in Childhood; CARATkids - Control of Allergic Rhinitis and Asthma Test for Children; PedMIDAS - Pediatric Migraine Disability Assessment). The study was approved by the local ethics committee. RESULTS: According to the ISAAC questionnaire, children with current allergic rhinoconjunctivitis in the last year showed higher scores on the PedMIDAS than those patients without atopy (median and interquartile range 26 [10-58] vs. 5 [1-13], p = 0.008). A significant positive correlation of CARATkids scores with PedMIDAS scores was found (p = 0.007, rho = 0.39). After including other putative predictors of migraine disability (age, body mass index, time since onset of migraine) in a multiple regression analysis, only the scores on the CARATkids remained a significant independent variable correlated with PedMIDAS scores (p = 0.001; R = 0.55; R2 = 0.30). CONCLUSIONS: Current allergic rhinoconjunctivitis is related to enhanced disability caused by headache in childhood migraine.

Is allergic rhinitis related to migraine disability in adults?

OBJECTIVE: Migraine is a chronic condition with complex pathophysiology. Although immunologic disturbances have been linked to migraine, only few attempts have been made to assess the possibility of allergic rhinitis as a worsening factor of migraine in adults. This survey aimed to compare migraine disability between adult migraineurs with and without current allergic rhinitis. METHODS: This cross-sectional study comprised 118 adult migraineurs who were consecutively assisted at an outpatient clinic. After ordinary neurological evaluation, participants were evaluated for headache disability using the Migraine Disability Assessment (MIDAS). The presence of current allergic rhinitis, allergic rhinoconjunctivitis and seasonal allergic rhinitis was scored for each participant according to the International Study of Asthma and Allergies in questionnaire. RESULTS: There was no significant difference between the MIDAS scores of those with current allergic rhinitis, allergic rhinoconjunctivitis, or seasonal allergic rhinitis and nonatopic migraineurs. The disability caused by allergic symptoms also did not influence the MIDAS scores of patients with allergic rhinitis. The frequency of headache days during the last three months was higher in the subset of patients without allergic rhinitis (median and interquartile range 12 [8-19.2] vs. 8 [4-14]; p = 0.03). CONCLUSIONS: Our results suggest that current allergic rhinitis, allergic rhinoconjunctivitis, and seasonal allergic rhinitis are not related to headache disability in adults with episodic migraine.

The influence of allergic rhinoconjunctivitis on migraine disability in children / A influência da rinoconjuntivite alérgica sobre a incapacidade secundária à enxaqueca em crianças

ABSTRACT Migraine is a common condition in the pediatric population and causes a significant impact on the quality of life. Atopic disorders are some of the migraine comorbidities. Objective We hypothesized that allergic rhinitis could aggravate migraine in the pediatric population. Methods This cross-sectional study consecutively evaluated 90 pediatric outpatients (46 children 6-12 years of age; 44 adolescents up to 18 years of age) who sought medical assistance because of migraine at a general neurology clinic in Passo Fundo, RS, Brazil. They, and their parents, were given three questionnaires, to evaluate the diagnosis of current allergic rhinitis, allergic rhinoconjunctivitis and seasonal allergic rhinitis, as well as the disability caused by headache (ISAAC - International Study of Asthma and Allergies in Childhood; CARATkids - Control of Allergic Rhinitis and Asthma Test for Children; PedMIDAS - Pediatric Migraine Disability Assessment). The study was approved by the local ethics committee. Results According to the ISAAC questionnaire, children with current allergic rhinoconjunctivitis in the last year showed higher scores on the PedMIDAS than those patients without atopy (median and interquartile range 26 [10-58] vs. 5 [1-13], p = 0.008). A significant positive correlation of CARATkids scores with PedMIDAS scores was found (p = 0.007, rho = 0.39). After including other putative predictors of migraine disability (age, body mass index, time since onset of migraine) in a multiple regression analysis, only the scores on the CARATkids remained a significant independent variable correlated with PedMIDAS scores (p = 0.001; R = 0.55; R2 = 0.30). Conclusions Current allergic rhinoconjunctivitis is related to enhanced disability caused by headache in childhood migraine.

RESUMO A enxaqueca é condição comum na população pediátrica e causa significativo impacto na qualidade de vida. Doenças atópicas estão entre as principais morbidades associadas. Objetivo Teorizamos que a rinite alérgica possa agravar a enxaqueca na população pediátrica. Métodos Este estudo transversal avaliou consecutivamente 90 pacientes pediátricos (46 crianças de 6 a 12 anos; 44 adolescentes até 18 anos) que procuraram assistência por enxaqueca em clínica neurológica de Passo Fundo, RS, Brasil. Eles e seus familiares responderam a três questionários para avaliar o diagnóstico de rinite alérgica, rinoconjuntivite alérgica e rinite alérgica sazonal, assim como a incapacidade causada pela cefaleia (ISAAC - International Study of Asthma and Allergies in Childhood; CARATkids - Control of Allergic Rhinitis and Asthma Test for Children; PedMIDAS - Pediatric Migraine Disability Assessment). A pesquisa foi aprovada por comitê de ética. Resultados Crianças com rinoconjuntivite alérgica atual de acordo com o questionário ISAAC exibiram escores mais altos no PedMIDAS do que aquelas sem atopia (mediana e intervalo interquartil 26 [10-58] vs. 5 [1-13], p=0,008). Correlação significativamente positiva do escore no questionário CARATkids sobre o escore do PedMIDAS foi encontrada (p = 0,007, rho = 0,39). Após inclusão de outros fatores teoricamente envolvidos com a incapacidade secundária à enxaqueca (idade, índice de massa corporal, tempo desde o início das crises de enxaqueca) em modelo de análise de regressão linear múltipla, apenas o escore do CARATkids permaneceu com significância como variável independente relacionada ao escore do PedMIDAS (p = 0,001; R = 0,55; R2 = 0,30). Conclusões Rinoconjuntivite alérgica está relacionada ao aumento da incapacidade pela enxaqueca em crianças.

Is allergic rhinitis related to migraine disability in adults? / Rinite alérgica está relacionada à incapacidade da migrânea em adultos?

ABSTRACT Migraine is a chronic condition with complex pathophysiology. Although immunologic disturbances have been linked to migraine, only few attempts have been made to assess the possibility of allergic rhinitis as a worsening factor of migraine in adults. Objective This survey aimed to compare migraine disability between adult migraineurs with and without current allergic rhinitis. Methods This cross-sectional study comprised 118 adult migraineurs who were consecutively assisted at an outpatient clinic. After ordinary neurological evaluation, participants were evaluated for headache disability using the Migraine Disability Assessment (MIDAS). The presence of current allergic rhinitis, allergic rhinoconjunctivitis and seasonal allergic rhinitis was scored for each participant according to the International Study of Asthma and Allergies in questionnaire. Results There was no significant difference between the MIDAS scores of those with current allergic rhinitis, allergic rhinoconjunctivitis, or seasonal allergic rhinitis and nonatopic migraineurs. The disability caused by allergic symptoms also did not influence the MIDAS scores of patients with allergic rhinitis. The frequency of headache days during the last three months was higher in the subset of patients without allergic rhinitis (median and interquartile range 12 [8-19.2] vs. 8 [4-14]; p = 0.03). Conclusions Our results suggest that current allergic rhinitis, allergic rhinoconjunctivitis, and seasonal allergic rhinitis are not related to headache disability in adults with episodic migraine.

RESUMO A migrânea é uma condição dolorosa crônica com fisiopatologia complexa. Apesar de disfunções imunológicas já terem sido ligadas à migrânea, poucas foram as tentativas, na literatura, de se avaliar a possibilidade da rinite alérgica como um fator agravante da migrânea em adultos, tornando a questão ainda não esclarecida. Objetivo Esta pesquisa visou comparar a incapacidade da migrânea em adultos com e sem rinite alérgica. Métodos Este estudo transversal incluiu 118 adultos com migrânea consecutivamente atendidos em uma clínica ambulatorial. Após o exame neurológico usual, os participantes foram avaliados com relação à incapacidade gerada pela cefaleia com o Migraine Disability Assessment (MIDAS), assim como para a presença atual de rinite alérgica, rinoconjuntivite alérgica e rinite alérgica sazonal de acordo com o questionário do International Study of Asthma and Allergies in Childhood (ISAAC). Resultados Não houve diferença nos escores do MIDAS entre migranosos com e sem alérgica, rinoconjuntivite alérgica e rinite alérgica sazonal. A incapacidade causada pelos sintomas alérgicos também não influenciou os escores do MIDAS dos pacientes com rinite alérgica. A frequência de dias com cefaleia durante os últimos 3 meses foi maior no subgrupo de pacientes sem rinite alérgica (mediana e intervalo interquartil 12 [8-19,2] vs. 8 [4-14]; p = 0,03). Conclusões Os resultados sugerem que rinite alérgica, rinoconjuntivite alérgica e rinite alérgica sazonal não estão relacionadas à incapacidade por cefaleia em pacientes adultos com migrânea episódica.

Low-dose agalsidase beta treatment in male pediatric patients with Fabry disease: A 5-year randomized controlled trial.

BACKGROUND: Fabry disease is a rare, X-linked, lifelong progressive lysosomal storage disorder. Severely deficient α-galactosidase A activity in males is associated with the classic phenotype with early-onset, multisystem manifestations evolving to vital organ complications during adulthood. We assessed the ability of 2 low-dose agalsidase beta regimens to lower skin, plasma, and urine globotriaosylceramide (GL-3) levels, and influence clinical manifestations in male pediatric Fabry patients. METHODS: In this multicenter, open-label, parallel-group, phase 3b study, male patients aged 5-18 years were randomized to receive agalsidase beta at 0.5 mg/kg 2-weekly (n = 16) or 1.0 mg/kg 4-weekly (n = 15) for 5 years. All had plasma/urine GL-3 accumulation but no clinically evident organ involvement. The primary outcome was GL-3 accumulation in superficial skin capillary endothelium (SSCE). RESULTS: The mean age was 11.6 (range: 5-18) years and all but one of the 31 patients had classic GLA mutations. In the overall cohort, shifts from non-0 to 0-scores for SSCE GL-3 were significant at years 1, 3, and 5, but results were variable. Plasma GL-3 normalized and urine GL-3 reduced substantially. Higher anti-agalsidase beta antibody titers were associated with less robust SSCE GL-3 clearance and higher urine GL-3 levels. Renal function remained stable and normal. Most Fabry signs and symptoms tended to stabilize; abdominal pain was significantly reduced (-26.3%; P = .0215). No new clinical major organ complications were observed. GL-3 accumulation and cellular and vascular injury were present in baseline kidney biopsies (n = 7). Treatment effects on podocyte GL-3 content and foot process width were highly variable. Fabry arteriopathy overall increased in severity. Two patients withdrew and 2 had their agalsidase beta dose increased. CONCLUSIONS: Our findings increase the limited amount of available data on long-term effects of enzyme replacement therapy in pediatric, classic Fabry patients. The low-dose regimens studied here over a period of 5 years did not demonstrate a consistent benefit among the patients in terms of controlling symptomatology, urine GL-3 levels, and pathological histology. The current available evidence supports treatment of pediatric, classic male Fabry patients at the approved agalsidase beta dose of 1.0 mg/kg 2-weekly if these patients are considered for enzyme replacement therapy with agalsidase beta.

Age-dependent influence of gender on symptoms of obstructive sleep apnea in adults.

OBJECTIVE: Obstructive Sleep Apnea (OSA) is linked to classical symptoms of snoring and excessive sleepiness. However, many women with OSA may present with a diverse profile. The influence of age on the clinical differences between genders is unclear. This survey aimed to compare the clinical and polysomnographic findings of OSA between adult males and females, but considering different age groups. METHODS: This cross-sectional study comprised a sample of 472 consecutive adult patients with OSA who underwent full-night polysomnography. Data from the medical and polysomnographic records was obtained, as well as the score on Portuguese validated version of the Epwoth Sleepiness Scale (ESS). Comparisons of main clinical aspects of OSA between genders were stratified according to three groups: young (< 30 years old), middle-aged (30 - 50 y.o.), and older patients (> 50 y.o.). RESULTS: Men comprised the majority of the sample (male/female ratio of 1.6). Apnea-Hypopnea Index (AHI) was higher in men than women (median [interquartile range]: 29.7 [18.1-47.8] vs. 21.9 [11.5-36.1]; p < 0.0001), and body mass index alike (mean ± standard deviation: 29.0±4.9 vs. 27.6±5.2; p = 0.004). Snoring was more common in male than in female patients (92% vs. 84.7%; p = 0.015). In the subset of subjects younger than 30 years-old the differences between genders were prominent (male/female; AHI: 19.6 [13.1-28.1] vs. 11.8 [7.7-18.8], p = 0.012; sno ring: 89.7% vs. 55.2%, p = 0.007), accompanied by a trend to lower score in ESS in male patients (7.1 ± 4.3 vs. 9.2 ± 4.3; p = 0.066). DISCUSSION: Results suggest that a classical clinical picture of snoring and severe daytime sleepiness is lacking in a considerable proportion of OSA sufferers, particularly young women, who tend to be sleepier than male patients. The awareness of OSA in young women should be based more in mild excessive daily sleepiness than in other typical OSA symptoms.