Effects of Systemic Physiology on Mapping Resting-State Networks Using Functional Near-Infrared Spectroscopy.

Resting-state functional connectivity (rsFC) has gained popularity mainly due to its simplicity and potential for providing insights into various brain disorders. In this vein, functional near-infrared spectroscopy (fNIRS) is an attractive choice due to its portability, flexibility, and low cost, allowing for bedside imaging of brain function. While promising, fNIRS suffers from non-neural signal contaminations (i.e., systemic physiological noise), which can increase correlation across fNIRS channels, leading to spurious rsFC networks. In the present work, we hypothesized that additional measurements with short channels, heart rate, mean arterial pressure, and end-tidal CO2 could provide a better understanding of the effects of systemic physiology on fNIRS-based resting-state networks. To test our hypothesis, we acquired 12 min of resting-state data from 10 healthy participants. Unlike previous studies, we investigated the efficacy of different pre-processing approaches in extracting resting-state networks. Our results are in agreement with previous studies and reinforce the fact that systemic physiology can overestimate rsFC. We expanded on previous work by showing that removal of systemic physiology decreases intra- and inter-subject variability, increasing the ability to detect neural changes in rsFC across groups and over longitudinal studies. Our results show that by removing systemic physiology, fNIRS can reproduce resting-state networks often reported with functional magnetic resonance imaging (fMRI). Finally, the present work details the effects of systemic physiology and outlines how to remove (or at least ameliorate) their contributions to fNIRS signals acquired at rest.

Randomized Trial of Botulinum Toxin Type A in Hereditary Spastic Paraplegia - The SPASTOX Trial.

BACKGROUND: Hereditary spastic paraplegia presents spasticity as the main clinical manifestation, reducing gait quality and producing incapacity. Management with botulinum toxin type A (BoNT-A) is not well elucidated. The objective of the current study was to evaluate the efficacy and safety of BoNT-A in patients with hereditary spastic paraplegias. METHODS: This was a double-blind, randomized, placebo-controlled crossover trial. Each participant was randomly assigned to receive 1 injection session of either BoNT-A (100 IU/2 mL of Prosigne in each adductor magnus and each triceps surae) or saline 0.9% (2 mL). The primary outcome measure was change from baseline in maximal gait velocity, and secondary outcome measures included changes in gait at self-selected velocity, spasticity, muscle strength, Spastic Paraplegia Rating Scale, pain, fatigue, and subjective perception of improvement. We also looked at adverse events reported by the patients. RESULTS: We enrolled 55 patients, 36 of whom were men and 41 with the pure phenotype. Mean age was 43 ± 13.4 years (range, 19-72 years), mean age of onset waws 27 ± 13.1 years (range, <1 to 55 yars), and mean disease duration was 17 ± 12.7 years (range, 1-62 years). Compared with baseline, we did not find significant differences between groups in primary and secondary outcomes, except for reduction in adductor tone (P = 0.01). The adverse events were transient and tolerable, and their incidence did not significantly differ between treatments (P = 0.17). CONCLUSIONS: BoNT-A was safe in patients with hereditary spastic paraplegias and reduced the adductor tone, but it was not able to produce functional improvement considering the doses, injection protocol, measures, and instruments used. © 2021 International Parkinson and Movement Disorder Society.

Evaluation of the efficacy and safety of icatibant and C1 esterase/kallikrein inhibitor in severe COVID-19: study protocol for a three-armed randomized controlled trial.

BACKGROUND: SARS-CoV-2, the virus that causes COVID-19, enters the cells through a mechanism dependent on its binding to angiotensin-converting enzyme 2 (ACE2), a protein highly expressed in the lungs. The putative viral-induced inhibition of ACE2 could result in the defective degradation of bradykinin, a potent inflammatory substance. We hypothesize that increased bradykinin in the lungs is an important mechanism driving the development of pneumonia and respiratory failure in COVID-19. METHODS: This is a phase II, single-center, three-armed parallel-group, open-label, active control superiority randomized clinical trial. One hundred eighty eligible patients will be randomly assigned in a 1:1:1 ratio to receive either the inhibitor of C1e/kallikrein 20 U/kg intravenously on day 1 and day 4 plus standard care; or icatibant 30 mg subcutaneously, three doses/day for 4 days plus standard care; or standard care alone, as recommended in the clinical trials published to date, which includes supplemental oxygen, non-invasive and invasive ventilation, antibiotic agents, anti-inflammatory agents, prophylactic antithrombotic therapy, vasopressor support, and renal replacement therapy. DISCUSSION: Accumulation of bradykinin in the lungs is a common side effect of ACE inhibitors leading to cough. In animal models, the inactivation of ACE2 leads to severe acute pneumonitis in response to lipopolysaccharide (LPS), and the inhibition of bradykinin almost completely restores the lung structure. We believe that inhibition of bradykinin in severe COVID-19 patients could reduce the lung inflammatory response, impacting positively on the severity of disease and mortality rates. TRIAL REGISTRATION: Brazilian Clinical Trials Registry Universal Trial Number (UTN) U1111-1250-1843. Registered on May/5/2020.

Knowledge on medical abortion among Brazilian medical residents in Gynecology and Obstetrics. / Conhecimento de médicos residentes em Ginecologia e Obstetrícia sobre o aborto medicamentoso.

Medical or drug-induced abortion has been proven as an effective means for termination of pregnancy. However, training of providers in the use of misoprostol has been limited. The current article aims to identify the degree of knowledge on medical abortion among Brazilian medical residents in Gynecology and Obstetrics. A multicenter cross-sectional study was performed with residents regularly enrolled in residency programs in Gynecology and Obstetrics in 21 teaching hospitals. A self-responded questionnaire was used. Correct responses to each of the alternatives were identified, and a binary response variable (≥ P70, < P70) was defined by the 70th percentile of the number of questions on misoprostol. Four hundred and seven medical residents returned the questionnaire, of which 404 were completed and three were blank. The majority (56.3%) of the residents were 27 years or younger, females (81.1%), and single or not living with a partner (70%). Two-thirds (68.2%) were in the first or second year of residency. Only 40.8% of the participants answered 70% or more of the questions correctly. In the multivariate analysis, enrollment in the third year of residency or greater (OR = 2.18; 95%CI: 1.350-3.535) and having participated in treatment of a woman with induced or probably induced abortion (OR = 4.12; 95%CI: 1.761-9.621) were associated with better knowledge on the subject. Among Brazilian medical residents in Gynecology and Obstetrics, knowledge on medical abortion is very limited and poses an obstacle to proper care in cases of legal termination of pregnancy.

O aborto medicamentoso ou farmacológico tem demonstrado ser um meio eficaz para a interrupção da gravidez. Entretanto, o treinamento de provedores no uso do misoprostol tem sido limitado. O presente artigo tem como objetivo identificar o grau de conhecimento dos médicos residentes em Ginecologia e Obstetrícia sobre aborto medicamentoso. Realizou-se um estudo transversal multicêntrico com residentes regularmente inscritos no programa de residência em Ginecologia e Obstetrícia de vinte e um hospitais de ensino. Foi utilizado um questionário de autorresposta. As respostas corretas a cada uma das alternativas foram identificadas e uma variável de resposta binária (≥ P70, < P70) foi definida pelo percentil 70 do número de perguntas sobre o misoprostol. Quatrocentos e sete médicos residentes devolveram o questionário, sendo que 404 estavam preenchidos e três em branco. A maioria (56,3%) dos residentes tinha até 27 anos de idade, era do sexo feminino (81,1%) e não vivia junto com um(a) companheiro(a) (70%). A maior proporção (68,2%) estava cursando o primeiro ou segundo ano da residência. Apenas 40,8% dos participantes acertaram 70% ou mais das afirmativas. Na análise múltipla, cursar o terceiro ano de residência ou superior (OR = 2,18; IC95%: 1,350-3,535) e ter participado do atendimento a uma mulher com abortamento induzido ou provavelmente induzido (OR = 4,12; IC95%: 1,761-9,621) mostraram-se associados a um maior conhecimento sobre o tema. Entre os médicos brasileiros residentes em Ginecologia e Obstetrícia, o conhecimento sobre o aborto medicamentoso é muito reduzido e constitui um obstáculo para o bom atendimento dos casos de interrupção legal da gestação.

El aborto con medicamentos o farmacológico ha demostrado ser un medio eficaz para la interrupción del embarazo. No obstante, la capacitación de los médicos en el uso del misoprostol ha sido limitada. El objetivo de este artículo es identificar el grado de conocimiento de los médicos residentes en Ginecología y Obstetricia sobre el aborto con medicamentos. Se realizó un estudio transversal multicéntrico con residentes regularmente inscritos en el programa de residencia en Ginecología y Obstetricia de veintiún hospitales de enseñanza. Se utilizó un cuestionario de autorrespuesta. Las respuestas correctas de cada una de las alternativas fueron identificadas y una variable de respuesta binaria (≥ P70, < P70) se definió por el percentil 70 del número de preguntas sobre el misoprostol. Cuatrocientos siete médicos residentes devolvieron el cuestionario, siendo que 404 estaban cumplimentados y tres en blanco. La mayoría (56,3%) de los residentes tenía hasta 27 años de edad, eran de sexo femenino (81,1%); no vivía junto a un(a) compañero(a) (70%). La mayor proporción (68,2%) estaba cursando el primero o segundo año de residencia. Solamente un 40,8% de los participantes acertaron un 70% o más de las afirmaciones. En el análisis múltiple, estar en el tercer año de residencia o superior (OR = 2,18; IC95%: 1,350-3,535) y haber estado implicado en la atención a una mujer con aborto inducido o probablemente inducido (OR = 4,12; IC95%: 1,761-9,621) se mostraron asociados a un mayor conocimiento sobre el tema. Entre los médicos brasileños residentes en Ginecología y Obstetricia, el conocimiento sobre aborto con medicamentos es muy reducido y constituye en obstáculo para una buena atención de los casos de interrupción legal de la gestación.

Conhecimento de médicos residentes em Ginecologia e Obstetrícia sobre o aborto medicamentoso / Conocimiento de médicos residentes en Ginecología y Obstetricia sobre el aborto con medicamentos / Knowledge on medical abortion among Brazilian medical residents in Gynecology and Obstetrics

O aborto medicamentoso ou farmacológico tem demonstrado ser um meio eficaz para a interrupção da gravidez. Entretanto, o treinamento de provedores no uso do misoprostol tem sido limitado. O presente artigo tem como objetivo identificar o grau de conhecimento dos médicos residentes em Ginecologia e Obstetrícia sobre aborto medicamentoso. Realizou-se um estudo transversal multicêntrico com residentes regularmente inscritos no programa de residência em Ginecologia e Obstetrícia de vinte e um hospitais de ensino. Foi utilizado um questionário de autorresposta. As respostas corretas a cada uma das alternativas foram identificadas e uma variável de resposta binária (≥ P70, < P70) foi definida pelo percentil 70 do número de perguntas sobre o misoprostol. Quatrocentos e sete médicos residentes devolveram o questionário, sendo que 404 estavam preenchidos e três em branco. A maioria (56,3%) dos residentes tinha até 27 anos de idade, era do sexo feminino (81,1%) e não vivia junto com um(a) companheiro(a) (70%). A maior proporção (68,2%) estava cursando o primeiro ou segundo ano da residência. Apenas 40,8% dos participantes acertaram 70% ou mais das afirmativas. Na análise múltipla, cursar o terceiro ano de residência ou superior (OR = 2,18; IC95%: 1,350-3,535) e ter participado do atendimento a uma mulher com abortamento induzido ou provavelmente induzido (OR = 4,12; IC95%: 1,761-9,621) mostraram-se associados a um maior conhecimento sobre o tema. Entre os médicos brasileiros residentes em Ginecologia e Obstetrícia, o conhecimento sobre o aborto medicamentoso é muito reduzido e constitui um obstáculo para o bom atendimento dos casos de interrupção legal da gestação.

El aborto con medicamentos o farmacológico ha demostrado ser un medio eficaz para la interrupción del embarazo. No obstante, la capacitación de los médicos en el uso del misoprostol ha sido limitada. El objetivo de este artículo es identificar el grado de conocimiento de los médicos residentes en Ginecología y Obstetricia sobre el aborto con medicamentos. Se realizó un estudio transversal multicéntrico con residentes regularmente inscritos en el programa de residencia en Ginecología y Obstetricia de veintiún hospitales de enseñanza. Se utilizó un cuestionario de autorrespuesta. Las respuestas correctas de cada una de las alternativas fueron identificadas y una variable de respuesta binaria (≥ P70, < P70) se definió por el percentil 70 del número de preguntas sobre el misoprostol. Cuatrocientos siete médicos residentes devolvieron el cuestionario, siendo que 404 estaban cumplimentados y tres en blanco. La mayoría (56,3%) de los residentes tenía hasta 27 años de edad, eran de sexo femenino (81,1%); no vivía junto a un(a) compañero(a) (70%). La mayor proporción (68,2%) estaba cursando el primero o segundo año de residencia. Solamente un 40,8% de los participantes acertaron un 70% o más de las afirmaciones. En el análisis múltiple, estar en el tercer año de residencia o superior (OR = 2,18; IC95%: 1,350-3,535) y haber estado implicado en la atención a una mujer con aborto inducido o probablemente inducido (OR = 4,12; IC95%: 1,761-9,621) se mostraron asociados a un mayor conocimiento sobre el tema. Entre los médicos brasileños residentes en Ginecología y Obstetricia, el conocimiento sobre aborto con medicamentos es muy reducido y constituye en obstáculo para una buena atención de los casos de interrupción legal de la gestación.

Medical or drug-induced abortion has been proven as an effective means for termination of pregnancy. However, training of providers in the use of misoprostol has been limited. The current article aims to identify the degree of knowledge on medical abortion among Brazilian medical residents in Gynecology and Obstetrics. A multicenter cross-sectional study was performed with residents regularly enrolled in residency programs in Gynecology and Obstetrics in 21 teaching hospitals. A self-responded questionnaire was used. Correct responses to each of the alternatives were identified, and a binary response variable (≥ P70, < P70) was defined by the 70th percentile of the number of questions on misoprostol. Four hundred and seven medical residents returned the questionnaire, of which 404 were completed and three were blank. The majority (56.3%) of the residents were 27 years or younger, females (81.1%), and single or not living with a partner (70%). Two-thirds (68.2%) were in the first or second year of residency. Only 40.8% of the participants answered 70% or more of the questions correctly. In the multivariate analysis, enrollment in the third year of residency or greater (OR = 2.18; 95%CI: 1.350-3.535) and having participated in treatment of a woman with induced or probably induced abortion (OR = 4.12; 95%CI: 1.761-9.621) were associated with better knowledge on the subject. Among Brazilian medical residents in Gynecology and Obstetrics, knowledge on medical abortion is very limited and poses an obstacle to proper care in cases of legal termination of pregnancy.

Visuospatial Reasoning Trajectories and Death in a Study of the Oldest Old: A Formal Evaluation of Their Association.

OBJECTIVES: To model trajectories of visuospatial reasoning measured using Kohs Block Design test under realistic missing data assumptions and evaluate their association with hazard of death. METHODS: A joint longitudinal-survival model was used to estimate trajectories of visuospatial reasoning under a missing not at random assumption of participants from the Origins of Variance in the Old-Old: Octogenarian Twins study. Sensitivity analyses to missing data assumptions were conducted. RESULTS: Visuospatial reasoning declined at constant rate. Baseline age, dementia status, education, and history of stroke were associated with visuospatial reasoning performance, but only dementia was associated with its rate of decline. Importantly, our results demonstrated an association between poorer visuospatial reasoning and increased hazard of death. Baseline age and sex were associated with risk of death. DISCUSSION: We confirmed an association between visuospatial reasoning and death under plausible missing data assumptions.

High-frequency Audiometry Hearing on Monitoring of Individuals Exposed to Occupational Noise: A Systematic Review

Abstract Introduction The literature reports on high-frequency audiometry as one of the exams used on hearing monitoring of individuals exposed to high sound pressure in their work environment, due to the method́ s greater sensitivity in early identification of hearing loss caused by noise. The frequencies that compose the exam are generally between 9 KHz and 20KHz, depending on the equipment. Objective This study aims to perform a retrospective and secondary systematic revision of publications on high-frequency audiometry on hearing monitoring of individuals exposed to occupational noise. Data Synthesis This systematic revision followed the methodology proposed in the Cochrane Handbook, focusing on the question: "Is High-frequency Audiometry more sensitive than Conventional Audiometry in the screening of early hearing loss individuals exposed to occupational noise?" The search was based on PubMed data, Base, Web of Science (Capes), Biblioteca Virtual em Saúde (BVS), and in the references cited in identified and selected articles. The search resulted in 6059 articles in total. Of these, only six studies were compatible with the criteria proposed in this study. Conclusion The performed meta-analysis does not definitively answer the study's proposed question. It indicates that the 16 KHz high frequency audiometry (HFA) frequency is sensitive in early identification of hearing loss in the control group (medium difference (MD = 8.33)), as well as the 4 KHz frequency (CA), this one being a little less expressive (MD = 5.72). Thus, others studies are necessary to confirm the HFA importance for the early screening of hearing loss on individuals exposed to noise at the workplace.

High-frequency Audiometry Hearing on Monitoring of Individuals Exposed to Occupational Noise: A Systematic Review.

INTRODUCTION: The literature reports on high-frequency audiometry as one of the exams used on hearing monitoring of individuals exposed to high sound pressure in their work environment, due to the method́s greater sensitivity in early identification of hearing loss caused by noise. The frequencies that compose the exam are generally between 9 KHz and 20KHz, depending on the equipment. OBJECTIVE: This study aims to perform a retrospective and secondary systematic revision of publications on high-frequency audiometry on hearing monitoring of individuals exposed to occupational noise. DATA SYNTHESIS: This systematic revision followed the methodology proposed in the Cochrane Handbook, focusing on the question: "Is High-frequency Audiometry more sensitive than Conventional Audiometry in the screening of early hearing loss individuals exposed to occupational noise?" The search was based on PubMed data, Base, Web of Science (Capes), Biblioteca Virtual em Saúde (BVS), and in the references cited in identified and selected articles. The search resulted in 6059 articles in total. Of these, only six studies were compatible with the criteria proposed in this study. CONCLUSION: The performed meta-analysis does not definitively answer the study's proposed question. It indicates that the 16 KHz high frequency audiometry (HFA) frequency is sensitive in early identification of hearing loss in the control group (medium difference (MD = 8.33)), as well as the 4 KHz frequency (CA), this one being a little less expressive (MD = 5.72). Thus, others studies are necessary to confirm the HFA importance for the early screening of hearing loss on individuals exposed to noise at the workplace.

Survival extrapolation in the presence of cause specific hazards.

Health economic evaluations require estimates of expected survival from patients receiving different interventions, often over a lifetime. However, data on the patients of interest are typically only available for a much shorter follow-up time, from randomised trials or cohorts. Previous work showed how to use general population mortality to improve extrapolations of the short-term data, assuming a constant additive or multiplicative effect on the hazards for all-cause mortality for study patients relative to the general population. A more plausible assumption may be a constant effect on the hazard for the specific cause of death targeted by the treatments. To address this problem, we use independent parametric survival models for cause-specific mortality among the general population. Because causes of death are unobserved for the patients of interest, a polyhazard model is used to express their all-cause mortality as a sum of latent cause-specific hazards. Assuming proportional cause-specific hazards between the general and study populations then allows us to extrapolate mortality of the patients of interest to the long term. A Bayesian framework is used to jointly model all sources of data. By simulation, we show that ignoring cause-specific hazards leads to biased estimates of mean survival when the proportion of deaths due to the cause of interest changes through time. The methods are applied to an evaluation of implantable cardioverter defibrillators for the prevention of sudden cardiac death among patients with cardiac arrhythmia. After accounting for cause-specific mortality, substantial differences are seen in estimates of life years gained from implantable cardioverter defibrillators.

Health benefits and cost effectiveness of endoscopic and nonendoscopic cytosponge screening for Barrett's esophagus.

BACKGROUND & AIMS: We developed a model to compare the health benefits and cost effectiveness of screening for Barrett's esophagus by either Cytosponge™ or by conventional endoscopy vs no screening, and to estimate their abilities to reduce mortality from esophageal adenocarcinoma. METHODS: We used microsimulation modeling of a hypothetical cohort of 50-year-old men in the United Kingdom with histories of gastroesophageal reflux disease symptoms, assuming the prevalence of Barrett's esophagus to be 8%. Participants were invited to undergo screening by endoscopy or Cytosponge (invitation acceptance rates of 23% and 45%, respectively), and outcomes were compared with those from men who underwent no screening. We estimated the number of incident esophageal adenocarcinoma cases prevented and the incremental cost-effectiveness ratio of quality-adjusted life years (QALYs) of the different strategies. Patients found to have high-grade dysplasia or intramucosal cancer received endotherapy. Model inputs included data on disease progression, test accuracy, post-treatment status, and surveillance protocols. Costs and benefits were discounted at 3.5% per year. Supplementary and sensitivity analyses comprised esophagectomy management of high-grade dysplasia or intramucosal cancer, screening by ultrathin nasal endoscopy, and different assumptions of uptake of screening invitations for either strategy. RESULTS: We estimated that compared with no screening, Cytosponge screening followed by treatment of patients with dysplasia or intramucosal cancer costs an additional $240 (95% credible interval, $196-$320) per screening participant and results in a mean gain of 0.015 (95% credible interval, -0.001 to 0.029) QALYs and an incremental cost-effectiveness ratio of $15.7 thousand (K) per QALY. The respective values for endoscopy were $299 ($261-$367), 0.013 (0.003-0.023) QALYs, and $22.2K. Screening by the Cytosponge followed by treatment of patients with dysplasia or intramucosal cancer would reduce the number of cases of incident symptomatic esophageal adenocarcinoma by 19%, compared with 17% for screening by endoscopy, although this greater benefit for Cytosponge depends on more patients accepting screening by Cytosponge compared with screening by endoscopy. CONCLUSIONS: In a microsimulation model, screening 50-year-old men with symptoms of gastroesophageal reflux disease by Cytosponge is cost effective and would reduce mortality from esophageal adenocarcinoma compared with no screening.