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Induction of remission in biologic-experienced individuals with moderate to severe Crohn’s disease (CD) can be a challenge. We hereby present a case of CD with secondary non-response to infliximab. Adding methotrexate and switching to ustekinumab plus methotrexate did not stop the inflammatory process. Therefore, combination therapy with two classes of biologics consisting of ustekinumab and adalimumab plus methotrexate was initiated. He achieved clinical remission in 4 weeks and remained on triple therapy for 6 months which was subsequently tailored to adalimumab/methotrexate combination therapy due to insurance restriction on ustekinumab. He remained in remission for the duration of follow-up, 14 months after initiation of triple therapy and 8 months after switching to methotrexate/adalimumab biologic monotherapy. Triple therapy with anti-TNF, IL-12/23 inhibitor and methotrexate could potentially be an option for induction of remission in biologic-experienced individuals with good initial clinical response to anti-TNF agents.

Background: Remdesivir is a broad-spectrum antiviral approved as promising medicine worldwide for deadly pandemic COVID-19 disease. The debate of its efficacy is interesting between different studies with consideration of several factors. We planned this study to evaluate a huge clinical outcome (primary composite outcome) of mortality rate, need for MV, and escalation of care among Remdesivir (RDV) and non-Remdesivir (NoRDV)groups.Methods: Patients with a PCR - confirmed diagnosis of moderate and severe COVID-19 were observed retrospectively as two comparative groups, before and after including remdesivir in the treatment protocol, from August 2020 to February 2021.Result: From 509 hospitalized patients; 35% received Remdesivir among them 64% were severe patients. Median age, 59 years, was equal in both groups, and there was no significant difference between the two groups regarding gender, baseline characteristics, and co-morbidities. Unlike, the median hospital length of stay was lower among the RDV group (8 days) than the NoRDV (9 days), P= 0.004.The composite outcome occurred in 17.7% in RDV and 22.2% in NoRDV but the difference was statistically insignificant (p-value 0.289). Adjusted logistic regression showed a non-significant lower association of the composite outcome with RDV use (OR 0.623, 95CI% 0.37-1.02), and a significant reduction occurred in patients Conclusion: Despite controlling all patient characteristics, treatment with RDV did not show any improved impact on patient outcomes over other antivirals and standard care. There is a pressing need for further studies to explore and evaluate new therapeutic approaches or combinations.

Hallux valgus is a progressive angular deformity of the big toe, the degree of which is aggravated in weightbearing stance. Hallux valgus and intermetatarsal angles on postoperative weightbearing images are usually larger than those of intraoperative fluoroscopic and immediate postoperative non-weightbearing images. Here, we hypothesized that various angular parameters of hallux valgus would increase postoperatively with weightbearing. A total of 66 feet (58 patients) of moderate to severe hallux valgus were reviewed on consecutive plain foot anteroposterior radiographs. The changes of hallux valgus, intermetatarsal, hallux valgus interphalangeal, and distal metatarsal articular angles were compared. Hallux valgus and intermetatarsal angles were significantly increased with weightbearing postoperatively (p.001). Hallux valgus interphalangeal and distal metatarsal articular angles did not show significant changes with weightbearing (p.5). Hallux valgus and intermetatarsal angles were increased with weightbearing after hallux valgus surgery. Mean angular changes were 5.3 and 2.7 degrees, respectively. These values should be considered in the preoperative planning and intraoperative correction processes.

Objective To investigate whether epileptiform discharge burden can identify those at risk for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). Methods Retrospective analysis of 113 moderate to severe grade SAH patients who had continuous EEG (cEEG) recordings during their hospitalization. We calculated the burden of epileptiform discharges (ED), measured as number of ED per hour. Results We find that many SAH patients have an increase in ED burden during the first 3–10 days following rupture, the major risk period for DCI. However, those who develop DCI have a significantly higher hourly burden from days 3.5–6 after SAH vs. those who do not. ED burden is higher in DCI patients when assessed in relation to the onset of DCI (area under the receiver operator curve 0.72). Finally, specific trends of ED burden over time, assessed by group-based trajectory analysis, also help stratify DCI risk. Conclusions These results suggest that ED burden is a useful parameter for identifying those at higher risk of developing DCI after SAH. The higher burden rate associated with DCI supports the theory of metabolic supply-demand mismatch which contributes to this complication. Significance ED burden is a novel biomarker for predicting those at high risk of DCI.

BACKGROUND: Garcinia cambogia, either alone or with green tea, is commonly promoted for weight loss. Sporadic cases of liver failure from G. cambogia have been reported, but its role in liver injury is controversial. METHODS: Among 1418 patients enrolled in the Drug-Induced Liver Injury Network (DILIN) from 2004 to 2018, we identified 22 cases (adjudicated with high confidence) of liver injury from G. cambogia either alone (n=5) or in combination with green tea (n=16) or Ashwagandha (n=1). Control groups consisted of 57 patients with liver injury from herbal and dietary supplements (HDS) containing green tea without G. cambogia and 103 patients from other HDS. RESULTS: Patients who took G. cambogia were between 17 to 54 years, with liver injury arising 13 to 223 days (median = 51) after the start. One patient died, one required liver transplantation, and 91% were hospitalized. The liver injury was hepatocellular with jaundice. Although the peak values of aminotransferases were significantly higher (2001 ± 1386 U/L) in G. cambogia group (p

espanolIntroduccion: La pandemia por COVID-19 puede tener consecuencias psicosociales importantes en la poblacion. Objetivo: Determinar los niveles de sintomas de ansiedad, depresion y conductas de autocuidado durante la pandemia de COVID-19 en poblacion general. Metodo: Encuesta en linea distribuida durante tres semanas mediante muestreo no probabilistico. Se empleo el Cuestionario sobre la Salud del Paciente PHQ-9, la Escala del Trastorno de Ansiedad Generalizada GAD-7 y la Escala analoga visual de conductas de autocuidado. Se realizaron analisis descriptivos y de comparacion entre los grupos con ansiedad y depresion. Resultados: Se incluyeron 1508 participantes, 20.8 % presento sintomas de ansiedad grave y 27.5 %, sintomas de depresion grave. Ser mujer, soltero(a) no tener hijos, presentar comorbilidad medica y antecedentes de atencion a la salud mental estuvieron relacionados con la presencia de mayores niveles de sintomas de ansiedad y depresion; 66 a 80 % de la poblacion cumplia con las recomendaciones de autocuidado. Se identifico la necesidad de recibir atencion de salud mental. Conclusion: Se observo mayor numero de individuos con sintomas de ansiedad y depresion moderadas a graves que en otras pandemias. Los efectos psicologicos de la pandemia de COVID-19 se consideran un problema de salud mental publica emergente, por lo que se recomienda la implementacion de programas para su atencion. EnglishIntroduction: The COVID-19 pandemic can have important psychosocial consequences in the population. Objective: To determine the levels of anxiety, depression and self-care symptoms during the COVID-19 pandemic in the general population. Method: Online survey distributed over three weeks using a non-probability sampling. The PHQ-9 Patient Health Questionnaire, the GAD-7 Generalized Anxiety Disorder Scale and Visual analog scale for self-care behaviors were used. Between-group (anxiety and depression) descriptive and comparison analyses were carried out. Results: Out of 1508 included participants, 20.8% had symptoms of severe anxiety, while 27.5% showed symptoms of severe depression. Being a woman, being single, having no children, having medical comorbidities and a history of mental health care were risk factors for developing symptoms of anxiety and depression; 66 to 80 % of the population complied with self-care recommendations. A need for receiving mental health care was identified in our study population. Conclusion: A larger number of individuals with moderate to severe anxiety and depression symptoms were observed than in other pandemics. COVID-19 pandemic psychological effects are considered an emerging public health problem, and implementation of programs for their care is therefore recommended.

Hypertrophy of adenotonsillar tissue is the most common cause of OSAS in otherwise healthy children, and therefore adenotonsillectomy is the first line treatment. Scientific societies recommend nocturnal follow-up PSG to assess for residual OSAS in children with preoperative evidence for moderate to severe OSAS, obesity, craniofacial anomalies that obstruct the upper airway and neurological disorders, based on the increasing trend of publications reporting residual OSAS after adenotonsillectomy. Follow-up PSG values in children with a pre-operative diagnosis of severe OSAS were analysed retrospectively, and compared to the parents' impression after ENT surgery. The study population included 41 healthy children with severe OSAS and adenotonsillar surgery. The percentage of children with normal PSG parameters (AHI

Therapeutic hypothermia acts as the standard of care for infants with moderate to severe hypoxic ischemic encephalopathy (HIE). A proportion of neonates who undergo hypothermia due to HIE have shown to develop various degrees of hearing impairment. Analyzing and identifying infants at high risk of developing hearing difficulties is fundamental for early intervention of such auditory complications. The aim was to assess clinical factors in the development of hearing impairment following therapeutic hypothermia in HIE infants. A retrospective analysis was performed on infants hospitalized in our neonatology department in Poznan University of Medical Sciences, Poland. All infants experienced moderate to severe HIE, and were treated with therapeutic hypothermia. Risk factors for hearing impairment were identified in all infants included in the study. Clinical data during hospital stay and follow-up hearing status were analyzed. A total of 87 HIE infants were included in the study. Seventy-six infants (40 male and 36 female) had otoacoustic emission (OAE) examination following birth, of which 14 (18.4%) demonstrated abnormal (positive) results. Infants with abnormal OAE results had significantly lower blood pH (6.86 ± 0.16

Objectives We examined the association between birthweight and objectively measured hearing loss in older men and women. Study design 893 community-dwelling participants aged 50+ years with pure-tone audiometry data and self-reported birthweight were included for cross-sectional analysis. Participants were asked how much they weighed at birth either in pounds and ounces or in kilograms and grams. Main outcome measures The pure-tone average of frequencies 0.5, 1.0, 2.0 and 4.0 kHz (PTA0.5-4kHz) >25 dB HL in the better ear established the presence of hearing loss. Results Around 31.9% and 50.0% of participants who self-reported low ( 4.5 kg), respectively, had hearing loss. The odds of experiencing any level of hearing loss (>25 dB HL) after multivariate adjustment was: OR 2.00 (95% CI 1.13-3.56) for low birthweight and OR 2.43 (95% CI 1.23-4.82) for high birthweight, compared with participants in the reference group who self-reported normal birthweight (3.1-4.0 kg). Additionally, participants with high birthweight had 2.4-fold greater odds of having mild hearing loss (25-40 dB HL), while participants with low birthweight had 2.6-fold greater odds of moderate to severe hearing loss. Conclusions We observed an independent U-shaped association between birthweight and age-related hearing loss, that is, persons born with low or high birthweight had a greater likelihood of experiencing any level of hearing loss in older age. These findings provide further evidence to address an important gap in the literature regarding the influence of foetal growth on the auditory system in later life.

STUDY OBJECTIVES: (1) To determine the sensitivity and specificity of the home sleep apnea test (HSAT) performed in typically developing children who were diagnosed with moderate to severe obstructive sleep apnea during overnight attended laboratory polysomnography (LPSG). (2) To determine the utility of a screening questionnaire to identify children at increased risk for obstructive sleep apnea. METHODS: Participants completed 2 consecutive study nights, the first night with the HSAT followed by LPSG on the second night. The SHOOTS questionnaire, composed of 6 questions (snoring, hyperactivity, obesity, observed apnea, tonsillar hypertrophy, and sleepiness) concerning sleep-disordered breathing, was administered by the clinician before the first study night. RESULTS: Thirty-eight participants completed both studies. The mean age was 13.8 ± 3.0 years. Twenty (53%) were male. Most participants were obese. The mean LPSG total sleep time was 7.34 ± 1.19 hours; the mean HSAT total recording time was 8.86 ± 1.73 hours (P < .001). The median obstructive apnea-hypopnea index for LPSG and HSAT was 6.6 and 0.8 events/h, respectively. For an obstructive apnea-hypopnea index ≥ 3.1 events/h by HSAT, the sensitivity was 71.43% (95% confidence interval, 41.9–91.6) and the specificity was 95.83% (95% confidence interval, 78.9–99.9) for identifying those with an LPSG obstructive apnea-hypopnea index of ≥ 10 events/h. For a SHOOTS score with ≥ 4 “yes” responses, the sensitivity and specificity were 85.7% (95% confidence interval, 57.2–98.2) and 54.2% (95% confidence interval, 32.8–74.4), respectively, for identifying those with an LPSG obstructive apnea-hypopnea index ≥ 10 events/h. CONCLUSIONS: Using HSAT, we clinically applied cutoff values to identify moderate to severe obstructive sleep apnea in typically developing children. The SHOOTS questionnaire may aid in identifying children at risk for obstructive sleep apnea and who are candidates for HSAT. CITATION: Revana A, Vecchio J, Guffey D, Minard CG, Glaze DG. Clinical application of home sleep apnea testing in children: a prospective pilot study. J Clin Sleep Med. 2022;18(2):533–540.

Background After treatment of intrauterine adhesions, the rate of re-adhesion is high and the pregnancy outcome unpredictable and unsatisfactory. This study established and verified a decision tree predictive model of live birth in patients after surgery for moderate-to-severe intrauterine adhesions (IUAs). Methods A retrospective observational study initially comprised 394 patients with moderate-to-severe IUAs diagnosed via hysteroscopy. The patients underwent hysteroscopic adhesiolysis from January 2013 to January 2017, in a university-affiliated hospital. Follow-ups to determine the rate of live birth were conducted by telephone for at least the first postoperative year. A classification and regression tree algorithm was applied to establish a decision tree model of live birth after surgery. Results Within the final population of 374 patients, the total live birth rate after treatment was 29.7%. The accuracy of the model was 83.8%, and the area under the receiver operating characteristic curve (AUC) was 0.870 (95% CI 7.699–0.989). The root node variable was postoperative menstrual pattern. The predictive accuracy of the multivariate logistic regression model was 70.3%, and the AUC was 0.835 (95% CI 0.667–0.962). Conclusions The decision tree predictive model is useful for predicting live birth after surgery for IUAs; postoperative menstrual pattern is a key factor in the model. This model will help clinicians make appropriate clinical decisions during patient consultations.

OBJECTIVE The reduction of goal-directed behavior, termed apathy, is a pervasive and debilitating syndrome after traumatic brain injury (TBI). However, understanding of apathy as a multifaceted construct is limited, especially in Southeast Asian nations. This study aimed to investigate the severity, insight, and psychosocial influences of apathy in executive, emotional, and initiation dimensions in Vietnam-a country with high prevalence of TBI. METHOD One hundred and eleven Vietnamese participants (61 individuals with moderate to severe TBI and 50 healthy controls) and their informants completed the self-rated and informant-rated Dimensional Apathy Scale (DAS) for the assessment of executive, emotional, and initiation apathy severity. Insight of apathy was calculated by subtracting DAS self-ratings from informant ratings. Additionally, carers completed measures assessing psychosocial factors of overall family health and overprotective behavior, while participants rated their own self-efficacy. RESULTS Our results showed greater informant-rated apathy for all three dimensions in individuals with TBI relative to controls. However, while people with TBI had greater self-rated initiation apathy, they regarded their executive apathy as lower and their emotional apathy as similar compared with controls. Reduced insight in patients was seen for executive and initiation apathy. Across participants, executive apathy was predicted by family functioning and overprotectiveness, emotional apathy was predicted by family functioning, and initiation apathy was predicted by self-efficacy. CONCLUSIONS These findings support the multidimensional characterizations and socio-cultural considerations of apathy after TBI, which will potentially develop both individual-specific and symptom-specific approaches in clinical practice. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Aim To identify the association between vitamin D (VD) concentrations and the activity of systemic lupus erythematosus (SLE) and determine a supplementation dose that allows patients to maintain adequate levels of VD. Methods Longitudinal, observational study. Serum levels of 25-hydroxy-VD were measured in 100 Paraguayan SLE patients from the Hospital de Clinicas between 2016 and 2018. To analyze the response to different doses of VD supplementation, 50 patients received 1000 IU/day and the other 50 patients received 2000 IU. SLE disease activity measured by SELENA-SLEDAIwas scored before and after supplementation. Results The mean age was 27.5 ± 9.8 years, 88.9% of patients presented mild disease activity and 11.1% presented moderate to severe activity. The mean VD concentration was 30.8 ± 11.8 ng/mL. A total of 34% of patients presented VD insufficiency and 13% VD deficiency. There was an inverse relationship between VD concentrations and SLE disease activity (p = 0.03). Increasing levels of serum VD are associated with supplementation of 2000 IU/day (p = 0.0224). Conclusion SLE activity was associated with low levels of VD. In our cohort, SLE patients required a supplementation dose equal to or greater than 2000 IU/day to increase their serum VD.

BackgroundNon-invasive oxygen saturation (SpO2) measurement is a central vital sign that supports the management of COVID-19 patients. However, reports on SpO2 characteristics (patterns and dynamics) are scarce and none, to our knowledge, has analysed high resolution continuous SpO2 in COVID-19. MethodsSpO2 signal sampled at 1Hz and clinical data were collected from COVID-19 departments at the Rambam Health Care Campus (Haifa, Israel) between May 1st, 2020 and February 1st, 2021. Data from a total of 367 COVID-19 patients, totalling 27K hours of continuous SpO2 recording, could be retrieved, including 205 non-critical and 162 critical cases. Desaturations based on different SpO2 threshold definitions and oximetry derived digital biomarkers (OBMs) were extracted and compared across severity and support levels. FindingsAn absolute SpO2 threshold at 93% was the most efficient in discriminating between critical and non-critical patients without support or under oxygen support. Under no support, the non-critical group depicted a fold change (FC) of 1 {middle dot}8 times more frequent desaturations compared to the critical group. However, the hypoxic burden was 1 {middle dot}6 times more important in critical versus non-critical patients. Other OBMs depicted significant differences, notably the percentage of time below 93% SpO2 (CT93) was the most discriminating OBM. Mechanical ventilation depicted a strong effect on SpO2 by significantly reducing the frequency (1 {middle dot}85 FC) and depth (1 {middle dot}21 FC) of desaturations. OBMs related to periodicity and hypoxic burden were markedly affected up to several hours before the initiation of the mechanical ventilation. InterpretationThis is the first report investigating continuous SpO2 measurements in hospitalized patients affected with COVID-19. SpO2 characteristics differ between critical and non-critical patients and are impacted by the level of support. OBMs from high resolution SpO2 signal may enable to anticipate clinically relevant events, monitoring of treatment response and may be indicative of future deterioration. FundingThe Milner Foundation, The Placide Nicod fundation and the Technion Machine Learning and Intelligent Systems center (MLIS).

Background: In JADE COMPARE, abrocitinib improved severity of atopic dermatitis (AD) and demonstrated rapid itch relief. Objectives: We examined clinically meaningful improvements in selected patient-reported outcomes (PROs). Methods: JADE COMPARE was a multicentre, phase 3 randomized, double-blind, placebo-controlled trial. Adults with moderate-to-severe AD were randomized 2:2:2:1 to receive 16 weeks of oral abrocitinib 200 or 100 mg once daily, dupilumab 300 mg subcutaneous injection every 2 weeks, or placebo, with background topical therapy. PROs included Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), Night Time Itch Scale (NTIS), Pruritus and Symptoms Assessment for Atopic Dermatitis, Patient Global Assessment, SCORing Atopic Dermatitis, and Hospital Anxiety and Depression Scale. Results: At week 16, the proportion of patients achieving POEM scores

Introduction The risk of experiencing psychiatric symptoms related to the COVID-19 pandemic is high among healthcare workers whose occupations are in public health, emergency medicine, and intensive or critical care. Materials and methods A cross-sectional study aimed to assess the prevalence of fear of COVID-19 among 411 frontline Egyptian physicians during the COVID-19 pandemic; identify determinants and predictors for fear of COVID-19; determine the impact of fear of COVID-19 on job satisfaction; and detect the impact of fear of COVID-19 on turnover intention. Three standardized scales (fear of COVID-19, job satisfaction, and turnover intention scores) were used for data collection via online Google Form. Results Regarding fear relating to the COVID-19 pandemic, 16.5% of the study subjects were classified as experiencing a severe fear level, while 78.1% experienced a moderate degree. A significant association between the level of fear relating to COVID-19 and the work department. The highest degree of fear is in a general-educational-university facility. Regarding job satisfaction, 42% of those having a severe level of fear are dissatisfied. Fear of COVID-19 is negatively associated with job satisfaction while positively significant correlated with turnover scores, a positive significant predictor of turnover intention. Job satisfaction is negatively associated with turnover intention; a negative significant predictor of turnover intention. Conclusions Frontline Egyptian physicians reported higher levels of fear relating to the COVID-19 pandemic (moderate to severe). Increased fear levels relating to COVID-19 have a relationship with lower levels of job satisfaction and higher levels of job turnover.

Background: COVID-19 disease is caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). In the first half of 2020 COVID-19 disease has already converted into a global pandemic. Many treatment options were explored through the world. Aims and Objectives: To compare the efficacy and outcome of methylprednisolone (MTP) and dexamethasone (DEXA) in moderate-to-severe COVID-19 disease. Materials and Methods: In this prospective study, a total of 140 moderate to severe COVID-19 patients were enrolled from 15 April to June 15, 2021. These patients were randomly allocated into two groups, 70 patients were received MTP 2 mg/kg/day for 3 days followed by 1.0 mg/kg/day for 3 days in divided doses while 70 patients received DEXA 8 mg/day in divided dose up to 10 days. Results: The mean age was 45.5 years in MTP group whereas 45.34 years in DEXA group. The clinical outcome in MTP group and DEXA group was assessed in terms of clinical improvement (92.85% vs. 81.42%), radiological improvement (82.85% vs. 68.57%), transfer to ICU (5.71 vs. 14.57%), needs of ventilatory support (2.85% vs. 8.57%) and mortality (7.14% vs. 18.57%) respectively. Conclusion: In this study, MTP demonstrated better outcome as compared to DEXA in COVID-19 patients.

OBJECTIVE: To review experience of fenestrated-branched endovascular aortic repair (F-BEVAR) for pararenal/thoraco-abdominal aortic aneurysms (PRAA/TAAA) and to assess the association between pre-operative moderate to severe chronic kidney disease (CKD) and post-operative outcomes. METHODS: All consecutive patients undergoing (elective and non-elective) F-BEVAR at a single centre (1 January 2011 - 1 July 2019) were identified. Renal function was calculated as the estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula. Accordingly, presence of moderate to severe CKD was defined as eGFR < 60 mL/min/1.73m2. RESULTS: Overall, 202 consecutive patients (mean age 72 ± 8 years; 25% women) underwent F-BEVAR for the treatment of PRAA/TAAA during the study period. Of these, 51 had a history of moderate to severe CKD (none on chronic haemodialysis). No statistically significant differences were found in demographics and major comorbidities between patients with or without a history of CKD. The overall peri-operative mortality rate was 2%, without statistically significant differences between study groups (p = .26). Patients with prior CKD had statistically significantly higher rates of acute kidney injury (AKI) (37% vs. 12%, p < .001). At three years, overall survival was statistically significantly lower in patients with history of CKD compared with those without pre-operative CKD (57% vs. 82%, p = .010). Similarly, freedom from renal function decline at three years was statistically significantly poorer in patients with prior history of CKD compared with those without pre-operative CKD (43% vs. 80%, p = .020). In a multivariable analysis CKD was independently associated with higher odds of peri-operative AKI (OR 2.8, 95% CI 1.9 - 5.8, p = .030), renal function decline (OR 4.9, 95% CI 1.7 - 9.2, p = .003), and all cause mortality (HR 3.2, 95% CI 1.2 - 8.6, p = .020). CONCLUSION: Despite low peri-operative mortality rates that are comparable to patients with unimpaired renal function, occurrence of AKI was statistically significantly higher in subjects with pre-existing moderate to severe CKD. History of CKD was independently associated to renal function decline and poorer midterm survival.

Resumen Introducción. Los pacientes con cáncer presentan niveles significativos de malestar emocional. La National Comprehensive Cancer Network (NCCN) desarrolló un instrumento (Distress Management) para evaluarlo de forma rápida en pacientes oncológicos. Para su utilización en Colombia, se hizo la adaptación transcultural y se validó. Objetivo. Determinar las características operativas del instrumento de malestar emocional, versión 2.2018, en pacientes atendidos en el Instituto Nacional de Cancerología. Materiales y métodos. Previa autorización de la NCCN, se procedió a la traducción, adaptación transcultural y evaluación de las características operativas del instrumento. Se incluyeron 343 pacientes con diagnóstico de cáncer atendidos en el Instituto Nacional de Cancerología, quienes diligenciaron el instrumento adaptado transculturalmente. Se efectuó un estudio de prueba diagnóstica como patrón de referencia mediante una entrevista semiestructurada. Resultados. Los pacientes tenían una edad promedio de 49,7 años (DE=15) y la mayoría (67 %) eran mujeres. El instrumento tuvo un área bajo la curva ROC de 0,81 (IC95% 0,77- 0,86); el punto de corte óptimo fue de 3,5, el cual se aproximó a 4; la sensibilidad fue de 0,81 (IC95% 0,76-0,85) y la especificidad de 0,69 (IC95% 0,64-0,74). El porcentaje de acuerdo entre el resultado de la entrevista y el instrumento fue de 73 % (kappa=0,64; p

Introduction. The high incidence of community-acquired pneumonia and the high complication rates in the cases of severe pneumonia actualize the search for new pharmacotherapy tools to improve the effectiveness of standard patient management regimens. A high level of severe inflammatory response underlies the high risk for developing septic complications of pneumonia, along with impaired immune responses.The aim is to evaluate the efficacy of azoximer bromide introduction in the combination therapy regimen for hospitalized patients with moderate to severe community-acquired pneumonia.Materials and methods. A prospective, open label, parallel group, randomized study comparing the efficacy of azoximer bromide introduction in the combination therapy of hospitalized patients with moderate to severe community-acquired pneumonia was conducted at the premises of Federal Scientific and Clinical Center for Reanimatology and Rehabilitation. 30 patients were included in the study group and 37 patients in the comparator group. The baseline characteristics were comparable in both groups. Results. The azoximer bromide introduction in the combination therapy of patients with community-acquired pneumonia led to a statistically significant reduction in the duration of hospital stay (Me (LQ; HQ): 9 (8; 10) days for the study group and 13 (10; 14) days for the comparator group, (p = 0.000078), duration of ICU stay (Me (LQ; HQ) 2 days (1.5; 2.5) and 5 days (5.0; 6.0), respectively, (p = 0.00001), the duration of febrile fever 5 (± 0.6) days versus 10 (± 1.2) days (p = 0.0000), the incidence of acute respiratory failure (13.33% in group 1 versus 37.84% in group 2, p = 0.024) and septic shock (10% in group 1 versus 32.43% in group 2, p = 0.0285).Conclusions. The azoximer bromide introduction in the standard therapy regimen for patients with community-acquired pneumonia allowed to reduce the duration of hospital stay, the duration of ICU stay, the length of febrile fever, the incidence of septic shock and respiratory failure. The possible mechanisms of action may include a reduction of the severe inflammatory reactions and an optimization of the patient's immune response to the infectious process.

Introduction We present certolizumab pegol (CZP) efficacy data across patient demographic and baseline disease characteristic subgroups from a phase 2/3 trial investigating CZP treatment in Japanese patients with moderate to severe plaque psoriasis (PSO; ClinicalTrials.gov identifier: NCT03051217). Methods Patients were randomised 1:2:2 to placebo once every 2 weeks (Q2W), CZP 400 mg Q2W and CZP 200 mg Q2W (400 mg weeks 0, 2 and 4) for 16 weeks. Patients who achieved ≥ 50% reduction in their baseline Psoriasis Area and Severity Index (PASI 50) score at week 16 continued therapy to week 52. PASI 75/90 (75% and 90% reduction, respectively) and Physician’s Global Assessment (PGA) 0/1 responder rates at weeks 16 and 52 were reported for patient demographic and baseline disease characteristic subgroups, including body mass index (BMI), PASI, disease duration and prior biologic use. Non-responder imputation was used. Results Of the randomised patients, 2/26 patients in the placebo group, 47/53 patients in the CZP 400 mg Q2W group and and 39/48 patients in the CZP 200 mg Q2W group completed week 52. In the subgroups evaluated, week 16 efficacy was generally maintained through week 52. At week 52, PASI 75 was achieved by 84.2, 85.7 and 80.0% of patients receiving CZP 400 mg Q2W in the low (15.0–23.7 kg/m2)/intermediate (> 23.7–27.4 kg/m2)/high (> 27.4–47.0 kg/m2) BMI subgroups, respectively, and by 77.8, 70.6 and 69.2%, respectively of patients treated with CZP 200 mg Q2W. PASI 75 at week 52 was achieved by 92.9, 75.0 and 84.2% of patients receiving CZP 400 mg Q2W in the low (12.0–18.0)/intermediate (> 18.0–27.0)/high (> 27.0–67.2) baseline PASI subgroups, respectively, and by 85.0, 58.3 and 68.8% of patients receiving CZP 200 mg Q2W, respectively. Similar responses were observed across other subgroups evaluated for both CZP doses in PASI 75/90 and PGA 0/1. Conclusion Clinically meaningful improvements in signs and symptoms of PSO were maintained through week 52 for CZP dosed at 400 mg Q2W or 200 mg Q2W, across patient subgroups. In general, a numerically greater response was observed for patients receiving CZP 400 mg Q2W versus those receiving CZP 200 mg Q2W across patient subgroups. Trial Registration ClinicalTrials.gov identifier, NCT03051217. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00645-2.

Introduction This retrospective consecutive study compared standalone implantation of multiple (2–3) trabecular micro-bypass stents (iStent inject ± iStent) (Multi-Stent group) vs trabeculectomy + mitomycin C (Trab group) in moderate to severe open-angle glaucoma (OAG). Methods Eligible patients underwent Multi-Stent or Trab surgery from 2018 to 2020 and had at least 3-month follow-up; visual field mean deviation (VF MD) − 6 dB or worse; inadequate prior response to maximum medications ± laser procedures; and had trabeculectomy as their next planned intervention. Primary effectiveness, safety-adjusted treatment success, was defined as ≥ 20% intraocular pressure (IOP) reduction on the same or fewer medications, without clinically significant safety events (severe complications, secondary surgeries, reinterventions). Secondary effectiveness included mean IOP and medications; qualified and complete attainment of target IOP (≤ 21/18/15/12 mmHg and > 6 mmHg); health-economic and quality-of-life (QoL) measures; and 2-vs-3-stent subgroup analysis. Results The baseline groups (n = 70 Multi-Stent/40 Trab) were similar: mean IOP (21.1 mmHg/22.3 mmHg); medications (2.87/3.10 medications); disease stage (30%/35% severe); VF MD (− 10.1 dB/− 10.4 dB); and mean last follow-up (LFU, 13.1 months/15.7 months) (all differences non-significant). Primary effectiveness: treatment success at LFU was 62.9% vs 30.0% in Multi-Stent vs Trab eyes, respectively (p = 0.001). Secondary effectiveness: At LFU in Multi-Stent vs Trab groups, respectively: mean IOP decreased by 31% to 14.2 mmHg (p

Objective To identify group-based patterns in suicidal ideation (SI) over the first 10 years after traumatic brain injury (TBI). Methods Participants included 9539 individuals in the TBI Model Systems National Database who responded to Patient Health Questionnaire-9 Item 9 assessing SI at 1, 2, 5, and/or 10 years post-injury. A k-means cluster analysis was conducted to determine group-based patterns of SI, and pre-injury variables were compared with ANOVAs and chi-square tests. Results SI and attempts decreased over time. Four group-based patterns emerged: Low, increasing, moderate, and decreasing SI. The low SI group comprised 89% of the sample, had the highest pre-injury employment, fewer mental health vulnerabilities, least severe injuries, and were oldest. The increasing SI group had the most severe TBIs, were youngest, and disproportionately Black or Asian/Pacific Islander. Conclusion These findings reinforce the importance of mental health and suicide risk assessment during chronic recovery from TBI.

Objective: To determine if a brief, one-on-one pain neuroscience education (PNE) session delivered by a physical therapist (PT) can influence depression. Methods: A convenience sample of patients with persistent low back pain (LBP) (n = 23) attending PT with moderate to severe depression (Patient Health Questionnaire-9 [PHQ-9]) participated in the study. Patients received a standardized, one-on-one 30-minute PNE session by a PT with pre- and post-intervention measures of low back and leg pain (Numeric Pain Rating Scale [NPRS]), pain catastrophization (Pain Catastrophization Scale [PCS]), pain knowledge (Revised Neurophysiology of Pain Questionnaire [rNPQ] and depression (PHQ-9). Results: Immediately following PNE, all measures improved, with low back and leg pain not being significant (pback = 0.345 and pleg = 0.633), while pain catastrophization (p = 0.047), pain knowledge (p = 0.001) and depression (p = 0.004) reaching significant improvements. The PNE session shifted various patients to lower levels of depression, with 21.8% of the patients’ improvement in depression meeting or exceeding the minimal clinical important difference. Conclusion: PNE may be a safe, clinically effective way to help a subgroup of patients attending PT with depression. More studies are needed to further explore the results from this pilot study.

Objective Although prior research has examined the prevalence of ACEs among children with attention deficit-hyperactivity disorder (ADHD), little is known about the household and family settings of children with ADHD. Our study utilizes a recent nationally representative dataset to examine the association between adverse childhood experiences (ACEs), child and household characteristics, and ADHD diagnosis and severity. Methods Using the 2017–2018 National Survey of Children's Health (NSCH), our sample consisted of children three years of age or older, as this is the youngest age at which the NSCH begins to ask caregivers if a child has been diagnosed with ADHD (n = 42,068). Multivariable logistic regression was used to examine the association between ACE type, score, and ADHD and ADHD severity, controlling for child and household characteristics. Results Children exposed to four or more ACEs had higher odds of ADHD (aOR 2.16; 95% CI 1.72–2.71) and moderate to severe ADHD (aOR 1.89; 95% CI 1.31–2.72) than children exposed to fewer than four ACEs. Other child characteristics positively associated with ADHD included age and public insurance; other Non-Hispanic races compared to Non-Hispanic White had lower odds of ADHD. Of children reported with ADHD, public insurance was also associated with caregiver-reported moderate to severe ADHD. Conclusions Children with ADHD have a higher prevalence of ACEs, making this study important for understanding the relationship between ACEs and ADHD at the population level.

Géotechnique (2021). doi:10.1680/jgeot.19.SiP.024, Published by ICE Publishing, London

Monoclonal antibodies targeting IgE, interleukin-4 and -13, and interleukin-5 are effective in treating severe type 2 asthma, but new targets are needed. Itepekimab is a new monoclonal antibody against the upstream alarmin interleukin-33. The efficacy and safety of itepekimab as monotherapy, as well as in combination with dupilumab, in patients with asthma are unclear.In a phase 2 trial, we randomly assigned, in a 1:1:1:1 ratio, adults with moderate-to-severe asthma receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs) to receive subcutaneous itepekimab (at a dose of 300 mg), itepekimab plus dupilumab (both at 300 mg; combination therapy), dupilumab (300 mg), or placebo every 2 weeks for 12 weeks. After randomization, LABA was discontinued at week 4, and inhaled glucocorticoids were tapered over weeks 6 through 9. The primary end point was an event indicating a loss of asthma control, assessed in the itepekimab group and the combination group, as compared with the placebo group. Secondary and other end points included lung function, asthma control, quality of life, type 2 biomarkers, and safety.A total of 296 patients underwent randomization. By 12 weeks, an event indicating a loss of asthma control occurred in 22% of the patients in the itepekimab group, 27% of those in the combination group, and 19% of those in the dupilumab group, as compared with 41% of those in the placebo group; the corresponding odds ratios as compared with placebo were as follows: in the itepekimab group, 0.42 (95% confidence interval [CI], 0.20 to 0.88; P = 0.02); in the combination group, 0.52 (95% CI, 0.26 to 1.06; P = 0.07); and in the dupilumab group, 0.33 (95% CI, 0.15 to 0.70). As compared with placebo, the forced expiratory volume in 1 second before bronchodilator use increased with the itepekimab and dupilumab monotherapies but not with the combination therapy. Itepekimab treatment improved asthma control and quality of life, as compared with placebo, and led to a greater reduction in the mean blood eosinophil count. The incidence of adverse events was similar in all four trial groups.Interleukin-33 blockade with itepekimab led to a lower incidence of events indicating a loss of asthma control than placebo and improved lung function in patients with moderate-to-severe asthma. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT03387852.).

The recent advent of numerous clinical trials for the treatment of moderate-to-severe atopic dermatitis has led to new and emerging therapeutic options for this chronic inflammatory skin disease. With this rapid development has come a lack of consistency in study designs, trial conduct, and statistical analyses. Healthcare providers are challenged to interpret how variations in study parameters may influence clinical trial results. Based on literature review and our experience as clinical trialists, we compiled a list of 22 key study parameters of contemporary clinical trials in moderate-to-severe atopic dermatitis and ranked the top study parameters that may have a significant effect on efficacy results. The top parameters included study comparators, rules for rescue treatment, washout periods for topical and systemic treatments, inclusion criteria such as disease severity by Eczema Area and Severity Index and/or Investigator Global Assessment scores, and the duration of the screening period. We describe considerations for these key parameters, with a focus on between-parameter interactions and effect on efficacy results. This may serve to inform the interpretation of atopic dermatitis clinical trials and raise the profile of the need to harmonize the clinical trial design., Plain Language Summary Atopic dermatitis (AD) is a skin disease characterized by red, itchy skin that is highly burdensome for patients. Patients with moderate-to-severe disease have large, inflamed skin areas with frequent itching. Recently, the number of clinical trials for drugs that treat moderate-to-severe AD has rapidly increased, with differences in how these trials are designed. There is a need for healthcare providers examining results from different clinical trials to understand how trial design factors might influence study outcomes. In this article, we identify key trial design factors that impact study outcomes, detail how these factors can impact clinical trial results, and explore how these factors interact with one another to affect study outcomes. The five most important design factors, as determined via author surveys, were study comparators (a placebo and/or another drug to which the drug being studied is compared); the rules for the use of rescue treatment (a form of treatment given if an enrolled participant has uncontrolled AD symptoms); washout periods (the time before the trial when previous treatments are stopped to allow them to be cleared from a patient’s system); inclusion criteria (that determine which participants are included); and the length of the screening period (the time when patients are assessed to determine if they qualify for participation). By understanding how these key trial design factors impact on study outcomes, healthcare providers may be equipped to better interpret different AD clinical trials. This work also emphasizes the value of harmonizing the AD clinical trial design. Graphic abstract

Parental depressive symptoms and their related factors have not been widely examined during the COVID‐19 pandemic. Therefore, the current study examined the actor and partner associations of work–family conflict and parental depressive symptoms. Considering the new demands and challenges for families during the COVID‐19 pandemic, we further explored the moderation effect of coparenting. A cross‐sectional online survey with 985 paired fathers and mothers was conducted in Mainland China. In 11.6% of families, only mothers reported moderate to severe depressive symptoms; in 10.6% families, only fathers reported moderate to severe depressive symptoms; in 9.5% families, the mother and father reported mild to moderate depressive symptoms. Results of the actor–partner interdependence model showed that parental family‐to‐work conflict was negatively associated with their own depressive symptoms. The negative actor association of maternal family‐to‐work conflict and depressive symptoms was moderated by undermining coparenting. The partner effects of maternal family‐to‐work and work‐to‐family conflicts on paternal depressive symptoms were moderated by undermining coparenting. Moreover, supportive coparenting moderated the actor association of work‐to‐family conflict and the depressive symptoms of fathers. Results highlight the importance of family‐to‐work conflict and family function for parental depressive symptoms. These findings can help promote parental well‐being during the COVID‐19 pandemic.

Introduction. Tofacitinib is the first member of a new class of targeted synthetic anti-inflammatory drugs for the treatment of ulcerative colitis (UC). The article presents a three-year Russian experience of tofacitinib use for the treatment of moderate and severe UC.Aim of the study. To evaluate the efficacy and safety of tofacitinib therapy in real clinical practice in moderate to severe UC patients during three years of follow-up. Methods. The study included 56 patients with UC who had moderate (60.7%) and severe (35.8%) states of disease, the total lesion was diagnosed in 67.8%, and extraintestinal manifestations in 57.1% of patients. Early achievement of clinical response, clinical and endoscopic, corticosteroid-free remission, and safety were evaluated.Results. Early response to tofacitinib therapy was obtained in 47 (83.9%) patients. Clinical remission was achieved in 36 (64.3%) at week 8 of therapy and clinical response was achieved in 13 (23.2%) patients. The majority of patients who achieved clinical remission at weeks 8 and 12 achieved healing of colon mucosa at week 24. Clinical and endoscopic remission rates after 24 weeks – 44 (78.6%) patients, clinical response in 7 (12.5%) patients, 5 (8.9%) did not respond to TFCB therapy. Corticosteroidfree remission was 77.6%. After 2 years of tofacitinib therapy, remission of UC was maintained in 46 (82.1%). After 36 months, remission of UC was maintained in 45 (80.3%) of the 56 patients who had been started on tofacitinib therapy. The cumulative effect of survival in the treatment of tofacitinib in UC was 87.5% after 6 months and persisted for one year, 82.1% after 2 years, and 80.3% after 3 years.Conclusions. The administration of tofacitinib in UC is effective in achieving rapid clinical response, clinical remission, and mucosal healing in patients who do not respond well to biological therapy.